Tetrahedron: Asymmetry 22 (2011) 970–979

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Tetrahedron: Asymmetry

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Synthesis of ferrocene-based amido-phosphine ligandsvia highly diastereoselective ortho-lithiation and their applicationin Pd-catalyzed asymmetric allylic alkylations

Irena Philipova a, Georgi Stavrakov a,b, Angel Chimov a, Rositsa Nikolova c, Boris Shivachev c,Vladimir Dimitrov a,⇑a Institute of Organic Chemistry with Center of Phytochemistry, Bulgarian Academy of Science, Acad. G. Bonchev 9, Sofia 1113, Bulgariab Faculty of Pharmacy, Medical University of Sofia, str. Dunav 2, Sofia 1000, Bulgariac Institute of Mineralogy and Crystallography ‘Acad. Ivan Kostov’, Bulgarian Academy of Sciences, Acad. G. Bonchev, bl. 107, Sofia 1113, Bulgaria

a r t i c l e i n f o

Article history:Received 13 April 2011Accepted 10 June 2011

0957-4166/$ - see front matter � 2011 Elsevier Ltd. Adoi:10.1016/j.tetasy.2011.06.014

⇑ Corresponding author. Tel.: +359 2 9606 157; faxE-mail address: vdim@orgchm.bas.bg (V. Dimitrov

a b s t r a c t

An efficient synthesis of novel planar chiral ferrocene-based amido-phosphine ligands was accomplishedvia highly diastereoselective ortho-lithiation and subsequent in situ trapping with chlorodiphenylphos-phine. The palladium complexes of mono-phosphino ferrocenecarboxamide, bis-phosphino ferrocenedi-carboxamide ligands, and analogues with a ferrocenophane framework were applied in the allylicalkylation of (E)-1,3-diphenyl-2-propenyl acetate. The reactions proceeded with excellent conversionsand ee’s of up to 82%, the most efficient being the camphane based mono-phosphino ferrocenecarboxa-mide 2.

� 2011 Elsevier Ltd. All rights reserved.

PPh2

NO

R*R

Pd

Ph

Ph

Fe E

N

OFe

N

N

OO

EE

Fe

N

N

OO

R

R

EE

R*

R*

RR*

I II

III IV

Figure 1.

1. Introduction

Ferrocene derivatives bearing suitable donor atoms and incor-porating both planar and central chirality are well established asone of the most important classes of ligands for asymmetric me-tal-catalyzed reactions.1 The key process for the introduction ofplanar chirality in the ferrocene core is the directed ortho-metalla-tion, influenced by a chiral auxiliary.2 It should be noted thatalthough a great number of chiral catalysts have been designedand tested, the ongoing development of highly selective and effi-cient ligands obtained by using simple synthetic methods contin-ues to be a great challenge.

Recently, we have accomplished the synthesis of planar chiralamido-ferrocenophanes by highly diastereoselective amide-direc-ted ortho-metallation (Fig. 1, I).3 We have also successfully elabo-rated upon an efficient method for the synthesis of 1,2-disubstituted planar chiral ferrocenecarboxamides by a short se-quence of lithiation/electrophilic quench steps (Fig. 1, II). The useof easily accessible amides with a camphane skeleton as directedmetallation groups led to single diastereoisomers with a varietyof electrophiles and allowed the introduction of versatile func-tional groups. Consequently, this approach allows the quick, twosteps synthesis of widely applicable amido-phosphine ligands(Scheme 1).4

ll rights reserved.

: +359 2 8700 225.).

Chiral bidentate ligands containing strong and weak donor het-eroatom pairs have emerged as an important class of ligands forPd-catalyzed asymmetric allylic alkylations, because the differentdonor atoms are able to generate electronic asymmetry on thetransition metal. The latter is mostly demonstrated by ligands withP,N- and P,S-coordination mode.5 By contrast, ligands of the P,O-type are still rather scarce,6 despite the unambiguous proof that

7, R* =

8, R* =

Fe

N

N

OO

R

R

R*

R*Fe

CO2H

CO2H

OH

OEt

4

R*NH2

EDC/HOBtCH2Cl2

NaH/EtIDMF

, R = H, (52%)

, R = Et, (24%)

Scheme 3.

Fe

N

O

O

Fe PPh2

N

O

O

2

1. sBuLiTMEDA

2. ClPPh2

1

Scheme 1.

I. Philipova et al. / Tetrahedron: Asymmetry 22 (2011) 970–979 971

the P,O mode of coordination with Pd gives a catalytically activecomplex (Fig. 1. IV).7

Hence, we directed our efforts towards the preparation of pla-nar chiral ferrocene and ferrocenophane based amido-phosphineligands and their catalytic utilization in the Pd-catalyzed asymmet-ric allylic alkylation. Herein we report a comparative study of theselectivity of mono-phosphino ferrocenecarboxamide (Fig. 1, II,E = PPh2) and bis-phosphino ferrocenedicarboxamide (Fig. 1, III,E = PPh2) ligands, and analogues with the ferrocenophane frame-work (Fig. 1, I, E = PPh2).

2. Results and discussion

Based on our experience that amides with a camphane skeletonare efficient directed metallation groups for the diastereoselectivedeprotonation of ferrocene, we became interested in exploring thereaction with other easily accessible sources from the chiral pool.(�)-b-pinene-derived aminoalcohols appeared as a logical exten-sion of the exploration for terpene-based chiral auxiliaries sincethey have served as chiral directors in a wide variety of organicreactions.8

The synthesis of (�)-b-pinene-derived ferrocenecarboxamide 6was achieved by a quick, two step sequence: condensation of fer-rocenecarboxylic acid 3 with the chosen aminoalcohol in the pres-ence of TBTU/HOBT, gave amide 5 and then its consecutivediethylation (Scheme 2).

5, R* =

R*NH2

6, R* =

Fe O

N R*R

Fe

CO2H

OH

3

OEt

NaH/EtIDMF

TBTU/HOBtCH2Cl2

, R = H, (75%)

, R = Et, (74%)

Scheme 2.

Fe O

N R*R

Fe O

N R*R

E

1. sBuLi/TMEDAPhMe, 3 h, -78 oC

2. EX, -78 oC

6, R* =

9, R* =

10, E = Me,95%, 94:6 dr

11, E = PPh2,90%, >99 dr

12, E = PPh2,61%, 91:9 dr

OEt, R = Et

, R = H

Scheme 4.

Encouraged by the recently reported highly diastereoselectivedirected ortho-metallation in the case of ferrocenecarboxamide1,4 we synthesized its bis-analogue 8 following routine condensa-tion/alkylation procedures (Scheme 3). Thus, 1,10-ferrocenedicar-boxylic acid 4 was converted to the secondary diamide 7, whichwas further alkylated to the desired 8. The yield of 8 was low

due to the stepwise abstraction of the amide groups under thereaction conditions. The formation of a mixed ethylester–amideand diethylester as a result of cleavage of one or both amide func-tions, was detected by NMR.

The key step in the synthesis of the planned planar chiralamido-phosphine ligands was the diastereoselective directedortho-metallation. Applying the established conditions for ortho-lithiation, we tested the newly synthesized (�)-b-pinene-derivedferrocenecarboxamide 6 as a directed metallation group. The useof MeI as an electrophile resulted in excellent yield and a diastere-oselectivity of 94:6 (Scheme 4 and 10). Thereby the desired 1,2-disubstituted planar chiral amido-phosphine ligand 11 was readilyprepared by quenching the reaction with ClPPh2. Oxidation of thephosphine to the corresponding phosphine oxide was minimizedby using a non-aqueous work-up procedure. Subjecting the reac-tion mixture directly to flash column chromatography on silicagel afforded 11 as a single diastereoisomer in excellent yield(Scheme 4). Therefore the high diastereoselectivity of >99% dr re-fers to the isolated 11. The formation of the other diastereoisomercannot be excluded over the course of the reaction sequence oflithiation/quenching with ClPPh2. The purified product is stablein air. It should be noted that ligand 11 exists as an equilibriumof two rotamers in a 60:40 ratio, as judged from its 31P NMR spec-trum at rt, which is probably due to hindered rotation of the amidebond.

972 I. Philipova et al. / Tetrahedron: Asymmetry 22 (2011) 970–979

The design of a secondary amido-phosphine ligand (Scheme 4,12) was considered as an alternative to the tertiary amide struc-tures 2 and 11, in order to open up the possibility for additionaltuning of the ligand properties. Following the above described pro-tocol, amide 9 was subjected to lithiation with an additional equiv-alent of sBuLi due to the presence of the NH group as recentlyreported.4 The desired ligand 12 was isolated after non-aqueouswork-up in good yield and excellent diastereoselectivity (91:9). Sil-ica gel column chromatography allowed a further improvement ofthe dr to 96:4.

The synthesis of a bis-phosphino ferrocenedicarboxamide li-gand was realized by the development of the lithiation procedureto the o,o0-dilithiation of ferrocenedicarboxamide 8. In order todetermine the optimum conditions for maximum conversion andgood diastereoselectivity, we examined the process by varyingthe amount of the lithiation agent and the reaction time. At first,MeI was used as a test electrophile. Optimal conditions wereachieved with 6.4 equiv sBuLi/TMEDA for 4 h at �78 �C (Scheme 5).After column chromatography, we isolated the desired bis-product13 (56% yield), its minor diastereoisomer 14 (7% yield), and theproduct of the mono-lithiation 15 (17% yield, >99 dr). The ratio ofthe major product 13 to the minor product 14 was 88:12, as re-vealed by 1H NMR of the crude reaction mixture.

Fe

N

N

OO

Et

Et

R*

R*

Fe

N

N

OO

Et

Et

R*

R*Fe

N

N

OO

Et

Et

R*

R*

8, R* = +

+

13

14 15

OEt

1. sBuLi/TMEDAPhMe, -78 oC

2. MeI, -78 oC

Scheme 5. Figure 2. ORTEP view of the molecular structure of 10, 50% of probability. H-atomsare presented with spheres of arbitrary radii.

The reaction with ClPPh2 as the electrophile allowed the prepa-ration of the targeted bis-phosphino ferrocenedicarboxamide li-gand (Scheme 6). Direct column chromatography of the reactionmixture gave 16 as a single diastereoisomer in 41% yield. Onlytrace amounts of the mono-substituted product were detected by1H NMR.

Fe

N

N

OO

Et

Et

PPh2Ph2P

R*

R*8

16

1. sBuLi/TMEDAPhMe, -78 oC

2. ClPPh2, -78 oC

Scheme 6.

Figure 3. ORTEP view of the molecular structure of 13, 50% of probability. H-atomsare presented with spheres of arbitrary radii. The second molecule is obtained by(�x, y, �z) symmetry operation.

The absolute configurations of planar chiral compounds 10 and13 were determined by X-ray crystallography as (Rp) and (Rp,Rp),respectively (Figs. 2 and 3 and Table 1). Both compounds crystal-lize in the monoclinic space group C2 (N�5) with one moleculeper asymmetric unit. The cyclopentadienyl rings in both structuresare nearly planar. In the case of compound 13, there is a 3.41(4)�deviation of the Cp-rings being coplanar. In the crystal structures,

no typical hydrogen bonding interactions could be detected. It isinteresting to note that compounds 10 and 13 exist as crystals inthe form of two different rotamers with respect to the space-posi-tion of the groups attached to the N-atoms (best illustrated bysuperposition of the both structures, Fig. 4). The crystals of 10and 13 are enantiomerically pure and the absolute configurationsof the molecules were determined by the diffraction experiment(Cu radiation and flack parameter of 0.002(3) and 0.016(13)). Theresolved structures revealed that the ortho-substituent, the Me-group, is on the side of the carbonyl oxygen. This is in agreementwith our previous discussion concerning the decisive role of the

1. TMPLiPhMe, 6 h, -78 oC

2.Ph 2PCl, -78 oC - rtFe

N

N

OO

17

Fe

N

N

OO

PPh2

18, 36%, >99 dr

Fe

N

N

OO

PPh2Ph2P

19, 19%, >99 dr

+

Scheme 7.

Figure 4. Superposition of the X-ray structures of 10 (in blue) and 13 H-atoms areomitted for clarity.

I. Philipova et al. / Tetrahedron: Asymmetry 22 (2011) 970–979 973

oxygen in the amide-directed ortho-lithiation.4 Since the diastere-oselectivity is dependent upon the ortho-lithiation step and not onthe reaction with the electrophile, the phosphine derivatives 11and 16 should posses the same sense of chirality as their methylanalogues.

Table 1Crystal data and structure refinement indicators for 10 and 13

10 13

Empirical formula C25H35FeNO2 C42H64FeN2O4

Molecular weight 437.40 716.80Crystal size (mm) 0.24 � 0.20 � 0.18 0.30 � 0.24 � 0.22Crystal system Monoclinic MonoclinicSpace group C2 C2T (K) 290 290Radiation wavelength (Å) 1.5418 (Cu Ka) 1.5418 (Cu Ka)a (Å) 21.0855(9) 34.9356(9)b (Å) 8.0943(7) 7.4795(3)c (Å) 13.6722(8) 7.4756(2)sV(Å3) 2333.5(3) 1950.9(2)Z 4 2a (�) 90 90b (�) 90.097(5) 92.837(2)c (�) 90 90d (mg m�3) 1.242 1.220l (mm�1) 5.323 3.422Reflections collected/unique 6841/2774 4393/2564R1 (I > 2r (I)) 0.089 0.048wR2 (all data) 0.206 0.114

Table 2Palladium-catalyzed asymmetric allylic alkylation of racemic (E)-1,3-diphenyl-2-propenyl acetate with dimethyl malonatea

Entry L⁄ Solvent Base Time (h) Yieldb (%) ee(%), confc

1 2 PhCH3 KOAc 3 99 82, (R)2 2 CH3CN KOAc 5 min 99 77, (R)3 2 THF KOAc 1 99 77, (R)4 2 CH2Cl2 KOAc 22 96 74, (R)5 2 PhCH3 NaOAc 22 99 47, (R)6 2 PhCH3 LiOAc 4 99 53, (R)7 2d PhCH3 KOAc 26 90 71, (R)d

8 11 PhCH3 KOAc 5 99 74, (R)9 12 PhCH3 KOAc 22 99 72, (R)10 16 PhCH3 KOAc 2 99 43, (S)11 18 PhCH3 KOAc 22 99 14, (S)12 19 PhCH3 KOAc 28 99 2, (S)13 20 PhCH3 KOAc 7 99 42, (S)

a Reaction conditions: 1 equiv substrate, 0.03 equiv [Pd(g3-C3H5)Cl]2, 0.06 equivligand, 3 equiv N,O-bis(trimethylsilyl)acetamide (BSA), 3 equiv dimethylmalonate,catalytic amount of additive salts.

b Isolated pure products after column chromatography.c Enantiomeric excess determined by HPLC analysis (Chiralpak IA chiral column).

The absolute configuration was determined by comparison of the specific rotationto the literature value, see Ref. 11.

d The reaction was carried out by using 1 mol % [Pd(g3-C3H5)Cl]2 and 4 mol %ligand.

Ferrocenophane based bis-phosphino ferrocenedicarboxamide19 (Scheme 7), which possesses a rigid backbone due to the pres-ence of an intramolecular bridge, was considered as a furtherextension of the undertaken ligand structure/activity study. Re-cently we published the synthesis of ferrocenophane with trans-1,2-diaminocyclohexane as a backbone of the chiral amide linkage17.3 The latter was successfully employed for the introduction ofplanar chirality by an amide directed highly diastereoselectiveortho-lithiation. Optimal conversions were achieved with lithium2,2,6,6-tetramethylpiperidide (TMPLi). Consequent quenchingwith MeI led to the formation of mono- and di-substituted ferroc-enophanes. Their absolute configuration was determined by de-tailed NMR analysis, which corresponded adequately with thepresent results obtained by X-ray crystallography. Analogous re-sults were achieved by performing the reaction with ClPPh2 as anelectrophile. Mono-phosphine 18 (36%) and bis-phosphine 19(19%) were isolated as single diastereoisomers after non-aqueouswork-up and silica gel separation (Scheme 7). The new planar chi-ral compounds 18 and 19 should posses the same sense of chiralityas their methyl analogues.

In all cases, the structures of the newly synthesized compoundswere confirmed by 1D and 2D NMR spectra. Due to the existence ofrotamers, an increase in temperature was necessary for the (�)-b-pinene-derived ferrocenecarboxamides 6, 10, and 11 in order toobtain well resolved 1H and 13C NMR spectra.

Noteworthy isomerization was detected while recording theNMR spectra of phosphine-amide 11 in toluene-d8 at 383 K. Start-ing with the pure diastereoisomer 11, at the end of the experiment,the formation of its diastereoisomer 20 was observed (ratio 11/20 = 60:40, according to the 31P{H} NMR spectrum, Scheme 8). Ina crossover experiment, compound 20 was synthesized by heating11 in toluene at 100 �C for 3 h. The isomer 20 was isolated in 17%yield after column chromatography. It was not possible to enhancethe conversion of 11 to 20 although several experiments were per-formed. There was clear evidence for the diastereomeric nature of11 and 20: (i) very similar but not identical 1H and 13C NMR spec-tra; (ii) different chemical shifts in 31P NMR, d = �19.19 ppm for 11,and �21.39 ppm for 20; (iii) equal molecular mass in CI-MS; and(iv) different ½a�20

D ¼ �103:5 for 11, and = +249.5 for 20. Further-more, the palladium-catalyzed allylic alkylation with 11 and 20as ligands, led to (R)- and (S)-configured products, respectively(see Table 2, entries 8 and 13).

974 I. Philipova et al. / Tetrahedron: Asymmetry 22 (2011) 970–979

A similar phenomenon was previously observed by van Eldiket al.9 who reported a detailed mechanistic study of the process.On the basis of the published mechanism we propose that coordi-nation of the iron to the carbonyl oxygen and the phosphorousatom stimulates the generation of a zwitterionic intermediate fol-lowed by a flip of the Cp-ring and coordination to the iron atom bythe other face of the Cp-ring (Scheme 8).

Fe PPh2N

O

R

*R

Fe PPh2N

O

R

*RFePh2P N

O

R

R*

FePh2P N

O

R

R*

11, R* =

20

OEt

, R = Et

Scheme 8.

Due to the possibility for isomerization, we examined the con-figurational stability of the other mono-phosphine ferrocenecarb-oxamide ligands 2 and 12 under the same conditions. No similarreactions were observed in either case.

The chiral amido-phosphine ligands were employed in the pal-ladium-catalyzed asymmetric allylic alkylation of racemic (E)-1,3-diphenyl-2-propenyl acetate with dimethyl malonate (Scheme 9).The reaction was performed in toluene, in the presence of3 mol % of [Pd(g3-C3H5)Cl]2 and 6 mol % of chiral ligand. The nucle-ophile was generated in situ by Trost0s procedure using N,O-bis(tri-methylsilyl)acetamide (BSA) and a catalytic amount of potassiumacetate.10 Under these conditions the reactions proceeded withexcellent conversion with all of the tested amido-phosphine li-gands. Ligand 2 induced the highest enantioselectivity in favor of(R)-enantiomer of the reaction product (82% ee, Table 1, entry 1).The absolute configuration was determined by comparison of thespecific rotation with the literature value.11 The reaction condi-tions were subsequently optimized for the palladium complex ofligand 2. The influence of several parameters, including solvent,salt additive, and ligand/Pd ratio was investigated. The reactionin CH3CN or THF proceeded much faster but led to a slight decreasein enantioselectivity (77% ee, entries 2 and 3). Poor reactivity and adecrease in the enantioselectivity were observed in CH2Cl2, whichis usually a good solvent for the Pd-catalyzed allylic alkylation (en-try 4). Using sodium acetate or lithium acetate instead of potas-sium acetate led to a large decrease in enantioselectivity (entries5 and 6). The reduction of the amount of [Pd(g3-C3H5)Cl]2 causeda decrease in the reaction rate, and in the enantioselectivity (71%ee, entry 7).

[Pd(C3H5)Cl]2ligand

CH2(COOMe)2

BSAbase, solvent

Ph Ph

OAc

Ph Ph

MeOOC COOMe

Scheme 9.

From the reaction conditions screening experiments, we se-lected a toluene as a solvent, and a potassium acetate as a basefor investigating the influence of ligands on the catalytic activityand enantioselectivity. The (�)-b-pinene derived ligand 11 inducedlower enantioselectivity (74% ee, entry 8) in comparison with thecamphane based analogue 2. Due to the hindered rotation of theamide bond, the P,O-chelate of 11 probably exists as two rotamersand thus affords lower enantioselectivity. The secondary amido-phosphine ligand 12, used with a diastereomeric purity 96:4 dr,also provided moderate enantiomeric excess (72% ee, entry 9).Obviously the catalytic performance (activities and enantioselec-tivities) is highly affected by the substituents on the amidenitrogen.

Contrary to our expectations, employing the bis-phosphino fer-rocenedicarboxamide ligand 16, which is a C2-symmetric analogueof ligand 2, the enantioselectivity greatly decreased (43% ee, entry10). It is also noteworthy that the alkylation product has the oppo-site (S)-configuration in contrast to the one observed with themono-phosphino amide ligands. Both mono-phosphino 18 andbis-phosphino 19 ferrocenophanes afforded excellent conversion.However, the substitution product was obtained with very lowenantioselectivity (14% ee, entry 11) or as a racemate (entry 12).The observed low asymmetric inductions could be explained bythe presence of more than one active catalyst species.

Once in hand, ligand 20, a diastereoisomer of 11 with respect tothe plane of chirality, was tested in the asymmetric allylic alkyl-ation reaction. The degree of asymmetric induction was reduced,compared to 11 favoring the opposite (S)-enantiomer (entry 13).

3. Conclusions

In conclusion, we have accomplished a practical synthesis ofnew ferrocene-based planar chiral amido-phosphine ligands, by ashort sequence of amide-directed ortho-lithiation/electrophilicquench steps. The application of these ligands in the Pd-catalyzedasymmetric allylic alkylation proceeded with a promising degreeof enantioselectivity (up to 82%). Further studies on the catalysisand reaction scope of such ligands are currently in progress.

4. Experimental section

4.1. General remarks

All reactions were run under anhydrous conditions and an ar-gon atmosphere unless otherwise stated. Reagents were commer-cial grade and used without further purification. PhMe wasdistilled from Na. CH2Cl2 and DMF were distilled from CaH2 (underreduced pressure for DMF). THF was dried with sodium/benzophe-none. Thin layer chromatography (TLC) was performed on alumi-num sheets pre-coated with Merck Kieselgel 60 F254 0.25 mm(Merck). Flash column chromatography was carried out using SilicaGel 60 230–400 mesh (Fluka). Melting points of the compoundswere determined using ‘Electrothermal’ MEL-TEMP apparatus(uncorrected). Optical rotation (½a�20

D ) was measured on a Perkin–Elmer 241 polarimeter. The NMR spectra were recorded on a Bru-ker Avance II+ 600 spectrometer (600.13 for 1H MHz, 150.92 MHzfor 13C NMR and 242.92 MHz for 31P NMR) with TMS and 85%H3PO4 for 31P as internal standards for chemical shifts (d, ppm).1H and 13C NMR data are reported as follows: chemical shift, mul-tiplicity (s = singlet, d = doublet, t = triplet, q = quartet, br = broad,m = multiplet), coupling constants (Hz). The assignment of the 1Hand 13C NMR spectra was made on the basis of DEPT, COSY, HSQC,HMBC and NOESY experiments. Cp stands for cyclopentadienyl.Mass spectra (MS) were recorded on a Thermo Scientific DFS (HighResolution Double Focusing Magnetic Sector) mass spectrometer

I. Philipova et al. / Tetrahedron: Asymmetry 22 (2011) 970–979 975

(Bremen, Germany) and are reported as fragmentation in m/z withrelative intensities (%) in parentheses. The high performance liquidchromatography (HPLC) separations were performed with an Agi-lent 1100 System fitted with diode array detector and manualinjector with a 20 lL injection loop. For enantiomeric excess deter-mination Chiralpak IA, 250 � 4.6 mm particle size 5 lm, and Chir-alpak IC 250 � 4.6 mm, particle size 5 lm stainless-steel columnsfrom Chiral Technologies Europe LTD were used. The analyses wereperformed at 25 �C with a flow rate of 1.0 mL/min. X-ray crystal-lography: crystals of 10 and 13 were mounted on a glass capillaryand all data were collected using Cu-Ka radiation (k = 1.5418 Å),performed at room temperature on an Oxford diffraction Super-nova diffractometer. The structures were solved with SHELXS-97and refined using full-matrix least-squares on F2 with the SHEL-XL-97 package.12 Elemental analyses were performed by Microan-alytical Service Laboratory of Faculty of Chemistry, University ofSofia, using Vario EL3 CHNS(O) and Microanalytical service Labora-tory of the Institute of Organic Chemistry, Bulgarian Academy ofSciences. The aminoalcohols (1R,2S,3R,5R)-3-amino-6,6-dim-ethylbicyclo[3.1.1]heptan-2-ol8 and (1S,2S,3R,4S)-3-amino-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol13 and amine (1S,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-amine14 were prepared accordingto published procedures.

4.2. Synthesis

4.2.1. N-((1R,2S,3R,5R)-2-Hydroxy-6,6-dimethylbicyclo[3.1.1]-heptan-3-yl)ferrocenecarboxamide 5

To a stirred solution of ferrocenecarboxylic acid (0.550 g,2.39 mmol), in 12 mL CH2Cl2 were added O-(benzotriazole-1-yl)-N,N,N0,N0-tetramethyluronium-tetrafluorborate (TBTU) (0.767 g,2.39 mmol) and 1-hydroxybenzotriazole hydrate (HOBt) (0.323 g,2.39 mmol), followed by (1R,2S,3R,5R)-3-amino-6,6-dimethylbicy-clo[3.1.1]heptan-2-ol (0.445 g, 2.87 mmol), and EtN(iPr)2

(0.80 mL, 4.78 mmol). The mixture was stirred at rt for 24 h. Itwas treated with satd aq K2CO3 and extracted with CH2Cl2. Thecombined organic phases were dried over Na2SO4, filtered andthe solvent was removed in vacuo. The residue was purified byflash column chromatography (silica gel, CH2Cl2/EtOAc = 10:1) togive 0.618 g (70%) of 5 as an orange solid, mp 106–107 �C.½a�25

D ¼ 0 (c 0.45, CHCl3). 1H NMR (CDCl3, 600 MHz) d = 1.10 (s,3H, 8-H), 1.25 (s, 3H, 9-H), 1.34 (d, JH,H = 10.6 Hz, 1H, 7-Hendo),1.71 (dd, JH,H = 13.6, 7.7 Hz, 1H, 4-Hexo), 2.00 (q, JH,H = 5.2 Hz, 1H,5-H), 2.22 (dt, JH,H = 10.4, 6.1 Hz, 1H, 7-Hexo), 2.29 (q, JH,H = 5.2 Hz,1H, 1-H), 2.36 (d, JH,H = 4.6 Hz, 1H, OH), 2.63 (ddd, JH,H = 13.6, 9.3,5.0 Hz, 1H, 4-Hendo), 4.21 (s, 5H, Cp5), 4.32–4.34 (m, 2H, Cp-H),4.47–4.50 (m, 1H, 2-H), 4.51–4.55 (m, 1H, 3-H), 4.67–4.68 (m,1H, Cp-H), 4.72–4.73 (m, 1H, Cp-H), 6.55 (d, JH,H = 6.5 Hz, 1H, NH)ppm. 13C NMR (CDCl3, 150.9 MHz) d = 22.71 (C-8), 25.25 (C-7),27.21 (C-9), 33.55 (C-4), 38.21 (C-6), 40.49 (C-5), 43.13 (C-3),46.85 (C-1), 68.01 (Cp-CH), 68.36 (Cp-CH), 69.74 (Cp5), 70.32 (2Cp-CH), 70.01 (C-2), 76.24 (Cp-C), 170.24 (CO) ppm. MS (CI) m/z(rel. int.) = 368 (29) [M+H]+, 213 (100). Anal. Calcd for C20H25FeNO2

(367.26): C, 65.41; H, 6.86; N, 3.81. Found: C, 65.33; H, 6.99; N,3.86.

4.2.2. N-((1R,2S,3R,5R)-2-Ethoxy-6,6-dimethylbicyclo[3.1.1]-heptan-3-yl)-N-ethylferrocenecarboxamide 6

To a stirred at solution of starting amide 5 (0.590 g, 1.60 mmol)in 18 mL DMF 0 �C was added NaH (0.580 g, 24.1 mmol). After stir-ring for 30 min at rt EtI (2 mL, 24.1 mmol) was added and the mix-ture was stirred at rt for 5 h. It was then cooled to 0 �C and treatedsequentially, by the slow addition of satd aq NH4Cl and water. Theorganic phase was separated, and the aqueous phase was extractedthree times with dichloromethane. The combined organic phaseswere dried over Na2SO4, filtered, and the solvent was removed in

vacuo. Purification by flash column chromatography (silica gel,hexane/EtOAc = 10:1) afforded 0.503 g (74%) of 6 as an orangeoil. ½a�20

D ¼ þ91:0 (c 0.48, CHCl3). 1H NMR (toluene-d8, 383.1 K,600 MHz) d = 1.08 (t, JH,H = 7.0 Hz, 3H, OCH2CH3), 1.16 (s, 3H, 9-H), 1.19 (s, 3H, 8-H), 1.20 (t, JH,H = 7.1 Hz, 3H, NCH2CH3), 1.31 (d,JH,H = 10.5 Hz, 1H, 7-Hendo), 1.84–1.88 (m, 1H, 4-Hendo), 1.89–1.91(m, 1H, 5-H), 1.98 (dt, JH,H = 10.5, 5.3 Hz, 1H, 7-Hexo), 2.17 (q,JH,H = 5.7 Hz, 1H, 1-H), 2.23 (t, JH,H = 11.9 Hz, 1H, 4-Hexo), 3.28–3.33 (m, 1H, OCH2CH3), 3.35–3.40 (m, 1H, OCH2CH3), 3.56 (dq,JH,H = 14.7, 7.1 Hz, 1H, NCH2CH3), 3.91 (dq, JH,H = 14.7, 7.1 Hz, 1H,NCH2CH3), 4.05–4.09 (m, 3H, 2-H, 2 Cp-H), 4.22 (s, 5H, Cp5), 4.53(br s, 1H, Cp-H), 4.67 (br s, 1H, Cp-H), 5.15–5.20 (m, 1H, 3-H)ppm. 13C NMR (toluene-d8, 383.1 K, 150.9 MHz) d = 15.63(OCH2CH3), 16.66 (NCH2CH3), 22.26 (C-8), 24.81 (C-7), 28.26 (C-9), 28.85 (C-4), 39.59 (C-6), 40.91 (NCH2CH3), 42.03 (C-5), 45.52(C-1), 51.07 (C-3), 65.45 (OCH2CH3), 68.39 (Cp-CH), 68.53 (Cp-CH), 69.89 (Cp-CH), 70.19 (Cp5), 70.45 (Cp-CH), 81.80 (C-2),83.38 (Cp-C), 169.73 (CO) ppm. MS (CI) m/z (rel. int.) = 424 (100)[M+H]+. Anal. Calcd for C24H33FeNO2 (423.37): C 68.09; H, 7.86;N, 3.31. Found: C, 68.23; H, 7.79; N, 3.36.

4.2.3. N,N0-Bis((1S,2R,3S,4R)-3-hydroxy-4,7,7-trimethylbicyclo-[2.2.1]heptan-2-yl)-1,10-ferrocenedicarboxamide 7

To a stirred solution of 1,10-ferrocenedicarboxylic acid (0.200 g,0.73 mmol), in 5 mL CH2Cl2 was added N-ethyl-N0-(3-dimethylami-nopropyl)-carbodiimide hydrochloride (EDC) (0.280 g, 1.46 mmol)and 1-hydroxybenzotriazole hydrate (HOBt) (0.197 g, 1.46 mmol)followed by (1S,2S,3R,4S)-3-amino-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (0.321 g, 1.90 mmol). The mixture was stirred at rtfor 72 h. It was then treated with satd aq K2CO3 and extracted withCH2Cl2. The combined organic phases were dried over Na2SO4,filtered and the solvent was removed in vacuo. The residue waspurified by flash column chromatography (silica gel, CH2Cl2/EtOAc = 5:1) to give 0.217 g (52%) of 7 as an orange solid. mp>145 �C decomp. ½a�20

D ¼ þ365:7 (c 0.24, CHCl3). 1H NMR (CDCl3,600 MHz) d = 0.82 (s, 6H, 9-H), 1.02 (s, 6H, 10-H), 1.09–1.18 (m,4H, 6-Hendo, 5-Hendo), 1.15 (s, 6H, 8-H), 1.52–1.57 (m, 2H, 6-Hexo),1.66 (d, JH,H = 4.3 Hz, 2H, 4-H), 1.71–1.76 (m, 2H, 5-Hexo), 3.91(dd, JH,H = 7.6, 4.2 Hz, 2H, 2-H), 3.96 (t, JH,H = 8.0 Hz, 2H, 3-H),4.33–4.34 (m, 2H, Cp-CH), 4.37–4.38 (m, 2H, Cp-H), 4.54–4.55(m, 2H, Cp-H), 4.72 (d, JH,H = 4.2 Hz, 2H, OH), 4.91–4.92 (m, 2H,Cp-H), 6.58 (d, JH,H = 8.0 Hz, 2H, NH) ppm. 13C NMR (CDCl3,150.9 MHz) d = 11.50 (C-10), 21.28 (C-8), 21.70 (C-9), 26.46 (C-5),33.90 (C-6), 46.94 (C-7), 48.82 (C-1), 51.39 (C-4), 56.52 (C-3),67.63 (Cp-CH), 69.53 (Cp-CH), 70.80 (Cp-CH), 71.20 (Cp-CH),78.78 (Cp-CCO), 79.53 (C-2), 167.59 (CO) ppm. MS (CI) m/z (rel.int.) = 577 (100) [M+H]+. Anal. Calcd for C32H44FeN2O4 (576.55):C, 66.66; H, 7.69; N, 4.86. Found: C, 66.53; H, 7.79; N, 4.83.

4.2.4. N,N0-Bis((1S,2R,3S,4R)-3-ethoxy-4,7,7-trimethylbicyclo-[2.2.1]heptan-2-yl)N,N0-diethyl-1,10-ferrocenedicarboxamide 8

To a stirred solution of 7 (0.560 g, 0.97 mmol) in 9 mL DMF wasadded NaH (0.280 g, 11.65 mmol) at 0 �C. After stirring for 30 minat rt EtI (0.94 mL, 11.64 mmol) was added and the mixture wasstirred at rt for 4 h. It was cooled to 0 �C and treated sequentially,by the slow addition of saturated aq.NH4Cl and water. The organicphase was separated, and the aqueous phase was extracted threetimes with dichloromethane. The combined organic phases weredried over Na2SO4, filtered and the solvent was removed in vacuo.The residue was purified by flash column chromatography (silicagel, hexane/EtOAc = 5:1) to give 0.144 g (24%) of 8 as an orange so-lid; mp 154–155 �C. ½a�20

D ¼ þ52:5 (c 0.28, CHCl3). 1H NMR (CDCl3,600 MHz) d = 0.78 (s, 6H, 9-H), 0.91 (s, 6H, 10-H), 0.96 (t,JH,H = 6.5 Hz, 6H, NCH2CH3), 1.02 (s, 6H, 8-H), 1.12–1.17 (m, 10H,5-Hendo, 6-Hendo, OCH2CH3), 1.44–1.49 (m, 2H, 6-Hexo), 1.72–1.77(m, 2H, 5-Hexo), 1.97 (d, JH,H = 4.0 Hz, 2H, 4-H), 3.17 (dq,

976 I. Philipova et al. / Tetrahedron: Asymmetry 22 (2011) 970–979

JH,H = 15.2, 7.0 Hz, 2H, NCH2CH3), 3.47–3.57 (m, 6H, 2-H, OCH2CH3),3.80–3.86 (m, 4H, 3-H, NCH2CH3), 4.34–4.35 (m, 2H, Cp-H), 4.42–4.43 (m, 2H, Cp-H), 4.48 (br s, 2H, Cp-H), 4.66 (br s, 2H, Cp-H)ppm. 13C NMR (CDCl3, 150.9 MHz) d = 11.66 (C-10), 15.86(OCH2CH3), 15.92 (NCH2CH3), 21.35 (C-9), 21.72 (C-8), 28.10 (C-5), 32.26 (C-6), 41.25 (NCH2CH3), 45.91 (C-4), 47.47 (C-7), 49.31(C-1), 64.29 (C-3), 68.83 (OCH2CH3), 69.98 (Cp-CH), 70.99 (2Cp-CH), 71.26 (Cp-CH), 84.55 (Cp-CCO), 89.96 (C-2), 169.82 (CO)ppm. MS (CI) m/z (rel. int.) = 689 (100) [M+H]+. Anal. Calcd forC40H60FeN2O4 (688.76): C, 69.75; H, 8.78; N, 4.07. Found: C,69.69; H, 8.81; N, 4.05.

4.2.5. (Rp)-2-Methyl-N-((1R,2S,3R,5R)-2-ethoxy-6,6-dimethyl-bicyclo[3.1.1]heptan-3-yl)-N-ethylferrocenecarboxamide 10

A solution of TMEDA (0.11 mL, 0.70 mmol) in 2 mL PhMe wascooled to -78 �C, and treated with sBuLi (0.54 mL, 1.3 M in cyclo-hexane, 0.70 mmol). After stirring for 20 min at �78 �C, a solutionof 6 (0.135 g, 0.32 mmol) in PhMe was added dropwise. The reac-tion mixture was stirred for 3 h at �78 �C, quenched with MeI(0.10 mL, 1.59 mmol) and allowed to reach rt on its own accord.The reaction was treated with satd aq NH4Cl, extracted with ether,dried above Na2SO4, filtered and concentrated to give 0.147 g ofcrude product (10a/10b = 94/6 by HPLC). Purification by flash col-umn chromatography (silica gel, hexane/EtOAc = 20:1) afforded0.124 g (89%) of 10a as an orange solid. The total yield of 10 was0.132 g (95%). CSP HPLC analysis (Chiralpak IC; eluent/hexane/i-PrOH, 99:1, flow 1.0 mL/min) determined dr = 94/6. Retentiontime: tR (major) = 10.55 min, tR (minor) = 12.31 min. Data for 10a:mp 54–55 �C, ½a�20

D ¼ þ45:2 (c 0.34, CHCl3). 1H NMR (toluene-d8,383.1 K, 600 MHz) d = 1.08–1.11 (m, 6H, OCH2CH3, NCH2CH3), 1.14(s, 3H, 9-H), 1.17 (s, 3H, 8-H), 1.22 (d, JH,H = 10.3 Hz, 1H, 7-Hendo),1.85–1.90 (m, 2H, 4-Hendo, 5-H), 1.92–1.96 (m, 1H, 7-Hexo), 2.08–2.11 (m, 1H, 1-H), 2.16 (s, 3H, Cp-CH3), 2.18–2.20 (m, 1H, 4-Hexo),3.28 (dq, JH,H = 14.0, 7.0 Hz, 1H, OCH2CH3), 3.36 (dq, JH,H = 13.9,7.0 Hz, 1H, OCH2CH3), 3.43 (dq, JH,H = 14.6, 7.1 Hz, 1H, NCH2CH3),3.82–3.85 (m, 1H, 2-H), 3.91 (t, JH,H = 2.4 Hz, 1H, Cp-H), 3.94–3.99(m, 1H, NCH2CH3), 4.02 (t, JH,H = 1.7 Hz, 1H, Cp-H), 4.17 (t,JH,H = 1.4 Hz, 1H, Cp-H), 4.23 (s, 5H, Cp5), 5.10–5.16 (m, 1H, 3-H)ppm. 13C NMR (toluene-d8, 383.1 K, 150.9 MHz) d = 13.43 (Cp-CH3),15.80 (OCH2CH3), 16.15 (NCH2CH3), 22.39 (C-8), 24.91 (C-7), 28.36(C-9), 28.90 (C-4), 39.65 (C-6), 40.78 (NCH2CH3), 42.07 (C-5), 45.55(C-1), 51.21 (C-3), 65.55 (Cp-CH), 65.61 (OCH2CH3), 66.37 (Cp-CH),69.43 (Cp-CH), 71.10 (Cp5), 82.17 (C-2), 86.12 (Cp-CCO), 86.67(Cp-CCH3), 169.47 (CO) ppm. MS (CI) m/z (rel. int.) = 438 (100)[M+H]+. Anal. Calcd for C25H35FeNO2 (437.40): C, 68.65; H, 8.07;N, 3.20. Found: C, 68.71; H, 8.12; N, 3.26.

4.2.6. (Sp)-2-(Diphenylphosphino)-N-((1R,2S,3R,5R)-2-ethoxy-6,6-dimethylbicyclo[3.1.1]heptan-3-yl)-N-ethylethylferro-cenecarboxamide 11

A solution of TMEDA (0.11 mL, 0.73 mmol) in 2 mL PhMe wascooled to -78 �C, and treated with sBuLi (0.56 mL, 1.3 M in cyclo-hexane, 0.73 mmol). After stirring for 20 min at �78 �C, a solutionof 6 (0.140 g, 0.33 mmol) in PhMe was added dropwise. The reac-tion mixture was stirred for 3 h at -78 �C and quenched withPh2PCl (0.13 mL, 0.73 mmol). After stirring for an additional30 min at �78 �C, the mixture was directly subjected to flash col-umn chromatography (silica gel, CH2Cl2) to give 0.181 g (90%) of11 as an orange solid. mp >58 �C decomp. ½a�20

D ¼ �103:3 (c 0.12,CHCl3). 1H NMR (toluene-d8, 383.1 K, 600 MHz) d = 0.92 (t,JH,H = 6.9 Hz, 3H, OCH2CH3), 1.04 (s, 3H, 9-H), 1.06 (s, 3H, 8-H),1.08 (t, JH,H = 7.0 Hz, 3H, NCH2CH3), 1.11 (d, JH,H = 10.6 Hz, 1H, 7-Hendo), 1.69–1.73 (m, 1H, 4-Hendo), 1.77 (q, JH,H = 5.8 Hz, 1H, 5-H),1.85 (dt, JH,H = 10.6, 5.8 Hz, 1H, 7-Hexo), 1.92 (q, JH,H = 5.6 Hz, 1H,1-H), 2.04–2.07 (m, 1H, 4-Hexo), 3.04–3.07 (m, 2H, OCH2CH3),3.39 (dq, JH,H = 14.6, 7.0 Hz, 1H, NCH2CH3), 3.54–3.57 (m, 1H, 2-

H), 3.88 (dq, JH,H = 14.6, 7.1 Hz, 1H, NCH2CH3), 3.95 (br s, 1H, Cp-H), 4.06 (t, JH,H = 2.5 Hz, 1H, Cp-H), 4.08 (s, 5H, Cp5), 4.43 (br s,1H, Cp-H), 4.76–4.80 (m, 1H, 3-H), 6.90–6.92 (m, 1H, arom.),6.94–6.97 (m, 2H, arom.), 7.03–7.08 (m, 3H, arom.), 7.25–7.27(m, 2H, arom.), 7.57–7.60 (m, 2H, arom.) ppm. 13C NMR (toluene-d8, 383.1 K, 150.9 MHz) d = 15.67 (OCH2CH3), 15.72 (NCH2CH3),22.38 (C-8), 24.79 (C-7), 28.24 (C-9), 28.79 (C-4), 39.62 (C-6),40.58 (NCH2CH3), 41.89 (C-5), 45.49 (C-1), 51.65 (C-3), 65.44(OCH2CH3), 69.23 (Cp-CH), 69.81 (Cp-CH), 71.57 (Cp5), 72.35 (d,J31P;13C = 3.9 Hz, Cp-CH), 80.85 (d, J31P;13C = 18.9 Hz, Cp-CCO), 81.82(C-2), 91.44 (d, J31P;13C = 30.6 Hz, Cp-CPPh2), 128.05 (d,J31P;13C = 6.1 Hz, 2 arom. CH), 128.16 (d, J31P;13C = 7.1 Hz, 2 arom.CH), 128.82 (1 arom. CH), 129.09 (1 arom. CH), 133.40 (d,J31P;13C = 19.7 Hz, 2 arom. CH), 135.49 (d, J31P;13C = 22.3 Hz, 2 arom.CH), 140.59 (d, J31P;13C = 15.7 Hz, 1 arom. C), 141.77 (d,J31P;13C = 14.6 Hz, 1 arom. C), 168.50 (CO) ppm. 31P NMR (toluene-d8, 383.1 K, 242.92 MHz) d = -19.19 (s) ppm. MS (CI) m/z (rel.int.) = 608 (100) [M+H]+. Anal. Calcd for C36H42FeNO2P (607.54):C, 71.17; H, 6.97; N, 2.31. Found: C, 71.21; H, 6.99; N, 2.29.

4.2.7. 2-(Diphenylphosphino)-N-((1R,2R,4R)-1,7,7-trimethyl-bicyclo[2.2.1]heptan-2-yl)ferrocenecarboxamide 12

A solution of TMEDA (0.29 mL, 1.95 mmol) in 4 mL PhMe wascooled to -78 �C, and treated with sBuLi (1.5 mL, 1.3 M in cyclohex-ane, 1.95 mmol). After stirring for 20 min at �78 �C, a solution of 9(0.223 g, 0.61 mmol) in 6 mL PhMe was added dropwise. The reac-tion mixture was stirred for 2 h at �78 �C, and quenched withPh2PCl (0.36 mL, 1.95 mmol). After stirring for an additional30 min at �78 �C, the mixture was directly subjected to flash col-umn chromatography (silica gel, CH2Cl2:Et2O = 100:1) to give0.202 g (60%) of 12 (dr = 91/9 by NMR) as an orange solid. mp61–63 �C; ½a�20

D ¼ �154:8 (c 0.16, CHCl3), 1H NMR (CDCl3,600 MHz) d = 0.53 (s, 3H, 9-H), 0.74 (s, 3H, 10-H), 0.94 (s, 3H, 8-H), 1.08–1.12 (m, 1H, 5-Hendo), 1.14–1.19 (m, 1H, 6-Hendo), 1.40–1.45 (m, 1H, 6-Hexo), 1.60–1.70 (m, 3H, 5-Hexo, 3-Hexo, 4-H), 1.91–1.95 (m, 1H, 3-Hendo), 3.70 (br s, 1H, Cp-H), 3.87–3.90 (m, 1H, 2-Hendo),4.01 (s, 5H, Cp5), 4.37 (t, JH,H = 2.5 Hz, 1H, Cp-H), 5.15–5.16 (m, 1H,Cp-H), 5.61–5.66 (m, 1H, NH), 7.02–7.04 (m, 2H, arom.), 7.16–7.17(m, 3H, arom.), 7.33–7.37 (m, 3H, arom.), 7.45–7.48 (m, 2H, arom.)ppm. 13C NMR (CDCl3, 150.9 MHz) d = 11.94 (d, J31P;13C = 3.4 Hz,C-9), 20.26 (C-10), 20.64 (d, J31P;13C = 4.9 Hz, C-8), 27.14 (C-5),36.31 (C-6), 40.18 (C-3), 44.93 (C-4), 47.13 (C-7), 48.34 (C-1),57.35 (C-2), 69.70 (d, J31P;13C = 6.4 Hz, Cp-CCO), 70.72 (Cp5), 71.45(Cp-CH), 74.19 (d, J31P;13C = 2.6 Hz, Cp-CH), 74.34 (d,J31P;13C = 3.0 Hz, Cp-CH), 81.42 (d, J31P;13C = 14.9 Hz, Cp-CPPh2),128.25 (1 arom. CH), 128.31 (d, J31P;13C = 18.5 Hz, 2 arom. CH),128.36 (d, J31P;13C = 20.3 Hz, 2 arom. CH), 129.81 (1 arom. CH),131.93 (d, J31P;13C = 17.1 Hz, 2 arom. CH), 135.29 (d,J31P;13C = 20.8 Hz, 2 arom. CH), 135.85 (d, J31P;13C = 5.7 Hz, 1 arom.C), 137.71 (d, J31P;13C = 5.8 Hz, 1 arom. C), 169.37 (d,J31P;13C = 3.4 Hz, CO) ppm. 31P NMR (CDCl3, 242.92 MHz):d = �21.50 (s). MS (CI) m/z (rel. int.) = 550 (100) [M+H]+. Anal.Calcd for C33H36FeNOP (549.46): C, 72.13; H, 6.60; N, 2.55. Found:C, 72.21; H, 6.79; N, 2.64.

4.2.8. (Rp,Rp)-2,20-Dimethyl-N,N0-bis((1S,2R,3S,4R)-3-ethoxy-4,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)N,N0-diethyl-1,10-ferrocenedicarboxmide 13, (Rp,Sp)-2,20-dimethyl-N,N0-bis((1S,2R,3S,4R)-3-ethoxy-4,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)N,N0-diethyl-1,10-ferrocenedicarboxmide 14 and (Rp)-2-methyl-N,N0-bis((1S,2R,3S,4R)-3-ethoxy-4,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)N,N0-diethyl-1,10-ferrocenedicarboxmide 15

A solution of TMEDA (0.08 mL, 0.53 mmol) in 2 mL PhMe wascooled to -78 �C, and treated with sBuLi (0.41 mL, 1.3 M in cyclo-hexane, 0.53 mmol). After stirring for 20 min at -78 �C, a solution

I. Philipova et al. / Tetrahedron: Asymmetry 22 (2011) 970–979 977

of 8 (0.057 g, 0.083 mmol) in PhMe was added dropwise. Thereaction was stirred for 6 h at �78 �C, quenched with MeI(0.05 mL, 0.83 mmol) and allowed to reach rt on its own accord.The mixture was treated with satd aq NH4Cl, extracted with ether,dried above Na2SO4, filtered and concentrated to give 0.06 g ofcrude product (13/14 = 88/12 by 1H NMR). Purification by flash col-umn chromatography (silica gel, hexane/EtOAc = 10:1) afforded0.033 g (56%) of 13, 0.004 g (7%) of 14 and 0.010 g (17%) of 15.½a�20

D 13: m.p. 190–192 �C, ½a�20D ¼ þ179:2 (c 0.63, CHCl3), 1H

NMR (CDCl3, 600 MHz) d = 0.73 (t, JH,H = 7.0 Hz, 6H, NCH2CH3),0.77 (s, 6H, 9-H), 0.93 (s, 6H, 10-H), 1.00 (s, 6H, 8-H), 1.15–1.20(m, 4H, 5-Hendo, 6-Hendo), 1.18 (t, JH,H = 7.0 Hz, 6H, OCH2CH3),1.45–1.49 (m, 2H, 6-Hexo), 1.70–1.77 (m, 2H, 5-Hexo), 1.91 (d,JH,H = 3.8 Hz, 2H, 4-H), 2.08 (s, 6H, Cp-CH3), 3.04 (dq, JH,H = 15.0,7.0 Hz, 2H, NCH2CH3), 3.51 (d, JH,H = 7.1 Hz, 2H, 2-H), 3.52–3.66(m, 6H, OCH2CH3, NCH2CH3), 3.86 (d, JH,H = 7.1 Hz, 2H, 3-H), 4.09(br s, 2H, Cp-H), 4.15 (t, JH,H = 2.3 Hz, 2H, Cp-H), 4.17 (br s, 2H,Cp-H) ppm. 13C NMR (CDCl3, 150.9 MHz) d = 11.57 (Cp-CH3),11.75 (C-10), 15.23 (NCH2CH3), 15.75 (OCH2CH3), 21.28 (C-9),21.61 (C-8), 27.95 (C-5), 32.25 (C-6), 42.13 (NCH2CH3), 45.96 (C-4), 47.46 (C-7), 49.35 (C-1), 63.41 (C-3), 66.02 (Cp-CH), 68.43(Cp-CH), 68.60 (OCH2CH3), 74.31 (Cp-CH), 86.57 (Cp-CCH3), 86.91(Cp-CCO), 89.27 (C-2), 170.38 (CO) ppm. MS (CI) m/z (rel.int.) = 717 (83) [M+H]+, 149 (100). Anal. Calcd for C42H64FeN2O4

(716.81): C, 70.37; H, 9.00; N, 3.91. Found: C, 70.41; H, 9.09; N,3.93.

Data for 14: mp 185–186� C, ½a�20D ¼ þ124:6(c 0.20, CHCl3), 1H

NMR (CDCl3, 600 MHz) d = 0.73 (t, JH,H = 6.8 Hz, 3H, NCH2CH3),0.77 (s, 3H, 9-H), 0.78 (s, 3H, 9-H), 0.79 (t, 3H, JH,H = 6.9 Hz,NCH2CH3), 0.93 (s, 3H, 10-H), 0.94 (s, 3H, 10-H), 1.00 (s, 3H, 8-H),1.02 (s, 3H, 8-H), 1.12–1.22 (m, 10H, 5-Hendo, 6-Hendo, OCH2CH3),1.46–1.51 (m, 2H, 6-Hexo), 1.71–1.76 (m, 2H, 5-Hexo), 1.92 (d,JH,H = 4.4 Hz, 1H, 4-H), 1.94 (d, JH,H = 4.5 Hz, 1H, 4-H), 2.00 (s, Cp-CH3), 2.18 (s, Cp-CH3), 3.02–3.09 (m, 2H, NCH2CH3), 3.24 (dq,JH,H = 15.0, 6.9 Hz, 1H, NCH2CH3), 3.51–3.55 (m, 3H, 2-H, OCH2CH3),3.57 (d, JH,H = 7.0 Hz, 1H, 2-H), 3.58–3.62 (m, 1H, NCH2CH3), 3.65–3.67 (m, 1H, OCH2CH3), 3.74–3.79 (m, 1H, OCH2CH3), 3.82–3.83 (m,2H, 3-H, Cp-H), 3.87 (d, JH,H = 7.0 Hz, 1H, 3-H), 4.12 (dd, JH,H = 2.3,1.4 Hz, 1H, Cp-H), 4.16 (t, JH,H = 1.6 Hz, 1H, Cp-H), 4.29–4.31 (m,2H, Cp-H), 4.46 (t, JH,H = 1.6 Hz, 1H, Cp-H) ppm. 13C NMR (CDCl3,150.9 MHz) d = 11.62 (C-10), 12.84 (Cp-CH3), 13.31 (Cp-CH3),14.12 (OCH2CH3), 15.16 (NCH2CH3), 15.74 (OCH2CH3), 15.88(NCH2CH3), 20.89 (C-8), 21.17 (C-9), 21.31 (C-9), 21.65 (C-8),27.78 (C-5), 28.00 (C-5), 32.30 (C-6), 32.44 (C-6), 41.78 (NCH2CH3),42.05 (NCH2CH3), 46.01 (C-4), 46.09 (C-4), 47.30 (C-7), 47.45 (C-7),49.37 (C-1), 49.55 (C-1), 63.40 (C-3), 63.61 (C-3), 67.38 (Cp-CH),68.57 (OCH2CH3), 68.79 (OCH2CH3), 70.00 (Cp-CH), 70.47 (Cp-CH), 72.37 (Cp-CH), 73.72 (Cp-CH), 74.55 (Cp-CH), 80.66 (Cp-CCH3), 86.47 (Cp-CCH3), 86.85 (Cp-CCO), 87.67 (Cp-CCO), 89.50(C-2), 170.25 (CO), 170.77 (CO) ppm. MS (CI) m/z (rel. int.) = 717(67) [M+H]+, 226 (100).

Data for 15: mp 164–167 �C, ½a�20D ¼ þ119:2 (c 2.10, CHCl3), 1H

NMR (CDCl3, 600 MHz) d = 0.73 (t, JH,H = 6.9 Hz, 3H, NCH2CH3),0.77 (s, 6H, 9-H), 0.91–0.93 (m, 9H, 10-H, NCH2CH3), 1.01 (s, 6H,8-H), 1.11–1.16 (m, 7H, OCH2CH3, 5-Hendo, 6-Hendo), 1.20 (t,JH,H = 7.0 Hz, 3H, OCH2CH3), 1.44–1.49 (m, 2H, 6-Hexo), 1.71–1.73(m, 2H, 5-Hexo), 1.90 (d, JH,H = 4.4 Hz, 1H, 4-H), 1.95 (d, JH,H = 4.0 Hz,1H, 4-H), 2.12 (s, 3H, Cp-CH3), 3.04 (dq, JH,H = 15.0, 7.0 Hz, 1H,NCH2CH3), 3.13 (dq, JH,H = 15.1, 7.0 Hz, 1H, NCH2CH3), 3.49–3.65(m, 7H, 2-H, OCH2CH3, NCH2CH3), 3.75 (dq, JH,H = 15.0, 7.0 Hz, 1H,NCH2CH3), 3.84–3.87 (m, 2H, 3-H), 4.14 (br s, 1H, Cp-H), 4.13 (brs, 1H, Cp-H), 4.32–4.34 (m, 4H, Cp-H), 4.53 (br s, 1H, Cp-H) ppm.13C NMR (CDCl3, 150.9 MHz) d = 11.57 (C-10), 11.63 (C-10), 12.87(Cp-CH3), 15.19 (NCH2CH3), 15.70 (NCH2CH3), 15.79 (OCH2CH3),15.81 (OCH2CH3), 21.28 (C-9), 21.33 (C-9), 21.59 (C-8), 21.70 (C-8), 27.95 (C-5), 28.08 (C-5), 32.24 (C-6), 32.25 (C-6), 41.43

(NCH2CH3), 42.01 (NCH2CH3), 45.94 (C-4), 47.42 (C-7), 47.45 (C-7), 49.30 (C-1), 49.34 (C-1), 63.53 (C-3), 64.06 (C-3), 66.91(Cp-CH), 68.29 (Cp-CH), 68.43 (Cp-CH), 68.58 (OCH2CH3), 68.73(OCH2CH3), 71.08 (Cp-CH), 72.28 (Cp-CH), 73.44 (Cp-CH), 73.65(Cp-CH), 84.73 (Cp-CCH3), 86.69 (Cp-CCO), 87.01 (Cp-CCO), 89.40(C-2), 89.76 (C-2), 169.98 (CO), 170.24 (CO) ppm. MS (CI) m/z(rel. int.) = 703 (100) [M+H]+. Anal. Calcd for C41H62FeN2O4

(702.79): C, 70.07; H, 8.99; N, 3.99. Found: C, 70.11; H, 9.03; N,4.02.

4.2.9. (Sp,Sp)-2,20-bis-(Diphenylphosphino)-N,N0-bis((1S,2R,3S,4R)-3-ethoxy-4,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)N,N0-diethyl-1,10-ferrocenedicarboxmide 16

A solution of TMEDA (0.14 mL, 0.93 mmol) in 2 mL PhMe wascooled to -78 �C, and treated with sBuLi (0.72 mL, 1.3 M in cyclo-hexane, 0.93 mmol). After stirring for 20 min at �78 �C, a solutionof 8 (0.100 g, 0.15 mmol) in 6 mL PhMe was added dropwise. Thereaction mixture was stirred for 4 h at �78 �C, and quenched withPh2PCl (0.17 mL, 0.93 mmol). After stirring for an additional 30 minat �78 �C, the mixture was directly subjected to flash column chro-matography (silica gel, CH2Cl2) to give 0.063 g (41%) of 16 as an or-ange solid. mp >134 �C decomp. ½a�20

D ¼ �147:2 (c 0.16, CHCl3). 1HNMR (CDCl3, 600 MHz) d = 0.34 (br s, 6H, NCH2CH3), 0.72 (s, 6H,9-H), 0.91 (s, 6H, 10-H), 0.94 (s, 6H, 8-H), 1.03–1.05 (m, 2H, 5-Hendo),1.11–1.17 (m, 2H, 6-Hendo), 1.17 (t, JH,H = 6.8 Hz, 6H, OCH2CH3),1.41–1.45 (m, 2H, 6-Hexo), 1.60–1.64 (m, 2H, 5-Hexo), 1.74 (br s, 2H,4-H), 2.95 (dq, JH,H = 14.5, 6.9 Hz, 2H, NCH2CH3), 3.25 (br s, 2H, Cp-H), 3.43–3.48 (m, 2H, OCH2CH3), 3.61 (d, JH,H = 7.0 Hz, 2H, 2-H),3.63–3.66 (m, 2H, NCH2CH3), 3.69 (d, JH,H = 7.0 Hz, 2H, 3-H), 3.88(dq, JH,H = 7.6 Hz, 2H, OCH2CH3), 4.69 (br s, 2H, Cp-H), 4.84 (br s,2H, Cp-H), 7.15 (br s, 10H, arom.), 7.20–7.22 (m, 4H, arom.),7.25–7.28 (m, 2H, arom.), 7.37–7.39 (m, 4H, arom.) ppm. 13CNMR (CDCl3, 150.9 MHz) d = 11.70 (C-10), 15.09 (NCH2CH3), 16.61(OCH2CH3), 21.16 (C-9), 21.67 (C-8), 27.92 (C-5), 32.34 (C-6),41.60 (NCH2CH3), 46.36 (C-4), 47.25 (C-7), 49.43 (C-1), 64.50(C-3), 68.40 (OCH2CH3), 73.49 (Cp-CH), 74.45 (Cp-CH), 74.75 (Cp-CH), 80.17 (d, J31P;13C = 17.5 Hz, Cp-CCO), 89.78 (C-2), 93.22 (d,J31P;13C = 28.2 Hz, Cp-CPPh2), 127.55 (2 arom. CH), 127.68 (d,J31P;13C = 6.0 Hz, 4 arom. CH), 128.12 (d, J31P;13C = 8.1 Hz, 4 arom.CH), 128.70 (2 arom. CH), 132.77 (d, J31P;13C = 19.3 Hz, 4 arom.CH), 134.97 (d, J31P;13C = 23.2 Hz, 4 arom. CH), 138.56 (d,J31P;13C = 12.2 Hz, 2 arom. C), 139.32 (d, J31P;13C = 11.53 Hz, 2 arom.C), 168.51 (CO) ppm. 31P NMR (CDCl3, 242.92 MHz): d = �23.87(s) ppm. MS (CI) m/z (rel. int.) = 1058 (0.24) [M+H]+, 226 (100).Anal. Calcd for C64H78FeNO2P2 (1057.11): C, 72.72; H, 7.44; N,2.65. Found: C, 72.78; H, 7.48; N, 2.68.

4.2.10. (R,R,Sp)-1,10-[N,N0-(1,2-Cyclohexane-1,2-diyl)bis(N-methylcarboxamide)]2-(diphenylphosphino)-ferrocene 18 and(R,R,Sp,Sp)-1,10-[N,N0-(1,2-cyclohexane-1,2-diyl)bis(N-methylcarboxamide)]2,20-bis-(diphenylphosphino)-ferrocene 19

To a stirred solution of 2,2,6,6-tetramethylpiperidine (0.078 ml,0.46 mmol) in toluene (3 ml) nBuLi (1.6 M in hexane, 0.29 ml,0.46 mmol) was added dropwise at �20 �C. The mixture was stir-red for 30 min at �20 �C and cooled to �78 �C. A solution of ferroc-enophane 17 (0.076 g, 0.2 mmol) in toluene (10 mL) was addeddropwise and the reaction was stirred at -78 �C for 6 h. Next,Ph2PCl (0.1 ml, 0.5 mmol) was added in one portion and the reac-tion was left to reach rt on its own accord. The mixture was directlysubjected to flash column chromatography (silica gel, CH2Cl2:E-t2O = 100:1)) to give 0.028 g (19%) of ferrocenophane 19 and0.041 g (36%) of ferrocenophane 18.

Data for 18: mp >183 �C decomp. ½a�20D ¼ �115:2 (c 0.11, CHCl3).

1H NMR (CDCl3, 600 MHz) d = 1.19–1.33 (m, 2H, H-9ax, H-10ax),1.53–1.62 (m, 2H, H-8ax, H-11ax), 1.62–1.69 (m, 2H, H-8 eq, H-11 eq), 1.69–1.79 (m, 2H, H-9 eq, H-10 eq), 3.06 (s, 3H, H-15),

978 I. Philipova et al. / Tetrahedron: Asymmetry 22 (2011) 970–979

3.13 (s, 3H, H-14), 3.30–3.32 (m, 1H, H-3), 4.00–4.02 (m, 1H, H-30),4.39–4.41 (m, 1H, H-40), 4.49 (t, JH,H = 2.6 Hz, 1H, H-4),4.62–4.71 (m, 2H, H-7, H-12), 4.97 (br s, 1H, H-50), 5.02 (br s, 1H,H-5), 5.15 (br s, 1H, H-20), 7.10–7.15 (m, 5H, arom.), 7.25–7.29(m, 3H, arom.), 7.36–7.40 (m, 2H, arom.) ppm. 13C NMR (CDCl3,150.9 MHz) d = 25.25, 25.34 (2C, C-9, C-10), 29.41 (2C, C-8, C-11),33.36 (C-14), 33.56 (C-15), 52.84, 53.16 (2C, C-7, C-12), 70.82 (C-30), 74.24 (d, J31

P,13

C = 3.7 Hz, C-3), 74.27 (C-4), 75.06 (C-40), 76.33(C-20), 77.14 (C-50), 77.26 (d, J31P;13C = 6.6 Hz, C-5) 78.59 (C-10),80.53 (d, J31P;13C = 6.7 Hz, C-1), 86.19 (d, J31P;13C = 15.3 Hz, C-2),127.70 (1 arom. CH), 128.13 (d, J31P;13C = 11.5 Hz, 2 arom CH),128.17 (d, J31P;13C = 12.3 Hz, 2 arom CH), 128.88 (1 arom. CH),131.88 (d, J31P;13C = 19.4 Hz, 2 arom CH), 135.42 (d,J31P;13C = 23.1 Hz, 2 arom CH), 140.11 (d, J31P;13C = 14.1 Hz, 1 aromC), 140.47 (d, J31P;13C = 18.6 Hz, 1 arom C), 172.03 (C-13), 172.45(d, J31P;13C = 3.2 Hz, C-6) ppm. 31P NMR (CDCl3, 242.92 MHz):d = �15.16 (s) ppm. MS (CI) m/z (rel. int.) = 565 (100) [M+H]+. Anal.Calcd for C32H33FeN2O2P (564.44): C, 68.09; H, 5.89; N, 4.96.Found: C, 67.84; H, 5.93; N, 4.59.

Data for 19: mp >192 �C decomp. ½a�20D ¼ �375:9 (c 0.17, CHCl3).

1H NMR (CDCl3, 600 MHz) d = 1.15–1.24 (m, 2H, H-9ax, H-10ax),1.48–1.60 (m, 2H, H-8ax, H-11ax), 1.61–1.67 (m, 2H, H-8 eq, H-11 eq), 1.67–1.71 (m, 2H, H-9 eq, H-10 eq), 3.18 (s, 6H, H-14, H-15), 3.25–3.26 (m, 2H, H-3, H-30), 4.34 (t, JH,H = 2.7 Hz, 2H, H-4,H-40), 4.63–4.68 (m, 2H, H-7, H-12), 5.19–5.20 (m, 2H, H-5, H-50),7.10–7.15 (m, 10H, arom.), 7.19–7.23 (m, 6H, arom.), 7.31–7.35(m, 4H, arom) ppm. 13C NMR (CDCl3, 150.9 MHz) d = 25.20 (2C,C-9, C-10), 29.40 (2C, C-8, C-11), 33.35 (d, J31P;13C = 2.5 Hz, 2C, C-14, C-15), 53.56 (2C, C-7, C-12), 75.09 (d, J31P;13C = 3.5 Hz, 2C, C-3,C-30), 75.35 (2C, C-4, C-40), 80.25 (d, J31P;13C = 6.4 Hz, 2C, C-5, C-50),82.41 (d, J31P;13C = 7.2 Hz, 2C, C-1, C-10), 85.37 (d, J31P;13C = 15.0 Hz,2C, C-2, C-20), 127.70 (2 arom. CH), 128.13 (dd, J31P;13C = 7.4 Hz, 4arom. CH), 128.93 (2 arom. CH), 131.82 (d, J31P;13C = 19.3 Hz, 4 arom.CH), 135.46 (d, J31P;13C = 23.2 Hz, 4 arom. CH), 140.00 (d,J31P;13C = 13.2 Hz, 2 arom. C), 140.48 (d, J31P;13C = 18.2 Hz, 2 arom.C), 172.25 (d, J31P;13C = 3.0 Hz, 2C, CO) ppm. 31P NMR (CDCl3,242.92 MHz): d = �14.70 (s) ppm. MS (CI) m/z (rel. int.) = 749(100) [M+H]+. Anal. Calcd for C44H42FeN2O2P2 (748.61): C, 70.59;H, 5.65; N, 3.74. Found: C, 70.84; H, 5.73; N, 3.97.

4.2.11. (Rp)-2-(Diphenylphosphino)-N-((1R,2S,3R,5R)-2-ethoxy-6,6-dimethylbicyclo[3.1.1]heptan-3-yl)-N-ethylethylferrocene-carboxamide 20

A solution of 11 (0.088 g, 0.14 mmol) in toluene (4 mL) washeated for 3 h at 100 �C. The crude mixture was directly subjectedto column chromatography (silica gel, CH2Cl2) to give 0.068 g (77%)of 11 and 0.015 g (17%) of 20.

Data for 20: mp >126 �C decomp. ½a�20D ¼ �249:5 (c 0.14, CHCl3).

1H NMR (toluene-d8, 378 K, 600 MHz) d = 0.90–0.94 (m, 2H, 4-Hendo,7-Hendo), 0.95 (t, JH,H = 6.9 Hz, 3H, OCH2CH3), 1.00 (s, 3H, 8-H), 1.01(s, 3H, 9-H), 1.16 (t, JH,H = 7.0 Hz, 3H, NCH2CH3), 1.50 (q,JH,H = 5.2 Hz, 1H, 5-H), 1.78 (dt, JH,H = 10.8, 5.2 Hz, 1H, 7-Hexo),1.82–1.87 (m, 1H, 4-Hendo), 2.00 (q, JH,H = 5.8 Hz, 1H, 1-H), 3.25(dt, JH,H = 15.0, 6.9 Hz, 2H, OCH2CH3), 3.32 (dq, JH,H = 14.0, 7.0 Hz,1H, NCH2CH3), 3.79 (br s, 1H, 2-H), 3.85–3.87 (m, 1H, NCH2CH3),3.96 (dd, JH,H = 2.1, 1.3 Hz, 1H, Cp-H), 4.09 (t, JH,H = 2.4 Hz, 1H,Cp-H), 4.10–4.11 (m, 1H, Cp-H), 4.10 (s, 5H, Cp5), 4.48–4.49 (m,1H, 3-H), 6.91–6.98 (m, 3H, arom.), 7.03–7.08 (m, 3H, arom.),7.30–7.33 (m, 2H, arom.), 7.58–7.61 (m, 2H, arom.) ppm. 13CNMR (toluene-d8, 378 K, 150.9 MHz) d = 15.64 (NCH2CH3), 15.69(OCH2CH3), 22.13 (C-8), 24.67 (C-7), 28.10 (C-4), 28.18 (C-9),39.57 (C-6), 40.89 (NCH2CH3), 41.76 (C-5), 45.41 (C-1), 65.64(OCH2CH3), 68.66 (Cp-CH), 69.85 (C-3), 71.28 (Cp-CH), 71.54(Cp5), 71.57 (Cp-CH), 79.89 (Cp-CCO), 82.63 (C-2), 95.21 (Cp-CPPh2), 128.17 (d, J31P;13C = 7.6 Hz, 2 arom. CH), 128.32 (d,J31P;13C = 6.3 Hz, 2 arom. CH), 128.91 (1 arom. CH), 129.08 (1 arom.

CH), 133.39 (d, J31P;13C = 20.0 Hz, 2 arom. CH), 135.35 (d,J31P;13C = 22.5 Hz, 2 arom. CH), 139.84 (d, J31P;13C = 12.8 Hz, 1 arom.C), 141.32 (d, J31P;13C = 13.8 Hz, 1 arom. C), 168.03 (CO) ppm. 31PNMR (toluene-d8, 378 K, 242.92 MHz) d = �21.39 (s) ppm. MS (CI)m/z (rel. int.) = 608 (100) [M+H]+.

4.3. General procedure for the palladium-catalyzed allylicalkylation

A mixture of chiral ligand (0.03 mmol), [Pd(g3-C3H5)Cl]2

(6.0 mg, 0.016 mmol), and base (0.05 mmol) in a dry solvent(3 mL) was stirred at rt in a Schlenk tube for 30 min. Then,rac-1,3-diphenylprop-2-en-1-yl acetate (126 mg, 0.5 mmol) wasintroduced, and then after stirring for another 5 min, N,O-bis-(trimethylsilyl)acetamide (BSA; 0.37 mL, 1.5 mmol) and dimethylmalonate (0.17 mL, 1.5 mmol) were added. The mixture wasstirred at rt until the reaction was complete (as evidenced byTLC), then the reaction mixture was diluted with diethyl ether(10 mL) and washed consecutively with satd. aq NH4Cl and water.The organic phase was dried over anhydrous Na2SO4, filtered andconcentrated in vacuo. The residue was purified by flash columnchromatography (silica gel, hexane/ethyl acetate, 9:1). The enanti-oselectivity was determined by HPLC analysis with a chiral column(Chiralpak IA; hexane/i-PrOH, 95:5; flow rate, 0.7 mL/ min; tR,14.321; tS, 17.871 min). The absolute configurations of the enanti-omers were determined by comparison of the retention times withthat of an authentic sample and by the measurement of the specificrotation of the product.

Acknowledgments

Financial support of National Science Fund, Bulgaria (DID02/33/2009) and DRNF-02/1, is gratefully acknowledged. We also thankDr. Nikolay Vassilev for performing the high temperature NMRspectra. The crystallographic data for the structures of 10 and 13have been deposited with the Cambridge Crystallographic DataCentre as supplementary publications no. CCDC 818928 and no.CCDC 818929. Copies of the data can be obtained free of chargeon application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK(tel: +44 1223 762910; fax: +44 1223 336033; e-mail:deposit@ccdc.cam.ac.uk).

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