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Synthetic CommunicationsAn International Journal for RapidCommunication of Synthetic Organic ChemistryPublication details, including instructions for authors and subscription information:http://www.informaworld.com/smpp/title~content=t713597304

Opening of Epoxide Rings Catalyzed by NiobiumPentachlorideMauricio Gomes Constantino a; Valdemar Lacerda Júnior b; Paulo RobertoInvernize a; Luiz Carlos da Silva Filho a; Gil Valdo José da Silva aa Faculty of Philosophy, Department of Chemistry, Sciences and Letters of RibeirãoPreto, University of São Paulo, Brazilb Department of Chemistry, Center of Exact Sciences, Federal University of EspíritoSanto, Vitória, Brazil

Online Publication Date: 01 January 2007To cite this Article: Constantino, Mauricio Gomes, Júnior, Valdemar Lacerda, Invernize, Paulo Roberto, Filho, LuizCarlos da Silva and da Silva, Gil Valdo José (2007) 'Opening of Epoxide Rings Catalyzed by Niobium Pentachloride',Synthetic Communications, 37:20, 3529 - 3539To link to this article: DOI: 10.1080/00397910701555790URL: http://dx.doi.org/10.1080/00397910701555790

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Opening of Epoxide Rings Catalyzedby Niobium Pentachloride

Mauricio Gomes Constantino

Faculty of Philosophy, Department of Chemistry, Sciences and Letters of

Ribeirao Preto, University of Sao Paulo, Brazil

Valdemar Lacerda Junior

Department of Chemistry, Center of Exact Sciences, Federal University

of Espırito Santo, Vitoria, Brazil

Paulo Roberto Invernize, Luiz Carlos da Silva Filho, and

Gil Valdo Jose da SilvaFaculty of Philosophy, Department of Chemistry, Sciences and Letters of

Ribeirao Preto, University of Sao Paulo, Brazil

Abstract: The behavior of several epoxides when treated with NbCl5 was studied. In

general, the studied epoxides reacted rapidly with NbCl5, giving, in most cases, more

than one product (chlorohydrins, products containing solvent residues, as well as

rearrangement products). A detailed study was performed to verify the effects of the

temperature (rt, 08C, or 2788C) and of the NbCl5 molar concentration on the compo-

sition of the products, yield, and time required for the reactions.

Keywords: epoxides, Lewis acid, niobium pentachloride

The epoxide ring is one of the most versatile functional groups in organic

chemistry. The polarity and strain of the three-membered ring allow many

reactions with a large number of reagents such as electrophiles, nucleophiles,

Received in the USA October 16, 2006

Address correspondence to Mauricio Gomes Constantino, Faculty of Philosophy,

Department of Chemistry, Sciences and Letters of Ribeirao Preto, University of

Sao Paulo, Av. Bandeirantes 3900, 14040-901 Ribeirao Preto-SP, Brazil. E-mail:

mgconsta@usp.br

Synthetic Communicationsw, 37: 3529–3539, 2007

Copyright # Taylor & Francis Group, LLC

ISSN 0039-7911 print/1532-2432 online

DOI: 10.1080/00397910701555790

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acids, bases, and radicals. The opening of epoxide rings has been a required trans-

formation in studies on the synthesis of natural products.[1,2] Boron trifluoride

etherate is the most commonly used Lewis acid for this purpose, but we have

already demonstrated[3–7] that the stronger Lewis acid NbCl5 can give similar

results under milder conditions. Moreover, in certain cases, different products

such as chlorohydrins are obtained with NbCl5. We decided to extend our inves-

tigations to a number of epoxides in an effort to establish the scope of the reaction.

In this article, we describe the behavior of epoxides 1–6 (Fig. 1) when

treated with NbCl5, performing a detailed study to verify the effects of the

temperature (rt, 08C, or 2788C) and of the NbCl5 molar ratio on the compo-

sition of the products, yield, and time required for the reactions.

Epoxides 1–6 were prepared by treatment of the respective olefins with

H2O2 in basic medium (epoxides 1, 4, and 6) or with 70% meta-chloroperoxy-

benzoic acid (MCPBA) (epoxides 2, 3, and 5). The results of these prep-

arations are shown in Table 1.

Reactions of epoxides 1–6 with NbCl5 were performed under a nitrogen

atmosphere, at three different temperatures (room temperature, 08C, and

2788C), using anhydrous ethyl acetate as solvent, and with different molar

Figure 1. Epoxides chosen for treatment with NbCl5.

Table 1. Preparation of epoxides 1–6

Starting olefin Conditions (temp, time) Yield (%) Epoxide

Isophorone 208C, 180 min 70 1

Cyclohexene rt, 90 min 65 2

(+)-a-Pinene 58C, 60 min 85 3

L-(2)-Verbenone 208C, 15 min 73 4

(2)-b-Pinene 58C, 90 min 65 5

L-(2)-Carvone 208C, 15 min 80 6

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ratios of NbCl5 (0.5 or 0.125 eq.). The results obtained in these studies are

summarized in Table 2.

All products were isolated and characterized by spectroscopic and spec-

trometric methods (1H NMR, 13C NMR, IR, and mass spectra). Relative

stereochemistry determination for most epoxides and products was accom-

plished through nuclear overhauser effect difference (NOEDIF) experiments

and comparison with literature data.[8]

As can be observed from Table 2, the reactions of epoxides with NbCl5 in

most cases are very fast (1 min), following different paths and mechanisms

depending on the structure of the epoxide and on the reaction medium, and

give in most cases more than one product: chlorohydrins, products containing

solvent residues, and rearrangement products.

Epoxides 1 and 3–6 have a fully substituted carbon in the epoxide ring that

could facilitate carbocation formation. The products obtained from these

epoxides clearly show that the epoxide bond to the more substituted carbon

atom was preferentially broken. Thus, the tertiary carbocation formed can

follow different paths: rearrangements, acyl group migration, additions of

Cl2 and solvent residues, and Hþ elimination. As an example, we have

chosen the ring opening of a-pinene epoxide (3) to illustrate these transform-

ations. In Scheme 1; a proposed mechanism for this reaction is shown.

The opening of the epoxide ring gives the tertiary carbocation; the tension

of the nearby four-membered ring is then relieved by either of the two familiar

pathways: migration of the isopropyl group or ring opening. Nucleophilic

addition of Cl2 can now occur to each of the carbocations 3a or 3b, thus

forming the chlorohydrins 14 (1.5%) and 12 (20%). The defined stereo-

chemistry of 14 suggests that the nucleophile could be one of the chlorine

atoms of the Lewis acid residue still attached to the oxygen. Compound 3bcan also lose Hþ to give 13 (18%), and 3a gives, as a major product, the

rearranged aldehyde 11. The general pattern of these rearrangements is

similar to those obtained with other Lewis acids.[9 – 12]

Epoxides that cannot give stable tertiary carbocations, such as 2 or 6, react

in a different way. The products obtained here suggest that the epoxide ring

opening should be assisted by a nucleophilic attack by Cl2 to form chlorohy-

drins 9 or 20, or by the solvent to give acetates 10 or 19.

The effect of the temperature and the NbCl5 molar ratio on these reactions

was evaluated: the results, summarized in Table 2, clearly show that NbCl5can be used in reactions at low temperatures (08C or 2788C), leading in

most cases to a higher selectivity and better yields.

A remarkable aspect of this work is the higher efficiency of NbCl5, as

compared to other Lewis acid catalysts (e.g., when epoxide 3 reacts with

BF3. Et2O, seven different products are obtained).[12] The possibility of

effecting the ring opening of epoxides at low temperatures and with short

reaction times is, in our opinion, the most important aspect shown in this research.

In conclusion, the scope and limitations of the NbCl5-mediated opening

of epoxide rings have been studied. The methodology allows us to obtain

Epoxide Ring Opening 3531

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Table 2. Opening of epoxides 1–6 catalyzed by NbCl5

Epoxides Products NbCl5 (eq.) Temp. (8C) Time (min) Yield (%)a Ratio (%)b

1 0.5 rt 1 81 80:20

0 1 70 86:14

278 20 86 95:6

0.125 rt 5 70 90:10

0 10 73 94:6

278 480c 77 97:3

2 0.5 rt 1 62 77:23

0 1 65 85:15

278 1 77 87:13

0.125 rt 1 69 85:15

0 1 70 90:10

278 1 75 91:9

3 0.5 rt 1 — Complex

mixture

0 1 — Complex

mixture

278 1 69 43:43:5:9

0.125 0 1 67 39:30:26:5

278 1 75 47:27:24:2

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4 0.5 rt 1 — Complex

mixture

278 60 69 —

0.125 rt 200 65 —

278 480c 71 —

5 0.5 rt 1 65 41:42:17

0 1 69 31:49:20

278 1 73 25:52:23

0.125 rt 1 67 25:56:19

0 1 70 21:65:14

278 1 75 12:75:13

6 0.5 rt 10 78 38:62

0 30 81 30:70

278 480c — —

0.125 rt 30 69 25:75

0 240 86 11:89

aBased on the major product. In cases where the starting material was partially recovered, the yield was calculated based on the unrecovered

starting material.bRatios determined by 1H NMR.cAfter this time, the reaction was quenched because the conversion of starting materials into products was already too slow or did not proceed at all.

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chlorohydrins, products containing solvent residues, and rearrangement

products. These results confirm the effectiveness of NbCl5 as a Lewis acid

in these reactions and make the procedure a promising tool because of the sim-

plicity and mildness of this methodology.

EXPERIMENTAL

General Methods and Materials

All reactions were carried out under an atmosphere of N2 unless otherwise

specified. Ethyl acetate was distilled from calcium hydride. All commercially

available reagents were used without further purification. Thin-layer chromato-

graphy (TLC) was performed on 0.2-mm Merck 60F254 silica-gel aluminum

sheets, which were visualized with a vanillin/methanol/water/sulfuric acid

mixture. ACROS 80-230 silica gel 60 was employed for column chromato-

graphy. A Perkin-Elmer RX IFTIR system was used to record IR spectra

(neat or film). Bruker DRX 400 and DRX 500 spectrometers were employed

for the NMR spectra (CDCl3 solutions) using tetramethylsilane as internal

Scheme 1. Proposed mechanism for opening of a-pinene epoxide (3) with NbCl5.

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reference for 1H and CDCl3 as an internal reference for 13C. Mass spectra were

obtained on a HP GC/MS system 5988–A.

General Procedure for Preparation of Epoxides 1, 4, and 6

To a solution containing (+)-isophorone (0.94 g, 6.8 mmol) or L-(2)-

verbenone (1.02 g, 6.8 mmol) or L-(2)-carvone (1.02 g, 6.8 mmol) and 30%

aqueous solution of hydrogen peroxide (2.0 mL, 0.67 g, 21 mmol) in

methanol (8 mL), a 6M aqueous solution of sodium hydroxide (0.60 mL,

0.13 g, 3.3 mmol) was added drop by drop, maintaining the reaction mixture

at 15–208C with a water bath. After the reaction was complete, the mixture

was diluted with water (8 mL) and extracted with ethyl ether (2 � 10 mL).

The solvent was removed under vacuum, and the products were purified by

column chromatography through silica gel using a mixture of hexane and

ethyl acetate (8:2) as eluent, yielding a colorless oil of the epoxide.

General Procedure for Preparation of Epoxides 2, 3, and 5

To a solution of MCPBA 70% (3.57 g, 14.5 mmol) and sodium bicarbonate

(1.56 g, 18.6 mmol) in methylene chloride (36.0 mL), a solution of cyclohexene

(1.17 g, 14.2 mmol) or (+)-a-pinene (1.93 g, 14.2 mmol) or (2)-b-pinene

(1.93 g, 14.2 mmol) in methylene chloride (3 mL) was added drop by drop,

maintaining the reaction mixture at 5–108C with a water bath. During the

addition, sodium m-chlorobenzoate began to crystallize, indicating that the

reaction was proceeding. After completion of the addition, stirring was

continued at the same temperature. After the reaction was complete, the

mixture was treated with 10% aqueous sodium sulfite solution (10.0 mL) and

stirred for 30 min at room temperature to remove the excess of peracid.

Water (7.0 mL) was added, and the methylene chloride phase was separated

and washed with 16.0 mL of 5% aqueous sodium carbonate. The two

aqueous washings were extracted with 10.0 mL of methylene chloride, and

the organic solutions were combined and dried over anhydrous magnesium

sulfate. Evaporation of the solvent under vacuum gave an oily residue that

was purified by column chromatography through silica gel using a mixture of

hexane and ethyl acetate (8:2) as eluent, yielding a colorless oil of the epoxide.

General Procedure for the Reactions of Epoxides 1–6 with NbCl5

To a solution of niobium pentachloride (0.135 g, 0.500 mmol or 0.033 g,

0.125 mmol) in anhydrous ethyl acetate (1 mL) (maintained at room tempera-

ture, 0, or 2788C and under nitrogen atmosphere), a solution of the epoxides 1

(0.154 g, 1.00 mmol) or 2 (0.981 g, 1.00 mmol) or 3 (0.152 g, 1.00 mmol) or 4

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(0.166 g, 1.00 mmol) or 5 (0.152 g, 1.00 mmol) or 6 (0.166 g, 1.00 mmol) in

anhydrous ethyl acetate (1 mL) was added. The reaction mixture was

quenched with a 10% aqueous citric acid solution (2.0 mL, when working

at room temperature and 08C) or with a 1:1 solution of water/THF (2.0 mL,

when working at 2788C). The mixture was diluted with water (5 mL) and

ethyl acetate (10 mL). The organic layer was separated, washed with 5%

aqueous sodium bicarbonate (3 � 10 mL) and saturated brine (2 � 10 mL),

and dried over anhydrous magnesium sulfate. The solvent was removed

under vacuum, and the products were purified by column chromatography

through silica gel using a mixture of hexane and ethyl acetate (8:2) as

eluent to give the products as pale yellow oils.

All compounds gave satisfactory spectroscopic data. Data for epoxides 1

and 2 and for compounds 7–10 are in accordance with those related in a

previous work.[3] Data for epoxides 3–6 are consistent with those related

in the literature.[8a – c] Data for compounds 11–20 are given next; for

compounds 11, 13, 16, 18, and 20, data were compared with literature.

Data

Compound (11): (+)-2,2,3-Trimethyl-cyclopent-3-ene-1-acetaldehyde[8a,d]

1H NMR (400 MHz, CDCl3): d 9.80 (t, 1H, J ¼ 2.5 Hz); 5.24 (ddq, 1H,

J1 ¼ 2.5, J2 ¼ 2.0, and J3 ¼ 1.8 Hz); 2.53 (ddd, 1H, J1 ¼ 15.5, J2 ¼ 4.0,

and J3 ¼ 2.5 Hz); 2.40 (m, 2H); 2.31 (m, 1H); 1.89 (dtd, 1H, J1 ¼ 4.0;

J2 ¼ 2.5, and J3¼ 1.8 Hz); 1.62 (m, 3H); 1.00 (s, 3H); 0.79 (s, 3H). 13C

NMR (100 MHz, CDCl3): d 203.1 (CHO); 148.0 (C); 121.6 (CH); 46.9 (C);

45.1 (CH2); 44.2 (CH); 35.5 (CH2); 25.6 (CH3); 20.0 (CH2); 12.6 (CH3). IR

(film) nmax: 2963; 2920; 1726; 1633; 1446; 1366; 1120; 1073 cm21. MS

m/z (rel. intensity) (%): 152 (M)þ (2); 137 (3); 119 (5); 108 (100); 105

(10); 93 (62); 67 (27); 41 (20).

Compound (12): (+)-trans-5-(1-Chloro-1-mehyl-ethyl)-2-mehyl-2-cyclo-

hexen-1-ol. 1H NMR (400 MHz, CDCl3): d 5.56 (dquint, 1H, J1 ¼ 4.5 and

J2 ¼ 1.5 Hz); 4.06 (t, 1H, J ¼ 3.5 Hz); 2.23 (dddd, 1H, J1 ¼ 14.2, J2 ¼ 7.0,

J3 ¼ 3.5, and J4¼ 1.5 Hz); 2.10 (ddt, 1H, J1 ¼ 13.4, J2¼ 4.5, and

J3 ¼ 1.5 Hz); 1.90 (m, 3H); 1.79 (s, 3H); 1.60 (s, 3H); 1.56 (s, 3H). 13C

NMR (100 MHz, CDCl3): d 134.6 (C); 125.2 (CH); 74.3 (C); 68.9 (CH);

40.7 (CH); 33.9 (CH2); 31.1 (CH3); 30.7 (CH3); 28.0 (CH2); 21.2 (CH3). IR

(film) nmax: 3327; 2993; 2933; 2872; 1455; 1438; 1370; 1158; 1124; 1056

cm21. MS m/z (rel. intensity) (%): 137 [(M-51)þ] (46); 109 (63); 93 (31);

69 (34); 55 (38); 43 (78); 41 (100); 27 (46).

Compound (13): (+)-trans-5-Isopropenyl-2-methyl-2-cyclohexen-1-ol.[8d]

1H NMR (400 MHz, CDCl3): d 5.59 (ddq, 1H, J1 ¼ 5.0, J2 ¼ 2.0, and

J3 ¼ 1.5 Hz); 4.75 (dq, 1H, J1 ¼ 2.0 and J2 ¼ 1.5 Hz); 4.73 (dq, 1H,

J1 ¼ 2.0 and J2 ¼ 1.0 Hz); 4.03 (dt, 1H, J1 ¼ 4.0, and J2 ¼ 2.0 Hz); 2.33

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(tddd, 1H, J1 ¼ 12.0, J2 ¼ 5.0, J3 ¼ 4.0, and J4¼ 2.0 Hz); 2.33 (tddd, 1H,

J1 ¼ 12.0, J2 ¼ 5.0, J3 ¼ 4.0, and J4 ¼ 4.0 Hz) 2.15 (dtt, 1H, J1 ¼ 17.0,

J2 ¼ 5.0, and J3 ¼ 1.5 Hz); 1.94 (dddd, 1H, J1 ¼ 13.6, J2 ¼ 4.0, J3 ¼ 2.0,

and J4 ¼ 1.5); 1.88 (m, 1H); 1.83 (m, 1H); 1.81 (m, 3H); 1.75 (s, 3H). 13C

NMR (100 MHz, CDCl3): d 149.2 (C); 134.1 (C); 125.4 (CH); 109.0 (CH2);

68.6 (CH); 36.7 (CH2); 35.2 (CH); 31.0 (CH2); 20.9 (2 CH3). IR (film)

nmax: 3388; 2963; 1646; 1446; 1374; 1289; 1260; 1056 cm21. MS m/z(rel. intensity) (%): 109 [(M-43)þ] (6); 70 (6); 69 (9); 61 (9); 55 (6); 43

(100); 29 (40); 27 (27).

Compound (14): (+)-cis-6-Chloro-1,7,7-trimethyl-bicyclo[2.2.1]-heptan-2-

ol. 1H NMR (400 MHz, CDCl3): d 4.39 (ddd, 1H, J1 ¼ 11.0, J2 ¼ 4.8, and

J3 ¼ 2.3 Hz); 4.18 (br.s, 1H); 2.66 (dddd, 1H, J1 ¼ 13.6, J2 ¼ 11.0,

J3 ¼ 4.8, and J4 ¼ 3.2 Hz); 2.51 (dddd, 1H, J1 ¼ 13.6, J2 ¼ 11.0, J3 ¼ 4.8,

and J4 ¼ 3.2 Hz), 1.80 (t, 1H, J ¼ 4.8 Hz); 1.72 (dd, 1H, J1 ¼ 13.6 and

J2 ¼ 4.8 Hz); 1.30 (dd, 1H, J1 ¼ 13.6 and J2 ¼ 4.8 Hz); 1.08 (s, 3H); 0.92

(s, 3H); 0.88 (s, 3H). 13C NMR (100 MHz, CDCl3): d 79.7 (CH); 67.0

(CH); 51.4 (C); 49.1 (C); 43.1 (CH); 40.7 (CH2); 39.5 (CH2); 20.1 (2 CH3);

11.6 (CH3). IR (film) nmax: 3327; 2993; 2933; 2872; 1455; 1438; 1370;

1158; 1124; 1056 cm21. MS m/z (rel. intensity) (%): 137 [(M-51)þ] (24);

135 (40); 109 (51); 108 (100); 93 (66); 67 (21); 41 (57); 27 (39).

Compound (15): trans-6-(1-Chloro-1-methyl-ethyl)-2-hydroxy-3-methyl-

cyclohex-3-enone. 1H NMR (400 MHz, CDCl3): d 5.61 (m, 1H); 4.78

(m, 1H); 2.69 (m, 1H); 2.58 (m, 2H); 1.81 (m, 3H); 1.73 (s, 3H); 1.65 (s, 3H).13C NMR (100 MHz, CDCl3): d 209.3 (C); 136.8 (C); 120.6 (CH); 75.6 (CH);

69.8 (C); 53.9 (CH); 32.1 (CH3); 31.3 (CH3); 26.6 (CH2); 17.9 (CH3).

Compound (16): (4-Isoproprenyl-cyclohex-1-enyl)-methanol.[8e] 1H NMR

(400 MHz, CDCl3): d 5.70 (m, 1H); 4.73 (m, 2H); 4.01 (m, 2H); 2.15

(m, 4H); 2.10 (br. s, 1H, OH); 1.97 (m, 1H); 1.87 (m, 1H); 1.73 (m, 4H).13C NMR (100 MHz, CDCl3): d 148.9 (C); 136.4 (C); 121.6 (CH); 107.8

(CH2); 66.4 (CH2); 40.2 (CH); 29.5 (CH2); 26.6 (CH2); 25.2 (CH2); 19.9

(CH3).

Compound (17): [4-(1-Chloro-1-methyl-ethyl)-cyclohex-1-enyl] methanol.1H NMR (400 MHz, CDCl3): d 5.68 (m, 1H); 4.01 (d, 1H, J ¼ 14.6 Hz);

3.99 (d, 1H, J ¼ 14.6 Hz); 2.26 (m, 1H); 2.17 (m, 1H); 2.10 (m, 1H); 1.98

(m, 1H); 1.77 (dddd, 1H, J1 ¼ 12.0, J2 ¼ 11.0, J3 ¼ 4.0, and J4 ¼ 2.0 Hz);

1.75 (m, 1H); 1.60 (s, 3H); 1.56 (m, 3H); 1.39 (ddd, 1H, J1 ¼ 12.0,

J2 ¼ 6.0, and J3 ¼ 1.0 Hz). 13C NMR (100 MHz, CDCl3): d 137.8 (C);

122.3 (CH); 74.6 (C); 67.3 (CH2); 46.9 (CH); 31.0 (CH3); 30.3 (CH3); 27.5

(CH2); 26.8 (CH2); 24.8 (CH2).

Compound (18): 2-[4-(Hydroxy-methyl)-cyclohex-3-enyl) propan-2-ol.[8f]

1H NMR (400 MHz, CDCl3): d 5.62 (m, 1H); 3.95 (d, 1H, J ¼ 14.0 Hz);

3.91 (d, 1H, J ¼ 14.0 Hz); 2.05 (m, 3H); 1.89 (m, 1H, dddt, J1 ¼ 11.0,

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J2 ¼ 5.0, J3 ¼ 2.5, and J4 ¼ 2.0 Hz); 1.79 (m, 1H); 1.48 (dddd, 1H, J1 ¼ 13.0,

J2 ¼ 12.0, J3 ¼ 5.0, and J4 ¼ 2.0 Hz); 1.20 (tdd, 1H, J1 ¼ 12.0, J2 ¼ 11.0,

and J3 ¼ 5.0 Hz); 1.14 (s, 3H); 1.12 (s, 3H). 13C NMR (100 MHz, CDCl3):

d 136.5 (C); 121.4 (CH); 71.7 (C); 66.1 (CH2); 44.1 (CH); 26.4 (CH3); 25.6

(CH2); 25.5 (CH2); 25.4 (CH3); 22.6 (CH2).

Compound (19): trans-2-Hydroxy-5-isopropenyl-2-methyl-3-oxo-cyclohexyl-

acetate. 1H NMR (400 MHz, CDCl3): d 4.88 (dd, 1H J1 ¼ 9.5 and

J2 ¼ 3.8 Hz); 4.81 (m, 1H); 4.67 (m, 1H); 2.80 (ddd, 1H, J1 ¼ 13.9,

J2 ¼ 5.0, and J3 ¼ 1.7 Hz); 2.64 (quint, 1H, J ¼ 5.0 Hz); 2.57 (dd, 1H,

J1 ¼ 13.9 and J2 ¼ 5.0 Hz); 2.30 (dddd, 1H, J1 ¼ 13.8, J2 ¼ 5.0, J3 ¼ 3.8,

and J4 ¼ 1.7 Hz); 2.02 (s, 3H); 1.83 (ddd, 1H, J1 ¼ 13.8, J2 ¼ 9.5, and

J3 ¼ 5.0 Hz); 1.72 (m, 3H); 1.30 (s, 3H). 13C NMR (100 MHz, CDCl3): d

211.1 (C); 170.5 (C); 145.6 (C); 112.9 (CH2); 78.0 (C); 76.2 (CH); 40.8

(CH2); 38.5 (CH); 30.4 (CH2); 21.9 (CH3); 21.5 (CH3); 20.7 (CH3).

Compound (20): trans-2-Chloro-3-hydroxy-5-isopropenyl-2-methyl-cyclo-

hexanone.[8g] 1H NMR (400 MHz, CDCl3): d 4.81 (m, 1H); 4.78 (m, 1H);

4.26 (dd, 1H, J1 ¼ 3.7 and J2 ¼ 2.6 Hz); 3.04 (dd, 1H, J1 ¼ 13.8 and

J2 ¼ 12.6 Hz); 2.84 (tt, 1H, J1 ¼ 12.6 and J2 ¼ 3.7 Hz); 2.43 (ddd, 1H,

J1 ¼ 14.1, J2 ¼ 12.6, and J3 ¼ 2.6 Hz); 2.38 (ddd, 1H, J1 ¼ 13.8, J2 ¼ 3.7,

and J3 ¼ 2.2 Hz); 1.93 (dtd, 1H, J1 ¼ 14.1, J2 ¼ 3.7, and J3 ¼ 2.2 Hz); 1.76

(m, 3H); 1.65 (s, 3H). 13C NMR (100 MHz, CDCl3): d 205.4 (C); 146.5

(C); 110.6 (CH2); 76.8 (CH); 68.0 (C); 41.1 (CH2); 39.0 (CH); 32.8 (CH2);

22.1 (CH3); 20.3 (CH3).

ACKNOWLEDGMENTS

The authors thank the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo

(FAPESP), the Conselho Nacional de Desenvolvimento Cientıfico e Tecnolo-

gico (CNPq), the Coordenadoria de Aperfeicoamento de Pessoal do Nıvel

Superior (CAPES), and the Financiadora de Estudos e Projetos (FINEP) for

financial support. We also thank CBMM–Companhia Brasileira de Mineralo-

gia e Mineracao for NbCl5 samples.

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