Construction of functionalized carbocycles having contiguous tertiary carbinol and all-carbon stereogenic centers

FULL PAPER

DOI: 10.1002/ejoc.201201382

Construction of Functionalized Carbocycles Having Contiguous Tertiary

Carbinol and All-Carbon Stereogenic Centers

Chennakesava Reddy,^[a]Srinivasarao Arulananda Babu,*^[a]Nayyar Ahmad Aslam,^[a]and

Vadla Rajkumar^[a]

Keywords: Carbocycles / Allylation / Diastereoselectivity / Indium / Lactones / Configuration determination

A highly stereoselective protocol is reported for customizing

functionalized carbocyclic building blocks (β-hydroxy esters)

and bicyclic lactones with a stereoarray that contains contig-

uous tertiary carbinol and all-carbon stereocenters. The ef-

ficient asymmetric induction and diastereofacial selective ad-

dition of allyl and propargyl indiums to hindered α,α-disub-

stituted cycloalkanones is presented. The stereochemistry of

representative products was unequivocally established from

single-crystal X-ray crystal structure analyses, and a plaus-

ible reaction pathway was proposed to support the high dia-

stereofacial selectivity.

Introduction

Polyfunctional carbocyclic frameworks that have tertiary exist many excellent methods to create new C–C bonds, but

carbinol and all-carbon- stereocenters are the backbone of establishing two or more adjacent stereocenters (including

several natural products (e.g., sesquiterpenoids and di- an all-carbon quaternary center) with the correct stereo-

terpenoids) and bioactive molecules (see Figure 1).^[1]There chemistry remains one of the most arduous problems of

Figure 1. Theme of this work and natural products with contiguous tertiary carbinol and all-carbon stereocenters.

chemical syntheses.^[1,2]In this line, the stereoselective instal-

[a] Department of Chemical Sciences, Indian Institute of Science

lation of a stereoarray that contains contiguous tertiary

Education and Research (IISER) Mohali,

carbinol and all-carbon stereocenters during a multistep

Knowledge City, Sector 81, SAS Nagar, Mohali, Manauli P. O.,

Punjab 140306, India

chemical synthesis is a laborious task.^[2c]In recent years,

there have been various brilliant efforts to address this

problem.^[2,3]

The stereoselective nucleophilic addition of organometal-

lic reagents (derived from Mg, Li, Zn, In, Sn, etc.) to a

Fax: +91-172-2240266

E-mail: sababu@iisermohali.ac.in

Homepage: http://ww w .iisermohali.ac.in/html/faculty/

babu.html

Supporting information for this article is available on the

WWW under http://dx.doi.org/10.1002/ejoc.201201382.

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Construction of Functionalized Carbocycles

prostereogenic center of a ketone is a challenging transfor- either a tetrahydrofuran (THF)/H₂O mixture or H₂O did

mation. Nevertheless, it is a versatile C–C bond-forming not give allylation products 3a and 4a (see Table 1, En-

process and an excellent route for generating tertiary carbi- tries 1–3).^[4v]In addition, the reaction in MeOH gave prod-

nol stereocenters. In this line, recent developments in the uct 3a in only 20% yield. Although the allylations of simple

area of indium-mediated allylations of carbonyls, which en- cyclic ketones are well-known in the literature, these results

able the construction of homoallylic alcohols along with the are perhaps a result of the low reactivity of the (hindered)

installation of stereogenic centers (2° and 3° carbinols), α,α-disubstituted cyclic ketone. Notably, the In-mediated

have been highly promising.^[4]Moreover, to the best of our allylation of 1a in the anhydrous solvents N,N,-dimethyl-

knowledge there exist no reports of an indium-mediated formamide (DMF), dichloromethane (DCM), and THF

construction of a stereoarray that consists of contiguous gave product 3a (trans isomer) in very high yields (95–97%,

tertiary carbinol and all-carbon stereocenters with the abso- dr 98:2; see Table 1, Entries 5, 7, and 10).^[4v,5a]

lute stereochemistry established.^[4]

Next, the scope of this In-mediated allylation protocol

Taking an impetus from the recent reports that focus on was investigated by using several α-alkyl-α-(ethoxycarb-

the development of indium-mediated stereoselective reac- onyl)cycloalkanones. As a result, we accomplished the

tions,^[1–4]we envisaged the indium-mediated construction of highly efficient and diastereoselective construction of the

functionalized carbocycles and bicyclic lactones with con- functionalized carbocyclic building blocks (β-hydroxy es-

secutively attached tertiary carbinol and all-carbon stereo- ters) 5a–5z and 5za (trans isomers), which contain a

centers. This is a theme that has not been explored, espe- stereoarray of contiguous tertiary carbinol and all-carbon

cially through an In-mediated diastereofacial selective allyl- stereocenters (see Table 2).^[5a,5b]Products 5i and 5j were ob-

ation and allenylation of (hindered) cycloalkanones.

tained in relatively low diastereoselectivity when Zn dust

We herein report the investigation of an efficient and was used instead of indium powder. The indium-mediated

highly diastereofacial selective addition of allyl and propar- allylation of ethyl 1-benzyl-3-(4-bromobenzyl)-4-oxopiper-

gyl indiums to (hindered) prostereogenic α,α-disubstituted idine-3-carboxylate and ethyl 3-allyl-1-benzyl-4-oxopiperid-

cycloalkanones, which results in the stereoselective instal- ine-3-carboxylate gave the corresponding functionalized

lation of a stereoarray that contains contiguous tertiary piperidine derivatives 5zb (dr 80:20), 5zc (dr 65:35), and 5zd

carbinol and all-carbon stereocenters in functionalized (dr 65:35, see Table 2), respectively.

carbocyclic building blocks and bicyclic lactones.

Next, to expand the scope of this diastereofacial selective

reaction, we tested the allylation protocol with α-alkyl-α-

(ethoxycarbonyl)cycloalkanones 6a–6d (see Table 3),^[5a,5b]

which were designed to undergo a facile in situ lacton-

ization during the In-mediated allylations and thereby af-

Results and Discussion

At the outset, the optimization of the In-mediated allyl- ford various bicyclic lactones with contiguous tertiary

ation of ethyl 1-benzyl-2-oxocyclopentane-1-carboxylate carbinol and all-carbon stereocenters. In an initial trial, the

(1a) was carried out under different reaction conditions (see indium-mediated allylation of ethyl 1-(2-ethoxycarbonyl-

Table 1). Surprisingly, the In-mediated allylation of 1a in ethyl)-2-oxocyclopentanecarboxylate (6a) gave bicyclic lact-

Table 1. Optimization of reaction conditions.

[a] The reaction was carried out at 70 °C.

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Table 2. Functionalized carbocycles with contiguous tertiary carbinol and all-carbon stereocenters.

[a] The stereochemistry based on the X-ray structures of representative compounds is shown for the major isomers. [b] Zn (0.85 mmol)

was used instead of indium powder.

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Construction of Functionalized Carbocycles

Table 3. Bicyclic lactones with contiguous tertiary carbinol and all-carbon stereocenters.

Scheme 1. In-mediated synthesis of bicyclic lactones 8g and 8h.

one^[6]8a (95% yield, dr 99:1), in which the transesterifica- of different reaction conditions (see Table 4)^[5a,5b]revealed

tion commendably promoted the cyclization under the ex- that THF was best for the allenylation of cycloalkanone 1a

perimental conditions. The generality of this inspiring (see Table 4, Entry 8), which afforded allene adduct 10a

stereoselective protocol was then tested with cycloalk- (trans isomer) with the formation of contiguous stereocen-

anones 6b–6d, and the corresponding bicyclic lactones 8b– ters with high regioselectivity and diastereoselectivity (85%

8f with contiguous stereocenters were obtained in high yield, dr 98:2). A similar trend was observed in DMF and

yields with excellent selectivity (59–95% yield, see Table 3). DCM (see Table 4, Entries 4 and 5), but the allenylations

Interestingly, the allylation of 2-(2-cyanoethyl)-2-methyl- of 1a in other solvents (e.g., THF/H₂O, water, or methanol)

cyclohexanone also afforded cyclic lactones 8g and 8h un- were ineffective. When we employed Zn dust in the reaction,

der the experimental conditions (see Scheme 1).^[5a–5d]

a low regioselectivity was observed, as products 10b and

Subsequently, we performed the allenylations of various 11b were obtained in 48 and 40% yield, respectively (see

α,α-disubstituted cycloalkanones. The optimization studies Table 4, Entry 7).

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Table 4. Highly diastereoselective allenylation.

[a] Zn (0.85 mmol) was used instead of indium powder.

Next, the addition of propargyl indium to α-alkyl-α- of the representative compounds in solid form (that were

(ethoxycarbonyl)cycloalkanones 1b–1e selectively furnished suitable for obtaining crystals) for single-crystal X-ray

the corresponding allene derivatives 10b–10d (trans isomers, structure analyses as well as to show the usefulness of this

81–92%, dr 98:2, see Table 5) with contiguous tertiary protocol for obtaining various carbocycles, we carried out

carbinol and all-carbon stereocenters. The In-mediated ad- some functional group transformations such as the re-

dition of 1-bromobut-2-yne to 1b gave products 10e and duction of the ester and protection of the alcohol groups

11e in 40 and 30% yield, respectively, and a relatively low of compounds listed in Tables 2, 3, 4, and 5 and Scheme 1.

regioselectivity was observed. This may be a result of the In this line, we carried out the LiAlH₄-mediated reduction

low reactivity of the propargyl indium derived from of the ester groups present in representative compounds 5a,

1-bromobut-2-yne. Additionally, the In-mediated allenyl- 5c, 5d, 5n, and 5t, which gave the functionalized building

ation of cycloalkanone 12a gave allene 10f (64%, trans iso- blocks (diols) 5aA, 5cA, 5dA, 5nA, and 5tA, respectively,

mer) and the minor product 11f (14%, trans isomer) with with contiguous tertiary carbinol and all-carbon stereocen-

adjacent stereogenic centers (see Table 5).^[5a,5b]

ters (see Scheme 2).^[5b]Next, the LiAlH₄-mediated re-

To establish the stereochemistry of the products in the duction of lactones 8b, 8c, and 8g (mixture of dia-

respective Tables, Schemes, and Figures and to obtain some stereomers) furnished the corresponding functionalized

Table 5. Construction of functionalized allenes.

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Scheme 2. Diols and triols with contiguous stereogenic centers. Reagents and conditions: (a) substrate (0.5 mmol), DCM (3 mL), MgBr₂

(1.5 mmol), Et₃N (3 mmol), (ArCO)₂O (1.5 mmol), room temp., overnight; (b) substrate (0.5 mmol), DCM (4 mL), Et₃N (1.5 mmol),

ArCOCl (1.5 mmol), 40 °C, overnight; (c) substrate (0.5 mmol), DCM (4–6 mL), Et₃N (3 mmol), ArCOCl (3 mmol), 40 °C, overnight.

building blocks (triols and diols, see Scheme 2) 8bA, 8cA, lowed by diesters 5nC and 5tC, respectively. Likewise, dies-

8gA,^[5c,5d]and 8gB.^[5c,5d]

ter 8bB was obtained by protecting the primary alcohol

The esterification reaction of tertiary carbinols 5q–5s, 5n, groups present in triol 8bA (see Scheme 2).

10b, and 10f afforded the respective compounds 5qC, 5rC,

We were then interested in extending the utility of this

5sC, 5nD, 10bC, and 10fA (see Scheme 2). Similarly, we se- synthetic protocol to construct carbocyclic ether derivatives

quentially protected the primary and tertiary alcohol that contain two contiguous stereocenters (see Scheme 3).

groups of compounds 5nA and 5tA, which afforded the cor- The selective O-allylation of the primary alcohol group

responding monoesterification products 5nB and 5tB fol- of derivatives 5cA and 5aA followed by a ring-closing

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Scheme 3. Carbocyclic ethers with contiguous stereogenic centers.

metathesis (RCM) reaction^[7b]afforded the functionalized the reactions exclusively gave the trans isomers as the major

carbocyclic skeletons 11h and 11j, respectively, with contig- compound. From the X-ray crystal structures of com-

uous stereogenic centers (see Scheme 3).^[5b]

pounds 5i, 5l, 5y, and 5zb, we found that the allyl and

benzyl groups were in the axial positions (trans stereochem-

istry). The observed trans stereochemistry of all the prod-

ucts (OH and COOEt groups are trans) obtained in this

work could be elucidated by using the popular chair-like

Stereochemistry^[5b,7a,8]

The stereochemistry of the adducts listed in Tables 1 and transition states such as 17 (through an axial approach of

2 were unambiguously established from the X-ray crystal the allyl indium when the benzyl group is in the axial posi-

structure analyses of the representative compounds (major tion, see Scheme 4) or 13 (through an equatorial approach

isomers) 3a, 5a, 5i, 5l, 5v, 5y, 5zb, 5nC (a derivative of 5n), of the allyl indium when the benzyl group is in the equato-

and 5tC (a derivative of 5t). The stereochemistry of lactones rial position, see Scheme 4).

8a–8g (see Table 3 and Scheme 1) and the adducts listed in

In a preliminary effort to understand the observed dia-

Tables 4 and 5 were assigned on the basis of the X-ray stereofacial selectivities, we have obtained the X-ray crystal

structures of representative compounds such as adduct 11f structures of the representative starting substrates 12a and

and the derivatives 8cA, 8gB, and 10fA, which were pre- 12b (and compound 23, see Supporting Information for the

pared from the lactones 8c (major isomer), 8gЈ (minor iso- ORTEP diagram), which reveal that the benzyl group is in

mer), and allene 10f (major isomer), respectively.

the equatorial position (see Scheme 4 and Figure 2). How-

The stereochemistry assignments based on the X-ray ever, the corresponding X-ray crystal structures of products

crystal structures of various key products revealed that all 5i and 5l reveal that the benzyl group is in the axial position

Scheme 4. Plausible reaction pathway [for structures 12–18, Y = Br (for a) and Y = Cl (for b)].

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Construction of Functionalized Carbocycles

after the addition of the allyl indium reagent, and under

the experimental conditions, there is a conformational ring-

flip. Plausibly, the conformational ring-flip could occur be-

fore the allylation reaction (starting compounds 12a and

12b to 16a and 16b, respectively) or after the allylation reac-

tion [products 15a and 15b to 5i and 5l (observed confor-

mation), respectively]. Considering these possibilities, on

the basis of the observed high stereoselectivity for all the

reactions and the X-ray crystal structure analyses of the key

compounds, a plausible reaction pathway, at this stage, is

proposed for the formation of the conformers 5i and 5l

(trans isomers, allyl and benzyl groups are trans, see

Scheme 4).

Conclusions

In summary, we have reported an efficient and highly

stereoselective protocol for customizing functionalized

carbocyclic building blocks and bicyclic lactones with a

stereoarray that contains contiguous tertiary carbinol and

all-carbon stereocenters as well as an efficient asymmetric

induction by using In-mediated allylation and allenylation

strategies. The assignments of the absolute stereochemistry

based on the X-ray crystal structures of various key prod-

ucts reveal that all the reactions exclusively gave the trans

isomers as the major compound. Further applications of

these functionalized carbocycles for the synthesis of natural

products and bioactive molecules are being explored in our

laboratory.

Experimental Section

General Methods: IR spectra were recorded by using thin films or

KBr pellets. The ¹H and ¹³C NMR spectroscopic data were re-

corded with 400 and 100 MHz spectrometers, respectively, and

TMS was used as an internal or external standard. Column

chromatography was carried out with silica gel (100–200 mesh) or

neutral Al₂O₃. The reactions were carried out in anhydrous sol-

vents^[11]under nitrogen, as required. Solutions were dried with an-

hydrous sodium sulfate. Reagents were added to the reaction flask

through a syringe. Thin layer chromatography was performed on

silica plates or neutral Al₂O₃, and components were visualized by

observation under iodine. The isolated yields of all the products

were reported (yields were not optimized). The ratios of the dia-

1

stereomers were determined from the H and ¹³C NMR spectra of

the crude reaction mixtures or after isolation of the product. The

ratio of diastereoselectivity (e.g., dr 98:2) refers to the presence of

the major diastereomer in the NMR spectrum of the crude reaction

mixture. Occasionally, during repetitive column purifications, the

corresponding minor diastereomers were isolated.

Figure 2. X-ray structures (ORTEP) of compounds 12a, 12b, 5i,

and 5l.

General Procedure for the Synthesis of α,α-Disubstituted Cycloalk-

anones: To a solution of the ethyl 2-oxocycloalkane-1-carboxylate

(1 mmol) in anhydrous THF or acetone (3–5 mL) were added the

allyl or benzyl bromide (1.1 mmol) and activated potassium car-

bonate (1.5 mmol) under an inert atmosphere, and the reaction

mixture was heated at reflux (75–80 °C) for 10–12 h. The progress

of the reaction was monitored by TLC. [If the cycloalkane-1-carb-

oxylate was not consumed, more allyl or benzyl bromide (0.2–

0.5 mmol) and activated potassium carbonate (0.5–0.75 mmol)

were added.] Then, the reaction mixture was filtered through a sil-

ica plug by rinsing with EtOAc. The organic layer was dried with

anhydrous sodium sulfate and evaporated under vacuum, and the

resulting crude reaction mixture was purified by silica gel column

chromatography to give the α,α-disubstituted cycloalkanones in

pure form.

Furthermore, we have carried out semiempirical PM3

calculations^[9a,9b]to obtain the relative heats of formation

for conformers 12a (observed in X-ray analysis), 16a, 15a,

and 5i (observed in X-ray analysis). Within the conforma-

tional space explored in this study, the semiempirical calcu-

lations predict conformer 12a to be relatively stable and the

energy difference between conformers 12a and 16a to be

3.46 kcal/mol. Likewise, the calculations predict conformer

5i to be relatively stable and the energy difference between

conformers 5i^[9c]and 15a to be 2.03 kcal/mol. Although the

calculations support the experimentally observed conform-

ers, it must be noted that all the energy differences have

been calculated using semiemperical computations. More

reliable values for these energies can only be obtained by

employing higher levels of theory, in which we are presently

engaged. Whether the conformational ring-flip occurs in

the reactant or the product will depend on the energy bar-

rier between the two sets of conformers. Unless the energy

barrier is computed, it is difficult, at this stage, to comment

on the role of the transition states that involve In^Ior In-

Procedure A. Indium-Mediated Addition of Various Allyl and Prop-

argyl Bromides to α,α-Disubstituted Cycloalkanones: To a solution

of α,α-disubstituted cycloalkanone (0.5 mmol) in anhydrous THF

(1.5 mL) was added allyl/propargyl bromide (1.2 mmol) and in-

dium metal powder (0.75 mmol) under an inert atmosphere. The

progress of the reaction was monitored by TLC, and the reaction

mixture was stirred at room temp. for 24 h. After this time, the

reaction mixture was quenched by adding water (2 mL). The re-

sulting mixture was transferred to a separatory funnel and ex-

tracted with ethyl acetate (3ϫ8 mL). The combined organic layers

.

^{III [10]}We are in the process of carrying out detailed ab initio

computational studies by using the molecules from this

work to resolve this question.

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were dried with anhydrous Na₂SO₄, and the solvent was evaporated

under vacuum. Purification of the crude reaction mixture by col-

umn chromatography on silica gel (EtOAc/hexane) gave the pure

product (for specific reactions, see the corresponding tables and

schemes).

second-generation catalyst (21 mg) under nitrogen, and the reac-

tion mixture was heated at reflux at 100 °C for 2 h. After this time,

Grubbs second generation catalyst (17 mg) was added again, and

the reaction mixture was heated at reflux for an additional 14 h.

After this time, the solvent was removed under vacuum, and the

crude mixture was purified by silica gel column chromatography

(EtOAc/hexane) to afford the corresponding products 11j or 11h.

Procedure B. Reduction of Esters and Lactones to Diols and Triols:

To a precooled solution (0 °C) of the ester/lactone (0.5 mmol) in

anhydrous THF (1.5 mL) was added LiAlH₄(0.37 mmol) under an

inert atmosphere, and the reaction mixture was stirred at room

temp. overnight. (The progress of the reaction was monitored by

TLC). After this time, EtOAc (few drops) was added, and the re-

sulting mixture was stirred for 5 min. Then, water (1–2 mL) was

added. The resulting mixture was transferred to a separatory funnel

and extracted with ethyl acetate (3ϫ8 mL). The combined organic

layers were dried with anhydrous Na₂SO₄, and the solvent was

evaporated under vacuum. Purification of the resulting crude reac-

tion mixture by column chromatography on silica gel (EtOAc/hex-

ane) gave the product (for specific reactions, see the corresponding

tables and schemes).

Preparation of 3a and 4a Following General Procedure A: The reac-

tion of the corresponding cyclic ketone (1 mmol) and allyl bromide

(2.4 mmol) mediated by In (1.5 mmol) gave products 3a (280 mg,

97%, trans isomer) and 4a (5 mg, 2%, cis isomer).

Ethyl (1S*,2S*)-2-Allyl-1-benzyl-2-hydroxycyclopentanecarboxylate

(3a): Purification by silica gel column chromatography (EtOAc/hex-

ane, 6:94) afforded compound 3a (trans, major isomer) as a white

solid; m.p. 59–61 °C. IR (KBr): ν = 3503, 1719, 1451, 1185 cm^–1.

˜

¹H NMR (400 MHz, CDCl₃): δ = 7.23–7.10 (m, 5 H), 6.01–5.91

(m, 1 H), 5.17–5.09 (m, 2 H), 4.11–4.06 (m, 2 H), 3.41 (d, J =

13.6 Hz, 1 H), 2.74 (d, J = 13.6 Hz, 1 H), 2.39 (br. s, 1 H), 2.31–

2.20 (m, 2 H), 2.00–1.63 (m, 6 H), 1.18 (t, J = 7.1 Hz, 3 H) ppm.

¹³C NMR (100 MHz, CDCl₃): δ = 175.3, 138.6, 134.0, 129.9, 128.1,

126.4, 118.7, 83.1, 61.6, 60.5, 42.2, 38.0, 34.2, 29.3, 18.2, 14.2 ppm.

HRMS (ESI): calcd. for C₁₈H₂₄O₃Na [M + Na]⁺311.1623; found

311.1629.

Procedure C. Protection of Primary Alcohols: To the solution of the

primary alcohol (0.5 mmol), obtained from Procedure B, in anhy-

drous dichloromethane (4 mL) were added Et₃N (1.5 mmol) and

the corresponding benzoyl chloride (1.5 mmol) under nitrogen, and

the reaction mixture was heated at reflux at 40 °C overnight. After

this time, the reaction mixture was quenched by the addition of

water (2 mL). The resulting mixture was transferred to a separatory

funnel and extracted with ethyl acetate (3ϫ8 mL). The combined

organic layers were dried with anhydrous sodium sulfate, and the

solvent was removed under vacuum. The crude reaction mixture

was purified by silica gel column chromatography (EtOAc/hexane)

to give the ester in pure form (for specific reactions, see the corre-

sponding tables and schemes).

Procedure D. Protection of Tertiary Alcohols:^[11b]To a precooled

solution (0 °C) of the tertiary alcohol (0.5 mmol) in anhydrous

dichloromethane (3.0 mL) were sequentially added MgBr₂

(1.5 mmol), Et₃N (3.0 mmol), and the corresponding benzoic anhy-

dride (1.5 mmol) under nitrogen. The reaction mixture was stirred

at room temp. overnight. Upon completion (as indicated by TLC),

the reaction mixture was quenched by the addition of water (3 mL).

The resulting mixture was transferred to a separatory funnel and

extracted with ethyl acetate (3ϫ8 mL). The combined organic lay-

ers were dried with anhydrous Na₂SO₄. The solvent was evaporated

under vacuum, and purification of the crude reaction mixture by

column chromatography on silica gel (EtOAc/hexane) gave the ester

in pure form (for specific reactions, see the corresponding tables

and schemes).

Ethyl (1S*,2R*)-2-Allyl-1-benzyl-2-hydroxycyclopentanecarboxylate

(4a): Purification by silica gel column chromatography (EtOAc/hex-

ane, 8:92) afforded compound 4a (cis, minor isomer) as a white

solid; m.p. 55–57 °C. IR (KBr): ν = 3480, 1711, 1495, 1194 cm^–1.

˜

¹H NMR (400 MHz, CDCl₃): δ = 7.29–7.09 (m, 5 H), 6.04–5.93

(m, 1 H), 5.26–5.21 (m, 2 H), 4.21–4.11 (m, 2 H), 3.31 (d, J =

1

2

13.2 Hz, 1 H), 2.91 (dd, J = 13.6 Hz, J = 8.1 Hz, 1 H), 2.48 (dd,

¹J = 13.6 Hz, J = 6.7 Hz, 1 H), 2.42 (d, J = 13.2 Hz, 1 H), 2.37–

2

2.31 (m, 1 H), 2.20 (br. s, 1 H), 2.04–1.70 (m, 5 H), 1.23 (t, J =

7.1 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 174.6, 137.8,

134.3, 129.7, 128.2, 126.6, 119.1, 84.3, 62.1, 60.5, 40.6, 38.7, 37.1,

29.3, 19.3, 14.2 ppm. MS (CI): m/z (%) = 290 (13) [M + 2]⁺, 289

(76) [M + 1]⁺, 271 (100), 217 (4), 197 (16).

Preparation of 5a and 5aЈ Following General Procedure A: The reac-

tion of the corresponding cyclic ketone (1 mmol) and allyl bromide

(2.4 mmol) mediated by In (1.5 mmol) gave products 5a (340 mg,

92%, trans isomer) and 5aЈ (5 mg, 2%, cis isomer).

Ethyl (1S*,2S*)-2-Allyl-1-(4-bromobenzyl)-2-hydroxycyclopentane-

carboxylate (5a): Purification by silica gel column chromatography

(EtOAc/hexane, 5:95) afforded compound 5a (trans, major isomer)

as a white solid; m.p. 71–73 °C. IR (KBr): ν = 3478, 1694, 1484,

˜

1

1210 cm^–1. H NMR (400 MHz, CDCl₃): δ = 7.35 (d, J = 8.4 Hz,

2 H), 6.99 (d, J = 8.4 Hz, 2 H), 5.98–5.88 (m, 1 H), 5.19–5.10 (m,

2 H), 4.12–4.07 (m, 2 H), 3.34 (d, J = 13.6 Hz, 1 H), 2.70 (d, J =

13.6 Hz, 1 H), 2.29–2.19 (m, 2 H), 2.12 (s, 1 H), 1.98–1.89 (m, 2

H), 1.80–1.67 (m, 4 H), 1.21 (t, J = 7.2 Hz, 3 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 175.0, 137.6, 133.7, 131.6, 131.2, 120.3,

119.0, 83.0, 61.4, 60.6, 42.1, 37.3, 34.4, 29.4, 18.3, 14.2 ppm. MS

(CI): m/z (%) = 368 (5) [M + 1]⁺, 367 (27) [M]⁺, 349 (100), 275

(93), 265 (44). HRMS (ESI): calcd. for C₁₈H₂₃BrNaO₃[M + Na]⁺

389.0728; found 389.0720.

Procedure E. Alkylation of 5aA and 5cA Using Allyl Bromide: To a

dry flask (maintained at 0 °C) that contained NaH (0.9 mmol) in

anhydrous THF (2 mL) was added 5aA or 5cA (0.75 mmol), and

the reaction mixture was stirred for 30 min. After this time, allyl

bromide (1.1 mmol) was added to the reaction mixture at 0 °C, and

then the resulting mixture was stirred at room temp. overnight.

Upon completion (as indicated by TLC), EtOH (few drops) was

added, and the solution was stirred for 5 min. followed by the ad-

dition of water (1–2 mL). The resulting mixture was transferred to

a separatory funnel and extracted with ethyl acetate (3ϫ8 mL).

The combined organic layers were dried with anhydrous Na₂SO₄,

and the solvent was evaporated under vacuum. Purification of the

crude mixture by column chromatography on silica gel (EtOAc/

hexane) gave the corresponding products 11i or 11g.

Ethyl (1S*,2R*)-2-Allyl-1-(4-bromobenzyl)-2-hydroxycyclopentane-

carboxylate (5aЈ): Purification by silica gel column chromatography

(EtOAc/hexane, 7:93) afforded compound 5aЈ (cis, minor isomer)

as a white solid; m.p. 68–70 °C. IR (KBr): ν = 3500, 1716, 1488,

˜

1

1186 cm^–1. H NMR (400 MHz, CDCl₃): δ = 7.37 (d, J = 8.4 Hz,

Procedure F. RCM Reaction of 11i and 11g: To a solution of 11i or

11g (0.5 mmol) in anhydrous toluene (8 mL) was added Grubbs’

2 H), 6.95 (d, J = 8.4 Hz, 2 H), 6.00–5.89 (m, 1 H), 5.22–5.18 (m,

2 H), 4.17–4.09 (m, 2 H), 3.23 (d, J = 13.2 Hz, 1 H), 2.85 (dd, J

1

2370

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Eur. J. Org. Chem. 2013, 2362–2380

Construction of Functionalized Carbocycles

2

1

2

= 13.2 Hz, J = 8.0 Hz, 1 H), 2.43 (dd, J = 6.9 Hz, J = 6.7 Hz, 1 J = 7.1 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 175.5,

H), 2.37–2.30 (m, 2 H), 1.99–1.60 (m, 6 H), 1.21 (t, J = 7.1 Hz, 3

H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 174.3, 136.8, 134.1,

131.4, 131.3, 120.6, 119.2, 84.2, 61.9, 60.7, 40.6, 38.1, 37.1, 29.3,

19.4, 14.2 ppm. HRMS: (ESI) calcd. for C₁₈H₂₃BrNaO₃[M +

Na]⁺389.0728; found 389.0738.

136.0, 135.4, 133.7, 132.6, 131.5, 129.4, 126.9, 118.9, 83.4, 61.2,

60.8, 41.7, 34.2, 33.9, 28.7, 18.3, 14.2 ppm. MS (CI): m/z (%) = 359

(33) [M + 2]⁺, 358 (20) [M + 1]⁺, 357 (50) [M]⁺, 339 (100), 315

(13). HRMS (ESI): calcd. for C₁₈H₂₂Cl₂NaO₃[M + Na]⁺

379.0843; found 379.0831.

Ethyl (1S*,2S*)-2-Allyl-1-(3-chlorobenzyl)-2-hydroxycyclopentane-

carboxylate (5b): Following general procedure A, purification by

silica gel column chromatography (EtOAc/hexane, 06:94) afforded

compound 5b (147 mg, 93%, trans, major isomer) as a colorless

Ethyl (1S*,2S*)-2-Allyl-2-hydroxy-1-(4-methylbenzyl)cyclopentane-

carboxylate (5e): Following general procedure A, purification by

silica gel column chromatography (EtOAc/hexane, 6:94) afforded

compound 5e (140 mg, 94%, trans, major isomer) as a colorless

liquid. IR (neat): ν = 3504, 1719, 1475, 1186 cm^–1. ¹H NMR

liquid. IR (neat): ν = 3496, 1718, 1367, 1184 cm^–1. ¹H NMR

˜

(400 MHz, CDCl₃): δ = 7.17–7.16 (m, 2 H), 7.13 (s, 1 H), 7.04–

6.99 (m, 1 H), 6.00–5.90 (m, 1 H), 5.20–5.11 (m, 2 H), 4.12 (q, J

= 7.2 Hz, 2 H), 3.38 (d, J = 13.6 Hz, 1 H), 2.73 (d, J = 13.6 Hz, 1

H), 2.32–2.20 (m, 3 H), 2.01–1.88 (m, 2 H), 1.85–1.68 (m, 4 H),

1.23 (t, J = 7.2 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

175.0, 140.7, 133.8, 133.8, 130.0, 129.3, 128.1, 126.5, 119.0, 83.0,

61.5, 60.7, 42.1, 37.6, 34.4, 29.5, 18.3, 14.2 ppm. MS (CI): m/z (%)

= 324 (15) [M + 2]⁺, 323 (16) [M + 1]⁺, 322 (57) [M]⁺, 304 (100),

262 (14), 189 (23). HRMS (ESI): calcd. for C₁₈H₂₃ClNaO₃[M +

Na]⁺345.1233; found 345.1226.

(400 MHz, CDCl₃): δ = 7.04 (d, J = 7.8 Hz, 2 H), 6.99 (d, J =

7.8 Hz, 2 H), 6.01–5.90 (m, 1 H), 5.18–5.10 (m, 2 H), 4.11 (q, J =

7.1 Hz, 2 H), 3.37 (d, J = 13.6 Hz, 1 H), 2.69 (d, J = 13.6 Hz, 1

H), 1.99–1.74 (m, 6 H), 2.29 (s, 3 H), 2.24 (d, J = 6.2 Hz, 2 H),

2.20 (br. s, 1 H), 1.23 (t, J = 7.1 Hz, 3 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 175.3, 135.8, 135.3, 133.9, 129.8, 128.8,

118.7, 83.0, 61.5, 60.5, 42.2, 37.5, 34.0, 29.0, 21.0, 18.1, 14.2 ppm.

MS (CI): m/z (%) = 303 (7) [M + 1]⁺, 302 (34) [M]⁺, 284 (100), 211

(15), 144 (14). HRMS (ESI): calcd. for C₁₉H₂₆NaO₃[M + Na]⁺

325.1779; found 325.1766.

Preparation of 5c and 5cЈ Following General Procedure A: The reac-

tion of the corresponding cyclic ketone (1 mmol) and allyl bromide

(2.4 mmol) mediated by In (1.5 mmol) gave products 5c (303 mg,

94%, trans isomer) and 5cЈ (5 mg, 2%, cis isomer).

Ethyl (1S*,2S*)-2-Allyl-2-hydroxy-1-(3-methylbenzyl)cyclopentane-

carboxylate (5f): Following general procedure A, purification by

silica gel column chromatography (EtOAc/hexane, 6:94) afforded

compound 5f (142 mg, 95%, trans, major isomer) as a colorless

liquid. IR (neat): ν = 3513, 1722, 1445, 1187 cm^–1. ¹H NMR

˜

Ethyl (1S*,2S*)-2-Allyl-1-(4-chlorobenzyl)-2-hydroxycyclopentane-

carboxylate (5c): Purification by silica gel column chromatography

(EtOAc/hexane, 6:94) afforded compound 5c (trans, major isomer)

(400 MHz, CDCl₃): δ = 7.14–7.10 (m, 1 H), 6.99 (d, J = 7.3 Hz, 1

H), 6.92 (s, 1 H), 6.90 (d, J = 9.4 Hz, 1 H), 6.01–5.90 (s, 1 H),

5.18–5.09 (m, 2 H), 4.11 (q, J = 7.1 Hz, 2 H), 3.38 (d, J = 13.5 Hz,

1 H), 2.69 (d, J = 13.5 Hz, 1 H), 2.29 (s, 3 H), 2.24 (d, J = 7.1 Hz,

2 H), 2.21 (br. s, 1 H), 1.97–1.65 (m, 6 H), 1.22 (t, J = 7.1 Hz, 3

H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 175.3, 138.4, 137.5,

134.0, 130.7, 128.0, 127.1, 126.9, 118.7, 83.0, 61.4, 60.4, 42.2, 37.9,

34.0, 29.0, 21.4, 18.1, 14.2 ppm. MS (CI): m/z (%) = 303 (7) [M +

1]⁺, 302 (41) [M]⁺, 284 (100), 243 (38), 211 (27), 144 (8). HRMS

(ESI): calcd. for C₁₉H₂₆NaO₃[M + Na]⁺325.1779; found 325.1766.

as a white solid; m.p. 65–67 °C. IR (KBr): ν = 3467, 1694, 1488,

˜

1

1092 cm^–1. H NMR (400 MHz, CDCl₃): δ = 7.20 (d, J = 8.4 Hz,

2 H), 7.04 (d, J = 8.4 Hz, 2 H), 5.99–5.88 (m, 1 H), 5.19–5.10 (m,

2 H), 4.12–4.07 (m, 2 H), 3.36 (d, J = 13.6 Hz, 1 H), 2.71 (d, J =

13.6 Hz, 1 H), 2.29–2.19 (m, 2 H), 2.14 (br. s, 1 H), 1.98–1.67 (m,

6 H), 1.21 (t, J = 7.1 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃):

δ = 175.0, 137.1, 133.7, 132.2, 131.2, 128.2, 119.0, 83.0, 61.5, 60.6,

42.1, 37.3, 34.4, 29.4, 18.3, 14.2 ppm. MS (CI): m/z (%) = 324 (13)

[M + 2]⁺, 323 (72) [M + 1]⁺, 322 (33) [M]⁺, 305 (100), 231 (8), 189

(12). HRMS (ESI): calcd. for C₁₈H₂₃ClNaO₃[M + Na]⁺345.1233;

found 345.1244.

Ethyl (1S*,2S*)-2-Allyl-1-(2-fluorobenzyl)-2-hydroxycyclopentane-

carboxylate (5g): Following general procedure A, purification by

silica gel column chromatography (EtOAc/hexane, 7:93) afforded

compound 5g (149 mg, 94%, trans, major isomer) as a colorless

Ethyl (1S*,2R*)-2-Allyl-1-(4-chlorobenzyl)-2-hydroxycyclopentane-

carboxylate (5cЈ): Purification by silica gel column chromatography

(EtOAc/hexane, 8:92) afforded compound 5cЈ (cis, minor isomer)

liquid. IR (neat): ν = 3503, 1716, 1494, 1110 cm^–1. ¹H NMR

˜

(400 MHz, CDCl₃): δ = 7.19–6.97 (m, 4 H), 6.02–5.91 (m, 1 H),

5.19–5.10 (m, 2 H), 4.13 (q, J = 7.1 Hz, 2 H), 3.32 (d, J = 13.9 Hz,

1 H), 3.02 (d, J = 13.9 Hz, 1 H), 2.33 (br. s, 1 H), 2.27–2.25 (m, 2

H), 2.01–1.77 (m, 6 H), 1.23 (t, J = 7.1 Hz, 3 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 175.3, 160.7 (d, J_C,F= 243.3 Hz), 133.9,

as a colorless semisolid. IR (KBr): ν = 3498, 1716, 1491, 1096 cm^–1.

˜

¹H NMR (400 MHz, CDCl₃): δ = 7.21 (d, J = 8.4 Hz, 2 H), 7.00

(d, J = 8.4 Hz, 2 H), 5.99–5.89 (m, 1 H), 5.21–5.18 (m, 2 H), 4.16–

1

4.08 (m, 2 H), 3.24 (d, J = 13.2 Hz, 1 H), 2.85 (dd, J = 13.6 Hz,

1

2

²J = 8.0 Hz, 1 H), 2.42 (dd, J = 13.6 Hz, J = 6.7 Hz, 1 H), 2.38–

2.31 (m, 2 H), 1.82–1.59 (m, 6 H), 1.20 (t, J = 7.2 Hz, 3 H) ppm.

¹³C NMR (100 MHz, CDCl₃): δ = 174.4, 136.2, 134.1, 132.5, 131.0,

128.4, 119.2, 84.2, 62.0, 60.6, 40.5, 38.0, 37.1, 29.4, 19.4, 14.2 ppm.

MS (CI): m/z (%) = 324 (18) [M + 2]⁺, 323 (100) [M + 1]⁺, 231 (5),

217 (8).

131.7 (d, J_C,F= 4.6 Hz), 128.2 (d, J_C,F= 8.2 Hz), 125.5 (d, J_C,F

=

15.7 Hz), 123.8 (d, J_C,F= 3.3 Hz), 118.7, 115.3 (d, J_C,F= 23.2 Hz),

83.1, 61.1, 60.6, 42.1, 33.6, 30.9, 28.9, 17.8, 14.1 ppm. MS (CI): m/z

(%) = 308 (2) [M + 2]⁺, 307 (7) [M + 1]⁺, 306 (37) [M]⁺, 289 (100),

215 (4). HRMS (ESI): calcd. for C₁₈H₂₃FNaO₃[M + Na]⁺

329.1528; found 329.1518.

Ethyl (1S*,2S*)-2-Allyl-1-(2,4-dichlorobenzyl)-2-hydroxycyclopent- Ethyl (1S*,2S*)-2-Allyl-1-(3,4-dichlorobenzyl)-2-hydroxycyclopent-

anecarboxylate (5d): Following general procedure A, purification

by silica gel column chromatography (EtOAc/hexane, 7:93) af-

forded compound 5d (170 mg, 96%, trans, major isomer) as a white

anecarboxylate (5h): Following general procedure A, purification

by silica gel column chromatography (EtOAc/hexane, 7:93) af-

forded compound 5h (158 mg, 90%, trans, major isomer) as a col-

solid; m.p. 57–59 °C. IR (KBr): ν = 3490, 1692, 1474, 1030 cm^–1.

orless liquid. IR (neat): ν = 3488, 1719, 1472, 1031 cm^–1. ¹H NMR

˜

¹H NMR (400 MHz, CDCl₃): δ = 7.37 (d, J = 2.2 Hz, 1 H), 7.12

(400 MHz, CDCl₃): δ = 7.28 (d, J = 8.2 Hz, 1 H), 7.23 (d, J =

1

2

1

2

(dd, J = 8.4, J = 2.2 Hz, 1 H), 7.06 (d, J = 8.4 Hz, 1 H), 6.01–

2.0 Hz, 1 H), 6.96 (dd, J = 8.2 Hz, J = 2.0 Hz, 1 H), 5.98–5.87

5.90 (m, 1 H), 5.21–5.11 (m, 2 H), 4.18–4.13 (m, 2 H), 3.38 (d, J (m, 1 H), 5.19–5.10 (m, 2 H), 4.11 (q, J = 7.1 Hz, 2 H), 3.34 (d, J

= 14.5 Hz, 1 H), 3.20 (d, J = 14.5 Hz, 1 H), 2.24 (d, J = 8.4 Hz, 2 = 13.7 Hz, 1 H), 2.71 (d, J = 13.7 Hz, 1 H), 2.30–2.18 (m, 3 H),

H), 2.23 (s, 1 H), 2.08–1.82 (m, 4 H), 1.79–1.65 (m, 2 H), 1.24 (t, 1.99–1.87 (m, 2 H), 1.80–1.69 (m, 4 H), 1.23 (t, J = 7.1 Hz, 3

Eur. J. Org. Chem. 2013, 2362–2380

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2371

C. Reddy, S. A. Babu, N. A. Aslam, V. Rajkumar

FULL PAPER

H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 174.8, 139.1, 133.6,

131.9, 131.8, 130.4, 130.0, 129.4, 119.1, 83.1, 61.5, 60.8, 42.0, 37.1,

34.7, 29.7, 18.5, 14.2 ppm. MS (CI): m/z (%) = 359 (5) [M + 2]⁺,

358 (23) [M + 1]⁺, 357 (16) [M]⁺, 338 (100), 223 (16). HRMS (ESI):

calcd. for C₁₈H₂₂Cl₂NaO₃[M + Na]⁺379.0843; found 379.0830.

5.12–5.04 (m, 2 H), 4.08–3.95 (m, 2 H), 3.57 (br. s, 1 H), 3.41 (d,

J = 13.7 Hz, 1 H), 3.02 (d, J = 13.7 Hz, 1 H), 2.60 (dd, ¹J =

14.2 Hz, ²J = 9.0 Hz, 1 H), 2.02–1.97 (m, 1 H), 1.74–1.58 (m, 8 H),

1.12 (t, J = 7.2 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

176.9, 136.3, 133.6, 132.4, 131.4, 128.2, 117.7, 74.9, 60.8, 55.5, 40.5,

34.3, 30.0, 25.8, 21.7, 20.5, 14.0 ppm. HRMS (ESI): calcd. for

C₁₉H₂₅ClNaO₃[M + Na]⁺359.1389; found 359.1373.

Ethyl (1S*,2S*)-2-Allyl-1-(4-bromobenzyl)-2-hydroxycyclohexane-

carboxylate (5i): Following general procedure A, purification by

silica gel column chromatography (EtOAc/hexane, 4:96) afforded

compound 5i [trans, major isomer, 150 mg, 79% (total yield of dia-

stereomers 5i and 5iЈ), dr 86:14] as a white solid. The minor isomer

5iЈ could not be separated from the major isomer, but some pure

Ethyl (1R*,2S*)-2-Allyl-2-hydroxy-1-methylcyclopentanecarboxyl-

ate (5m): Following general procedure A, purification by silica gel

column chromatography (EtOAc/hexane, 4:96) afforded compound

5m (103 mg, 97%, trans, major isomer) as a colorless liquid. IR

(neat): ν = 3523, 2976, 1721, 1119 cm^–1. ¹H NMR (400 MHz,

˜

fractions of 5i were obtained, m.p. 107–109 °C. IR (KBr): ν = 3500,

˜

1

1684, 1487, 1247 cm^–1. H NMR (400 MHz, CDCl₃): δ = 7.36 (d,

CDCl₃): δ = 5.98–5.87 (m, 1 H), 5.17–5.08 (m, 2 H), 4.20–4.11 (m,

2 H), 2.26–2.14 (m, 3 H), 1.98–1.92 (m, 2 H), 1.80–1.65 (m, 4 H),

1.28 (t, J = 7.1 Hz, 3 H), 1.27 (s, 3 H) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ = 176.6, 134.0, 118.6, 82.4, 60.5, 56.0, 41.6, 35.1, 34.2,

19.6, 18.9, 14.2 ppm. MS (CI): m/z (%) = 213 (26) [M + 1]⁺, 212

(5) [M]⁺, 209 (45), 195 (50), 73 (28). HRMS (ESI): calcd. for

C₁₂H₂₀O₃Na [M + Na]⁺235.1310; found 235.1306.

J = 8.4 Hz, 2 H), 6.96 (d, J = 8.4 Hz, 2 H), 5.99–5.88 (m, 1 H),

5.13–5.05 (m, 2 H), 4.08–3.99 (m, 2 H), 3.58 (br. s, 1 H), 3.40 (d,

J = 13.7 Hz, 1 H), 3.02 (d, J = 13.7 Hz, 1 H), 2.61 (dd, ¹J =

14.2 Hz, ²J = 9.0 Hz, 1 H), 2.03–1.97 (m, 1 H), 1.75–1.57 (m, 8 H),

1.14 (t, J = 7.2 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

176.9, 136.9, 133.6, 131.7, 131.2, 120.5, 117.7, 74.9, 60.8, 55.5, 40.5,

34.4, 30.0, 25.8, 21.7, 20.5, 14.0 ppm. HRMS (ESI): calcd. for

C₁₉H₂₅BrNaO₃[M + Na]⁺403.0884; found 403.0880.

Preparation of 5n and 5nЈ Following General Procedure A: The reac-

tion of the corresponding cyclic ketone (1 mmol) and allyl bromide

(2.4 mmol) mediated by In (1.5 mmol) gave products 5n (214 mg,

90%, trans isomer) and 5nЈ (4 mg, 2%, cis isomer).

Ethyl (1S*,2S*)-2-Allyl-1-(3-chlorobenzyl)-2-hydroxycyclohexane-

carboxylate (5j): Following general procedure A, purification by

silica gel column chromatography (EtOAc/hexane, 4:96) afforded

compound 5j [trans, major isomer, 141 mg, 84% (total yield of dia-

stereomers 5j and 5jЈ)] as a colorless liquid. The minor isomer 5jЈ

could not be separated from the major isomer, but some pure frac-

Ethyl

(1S*,2S*)-1,2-Diallyl-2-hydroxycyclopentanecarboxylate

(5n):^[11c]Purification by silica gel column chromatography (EtOAc/

hexane, 7:93) afforded compound 5n (trans, major isomer) as a col-

orless liquid. IR (neat): ν = 3539, 2978, 1722, 1200 cm^–1. ¹H NMR

˜

tions of 5j were obtained. IR (neat): ν = 3498, 1693, 1460,

(400 MHz, CDCl₃): δ = 5.97–5.86 (m, 1 H), 5.71–5.61 (m, 1 H),

˜

1

1080 cm^–1. H NMR (400 MHz, CDCl₃): δ = 7.18–7.17 (m, 2 H), 5.16–5.10 (m, 2 H), 5.08–5.02 (m, 2 H), 4.20–4.11 (m, 2 H), 2.80–

7.07 (s, 1 H), 6.98–6.96 (m, 1 H), 5.99–5.88 (m, 1 H), 5.16–5.05 (m,

2.75 (m, 1 H), 2.22–2.09 (m, 4 H), 2.05 (br. s, 1 H), 1.92–1.63 (m,

2 H), 4.05 (q, J = 7.1 Hz, 2 H), 3.61 (br. s, 1 H), 3.42 (d, J = 5 H), 1.28 (t, J = 7.2 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃):

1

13.6 Hz, 1 H), 3.04 (d, J = 13.6 Hz, 1 H), 2.60 (dd, J = 14.2 Hz,

δ = 175.2, 134.6, 133.8, 118.7, 117.9, 82.5, 60.5, 60.0, 42.0, 37.1,

²J = 8.7 Hz, 1 H), 2.04–1.99 (m, 1 H), 1.64–1.59 (m, 8 H), 1.14 (t, 34.8, 29.9, 18.4, 14.3 ppm. MS (CI): m/z (%) = 239 (55) [M + 1]⁺,

J = 7.1 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 176.9,

140.0, 133.9, 133.6, 130.0, 129.3, 128.3, 126.7, 117.7, 74.9, 60.9,

55.5, 40.5, 34.7, 30.0, 25.8, 21.7, 20.5, 14.0 ppm. HRMS (ESI):

calcd. for C₁₉H₂₅ClNaO₃[M + Na]⁺359.1389; found 359.1375.

238 (8) [M]⁺, 222 (26), 221 (100), 147 (43). HRMS (ESI): calcd. for

C₁₄H₂₂O₃Na [M + Na]⁺261.1466; found 261.1457.

Ethyl

(1S*,2R*)-1,2-Diallyl-2-hydroxycyclopentanecarboxylate

(5nЈ): Purification by silica gel column chromatography (EtOAc/

hexane, 9:91) afforded compound 5nЈ (cis, minor isomer) as a color-

Ethyl (1S*,2S*)-2-Allyl-1-benzyl-2-hydroxycyclohexanecarboxylate

(5k): Following general procedure A, purification by silica gel col-

umn chromatography (EtOAc/hexane, 3:97) afforded compound 5k

[trans, major isomer, 121 mg, 80% (total yield of diastereomers 5k

and 5kЈ), dr 78:22] as a colorless liquid. The minor isomer 5kЈ

could not be separated from the major isomer, but some pure frac-

less liquid. IR (neat): ν = 3502, 1719, 1217 cm^–1. ¹H NMR

˜

(400 MHz, CDCl₃): δ = 5.97–5.87 (m, 1 H), 5.72–5.63 (m, 1 H),

5.17–5.12 (m, 2 H), 5.09–5.04 (m, 2 H), 4.22–4.14 (m, 2 H), 2.73–

2.67 (m, 1 H), 2.65–2.60 (m, 1 H), 2.47–2.39 (m, 2 H), 2.35–2.30

(m, 1 H), 1.98–1.93 (m, 1 H), 1.84–1.75 (m, 4 H), 1.64–1.57 (m, 1

H), 1.28 (t, J = 7.1 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃):

δ = 174.9, 134.4, 134.2, 118.6, 118.0, 84.0, 60.6, 60.2, 40.7, 38.1,

37.3, 30.9, 19.5, 14.3 ppm. HRMS (ESI): calcd. for C₁₄H₂₂O₃Na

[M + Na]⁺261.1466; found 261.1460.

tions of 5k were obtained. IR (neat): ν = 3502, 1692, 1460,

˜

1

1026 cm^–1. H NMR (400 MHz, CDCl₃): δ = 7.24–7.17 (m, 3 H),

7.08–7.05 (m, 2 H), 5.99–5.88 (m, 1 H), 5.15–5.03 (m, 2 H), 4.04–

3.97 (m, 2 H), 3.66 (br. s, 1 H), 3.43 (d, J = 13.6 Hz, 1 H), 3.05 (d,

2

J = 13.6 Hz, 1 H), 2.60 (dd, ¹J = 14.3 Hz, J = 8.9 Hz, 1 H), 2.03–

Ethyl

(1S*,2S*)-2-Allyl-1-cinnamyl-2-hydroxycyclopentanecarb-

1.98 (m, 1 H), 1.74–1.56 (m, 8 H), 1.09 (t, J = 7.2 Hz, 3 H) ppm.

¹³C NMR (100 MHz, CDCl₃): δ = 177.1, 137.8, 133.8, 130.0, 128.1,

126.5, 117.5, 74.9, 60.6, 55.5, 40.5, 34.9, 30.0, 25.9, 21.8, 20.5,

14.0 ppm. HRMS (ESI): calcd. for C₁₉H₂₆NaO₃[M + Na]⁺

325.1779; found 325.1791.

oxylate (5o): Following general procedure A, purification by silica

gel column chromatography (EtOAc/hexane, 7:93) afforded com-

pound 5o (110 mg, 70%, trans, major isomer) as a colorless viscous

1

liquid. IR (neat): ν = 3518, 1715, 1445 cm^–1. H NMR (400 MHz,

˜

CDCl₃): δ = 7.33–7.18 (m, 5 H), 6.45 (d, J = 15.7 Hz, 1 H), 6.16–

1

5.89 (m, 2 H), 5.19–5.10 (m, 2 H), 4.25–4.10 (m, 2 H), 2.94 (dd, J

Ethyl (1S*,2S*)-2-Allyl-1-(4-chlorobenzyl)-2-hydroxycyclohexane-

carboxylate (5l): Following general procedure A, purification by

silica gel column chromatography (EtOAc/hexane, 4:94) afforded

compound 5l [trans, major isomer, 131 mg, 78% (total yield of dia-

stereomers 5l and 5lЈ), dr 82:18] as a white solid. The minor isomer

5lЈ could not be separated from the major isomer, but some pure

2

= 13.8 Hz, J = 7.1 Hz, 1 H), 2.40–2.35 (m, 1 H), 2.29–2.14 (m, 3

H), 2.08 (br. s, 1 H), 1.96–1.67 (m, 5 H), 1.27 (t, J = 7.2 Hz, 3

H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 175.3, 137.5, 133.8,

133.1, 128.5, 127.1, 126.4, 126.1, 118.9, 82.7, 60.6, 60.5, 42.1, 36.3,

34.9, 30.2, 18.6, 14.4 ppm. HRMS (ESI): calcd. for C₂₀H₂₆O₃

[M]⁺314.1882; found 314.1833.

fractions of 5l were obtained, m.p. 101–103 °C. IR (KBr): ν = 3498,

˜

1

1692, 1491, 1016 cm^–1. H NMR (400 MHz, CDCl₃): δ = 7.20 (d, Ethyl (1S*,2S*)-2-Allyl-2-hydroxy-1-(3-methylbut-2-en-1-yl)cyclo-

J = 8.4 Hz, 2 H), 7.0 (d, J = 8.4 Hz, 2 H), 5.97–5.87 (m, 1 H), pentanecarboxylate (5p): Following general procedure A, purifica-

2372

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Eur. J. Org. Chem. 2013, 2362–2380

Construction of Functionalized Carbocycles

tion by silica gel column chromatography (EtOAc/hexane, 5:95) af-

δ = 178.1, 134.0, 117.4, 74.0, 60.7, 49.9, 40.1, 31.2, 30.0, 21.8, 20.6,

18.6, 14.2 ppm. MS (CI): m/z (%) = 228 (28) [M + 2]⁺, 227 (5) [M

+ 1]⁺, 210 (18), 135 (96). HRMS (ESI): calcd. for C₁₃H₂₂NaO₃[M

forded compound 5p (120 mg, 90%, trans, major isomer) as a col-

orless liquid. IR (neat): ν = 3467, 2977, 1720, 1179 cm^–1. ¹H NMR

˜

(400 MHz, CDCl₃): δ = 5.98–5.88 (m, 1 H), 5.17–5.07 (m, 2 H), + Na]⁺249.1466; found 249.1467.

1

5.0–4.95 (m, 1 H), 4.16 (q, J = 7.1 Hz, 2 H), 2.72–2.67 (dd, J =

Ethyl (1R*,2R*)-2-Allyl-2-hydroxy-1-methylcyclohexanecarboxylate

(5tЈ): Purification by silica gel column chromatography (EtOAc/

14.0 Hz, ²J = 6.6 Hz, 1 H), 2.21–2.09 (m, 5 H), 1.93–1.85 (m, 1 H),

1.80–1.61 (m, 4 H), 1.69 (s, 3 H), 1.63 (s, 3 H), 1.27 (t, J = 7.1 Hz,

3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 175.6, 134.2, 133.9,

120.0, 118.5, 82.5, 60.4, 42.1, 34.4, 31.0, 29.7, 26.0, 18.3, 18.0,

14.3 ppm. HRMS (ESI): calcd. for C₁₆H₂₆O₃Na [M + Na]⁺

289.1779; found 289.1791.

hexane, 3:97) afforded compound 5tЈ (cis, minor isomer) as a color-

1

less liquid. IR (neat): ν = 3477, 2939, 1698, 1247 cm^–1. H NMR

˜

(400 MHz, CDCl₃): δ = 5.95–5.85 (m, 1 H), 5.06–5.00 (m, 2 H),

4.64 (br. s, 1 H), 4.17–4.11 (m, 2 H), 2.33–2.27 (m, 1 H), 2.21–2.11

(m, 2 H), 1.71–1.38 (m, 7 H), 1.26 (t, J = 7.2 Hz, 3 H), 1.24 (s, 3

Ethyl (1R*,2S*)-2-Allyl-2-hydroxy-1-octylcyclopentanecarboxylate H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 179.3, 134.2, 117.4,

(5q): Following general procedure A, purification by silica gel col-

umn chromatography (EtOAc/hexane, 05:95) afforded compound

5q (150 mg, 97% yield, trans, major isomer) as a colorless liquid.

74.1, 60.8, 49.4, 41.6, 33.6, 32.8, 21.3, 21.1, 18.9, 14.0 ppm. MS

(CI): m/z (%) = 228 (12) [M + 2]⁺, 227 (2) [M + 1]⁺, 209 (15), 181

(14), 135 (100). HRMS (ESI): calcd. for C₁₃H₂₂NaO₃[M + Na]⁺

IR (neat): ν = 3512, 1720, 1130 cm^–1. ¹H NMR (400 MHz, CDCl ): 249.1466; found 249.1473.

˜

3

δ = 5.96–5.86 (m, 1 H), 5.14–5.06 (m, 2 H), 4.20–4.09 (m, 2 H),

Ethyl

(1S*,2S*)-1,2-Diallyl-2-hydroxycyclohexanecarboxylate

2.19–2.13 (m, 3 H), 1.98 (s, 2 H), 1.82–1.66 (m, 6 H), 1.41–1.35 (m,

2 H), 1.28–1.25 (m, 10 H), 1.27 (t, J = 7.1 Hz, 3 H), 0.86 (t, J =

6.5 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 175.8, 134.0,

118.5, 82.6, 60.5, 60.3, 41.9, 34.7, 32.2, 31.9, 30.3, 30.0, 29.4, 29.2,

25.3, 22.7, 18.6, 14.3, 14.1 ppm. MS (CI): m/z (%) = 311 (41) [M

+ 1]⁺, 312 (6) [M + 2]⁺, 293 (100), 117 (12). HRMS (ESI): calcd.

for C₁₉H₃₄O₃Na [M + Na]⁺333.2406; found 333.2409.

(5u):^[11c]Following general procedure A, purification by silica gel

column chromatography (EtOAc/hexane, 3:97) afforded compound

5u [trans, major isomer, 95 mg, 75% (total yield of diastereomers

5u and 5uЈ), dr 74:26] as a colorless liquid. The corresponding

minor isomer 5uЈ could not be separated from the major isomer,

but some pure fractions of 5u were obtained. IR (neat): ν = 3661,

˜

2927, 1738, 1229 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 5.95–5.85

Ethyl (1R*,2S*)-2-Allyl-2-hydroxy-1-pentylcyclopentanecarboxylate (m, 1 H), 5.62–5.51 (m, 1 H), 5.10–5.03 (m, 4 H), 4.20–4.15 (q, J

(5r): Following general procedure A, purification by silica gel col-

umn chromatography (EtOAc/hexane, 5:95) afforded compound 5r

= 7.1 Hz, 2 H), 3.31 (br. s, 1 H), 2.86–2.81 (m, 1 H), 2.61–2.50 (m,

2 H), 1.99–1.94 (m, 1 H), 1.88–1.82 (m, 1 H), 1.69–1.47 (m, 6 H),

(130 mg, 97%, trans, major isomer) as a colorless liquid. IR (neat): 1.41–1.35 (m, 1 H), 1.29 (t, J = 7.1 Hz, 3 H) ppm. ¹³C NMR

ν = 3514, 1721, 1189 cm^–1. ¹H NMR (400 MHz, CDCl ): δ = 5.98–

(100 MHz, CDCl₃): δ = 176.8, 133.8, 133.7, 118.3, 117.6, 74.3, 60.8,

˜

3

5.87 (m, 1 H), 5.16–5.08 (m, 2 H), 4.24–4.11 (m, 2 H), 2.24–2.13

54.0, 40.4, 34.0, 30.1, 26.4, 21.7, 20.0, 14.3 ppm. HRMS (ESI):

(m, 5 H), 1.98 (s, 2 H), 1.84–1.67 (m, 5 H), 1.40–1.26 (m, 8 H), calcd. for C₁₅H₂₄NaO₃[M + Na]⁺275.1623; found 275.1635.

1.28 (t, J = 7.1 Hz, 3 H), 0.87 (t, J = 6.7 Hz, 3 H) ppm. ¹³C NMR

Ethyl (1S*,2S*)-1-(4-Bromobenzyl)-2-hydroxy-2-(2-methylallyl)cy-

(100 MHz, CDCl₃): δ = 175.8, 134.0, 118.5, 82.6, 60.5, 60.3, 41.9,

clopentanecarboxylate (5v): Following general procedure A, purifi-

34.7, 32.4, 32.1, 30.0, 25.0, 22.5, 18.6, 14.3, 14.0 ppm. MS (CI): m/z

cation by silica gel column chromatography (EtOAc/hexane, 5:95)

afforded compound 5v (165 mg, 87%, trans, major isomer) as a

(%) = 269 (38) [M + 1]⁺, 252 (100), 265 (24), 227 (18), 176 (26).

HRMS (ESI): calcd. for C₁₆H₂₈O₃Na [M + Na]⁺291.1936; found

white solid; m.p. 87–89 °C. IR (KBr): ν = 3503, 1711, 1488,

˜

291.1926.

1

1185 cm^–1. H NMR (400 MHz, CDCl₃): δ = 7.34 (d, J = 8.4 Hz,

Ethyl (1R*,2S*)-2-Allyl-2-hydroxy-1-propylcyclopentanecarboxylate 2 H), 7.00 (d, J = 8.4 Hz, 2 H), 4.94–4.93 (m, 1 H), 4.76 (s, 1 H),

(5s): Following general procedure A, purification by silica gel col-

umn chromatography (EtOAc/hexane, 6:94) afforded compound 5s

4.13–4.05 (m, 2 H), 3.31 (d, J = 13.6 Hz, 1 H), 2.72 (d, J = 13.6 Hz,

1 H), 2.27–2.13 (m, 3 H), 1.97–1.90 (m, 2 H), 1.84 (s, 3 H), 1.82–

1.67 (m, 4 H), 1.20 (t, J = 7.2 Hz, 3 H) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ = 175.1, 142.7, 137.7, 131.7, 131.2, 120.3, 115.3, 83.0,

61.9, 60.6, 45.1, 37.2, 34.4, 29.3, 24.5, 18.6, 14.2 ppm. HRMS

(ESI): calcd. for C₁₉H₂₅BrNaO₃[M + Na]⁺403.0884; found

403.0866.

(105 mg, 88%, trans, major isomer) as a colorless liquid. IR (neat):

1

ν = 3511, 2961, 1719, 1128 cm^–1. H NMR (400 MHz, CDCl ): δ

˜

3

= 5.98–5.87 (m, 1 H), 5.16–5.07 (m, 2 H), 4.23–4.09 (m, 2 H), 2.25–

2.13 (m, 3 H), 1.98 (br. s, 1 H), 2.00–1.93 (m, 1 H), 1.85–1.65 (m,

5 H), 1.43–1.29 (m, 2 H), 1.28 (t, J = 7.1 Hz, 3 H), 1.13–1.02 (m,

1 H), 0.93 (t, J = 7.2 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃):

δ = 175.8, 134.0, 118.5, 82.6, 60.5, 60.3, 41.9, 34.7, 34.5, 30.1, 18.7,

18.6, 14.8, 14.3 ppm. MS (CI): m/z (%) = 242 (30) [M + 2]⁺, 241

(61) [M + 1]⁺, 240 (11) [M]⁺, 223 (100), 209 (16). HRMS (ESI):

calcd. for C₁₄H₂₄NaO₃[M + Na]⁺263.1623; found 263.1625.

Ethyl (1S*,2S*)-1-Benzyl-2-hydroxy-2-(2-methylallyl)cyclopentane-

carboxylate (5w): Following general procedure A, purification by

silica gel column chromatography (EtOAc/hexane, 06:94) afforded

compound 5w (110 mg, 75%, trans, major isomer) as a white solid;

m.p. 66–68 °C. IR (KBr): ν = 3513, 1719, 1451, 1191 cm^–1. ¹H

˜

Preparation of 5t and 5tЈ Following General Procedure A: The reac-

tion of the corresponding cyclic ketone (1 mmol) and allyl bromide

(2.4 mmol) mediated by In (1.5 mmol) gave products 5t (103 mg,

46%, trans isomer) and 5tЈ (55 mg, 24%, cis isomer).

NMR (400 MHz, CDCl₃): δ = 7.26–7.12 (m, 5 H), 4.94 (s, 1 H),

4.77 (s, 1 H), 4.11 (q, J = 7.1 Hz, 2 H), 3.39 (d, J = 13.6 Hz, 1 H),

2.76 (d, J = 13.6 Hz, 1 H), 2.30 (br. s, 1 H), 2.26 (d, J = 13.7 Hz,

1 H), 2.18 (d, J = 13.7 Hz, 1 H), 2.00–1.74 (m, 6 H), 1.86 (s, 3 H),

1.20 (t, J = 7.1 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

175.4, 142.8, 138.6, 130.0, 128.1, 126.3, 115.2, 83.0, 62.0, 60.5, 45.2,

37.9, 33.9, 29.0, 24.5, 18.4, 14.2 ppm. HRMS (ESI): calcd. for

C₁₉H₂₆NaO₃[M + Na]⁺325.1779; found 325.1792.

Ethyl (1R*,2S*)-2-Allyl-2-hydroxy-1-methylcyclohexanecarboxylate

(5t): Purification by silica gel column chromatography (EtOAc/hex-

ane, 3:97) afforded compound 5t (trans, major isomer) as a color-

1

less liquid. IR (neat): ν = 3512, 2944, 1725, 1147 cm^–1. H NMR

˜

(400 MHz, CDCl₃): δ = 5.96–5.86 (m, 1 H), 5.11–5.02 (m, 2 H), Ethyl (1S*,2S*)-1-(4-Chlorobenzyl)-2-hydroxy-2-(2-methylallyl)cy-

1

4.18 (q, J = 7.1 Hz, 2 H), 3.22 (br. s, 1 H), 2.56 (dd, J = 14.2 Hz,

²J = 8.7 Hz, 1 H), 2.08–2.02 (m, 1 H), 1.85–1.42 (m, 8 H), 1.33 (s, cation by silica gel column chromatography (EtOAc/hexane, 4:96)

3 H), 1.29 (t, J = 7.1 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃):

afforded compound 5x (141 mg, 85%, trans, major isomer) as a

clopentanecarboxylate (5x): Following general procedure A, purifi-

Eur. J. Org. Chem. 2013, 2362–2380

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2373

C. Reddy, S. A. Babu, N. A. Aslam, V. Rajkumar

FULL PAPER

white solid; m.p. 81–83 °C. IR (KBr): ν = 3516, 1717, 1491, H), 6.79 (d, J = 8.4 Hz, 2 H), 5.94–5.84 (m, 1 H), 5.12–5.03 (m, 2

˜

1

1094 cm^–1. H NMR (400 MHz, CDCl₃): δ = 7.21 (d, J = 8.4 Hz, H), 4.04–3.92 (m, 2 H), 3.54 (d, J = 12.8 Hz, 1 H), 3.46 (d, J =

2 H), 7.07 (d, J = 8.4 Hz, 2 H), 4.95 (s, 1 H), 4.77 (s, 1 H), 4.13–

4.08 (m, 2 H), 3.34 (d, J = 13.6 Hz, 1 H), 2.74 (d, J = 13.6 Hz, 1

12.9 Hz, 1 H), 3.41 (d, J = 12.8 Hz, 1 H), 3.38 (br. s, 1 H), 3.25 (d,

J = 12.9 Hz, 1 H), 2.82–2.74 (m, 2 H), 2.67 (dd, J = 14.3 Hz, J

1

2

H), 2.26 (d, J = 13.6 Hz, 1 H), 2.20 (br. s, 1 H), 2.16 (d, J = 13.6 Hz, = 9.0 Hz, 1 H), 2.22 (d, J = 12.8 Hz, 1 H), 2.06–1.99 (m, 2 H),

1 H), 1.98–1.91 (m, 2 H), 1.85 (s, 3 H), 1.83–1.63 (m, 4 H), 1.22 (t,

J = 7.2 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 175.1,

142.7, 137.2, 132.2, 131.3, 128.2, 115.4, 82.9, 62.0, 60.6, 45.1, 37.2,

34.3, 29.2, 24.5, 18.6, 14.2 ppm. HRMS (ESI): calcd. for

C₁₉H₂₅ClNaO₃[M + Na]⁺359.1389; found 359.1381.

1.92–1.84 (m, 1 H), 1.73–1.68 (m, 1 H), 1.10 (t, J = 7.2 Hz, 3

H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 175.1, 138.4, 136.9,

133.2, 132.0, 131.0, 129.4, 128.4, 127.3, 120.3, 118.2, 73.7, 62.7,

60.8, 56.0, 52.5, 50.0, 40.1, 34.8, 30.0, 14.0 ppm. HRMS (ESI):

calcd. for C₂₅H₃₁NO₃Br [M + H]⁺472.1487; found 472.1466.

Ethyl (1S*,2S*)-1-(4-Bromobenzyl)-2-hydroxy-2-(2-methylallyl)cy-

clohexanecarboxylate (5y): Following general procedure A, purifi-

cation by silica gel column chromatography (EtOAc/hexane, 4:96)

afforded compound 5y [trans, major isomer, 174 mg, 88% (total

yield of diastereomers 5y and 5yЈ), dr 81:19] as a white solid. The

minor isomer 5yЈ could not be separated from the major isomer,

but some pure fractions of 5y were obtained, m.p. 117–119 °C. IR

Ethyl (3R*,4R*)-3,4-Diallyl-1-benzyl-4-hydroxypiperidine-3-carb-

oxylate (5zc): Following general procedure A, purification by silica

gel column chromatography (EtOAc/hexane, 9:91) afforded com-

pound 5zc [trans, major isomer, 100 mg, 58% (total yield of dia-

stereomers 5zc and 5zcЈ), dr 65:35] as a colorless semisolid. The

minor isomer 5zcЈ could not be separated from the major isomer,

but some pure fractions of 5zc were obtained. IR (KBr): ν = 3513,

˜

1

(KBr): ν = 3505, 1693, 1488, 1076 cm^–1. ¹H NMR (400 MHz, 1732, 1123 cm^–1. H NMR (400 MHz, CDCl₃): δ = 7.26–7.18 (m,

˜

CDCl₃): δ = 7.36 (d, J = 8.4 Hz, 2 H), 6.96 (d, J = 8.4 Hz, 2 H),

5 H), 5.87–5.77 (m, 1 H), 5.45–5.34 (m, 1 H), 5.07–4.87 (m, 4 H),

4.90 (s, 1 H), 4.74 (s, 1 H), 4.08–4.01 (m, 2 H), 3.55 (br. s, 1 H), 4.12–4.10 (q, J = 7.1 Hz, 2 H), 3.43 (s, 2 H), 2.94 (dd, ¹J = 13.2 Hz,

3.41 (d, J = 13.8 Hz, 1 H), 3.00 (d, J = 13.8 Hz, 1 H), 2.67 (d, J = ²J = 7.6 Hz, 1 H), 2.81 (dd, J = 13.2 Hz, J = 1.8 Hz, 1 H), 2.71–

1

2

1

2

13.8 Hz, 1 H), 1.87 (s, 3 H), 1.86 (d, J = 13.8 Hz, 1 H), 1.79–1.57

2.64 (m, 2 H), 2.61 (dd, J = 14.4 Hz, J = 9.0 Hz, 1 H), 2.22 (d,

(m, 8 H), 1.14 (t, J = 7.1 Hz, 3 H) ppm. ¹³C NMR (100 MHz, J = 12.7 Hz, 1 H), 2.00–1.91 (m, 2 H), 1.77–1.59 (m, 3 H), 1.20 (t,

CDCl₃): δ = 177.0, 142.4, 137.0, 131.7, 131.2, 120.4, 114.9, 75.4,

60.8, 55.8, 43.7, 34.4, 29.8, 26.0, 24.6, 22.4, 20.5, 14.0 ppm. HRMS

(ESI): calcd. for C₂₀H₂₇BrNaO₃[M + Na]⁺417.1041; found

417.1030.

J = 7.1 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 175.1,

138.8, 133.7, 133.3, 128.9, 128.2, 127.1, 118.7, 118.1, 73.2, 62.6,

60.7, 54.6, 53.0, 50.0, 40.0, 34.3, 30.3, 14.3 ppm. HRMS (ESI):

calcd. for C₂₁H₂₉NO₃Na [M + Na]⁺366.2045; found 366.2073.

Ethyl (1R*,2S*)-2-Hydroxy-2-(2-methylallyl)-1-octylcyclopentane-

carboxylate (5z): Following general procedure A, purification by

silica gel column chromatography (EtOAc/Hexane, 05:95) afforded

Ethyl

(3R*,4R*)-3-Allyl-1-benzyl-4-hydroxy-4-(2-methylallyl)-

piperidine-3-carboxylate (5zd): Following general procedure A, pu-

rification by silica gel column chromatography (EtOAc/hexane,

9:91) afforded compound 5zd (107 mg, 60%, dr 65:35) as a mixture

compound 5z (136 mg, 84%, trans, major isomer) as a colorless

1

liquid. IR (neat): ν = 3534, 1722, 1464 cm^–1. H NMR (400 MHz, of diastereomers and as a colorless semisolid. Data for mixture

˜

1

CDCl₃): δ = 4.89 (s, 1 H), 4.72 (s, 1 H), 4.20–4.10 (m, 2 H), 2.20–

of diastereomers: IR (KBr): ν = 3500, 1714, 1223 cm^–1. H NMR

˜

2.05 (m, 4 H), 1.98–1.84 (m, 3 H), 1.81 (s, 3 H), 1.76–1.63 (m, 4

(400 MHz, CDCl₃): δ = 7.21–7.13 (m, 5 H), 5.66–5.32 (m, 1 H),

H), 1.29–1.25 (m, 12 H), 1.27 (t, J = 7.1 Hz, 3 H), 0.87 (t, J = 4.96–4.76 (m, 3 H), 4.63 (s, 1 H), 4.14–4.39 (m, 2 H), 3.42 (d, J =

6.4 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 175.8, 142.9,

13.1 Hz, 1 H), 3.30 (d, J = 13.1 Hz, 1 H), 3.04–2.63 (m, 3 H), 2.48–

114.8, 82.6, 60.9, 60.2, 44.9, 34.5, 32.0, 31.8, 30.3, 29.8, 29.4, 29.2, 2.35 (m, 4 H), 2.23–2.18 (m, 1 H), 2.02–1.60 (m, 3 H), 1.76 (s, 3

25.4, 24.5, 22.6, 18.9, 14.3, 14.1 ppm. HRMS (ESI): calcd. for

H), 1.20–1.13 (m, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

175.3, 175.2, 142.8, 142.1, 138.9, 138.8, 134.4, 133.9, 129.0, 128.9,

128.2, 128.1, 127.1, 127.0, 118.6, 117.6, 115.3, 115.3, 73.6, 73.5,

62.8, 62.7, 60.7, 60.7, 55.0, 54.9, 53.2, 50.6, 50.2, 43.3, 36.2, 36.1,

34.4, 34.0, 30.1, 29.7, 25.2, 24.7, 14.4, 14.2 ppm. HRMS (ESI):

calcd. for C₂₂H₃₁NO₃Na [M + Na]⁺380.2202; found 380.2213.

C₂₀H₃₆O₃Na [M + Na]⁺347.2562; found 347.2566.

Ethyl

(1R*,2S*)-2-Hydroxy-1-methyl-2-(2-methylallyl)cyclopent-

anecarboxylate (5za): Following general procedure A, purification

by silica gel column chromatography (EtOAc/hexane, 6:94) af-

forded compound 5za [99 mg, 88% (total yield of diastereomers

5za and 5zaЈ)] as a mixture of diastereomers (trace amount of

Ethyl (4aS*,7aS*)-7a-Allyl-2-oxooctahydrocyclopenta[b]pyran-4a-

carboxylate (8a): Following general procedure A, purification by

minor isomer was present with the major isomer) and as a colorless

1

liquid. IR (neat): ν = 3524, 1720, 1116 cm^–1. H NMR (400 MHz, silica gel column chromatography (EtOAc/hexane, 16:84) afforded

˜

CDCl₃): δ = 4.92 (s, 1 H), 4.75 (s, 1 H), 4.20–4.12 (m, 2 H), 2.50

compound 8a (120 mg, 95%) as a colorless liquid. IR (neat): ν =

˜

(br. s, 1 H), 2.23–2.14 (m, 2 H), 2.10 (d, J = 13.7 Hz, 1 H), 2.04– 2979, 1724, 1207 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 5.94–5.84

1.97 (m, 1 H), 1.84 (s, 3 H), 1.77–1.66 (m, 4 H), 1.28 (t, J = 7.1 Hz,

3 H), 1.27 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 176.7,

142.9, 114.9, 82.4, 60.4, 56.5, 44.4, 35.1, 33.9, 24.4, 19.3, 19.1,

14.2 ppm. HRMS (ESI): calcd. for C₁₃H₂₂O₃Na [M + Na]⁺

249.1467; found 249.1487.

(m, 1 H), 5.14–5.06 (m, 2 H), 4.23–4.17 (m, 2 H), 2.72–2.61 (m, 1

H), 2.56–2.48 (m, 2 H), 2.43–2.29 (m, 3 H), 2.05–2.01 (m, 2 H),

1.92–1.74 (m, 4 H), 1.30 (t, J = 7.2 Hz, 3 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 174.3, 171.0, 132.1, 119.2, 94.9, 61.3, 52.6,

41.5, 38.6, 34.5, 26.5, 26.2, 21.1, 14.1 ppm. HRMS (ESI): calcd. for

C₁₄H₂₀O₄Na [M + Na]⁺275.1259; found 275.1262.

Ethyl

(3R*,4R*)-4-Allyl-1-benzyl-3-(4-bromobenzyl)-4-hydroxy-

piperidine-3-carboxylate (5zb): Following general procedure A, pu-

rification by silica gel column chromatography (EtOAc/hexane,

9:91) afforded compound 5zb [trans, major isomer, 130 mg, 55%

(total yield of diastereomers 5zb and 5zbЈ), dr 80:20] as a white

solid. The minor isomer 5zbЈ could not be separated from the

major isomer, but some pure fractions of 5zb were obtained, m.p.

Ethyl (3aS*,6aS*)-6a-Allyl-2-oxohexahydro-2H-cyclopenta[b]furan-

3a-carboxylate (8b): Following general procedure A, purification by

silica gel column chromatography (EtOAc/hexane, 14:86) afforded

compound 8b (113 mg, 95%) as a colorless liquid. IR (neat): ν =

˜

2978, 1780, 1728, 1238 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ =

5.83–5.74 (m, 1 H), 5.14–5.09 (m, 2 H), 4.22 (q, J = 7.2 Hz, 2 H),

3.45 (d, J = 18.4 Hz, 1 H), 2.57–2.36 (m, 4 H), 2.15–2.10 (m, 1

H), 1.95–1.75 (m, 4 H), 1.31 (t, J = 7.2 Hz, 3 H) ppm. ¹³C NMR

124–126 °C. IR (KBr): ν = 3494, 1703, 1246 cm^–1. ¹H NMR

˜

(400 MHz, CDCl₃): δ = 7.36–7.31 (m, 5 H), 7.19 (d, J = 8.4 Hz, 2

2374

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Eur. J. Org. Chem. 2013, 2362–2380

Construction of Functionalized Carbocycles

(100 MHz, CDCl₃): δ = 174.7, 172.7, 131.6, 119.6, 98.2, 61.7, 57.6,

40.0, 39.9, 39.4, 37.9, 23.1, 14.1 ppm. HRMS (ESI): calcd. for

C₁₃H₁₈O₄Na [M + Na]⁺261.1102; found 261.1114.

1.79 (s, 3 H), 1.59–1.48 (m, 4 H), 1.31 (t, J = 7.1 Hz, 3 H) ppm.

¹³C NMR (100 MHz, CDCl₃): δ = 174.6, 172.2, 140.3, 116.6, 86.0,

61.4, 51.8, 44.0, 39.7, 32.1, 30.5, 24.0, 20.8, 20.5, 14.1 ppm. HRMS

(ESI): calcd. for C₁₅H₂₂O₄Na [M + Na]⁺289.1416; found 289.1411.

Preparation of 8c and 7c Following General Procedure A: The reac-

tion of the corresponding cyclic ketone (0.5 mmol) and allyl brom-

ide (1.2 mmol) mediated by In (0.75 mmol) gave products 8c

(79 mg, 59%) and 7c (23 mg, 15%).

(4aR*,8aS*)-8a-Allyl-4a-methyloctahydro-2H-chromen-2-one (8g):

Following general procedure A, purification by silica gel column

chromatography (EtOAc/hexane, 13:87) afforded compound 8g as a

mixture of diastereomers (75 mg, 72%, dr 88:12) and as a colorless

Ethyl (4aS*,8aS*)-8a-Allyl-2-oxooctahydro-2H-chromene-4a-carb-

oxylate (8c): Purification by silica gel column chromatography

(EtOAc/hexane, 15:85) afforded compound 8c as a colorless liquid.

viscous liquid. IR (neat): ν = 1732, 1239, 1051 cm^–1. ¹H NMR

˜

(400 MHz, CDCl₃, mixture of diastereomers): δ = 5.77–5.67 (m, 1

H), 4.96–4.87 (m, 2 H), 2.51–2.33 (m, 3 H), 2.12 (dd, ¹J = 14.5 Hz,

²J = 8.7 Hz, 1 H), 1.69–1.28 (m, 9 H), 1.10–1.05 (m, 1 H), 0.90 (s,

3 H) ppm. ¹³C NMR (100 MHz, CDCl₃, major isomer 8g): δ =

171.6, 132.6, 118.5, 87.4, 40.2, 34.1, 34.0, 31.5, 30.1, 26.3, 22.9,

21.4, 20.5 ppm. HRMS (ESI): calcd. for C₁₃H₂₁O₂[M + H]⁺

209.1542; found 209.1534.

IR (neat): ν = 2940, 1724, 1236 cm^–1. ¹H NMR (400 MHz, CDCl ):

˜

3

δ = 5.97–5.86 (m, 1 H), 5.16–5.08 (m, 2 H), 4.23–4.11 (m, 2 H),

2.77–2.59 (m, 3 H), 2.52–2.47 (m, 1 H), 2.19–2.14 (m, 2 H), 2.06–

2.00 (m, 1 H), 1.95–1.89 (m, 1 H), 1.79–1.72 (m, 2 H), 1.64–1.45

(m, 4 H), 1.29 (t, J = 7.1 Hz, 3 H) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ = 173.4, 170.6, 131.9, 118.8, 84.9, 61.0, 45.9, 40.7, 31.8,

30.3, 25.9, 25.0, 21.0, 20.8, 14.0 ppm. HRMS (ESI): calcd. for

C₁₅H₂₂O₄Na [M + Na]⁺289.1415; found 289.1410.

(4aR*,8aS*)-4a-Methyl-8a-(2-methylallyl)octahydro-2H-chromen-2-

one (8h): Following general procedure A, purification by silica gel

column chromatography (EtOAc/hexane, 15:85) afforded com-

pound 8h [78 mg, 70% (total yield of both the diastereomers), dr

89:11] as a colorless viscous liquid. The minor isomer could not be

separated in pure form, and the data provided are for the major

Ethyl 2-Allyl-1-(3-ethoxy-3-oxopropyl)-2-hydroxycyclohexanecarb-

oxylate (7c): Purification by silica gel column chromatography

(EtOAc/hexane, 8:92) afforded compound 7c as a colorless liquid.

The stereochemistry was not established because the compound

isomer. IR (neat): ν = 3073, 1727, 1241 cm^–1. ¹H NMR (400 MHz,

was obtained in liquid form. IR (neat): ν = 3459, 1732, 1027 cm^–1.

˜

¹H NMR (400 MHz, CDCl₃): δ = 5.97–5.86 (m, 1 H), 5.11–5.05

(m, 2 H), 4.25–4.16 (m, 2 H), 4.12 (q, J = 7.1 Hz, 2 H), 2.56–2.12

(m, 6 H), 1.88–1.33 (m, 9 H), 1.30 (t, J = 7.1 Hz, 3 H), 1.25 (t, J

= 7.1 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 177.0,

173.4, 133.9, 117.7, 74.8, 61.0, 60.4, 53.0, 39.4, 34.0, 30.7, 30.4,

28.2, 21.8, 21.7, 14.2, 14.1 ppm. HRMS (ESI): calcd. for

C₁₇H₂₈O₅Na [M + Na]⁺335.1834; found 335.1835.

CDCl₃): δ = 4.95–4.94 (s, 1 H), 4.72 (s, 1 H), 2.69–2.54 (m, 2 H),

2.42 (d, J = 14.0 Hz, 1 H), 2.35 (d, J = 14.0 Hz, 1 H), 1.92–1.65

(m, 4 H), 1.85 (s, 3 H), 1.60–1.50 (m, 5 H), 1.26–1.23 (m, 1 H),

1.09 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 171.7, 141.3,

116.2, 87.7, 43.6, 34.3, 34.0, 31.1, 30.1, 26.3, 24.5, 23.2, 21.6,

20.6 ppm. HRMS (ESI): calcd. for C₁₄H₂₂O₂Na [M + Na]⁺

245.1517; found 245.1522.

Ethyl (1S*,2S*)-1-Benzyl-2-hydroxy-2-(propa-1,2-dien-1-yl)cyclo-

pentanecarboxylate (10a): Following general procedure A, purifica-

tion by silica gel column chromatography (EtOAc/hexane, 7:93) af-

Ethyl (3aS*,7aS*)-7a-Allyl-2-oxooctahydrobenzofuran-3a-carboxyl-

ate (8d): Following general procedure A, purification by silica gel

column chromatography (EtOAc/hexane, 14:86) afforded com-

forded compound 10a (114 mg, 80%) as a colorless viscous liquid.

pound 8d (88 mg, 70%) as a colorless liquid. IR (neat): ν = 2941,

˜

1

IR (neat): ν = 3491, 1956, 1722, 1454 cm^–1. H NMR (400 MHz,

1787, 1727, 1219 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 5.85–5.75

(m, 1 H), 5.16–5.07 (m, 2 H), 4.21 (q, J = 7.2 Hz, 2 H), 3.18 (d, J

˜

CDCl₃): δ = 7.24–7.19 (m, 3 H), 7.08 (d, J = 6.7 Hz, 2 H), 5.33 (t,

J = 6.6 Hz, 1 H), 4.96–4.88 (m, 2 H), 4.12–4.05 (m, 2 H), 3.40 (d,

J = 13.7 Hz, 1 H), 2.70 (d, J = 13.7 Hz, 1 H), 2.08–2.03 (m, 2

H), 1.96–1.66 (m, 5 H), 1.19 (t, J = 7.2 Hz, 3 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 205.9, 174.8, 138.1, 129.8, 128.2, 126.5,

96.4, 81.4, 78.9, 61.7, 60.5, 37.6, 35.3, 28.0, 17.8, 14.2 ppm. HRMS

(ESI): calcd. for C₁₈H₂₂O₃Na [M + Na]⁺309.1466; found 309.1478.

1

2

= 17.5 Hz, 1 H), 2.48–2.40 (m, 2 H), 2.26 (dd, J = 14.3 Hz, J =

8.4 Hz, 1 H), 2.03–1.98 (m, 2 H), 1.82–1.43 (m, 6 H), 1.31 (t, J =

7.2 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 174.5, 172.0,

131.6, 119.7, 85.7, 61.4, 51.0, 41.5, 40.6, 33.1, 30.9, 20.8, 20.2,

14.1 ppm. HRMS (ESI): calcd. for C₁₄H₂₀O₄Na [M + Na]⁺

275.1259; found 275.1261.

Ethyl (1S*,2S*)-1-(4-Bromobenzyl)-2-hydroxy-2-(propa-1,2-dien-1-

yl)cyclopentanecarboxylate (10b): Following general procedure A,

purification by silica gel column chromatography (EtOAc/hexane,

6:94) afforded compound 10b (167 mg, 92%) as a colorless sticky

Ethyl

(3aS*,6aS*)-6a-(2-Methylallyl)-2-oxohexahydro-2H-cyclo-

penta[b]furan-3a-carboxylate (8e): Following general procedure A,

purification by silica gel column chromatography (EtOAc/hexane,

11:89) afforded compound 8e (101 mg, 80%) as a colorless liquid.

liquid. IR (neat): ν = 3502, 1956, 1719, 1488 cm^–1. ¹H NMR

IR (neat): ν = 2975, 1784, 1728, 1226 cm^–1. H NMR (400 MHz,

1

˜

(400 MHz, CDCl₃): δ = 7.36 (d, J = 8.4 Hz, 2 H), 7.0 (d, J =

8.4 Hz, 2 H), 5.32 (t, J = 6.6 Hz, 1 H), 4.97–4.89 (m, 2 H), 4.11–

4.03 (m, 2 H), 3.34 (d, J = 13.7 Hz, 1 H), 2.91 (br. s, 1 H), 2.66 (d,

J = 13.7 Hz, 1 H), 2.06–1.67 (m, 6 H), 1.19 (t, J = 7.1 Hz, 3

H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 205.8, 174.6, 137.1,

131.6, 131.3, 120.5, 96.2, 81.5, 79.1, 61.7, 60.7, 37.0, 35.5, 28.2,

18.0, 14.2 ppm. HRMS (ESI): calcd. for C₁₈H₂₁BrNaO₃[M +

Na]⁺387.0571; found 387.0576.

CDCl₃): δ = 4.91 (s, 1 H), 4.76 (s, 1 H), 4.23 (q, J = 7.1 Hz, 2 H),

3.48 (d, J = 18.3 Hz, 1 H), 2.56–2.48 (m, 2 H), 2.43 (d, J = 13.8 Hz,

1 H), 2.26 (d, J = 13.8 Hz, 1 H), 2.18–2.12 (m, 1 H), 1.94–1.72 (m,

4 H), 1.82 (s, 3 H), 1.32 (t, J = 7.1 Hz, 3 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 174.8, 172.7, 140.9, 115.8, 98.7, 61.8, 58.7,

43.3, 39.5, 38.6, 37.3, 23.9, 23.1, 14.2 ppm. HRMS (ESI): calcd. for

C₁₄H₂₀O₄Na [M + Na]⁺275.1259; found 275.1254.

Ethyl (3aS*,7aS*)-7a-(2-Methylallyl)-2-oxooctahydrobenzofuran-

3a-carboxylate (8f): Following general procedure A, purification by

silica gel column chromatography (EtOAc/hexane, 11:89) afforded

Preparation of 10b and 11b Following General Procedure A: The

reaction of the corresponding cyclic ketone (0.5 mmol) and prop-

argyl bromide (1.2 mmol) mediated by zinc dust (0.75 mmol) gave

products 10b (88 mg, 48%) and 11b (72 mg, 40%). The data for

10b is the same as those from the indium-mediated reaction, which

was already provided.

compound 8f (93 mg, 70%) as a colorless liquid. IR (neat): ν =

˜

1

1789, 1727, 1219 cm^–1. H NMR (400 MHz, CDCl₃): δ = 4.94 (s,

1 H), 4.74 (s, 1 H), 4.22 (q, J = 7.1 Hz, 2 H), 3.09 (d, J = 17.4 Hz,

1 H), 2.47 (d, J = 17.4 Hz, 1 H), 2.29 (s, 2 H), 2.03–1.67 (m, 4 H),

Eur. J. Org. Chem. 2013, 2362–2380

www.eurjoc.org

2375

C. Reddy, S. A. Babu, N. A. Aslam, V. Rajkumar

Ethyl (1S*,2S*)-1-(4-Bromobenzyl)-2-hydroxy-2-(prop-2-yn-1-yl)- 131.2, 120.3, 82.3, 79.2, 74.7, 60.9, 60.7, 37.2, 36.2, 30.2, 28.8, 18.4,

FULL PAPER

cyclopentanecarboxylate (11b): Purification by silica gel column

chromatography (EtOAc/hexane, 6:94) afforded compound 11b as

14.1, 3.6 ppm.

Preparation of 10f and 11f Following General Procedure A: The re-

action of the corresponding cyclic ketone (0.5 mmol) and allyl

bromide (1.2 mmol) mediated by indium (0.75 mmol) gave prod-

ucts 10f (121 mg, 64%) and 11f (27 mg, 14%).

a colorless sticky liquid. IR (neat): ν = 3500, 2360, 1713, 1487 cm^–1.

˜

¹H NMR (400 MHz, CDCl₃): δ = 7.37 (d, J = 8.2 Hz, 2 H), 7.01

(d, J = 8.2 Hz, 2 H), 4.14–4.06 (m, 2 H), 3.36 (d, J = 13.6 Hz, 1

H), 2.78 (d, J = 13.6 Hz, 1 H), 2.57–2.47 (m, 2 H), 2.43 (s, 1 H),

2.11 (br. s, 1 H), 2.07–1.70 (m, 6 H), 1.23 (t, J = 7.2 Hz, 3 H) ppm.

¹³C NMR (100 MHz, CDCl₃): δ = 174.4, 137.3, 131.6, 131.2, 120.4,

82.1, 80.3, 71.5, 61.0, 60.9, 37.2, 36.0, 30.1, 28.5, 18.3, 14.1 ppm.

MS (CI): m/z (%) = 365 (29) [M + 1]⁺, 366 (9) [M + 2]⁺, 321 (42),

319 (55), 271 (20), 217 (15).

Ethyl (1S*,2S*)-1-(4-Bromobenzyl)-2-hydroxy-2-(propa-1,2-dien-1-

yl)cyclohexanecarboxylate (10f): Purification by silica column

chromatography (EtOAc/hexane, 5:95) afforded compound 10f as

a colorless semisolid. IR (neat): ν = 3500, 1955, 1714, 1488 cm^–1.

˜

¹H NMR (400 MHz, CDCl₃): δ = 7.36 (d, J = 8.4 Hz, 2 H), 6.95

(d, J = 8.4 Hz, 2 H), 5.52 (t, J = 6.7 Hz, 1 H), 4.92–4.83 (m, 2 H),

4.05–3.96 (m, 3 H), 3.39 (d, J = 13.7 Hz, 1 H), 2.99 (d, J = 13.7 Hz,

1 H), 1.92–1.84 (m, 1 H), 1.79–1.47 (m, 7 H), 1.12 (t, J = 7.1 Hz,

3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 206.6, 176.0, 136.7,

131.7, 131.2, 120.5, 95.9, 78.5, 73.5, 60.7, 55.3, 34.6, 33.8, 26.1,

22.4, 20.6, 14.0 ppm. HRMS (ESI): calcd. for C₁₉H₂₃BrNaO₃[M

+ Na]⁺401.0728; found 401.0709.

Ethyl (1S*,2S*)-1-(4-Chlorobenzyl)-2-hydroxy-2-(propa-1,2-dien-1-

yl)cyclopentanecarboxylate (10c): Following general procedure A,

purification by silica gel column chromatography (EtOAc/hexane,

07:93) afforded compound 10c (136 mg, 85%) as a colorless viscous

liquid. IR (neat): ν = 3479, 1957, 1722, 1492 cm^–1. ¹H NMR

˜

(400 MHz, CDCl₃): δ = 7.21 (d, J = 8.4 Hz, 2 H), 7.03 (d, J =

8.4 Hz, 2 H), 5.33 (t, J = 6.6 Hz, 1 H), 4.98–4.90 (m, 2 H), 4.12–

4.04 (m, 2 H), 3.36 (d, J = 13.7 Hz, 1 H), 2.69 (d, J = 13.7 Hz, 1

H), 2.63 (s, 1 H), 2.07–1.65 (m, 6 H), 1.20 (t, J = 7.2 Hz, 3 H) ppm.

¹³C NMR (100 MHz, CDCl₃): δ = 205.8, 174.6, 136.6, 132.4, 131.2,

128.3, 96.2, 81.4, 79.1, 61.7, 60.6, 36.9, 35.5, 28.2, 17.9, 14.2 ppm.

HRMS (ESI): calcd. for C₁₈H₂₁ClNaO₃[M + Na]⁺343.1076;

found 343.1079.

Ethyl (1S*,2S*)-1-(4-Bromobenzyl)-2-hydroxy-2-(prop-2-yn-1-yl)cy-

clohexanecarboxylate (11f): Purification by silica gel column

chromatography (EtOAc/hexane, 6:94) afforded compound 11f as

a white solid; m.p. 114–116 °C. IR (KBr): ν = 3483, 1699,

˜

1

1460 cm^–1. H NMR (400 MHz, CDCl₃): δ = 7.37 (d, J = 8.4 Hz,

2 H), 6.96 (d, J = 8.4 Hz, 2 H), 4.12–3.96 (m, 2 H), 3.68 (br. s, 1

H), 3.40 (d, J = 13.7 Hz, 1 H), 3.03 (d, J = 13.7 Hz, 1 H), 2.79 (dd,

2

¹J = 16.9 Hz, J = 2.7 Hz, 1 H), 2.34–2.29 (m, 1 H), 2.11–2.06 (m,

Ethyl (1S*,2S*)-1-Allyl-2-hydroxy-2-(propa-1,2-dien-1-yl)cyclopent-

anecarboxylate (10d): Following general procedure A, purification

by silica gel column chromatography (EtOAc/hexane, 6:94) af-

2 H), 1.80–1.30 (m, 7 H), 1.14 (t, J = 7.2 Hz, 3 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 176.2, 136.5, 131.7, 131.2, 120.6, 80.0, 74.2,

71.3, 61.0, 54.9, 34.9, 31.5, 27.6, 26.3, 22.1, 20.7, 14.0 ppm. HRMS

(ESI): calcd. for C₁₉H₂₃BrNaO₃[M + Na]⁺401.0728; found

401.0729.

forded compound 10d (96 mg, 81%) as a colorless liquid. IR (neat):

1

ν = 3494, 2979, 1958, 1722 cm^–1. H NMR (400 MHz, CDCl ): δ

˜

3

= 5.71–5.60 (m, 1 H), 5.31 (t, J = 6.6 Hz, 1 H), 5.10–5.03 (m, 2

H), 4.95–4.86 (m, 2 H), 4.18–4.10 (m, 2 H), 2.77 (dd, ¹J = 13.8 Hz,

²J = 6.9 Hz, 1 H), 2.61 (br. s, 1 H), 2.12 (dd, ¹J = 13.8 Hz, ²J =

8.3 Hz, 1 H), 2.13–1.65 (m, 6 H), 1.27 (t, J = 7.1 Hz, 3 H) ppm.

¹³C NMR (100 MHz, CDCl₃): δ = 205.8, 174.7, 134.2, 118.0, 96.1,

80.9, 78.8, 60.5, 60.3, 36.6, 35.9, 28.9, 18.1, 14.3 ppm. HRMS

(ESI): calcd. for C₁₄H₂₀O₃Na [M + Na]⁺259.1310; found 259.1311.

(1S*,2R*)-1-Allyl-2-[(allyloxy)methyl]-2-(4-chlorobenzyl)cyclo-

pentanol (11g): Following general procedure E, compound 5cA af-

forded the crude product that was purified by silica gel column

chromatography (EtOAc/hexane, 6:94) to give compound 11g

(166 mg, 69%) as a colorless liquid. IR (neat): ν = 3564, 2964,

˜

1490, 1094 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.22 (d, J =

8.4 Hz, 2 H), 7.14 (d, J = 8.4 Hz, 2 H), 6.04–5.89 (m, 2 H), 5.31–

5.26 (m, 1 H), 5.21–5.09 (m, 3 H), 3.89 (d, J = 5.5 Hz, 2 H), 3.17

(d, J = 9.6 Hz, 1 H), 3.13 (d, J = 13.2 Hz, 1 H), 3.00 (d, J = 9.6 Hz,

1 H), 2.63 (d, J = 13.2 Hz, 1 H), 2.37 (dd, ¹J = 13.7 Hz, ²J =

Preparation of 10e and 11e Following General Procedure A: The

reaction of the corresponding cyclic ketone (0.5 mmol) and allyl

bromide (1.2 mmol) mediated by indium (0.75 mmol) gave prod-

ucts 10e (76 mg, 40%) and 11e (57 mg, 30%).

1

2

6.9 Hz, 1 H), 2.27 (dd, J = 13.7 Hz, J = 7.7 Hz, 1 H), 1.97 (s, 1

H), 1.96–1.91 (m, 1 H), 1.82–1.67 (m, 3 H), 1.59–1.51 (m, 1 H),

1.18–1.11 (m, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 138.2,

135.2, 134.5, 132.1, 131.7, 127.9, 118.4, 117.0, 83.4, 72.0, 71.9, 52.1,

41.6, 35.6, 35.2, 31.2, 18.8 ppm. MS (CI): m/z (%) = 321 (3) [M +

1]⁺, 303 (25), 279 (39), 245 (38), 212 (17).

Ethyl

(1S*,2S*)-1-(4-Bromobenzyl)-2-(buta-2,3-dien-2-yl)-2-hy-

droxycyclopentanecarboxylate (10e): Purification by silica gel col-

umn chromatography (EtOAc/hexane, 5:95) afforded compound

10e as a colorless liquid. IR (neat): ν = 3499, 1954, 1722, 1488 cm^–1.

˜

¹H NMR (400 MHz, CDCl₃): δ = 7.36 (d, J = 8.4 Hz, 2 H), 6.99

(d, J = 8.4 Hz, 2 H), 4.75–4.67 (m, 2 H), 4.06–4.00 (m, 2 H), 3.40

(d, J = 13.6 Hz, 1 H), 2.74 (d, J = 13.6 Hz, 1 H), 2.39 (s, 1 H),

2.20–2.14 (m, 1 H), 2.07–1.70 (m, 5 H), 1.81 (t, J = 3.1 Hz, 3 H),

1.18 (t, J = 7.1 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

205.0, 175.0, 137.5, 131.7, 131.1, 120.3, 103.2, 83.7, 76.9, 62.0, 60.5,

38.3, 36.0, 29.6, 18.7, 15.8, 14.0 ppm. HRMS (ESI): calcd. for

C₁₉H₂₃BrNaO₃[M + Na]⁺401.0728; found 401.0715.

(6aS*,9aR*,Z)-9a-(4-Chlorobenzyl)-1,3,6,6a,7,8,9,9a-octahydro-

cyclopenta[c]oxocin-6a-ol (11h): Following general procedure F,

compound 11g afforded the crude product that was purified by

silica gel column chromatography (EtOAc/hexane, 15:85) to give

compound 11h (74 mg, 51%) as a white solid; m.p. 93–95 °C. IR

(KBr): ν = 3456, 2934, 1489, 1097 cm^{–1 1}H NMR (400 MHz,

.

˜

CDCl₃): δ = 7.25 (d, J = 8.5 Hz, 2 H), 7.21 (d, J = 8.5 Hz, 2 H),

5.74–5.66 (m, 1 H), 5.46–5.42 (m, 1 H), 4.38 (d, J = 17.2 Hz, 1 H),

3.93 (d, J = 17.2 Hz, 1 H), 3.33 (br. s, 1 H), 3.19 (d, J = 11.4 Hz,

1 H), 3.07–3.00 (m, 2 H), 2.66 (d, J = 12.6 Hz, 1 H), 2.24–2.04 (m,

2 H), 1.87–1.34 (m, 6 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

138.0, 132.2, 131.5, 129.7, 127.9, 126.6, 84.5, 70.3, 69.5, 51.7, 36.2,

35.3, 35.1, 31.0, 19.5 ppm.

Ethyl (1S*,2S*)-1-(4-Bromobenzyl)-2-(but-2-yn-1-yl)-2-hydroxycy-

clopentanecarboxylate (11e): Purification by silica gel column

chromatography (EtOAc/hexane, 5:95) afforded compound 11e as

a white solid; m.p. 68–70 °C. IR (KBr): ν = 3526, 1722, 1184 cm^–1.

˜

¹H NMR (400 MHz, CDCl₃): δ = 7.36 (d, J = 8.4 Hz, 2 H), 7.01

(d, J = 8.4 Hz, 2 H), 4.14–4.05 (m, 2 H), 3.37 (d, J = 13.7 Hz, 1

H), 2.76 (d, J = 13.7 Hz, 1 H), 2.52–2.47 (m, 1 H), 2.44 (s, 1 H),

2.41–2.35 (m, 1 H), 2.02–1.71 (m, 9 H), 1.23 (t, J = 7.2 Hz, 3 (1S*,2R*)-1-Allyl-2-[(allyloxy)methyl]-2-(4-bromobenzyl)cyclo-

H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 174.5, 137.6, 131.6,

pentanol (11i): Following general procedure E, compound 5aA af-

2376

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Eur. J. Org. Chem. 2013, 2362–2380

Construction of Functionalized Carbocycles

1

2

forded the crude product that was purified by silica gel column

chromatography (EtOAc/hexane, 6:94) to give compound 11i

J = 8.6 Hz, 2 H), 7.16 (dd, J = 8.6 Hz, J = 2.1 Hz, 1 H), 6.03–

5.93 (m, 1 H), 5.21–5.15 (m, 2 H), 3.56 (d, J = 11.3 Hz, 1 H), 3.41

1

2

(273 mg, 71%) as a colorless viscous liquid. IR (neat): ν = 3566,

(dd, J = 11.3 Hz, J = 3.3 Hz, 1 H), 3.20 (d, J = 13.9 Hz, 1 H),

˜

2962, 1487, 1073 cm^–1. H NMR (400 MHz, CDCl₃): δ = 7.37 (d, 2.97 (d, J = 13.9 Hz, 1 H), 2.45 (dd, J = 13.6 Hz, J = 7.4 Hz, 1

J = 8.3 Hz, 2 H), 7.08 (d, J = 8.3 Hz, 2 H), 6.04–5.88 (m, 2 H), H), 2.31 (dd, ¹J = 13.6 Hz, ²J = 7.2 Hz, 1 H), 2.07 (br. s, 1 H),

5.31–5.09 (m, 4 H), 3.89 (d, J = 5.5 Hz, 2 H), 3.17 (d, J = 9.6 Hz, 1.97–1.79 (m, 4 H), 1.69–1.52 (m, 2 H), 1.24–1.16 (m, 1 H) ppm.

1

2

1 H), 3.11 (d, J = 13.2 Hz, 1 H), 2.99 (d, J = 9.6 Hz, 1 H), 2.62 (d,

¹³C NMR (100 MHz, CDCl₃): δ = 136.0, 135.7, 134.4, 133.9, 132.4,

129.2, 126.8, 119.1, 83.7, 64.3, 53.0, 40.6, 35.5, 31.7, 29.7,

18.9 ppm. HRMS (ESI): calcd. for C₁₆H₂₀Cl₂NaO₂[M + Na]⁺

337.0738; found 337.0662.

1

2

J = 13.2 Hz, 1 H), 2.38 (dd, J = 13.7 Hz, J = 6.9 Hz, 1 H), 2.27

(dd, ¹J = 13.7 Hz, ²J = 7.6 Hz, 1 H), 1.97 (br. s, 1 H), 1.95–1.91

(m, 1 H), 1.82–1.67 (m, 3 H), 1.59–1.51 (m, 1 H), 1.18–1.11 (m, 1

H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 138.7, 135.2, 134.5,

132.5, 130.9, 119.8, 118.4, 117.0, 83.4, 72.0, 71.9, 52.0, 41.6, 35.6,

35.3, 31.2, 18.8 ppm. MS (CI): m/z (%) = 367 (1) [M + 2]⁺, 349

(26), 346 (26), 291 (100), 328 (11).

(1S*,2R*)-1,2-Diallyl-2-(hydroxymethyl)cyclopentanol (5nA): Fol-

lowing general procedure B, compound 5n afforded the crude prod-

uct that was purified by silica gel column chromatography (EtOAc/

hexane, 18:82) to give compound 5nA (74 mg, 75%) as a colorless

1

liquid. IR (neat): ν = 3408, 1638, 1439 cm^–1. H NMR (400 MHz,

(6aS*,9aR*,Z)-9a-(4-Bromobenzyl)-1,3,6,6a,7,8,9,9a-octahydro-

cyclopenta[c]oxocin-6a-ol (11j): Following general procedure F,

compound 11i afforded the crude product that was purified by sil-

ica gel column chromatography (EtOAc/hexane, 15:85) to give

compound 11j (89 mg, 53%) as a white solid; m.p. 87–89 °C. IR

˜

CDCl₃): δ = 6.01–5.89 (m, 2 H), 5.19–5.07 (m, 4 H), 3.58 (d, J =

11.3 Hz, 1 H), 3.48 (d, J = 11.3 Hz, 1 H), 2.52–2.41 (m, 2 H), 2.31–

2.24 (m, 2 H), 1.91–1.83 (m, 3 H), 1.80–1.45 (m, 5 H) ppm. ¹³C

NMR (100 MHz, CDCl₃): δ = 136.8, 134.6, 118.7, 117.2, 83.2, 65.7,

52.0, 40.9, 36.3, 35.6, 30.9, 19.0 ppm. HRMS (ESI): calcd. for

C₁₂H₂₀NaO₂[M + Na]⁺219.1361; found 219.1354.

(KBr): ν = 3328, 1582, 1485, 1095 cm^{–1 1}H NMR (400 MHz,

.

˜

CDCl₃): δ = 7.36 (d, J = 8.4 Hz, 2 H), 7.19 (d, J = 8.4 Hz, 2 H),

5.73–5.65 (m, 1 H), 5.45–5.41 (m, 1 H), 4.38 (d, J = 17.1 Hz, 1 H),

3.92 (d, J = 17.1 Hz, 1 H), 3.32 (br. s, 1 H), 3.18 (d, J = 11.4 Hz,

1 H), 3.05 (d, J = 11.4 Hz, 1 H), 2.99 (d, J = 12.6 Hz, 1 H), 2.63

(d, J = 12.6 Hz, 1 H), 2.23–2.02 (m, 2 H), 1.86–1.24 (m, 6 H) ppm.

¹³C NMR (100 MHz, CDCl₃): δ = 138.5, 132.6, 130.8, 129.7, 126.6,

119.7, 84.5, 70.3, 69.5, 51.7, 36.2, 35.4, 35.1, 31.0, 19.5 ppm.

(1S*,2S*)-1-Allyl-2-(hydroxymethyl)-2-methylcyclohexanol (5tA):

Following general procedure B, compound 5t afforded the crude

product that was purified by silica gel column chromatography

(EtOAc/hexane, 17:83) to give compound 5tA (76 mg, 83%) as a

colorless viscous liquid. IR (neat): ν = 3364, 2942, 1456, 1017 cm^–1.

˜

¹H NMR (400 MHz, CDCl₃): δ = 6.00–5.89 (m, 1 H), 5.15–5.09

(m, 2 H), 3.78 (d, J = 10.5 Hz, 1 H), 3.35 (br. s, 1 H), 3.24 (d, J =

10.5 Hz, 1 H), 2.93 (br. s, 1 H), 2.54 (dd, ¹J = 14.0 Hz, ²J = 8.3 Hz,

1 H), 2.42 (dd, ¹J = 14.0 Hz, ²J = 6.2 Hz, 1 H), 1.59–1.44 (m, 5

H), 1.29–1.15 (m, 3 H), 1.19 (s, 3 H) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ = 134.6, 117.8, 76.4, 71.0, 41.2, 38.3, 32.3, 31.5, 22.3,

20.3, 17.9 ppm. HRMS (ESI): calcd. for C₁₁H₂₀NaO₂[M + Na]⁺

207.1361; found 207.1361.

(1S*,2R*)-1-Allyl-2-(4-bromobenzyl)-2-(hydroxymethyl)cyclo-

pentanol (5aA): Following general procedure B, compound 5a af-

forded the crude product that was purified by silica gel column

chromatography (EtOAc/hexane, 16:84) to give compound 5aA

(138 mg, 85%) as a white solid; m.p. 81–83 °C. IR (KBr): ν = 3377,

˜

1

1639, 1487, 1029 cm^–1. H NMR (400 MHz, CDCl₃): δ = 7.40 (d,

J = 8.2 Hz, 2 H), 7.17 (d, J = 8.2 Hz, 2 H), 6.02–5.92 (m, 1 H),

5.22–5.14 (m, 2 H), 3.53 (d, J = 10.7 Hz, 1 H), 3.33 (dd, ¹J =

2

10.9 Hz, J = 4.7 Hz, 1 H), 3.11 (d, J = 13.4 Hz, 1 H), 2.67 (d, J

(1S*,2R*)-1-Allyl-2-(2-hydroxyethyl)-2-(hydroxymethyl)cyclo-

pentanol (8bA): Following general procedure B, compound 8b af-

forded the crude product that was purified by silica gel column

chromatography (EtOAc/hexane, 75:25) to give compound 8bA

= 13.4 Hz, 1 H), 2.41 (dd, ¹J = 13.4 Hz, ²J = 7.6 Hz, 1 H), 2.28

1

2

(dd, J = 13.4 Hz, J = 7.0 Hz, 1 H), 1.99–1.93 (m, 1 H), 1.97 (br.

s, 1 H), 1.83–1.56 (m, 5 H), 1.26–1.19 (m, 1 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 138.5, 134.4, 132.5, 131.1, 119.9, 119.3,

83.4, 64.1, 52.5, 41.0, 36.0, 35.0, 30.4, 18.8 ppm. MS (CI): m/z (%)

= 327 (20) [M + 2]⁺, 326 (100) [M + 1]⁺, 279 (1).

(77 mg, 77%) as a colorless viscous liquid. IR (neat): ν = 3283,

˜

1

1606, 1032 cm^–1. H NMR (400 MHz, CDCl₃): δ = 5.96–5.86 (m,

1 H), 5.16–5.11 (m, 2 H), 4.23 (br. s, 2 H), 3.82–3.77 (m, 1 H),

3.69–3.64 (m, 1 H), 3.48 (d, J = 11.3 Hz, 1 H), 3.39 (d, J = 11.3 Hz,

1 H), 2.32 (dd, ¹J = 13.7 Hz, ²J = 7.8 Hz, 1 H), 2.18 (dd, ¹J =

13.7 Hz, ²J = 6.9 Hz, 1 H), 1.90–1.56 (m, 9 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 134.5, 118.8, 83.0, 65.7, 59.7, 52.7, 40.3,

37.2, 34.3, 30.6, 19.0 ppm. HRMS (ESI): calcd. for C₁₁H₂₀O₃Na

[M + Na]⁺223.1310; found 223.1303.

(1S*,2R*)-1-Allyl-2-(4-chlorobenzyl)-2-(hydroxymethyl)cyclo-

pentanol (5cA): Following general procedure B, compound 5c af-

forded the crude product that was purified by silica gel column

chromatography (EtOAc/hexane, 16:84) to give compound 5cA

(118 mg, 84%) as a white solid; m.p. 73–75 °C. IR (KBr): ν = 3386,

˜

1638, 1490, 1032 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.25–7.20

(m, 4 H), 6.02–5.91 (m, 1 H), 5.21–5.13 (m, 2 H), 3.52 (d, J =

11.0 Hz, 1 H), 3.32 (d, J = 11.0 Hz, 1 H), 3.12 (d, J = 13.4 Hz, 1

(1R*,2S*)-1-Allyl-2-(hydroxymethyl)-2-(3-hydroxypropyl)cyclohex-

anol (8cA): Following general procedure B, compound 8c afforded

the crude product that was purified by silica gel column chromatog-

raphy (EtOAc/hexane, 75:25) to give compound 8cA as a white so-

2

H), 2.67 (d, J = 13.4 Hz, 1 H), 2.40 (dd, ¹J = 13.4 Hz, J = 7.6 Hz,

1 H), 2.27 (dd, ¹J = 13.5 Hz, ²J = 7.0 Hz, 1 H), 1.98–1.54 (m, 7

H), 1.26–1.19 (m, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

137.9, 134.5, 132.1, 131.9, 128.1, 119.3, 83.4, 64.1, 52.5, 41.0, 36.0,

34.9, 30.4, 18.8 ppm. MS (CI): m/z (%) = 282 (30) [M + 1]⁺, 281

(97) [M]⁺, 255 (78), 158 (53).

lid (74 mg, 65 %); m.p. 102–104 °C. IR (KBr): ν = 3298, 1357,

˜

1

1056 cm^–1. H NMR (400 MHz, CDCl₃): δ = 6.03–5.93 (m, 1 H),

5.13 (s, 1 H), 5.09 (d, J = 7.2 Hz, 1 H), 4.84 (br. s, 1 H), 3.99 (br.

s, 1 H), 3.84–3.79 (m, 1 H), 3.60 (d, J = 11.1 Hz, 2 H), 3.46 (d, J

(1S*,2R*)-1-Allyl-2-(2,4-dichlorobenzyl)-2-(hydroxymethyl)cyclo- = 11.1 Hz, 1 H), 2.60 (dd, ¹J = 14.0 Hz, ²J = 9.0 Hz, 1 H), 2.49

pentanol (5dA): Following general procedure B, compound 5d af-

forded the crude product that was purified by silica gel column

chromatography (EtOAc/hexane, 17:83) to give compound 5dA

(dd, ¹J = 14.0 Hz, ²J = 4.7 Hz, 1 H), 2.15 (t, J = 14.2 Hz, 1 H),

1.64–1.22 (m, 11 H), 1.03–0.91 (m, 1 H) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ = 134.9, 117.1, 77.5, 65.6, 63.0, 43.1, 38.8, 30.2, 27.0,

25.6, 22.5, 21.9, 19.9 ppm. HRMS (ESI): calcd. for C₁₃H₂₅O₃[M

(110 mg, 70%) as a white solid; m.p. 73–75 °C. IR (KBr): ν = 3386,

˜

1638, 1490, 1032 cm^–1. H NMR (400 MHz, CDCl₃): δ = 7.38 (d, + H]⁺229.1804; found 229.1796.

1

Eur. J. Org. Chem. 2013, 2362–2380

www.eurjoc.org

2377

C. Reddy, S. A. Babu, N. A. Aslam, V. Rajkumar

FULL PAPER

Preparation of 8gA and 8gB Following General Procedure B: Com-

pounds 8g and 8gЈ (mixture of diastereomers) afforded the crude

product that was purified by silica gel column chromatography to

give the corresponding pure diastereomers 8gA (73 mg, 78%, major

isomer) and 8gB (10 mg, 11%, minor isomer).

4.94 (m, 2 H), 4.22–4.09 (m, 2 H), 2.97 (dd, ¹J = 15.0 Hz, ²J =

1

2

7.4 Hz, 1 H), 2.65 (dd, J = 15.0 Hz, J = 7.1 Hz, 1 H), 2.48–2.40

(m, 1 H), 2.32–2.16 (m, 3 H), 1.82–1.67 (m, 3 H), 1.51–1.25 (m, 3

H), 1.31 (t, J = 7.1 Hz, 3 H), 0.93 (t, J = 7.2 Hz, 3 H) ppm. ¹³C

NMR (100 MHz, CDCl₃): δ = 174.3, 164.4, 132.9, 131.7, 131.0,

130.5, 127.8, 118.1, 92.8, 61.5, 60.5, 39.4, 35.1, 34.9, 29.8, 19.0,

18.7, 14.9, 14.1 ppm. HRMS (ESI): calcd. for C₂₁H₂₇BrNaO₄[M

+ Na]⁺445.0990; found 445.0993.

(1S*,2R*)-1-Allyl-2-(3-hydroxypropyl)-2-methylcyclohexanol (8gA):

Purification by silica gel column chromatography (EtOAc/hexane,

31:69) afforded compound 8gA (cis, major isomer) as a white solid;

m.p. 67–69 °C. IR (KBr): ν = 3390, 1638, 1060 cm^–1. ¹H NMR

˜

(1S*,2S*)-1,2-Diallyl-2-(ethoxycarbonyl)cyclopentyl 3,4-Dichloro-

benzoate (5nD): Following general procedure D, compound 5n

afforded the crude product that was purified by silica gel column

chromatography (EtOAc/hexane, 5:95) to give compound 5nD

(400 MHz, CDCl₃): δ = 5.93–5.83 (m, 1 H), 5.16–5.06 (m, 2 H),

3.63 (t, J = 6.3 Hz, 2 H), 2.37 (dd, ¹J = 13.7 Hz, ²J = 7.4 Hz, 1 H),

2.20 (dd, ¹J = 13.7 Hz, ²J = 7.4 Hz, 1 H), 1.63–1.24 (m, 14 H), 0.90

(s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 134.7, 118.5, 75.5,

63.7, 39.6, 39.4, 32.9, 32.2, 30.7, 26.9, 21.8, 21.3, 20.3 ppm. HRMS

(ESI): calcd. for C₁₃H₂₄O₂Na [M + Na]⁺235.1674; found 235.1674.

(144 mg, 70%) as a colorless liquid. IR (neat): ν = 2927, 1725,

˜

1

1467, 1296 cm^–1. H NMR (400 MHz, CDCl₃): δ = 8.13 (s, 1 H),

7.88 (d, J = 8.3 Hz, 1 H), 7.54 (d, J = 8.3 Hz, 1 H), 5.81–5.63 (m,

2 H), 5.16–4.99 (m, 4 H), 4.26–4.13 (m, 2 H), 3.06 (dd, ¹J =

(1S*,2S*)-1-Allyl-2-(3-hydroxypropyl)-2-methylcyclohexanol (8gB):

Purification by silica gel column chromatography (EtOAc/hexane,

30:70) afforded compound 8gB (trans, minor isomer) as a white

2

1

2

13.6 Hz, J = 6.2 Hz, 1 H), 2.96 (dd, J = 15.0 Hz, J = 7.2 Hz, 1

1

2

H), 2.70 (dd, J = 15.0 Hz, J = 7.3 Hz, 1 H), 2.42 (t, J = 8.0 Hz,

2 H), 2.30–2.20 (m, 2 H), 1.90–1.74 (m, 3 H), 1.36 (t, J = 7.2 Hz,

3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 173.5, 163.2, 137.4,

134.0, 132.9, 132.4, 131.5, 131.2, 130.6, 128.6, 118.7, 118.5, 92.7,

60.7, 60.5, 39.5, 37.4, 35.2, 29.2, 18.6, 14.1 ppm. HRMS (ESI):

calcd. for C₂₁H₂₄Cl₂NaO₄[M + Na]⁺433.0949; found 433.0938.

solid; m.p. 114–116 °C. IR (KBr): ν = 3368, 2939, 1637, 1059 cm^–1.

˜

¹H NMR (400 MHz, CDCl₃): δ = 5.95–5.84 (m, 1 H), 5.17–5.08

(m, 2 H), 3.65 (t, J = 6.2 Hz, 2 H), 2.35–2.20 (m, 2 H), 1.57–1.28

(m, 14 H), 0.95 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

134.6, 118.7, 75.2, 64.0, 39.8, 39.4, 32.6, 32.3, 31.1, 27.3, 21.9, 21.2,

19.8 ppm. HRMS (ESI): calcd. for C₁₃H₂₄NaO₂[M + Na]⁺

235.1674; found 235.1658.

(1S*,2S*)-2-(4-Bromobenzyl)-2-(ethoxycarbonyl)-1-(propa-1,2-

dien-1-yl)cyclopentyl 3,4-Dichlorobenzoate (10bC): Following gene-

ral procedure D, compound 10b afforded the crude product that

was purified by silica gel column chromatography (EtOAc/hexane,

6:94) to give compound 10bC (174 mg, 65%) as a colorless viscous

(1S*,2R*)-1-Allyl-2-(ethoxycarbonyl)-2-octylcyclopentyl 4-Bromo-

benzoate (5qC): Following general procedure D, compound 5q af-

forded the crude product that was purified by silica gel column

chromatography (EtOAc/hexane, 5:95) to give compound 5qC

liquid. IR (neat): ν = 2979, 1728, 1488, 1288 cm^{–1 1}H NMR

.

˜

(400 MHz, CDCl₃): δ = 8.17 (s, 1 H), 7.92 (d, J = 8.4 Hz, 1 H),

7.54 (d, J = 8.4 Hz, 1 H), 7.40 (d, J = 8.3 Hz, 2 H), 7.01 (d, J =

8.3 Hz, 2 H), 5.24 (t, J = 6.5 Hz, 1 H), 5.00–4.88 (m, 2 H), 4.20–

4.12 (m, 2 H), 3.62 (d, J = 13.6 Hz, 1 H), 2.85–2.78 (m, 1 H), 2.73

(d, J = 13.6 Hz, 1 H), 2.36–2.28 (m, 1 H), 2.03–1.95 (m, 1 H), 1.89–

1.67 (m, 3 H), 1.29 (t, J = 7.2 Hz, 3 H) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ = 207.8, 172.8, 163.1, 137.6, 136.4, 133.0, 131.6, 131.5,

131.4, 131.0, 130.7, 128.7, 120.8, 92.8, 89.3, 78.9, 62.8, 60.9, 36.9,

33.5, 27.0, 18.7, 14.2 ppm. HRMS (ESI): calcd. for C₂₅H₂₃BrCl₂O₄

[M]⁺536.0157; found 536.1453.

(171 mg, 70%) as a colorless liquid. IR (neat): ν = 2927, 1722,

˜

1466, 1265 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.88 (d, J =

8.6 Hz, 2 H), 7.57 (d, J = 8.6 Hz, 2 H), 5.82–5.71 (m, 1 H), 5.02–

1

2

4.93 (m, 2 H), 4.15 (q, J = 7.2 Hz, 2 H), 2.96 (dd, J = 14.9 Hz, J

= 7.3 Hz, 1 H), 2.63 (dd, ¹J = 14.9 Hz, ²J = 7.1 Hz, 1 H), 2.46–

2.39 (m, 1 H), 2.31–2.18 (m, 3 H), 1.81–1.64 (m, 3 H), 1.50–1.42

(m, 1 H), 1.30 (t, J = 7.1 Hz, 3 H), 1.28–1.24 (m, 12 H), 0.86 (t, J

= 6.6 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 174.3,

164.4, 132.9, 131.7, 131.1, 130.5, 127.8, 118.0, 92.7, 61.5, 60.5, 39.4,

35.1, 32.6, 31.9, 30.3, 29.7, 29.7, 29.4, 29.2, 25.3, 22.7, 19.0,

14.1 ppm.

(1S*,2S*)-2-(4-Bromobenzyl)-2-(ethoxycarbonyl)-1-(propa-1,2-

dien-1-yl)cyclohexyl 3,4-Dichlorobenzoate (10fA): Following general

procedure D, compound 10f afforded the crude product that was

purified by silica gel column chromatography (EtOAc/hexane, 5:95)

to give compound 10fA (196 mg, 69%) as a white solid; m.p. 128–

(1S*,2R*)-1-Allyl-2-(ethoxycarbonyl)-2-pentylcyclopentyl 3,4-

Dichlorobenzoate (5rC): Following general procedure D, compound

5r afforded the crude product that was purified by silica gel column

chromatography (EtOAc/hexane, 6:94) to give compound 5rC

130 °C. IR (KBr): ν = 1732, 1720, 1489, 1289 cm^–1

.

¹H NMR

˜

(160 mg, 73%) as a colorless liquid. IR (neat): ν = 2958, 1725,

˜

1

1467, 1110 cm^–1. H NMR (400 MHz, CDCl₃): δ = 8.10 (s, 1 H),

(400 MHz, CDCl₃): δ = 8.19 (d, J = 1.8 Hz, 1 H), 7.91 (dd, J =

2

8.3 Hz, J = 1.8 Hz, 1 H), 7.56 (d, J = 8.3 Hz, 1 H), 7.41 (d, J =

7.85 (d, J = 8.3 Hz, 1 H), 7.52 (d, J = 8.3 Hz, 1 H), 5.81–5.70 (m,

1

8.3 Hz, 2 H), 7.05 (d, J = 8.3 Hz, 2 H), 5.65 (t, J = 6.7 Hz, 1 H),

4.88 (d, J = 6.7 Hz, 2 H), 4.17–4.02 (m, 2 H), 3.53 (d, J = 13.6 Hz,

1 H), 3.08 (d, J = 13.6 Hz, 1 H), 2.56–2.42 (m, 2 H), 1.94–1.89 (m,

1 H), 1.76–1.60 (m, 5 H), 1.22 (t, J = 7.2 Hz, 3 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 208.2, 172.8, 162.4, 137.4, 136.0, 132.9,

132.0, 131.5, 131.5, 131.3, 130.6, 128.6, 120.7, 91.9, 84.9, 78.6, 60.8,

56.6, 37.3, 30.8, 28.3, 21.6, 21.2, 14.1 ppm. HRMS (ESI): calcd. for

C₂₆H₂₅BrCl₂O₄[M]⁺550.0313; found 550.0681.

1 H), 5.03–5.00 (m, 2 H), 4.17 (q, J = 7.2 Hz, 2 H), 2.94 (dd, J =

2

1

2

14.9 Hz, J = 7.4 Hz, 1 H), 2.64 (dd, J = 14.9 Hz, J = 7.1 Hz, 1

H), 2.46–2.17 (m, 4 H), 1.82–1.67 (m, 3 H), 1.49–1.25 (m, 7 H),

1.33 (t, J = 7.2 Hz, 3 H), 0.88 (t, J = 6.6 Hz, 3 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 174.2, 163.2, 137.3, 132.9, 132.7, 131.5,

131.4, 130.5, 128.6, 118.3, 93.1, 61.4, 60.6, 39.4, 35.0, 32.5, 32.4,

29.6, 24.9, 22.5, 18.9, 14.2, 14.0 ppm. HRMS (ESI): calcd. for

C₂₃H₃₀Cl₂NaO₄[M + Na]⁺463.1419; found 463.1426.

(1S*,2R*)-1-Allyl-2-(ethoxycarbonyl)-2-propylcyclopentyl 4-Bromo-

benzoate (5sC): Following general procedure D, compound 5s af-

forded the crude product that was purified by silica gel column

chromatography (EtOAc/hexane, 6:94) to give compound 5sC

(1R*,2S*)-(1,2-Diallyl-2-hydroxycyclopentyl)methyl 3,5-Dinitro-

benzoate (5nB): Following general procedure C, compound 5nA af-

forded the crude product that was purified by silica gel column

chromatography (EtOAc/hexane, 12:88) to give compound 5nB

(177 mg, 84%) as a colorless liquid. IR (neat): ν = 2966, 1722,

(137 mg, 70%) as a colorless liquid. IR (neat): ν = 3564, 1731,

˜

1

1590, 1265 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.89 (d, J =

8.6 Hz, 2 H), 7.58 (d, J = 8.6 Hz, 2 H), 5.83–5.73 (m, 1 H), 5.03–

1276 cm^–1. H NMR (400 MHz, CDCl₃): δ = 9.24 (t, J = 2.1 Hz,

1 H), 9.16 (d, J = 2.1 Hz, 2 H), 6.00–5.87 (m, 2 H), 5.25–5.19 (m,

2378

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Eur. J. Org. Chem. 2013, 2362–2380

Construction of Functionalized Carbocycles

2 H), 5.12–5.07 (m, 2 H), 4.34 (s, 2 H), 2.36 (d, J = 8.1 Hz, 2 H),

Supporting Information (see footnote on the first page of this arti-

2

2.48–2.45 (m, 1 H), 2.30 (dd, ¹J = 6.9 Hz, J = 6.5 Hz, 1 H), 2.00–

cle): X-ray structures (ORTEP diagram) of representative com-

1.66 (m, 7 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 162.5, 148.8, pounds and copies of H and ¹³C NMR spectra of all of the prod-

1

135.5, 133.9, 133.5, 129.4, 122.5, 119.9, 117.6, 82.6, 69.2, 51.4, 41.0,

37.9, 36.2, 32.5, 19.3 ppm. HRMS (ESI): calcd. for C₁₉H₂₂N₂O₇Na

[M + Na]⁺413.1325; found 413.1314.

ucts.

Acknowledgments

(1S*,2R*)-1,2-Diallyl-2-{[(3,5-dinitrobenzoyl)oxy]methyl}cyclo-

pentyl 3,4-Dichlorobenzoate (5nC): Following general procedure D,

compound 5nB afforded the crude product that was purified by

silica gel column chromatography (EtOAc/hexane, 7:93) to give

This research was funded by the Indian Institute of Science Educa-

tion and Research Mohali (IISER-M), and the authors are also

grateful to the Department of Science and Technology (DST), New

Delhi for financial support. The authors thank IISER-Mohali for

the NMR and X-ray facilities and Mr. K. Maheswararao for the

help with solving the X-ray structures. C. R., N. A. A., and V. R.

thank the Indian Institute of Science Education and Research Mo-

hali (IISER-M) and the Council of Scientific and Industrial Re-

search (CSIR)/University Grants Commission (UGC), New Delhi

for the fellowships. The authors thank CDRI-Lucknow and

NIPER-Mohali for providing the mass spectral data. The authors

are grateful to Prof. K. S. Viswanathan (IISER-M) for his help and

thank the reviewers of this article for their valuable suggestions.

compound 5nC (295 mg, 73%) as a white solid; m.p. 97–99 °C. IR

1

(KBr): ν = 1741, 1714, 1343 cm^–1. H NMR (400 MHz, CDCl ): δ

˜

3

= 9.23 (s, 1 H), 9.16 (s, 2 H), 8.00 (d, J = 1.7 Hz, 1 H), 7.80 (dd,

¹J = 8.4 Hz, ²J = 1.7 Hz, 1 H), 7.51 (d, J = 8.4 Hz, 1 H), 5.95–5.81

(m, 2 H), 5.15–5.06 (m, 4 H), 4.55 (q, J = 11.9 Hz, 2 H), 3.10–2.98

(m, 2 H), 2.70–2.49 (m, 3 H), 2.34–2.27 (m, 1 H), 2.04–1.70 (m, 4

H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 163.5, 162.4, 148.8,

137.6, 134.2, 133.7, 132.9, 132.7, 131.3, 131.1, 130.7, 129.4, 128.5,

122.5, 119.0, 118.7, 94.7, 68.7, 52.6, 38.2, 37.1, 35.9, 32.1,

18.9 ppm. HRMS (ESI): calcd. for C₂₆H₂₅Cl₂N₂O₈[M + H]⁺

563.0988; found 563.0012.

[1] For selected articles and reviews on the syntheses of natural

products with adjacent stereocenters, see: a) C. Che, L. Liu, J.

Gong, Y. Yang, G. Wang, Org. Lett. 2010, 12, 488; b) C.

Schäfer, M. Miesch, L. Miesch, Org. Biomol. Chem. 2012, 10,

3253; c) A. J. Pihko, A. M. P. Koskinen, Tetrahedron 2005, 61,

8769; d) A. Steven, L. E. Overman, Angew. Chem. 2007, 119,

5584; Angew. Chem. Int. Ed. 2007, 46, 5488; e) J. Kim, M.

Movassaghi, Chem. Soc. Rev. 2009, 38, 3035; f) Z. W. Zuo,

D. W. Ma, Isr. J. Chem. 2011, 51, 434.

[(1S*,2S*)-2-Allyl-2-hydroxy-1-methylcyclohexyl]methyl 3,5-Di-

nitrobenzoate (5tB): Following general procedure C, compound 5tA

afforded the crude product that was purified by silica gel column

chromatography (EtOAc/hexane, 11:89) to give compound 5tB

(164 mg, 87%) as a colorless viscous liquid. IR (neat): ν = 3568,

˜

1

1731, 1462, 1279 cm^–1. H NMR (400 MHz, CDCl₃): δ = 9.24 (t,

J = 2.2 Hz, 1 H), 9.16 (d, J = 2.2 Hz, 2 H), 5.96–5.86 (m, 1 H),

5.23–5.15 (m, 2 H), 4.48 (d, J = 11.0 Hz, 1 H), 4.42 (d, J = 11.0 Hz,

1 H), 2.40 (d, J = 7.3 Hz, 2 H), 1.67–1.45 (m, 9 H), 1.20 (s, 3 [2] For selected articles and reviews, see: a) B. Linclau, E. Cini,

H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 162.6, 148.7, 134.1,

133.3, 129.4, 122.4, 119.5, 73.9, 71.1, 41.6, 39.6, 32.9, 32.1, 22.0,

20.8, 18.5 ppm.

C. S. Oakes, S. Josse, M. Light, V. Ironmonger, Angew. Chem.

2012, 124, 1258; Angew. Chem. Int. Ed. 2012, 51, 1232; b) C. J.

Douglas, L. E. Overman, Proc. Natl. Acad. Sci. USA 2004,

101, 5363; c) E. A. Peterson, L. E. Overman, Proc. Natl. Acad.

Sci. USA 2004, 101, 11943; d) B. M. Trost, C. Jiang, Synthesis

2006, 369; e) D. Seebach, Angew. Chem. 2011, 123, 99; Angew.

Chem. Int. Ed. 2011, 50, 96; f) J. Christoffers, A. Mann, Angew.

Chem. 2001, 113, 4725; Angew. Chem. Int. Ed. 2001, 40, 4591;

g) J. P. Das, H. Chechik, I. Marek, Nat. Chem. 2009, 1, 128; h)

T. Hashimoto, Y. Naganawa, K. Maruoka, J. Am. Chem. Soc.

2009, 131, 6614; i) K. Fuji, Chem. Rev. 1993, 93, 2037; j) O.

Riant, J. Hannedouche, Org. Biomol. Chem. 2007, 5, 873; k) A.

Steven, L. E. Overman, Angew. Chem. 2007, 119, 5584; Angew.

Chem. Int. Ed. 2007, 46, 5488; l) H. Yanai, Y. Yoshino, A.

Takahashi, T. Taguchi, J. Org. Chem. 2010, 75, 5375; for studies

of the addition of organolithiums to monosubstituted cycloalk-

anones, see: m) K. Maruoka, T. Itoh, M. Sakurai, K. Nonosh-

ita, H. Yamamoto, J. Am. Chem. Soc. 1988, 110, 3588; n) F. A.

Carey, R. J. Sundberg, Advanced Organic Chemistry, Part A and

B, Springer, New York, 2007; o) M. Yasuda, K. Chiba, N. Ohi-

gashi, Y. Katoh, A. Baba, J. Am. Chem. Soc. 2003, 125, 7291.

[3] a) A. W. J. Logan, J. S. Parker, M. S. Hallside, J. W. Burton,

Org. Lett. 2012, 14, 2940; b) C. A. M. Fraga, L. H. P. Teixeira,

(1S*,2S*)-1-Allyl-2-{[(3,5-dinitrobenzoyl)oxy]methyl}-2-methyl-

cyclohexyl 3,4-Dichlorobenzoate (5tC): Following general procedure

D, compound 5tB afforded the crude product that was purified by

silica gel column chromatography (EtOAc/hexane, 07:93) to give

compound 5tC as a pale yellow solid (151 mg, 55%); m.p. 101–

103 °C. IR (neat): ν = 2929, 1728, 1545, 1274 cm^{–1 1}H NMR

.

˜

(400 MHz, CDCl₃): δ = 9.23 (t, J = 2.0 Hz, 1 H), δ = 9.12 (d, J =

2

2.0 Hz, 2 H), 8.02 (d, J = 1.8 Hz, 1 H), 7.82 (dd, ¹J = 8.4 Hz, J =

1.8 Hz, 1 H), 7.51 (d, J = 8.4 Hz, 1 H), 5.93–5.83 (m, 1 H), 5.18–

5.07 (m, 2 H), 4.63 (d, J = 11.2 Hz, 1 H), 4.56 (d, J = 11.2 Hz, 1

H), 3.04 (t, J = 8.1 Hz, 2 H), 2.55–2.51 (m, 1 H), 2.11–2.04 (m, 1

H), 1.79–1.67 (m, 3 H), 1.40–1.23 (m, 3 H), 1.37 (s, 3 H) ppm. ¹³C

NMR (100 MHz, CDCl₃): δ = 163.2, 162.5, 148.7, 137.5, 133.8,

133.5, 133.0, 131.4, 131.3, 130.6, 129.3, 128.5, 122.5, 118.5, 88.7,

70.4, 43.4, 38.5, 33.1, 30.9, 21.9, 20.7, 20.3 ppm.

2-((1R*,2S*)-2-Allyl-1-{[(3,5-dinitrobenzoyl)oxy]methyl}-2-hy-

droxycyclopentyl)ethyl 3,5-Dinitrobenzoate (8bB): Following general

procedure C, compound 8bA afforded the crude product that was

purified by silica gel column chromatography (EtOAc/hexane,

08:92) to give compound 8bB (264 mg, 90%) as a colorless semi-

C. M.

de S. Menezes,

C. M. R.

Sant’Anna,

M.

da C. K. V. Ramos, F. R. de Aquino Neto, E. J. Barreiro, Tetra-

hedron 2004, 60, 2745.

[4] For selected articles and reviews, see: a) S. Araki, H. Ito, Y.

Butsugan, J. Org. Chem. 1988, 53, 1831; b) B. C. Ranu, Eur. J.

Org. Chem. 2000, 2347; c) T. H. Chan, Y. Yang, J. Am. Chem.

Soc. 1999, 121, 3228; d) S. H. Kim, H. S. Lee, K. H. Kim, S. H.

Kim, J. N. Kim, Tetrahedron 2010, 66, 7065; e) J. S. Yadav, A.

Antony, J. George, B. V. Subba Reddy, Eur. J. Org. Chem. 2010,

591; f) U. K. Roy, S. Roy, Chem. Rev. 2010, 110, 2472; g) R. B.

Kargbo, G. R. Cook, Curr. Org. Chem. 2007, 11, 1287; h) J. A.

Marshall, J. Org. Chem. 2007, 72, 8153; i) P. H. Lee, Bull. Ko-

rean Chem. Soc. 2007, 28, 17; j) V. Nair, S. Ros, C. N. Jayan,

solid. IR (neat): ν = 3556, 1731, 1547, 1279 cm^{–1 1}H NMR

.

˜

(400 MHz, CDCl₃): δ = 9.27 (s, 1 H), 9.23 (s, 2 H), 9.17 (s, 2 H),

9.12 (s, 1 H), 5.99–5.88 (m, 1 H), 5.31–5.24 (m, 2 H), 4.78–4.58 (m,

2 H), 4.40 (s, 2 H), 2.47–1.83 (m, 9 H), 1.30–1.24 (m, 2 H) ppm.

¹³C NMR (100 MHz, CDCl₃): δ = 162.6, 162.5, 148.8, 133.8, 133.4,

132.9, 129.9, 129.4, 123.0, 122.7, 122.5, 120.8, 82.8, 69.2, 64.8, 50.6,

40.8, 37.7, 32.6, 30.2, 19.5 ppm. HRMS (ESI): calcd. for

C₂₅H₂₄N₄O₁₃[M]⁺588.1340; found 588.0788.

Eur. J. Org. Chem. 2013, 2362–2380

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2379

C. Reddy, S. A. Babu, N. A. Aslam, V. Rajkumar

FULL PAPER

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Synth. 2004, 7, 413; m) W. J. Bowyer, B. Singaram, A. M. [8] For a recent discussion about active indium species, see: a)

Sessler, Tetrahedron 2011, 67, 7449; n) S. E. Denmark, J. Fu,

Chem. Rev. 2003, 103, 2763; o) C.-J. Li, Chem. Rev. 2005, 105,

3095; p) L. A. Paquette, Synthesis 2003, 765; q) C.-J. Li, D.-L.

Chen, Y.-Q. Lu, J. X. Haberman, J. T. Mague, Tetrahedron

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Chem. 2007, 72, 10264; s) S. A. Babu, M. Yasuda, I. Shibata,

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Rajkumar, C. Reddy, M. Yasuda, A. Baba, S. A. Babu, Eur. J.

Org. Chem. 2012, 4395; u) S. A. Babu, Synlett 2002, 531; v) We

also carried out the reaction of 1a (ketone), 2a (allyl bromide),

and indium powder in various proportions of water and THF.

However, none of our efforts were fruitful to obtain product 3/

4. Even the presence of a trace amount of water in THF (as a

solvent mixture) failed to afford product 3/4.

T. D. Haddad, L. C. Hirayama, B. Singaram, J. Org. Chem.

2010, 75, 642; b) M. Yasuda, M. Haga, Y. Nagaoka, A. Baba,

Eur. J. Org. Chem. 2010, 5359; c) see ref.^[4a,4c]; d) M. Yasuda,

M. Haga, A. Baba, Organometallics 2009, 28, 1998; e) M. Ya-

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Lett. 2006, 8, 3029; g) K. Koszinowski, J. Am. Chem. Soc.

2010, 132, 6032; h) G. Hilt, K. I. Smolko, C. Waloch, Tetrahe-

dron Lett. 2002, 43, 1437.

[9] a) The energy was minimized by using MM2 minimizations

followed by a semiempirical molecular orbital PM3 method

with R-Closed-Shell wave function using GAMESS Interface

in the ChemBio3D Ultra Ver. 12.0; b) The relative energy cal-

culations were carried out using the molecules 12a, 16a, 15a,

and 5i where Y = Br; c) In the X-ray structures of compounds

5i and 5l (experimentally observed conformers), the distance

between the hydrogen of the O–H group and the oxygen of the

C=O group (ester carbonyl group) was found to be 2.109 Å

and 2.169 Å, respectively, and the distance observed is in the

range of a typical intramolecular hydrogen-bonding distance.

For details, see: J. N. Woodford, J. Phys. Chem. A 2007, 111,

8519; d) For the intramolecular hydrogen-bonding distances

[O–H group and the oxygen of the C=O group (ester carbonyl

group)] from the X-ray crystal structures of other related com-

pounds reported in this work, see the Supporting Information.

[10] One reviewer suggested the involvement of a 1:2 stoichiometry

in the transition state for the ketone/allylindium. This possibil-

ity cannot be ignored, as the nature of the active indium species

remains subtle because of its fleeting character, see ref.^[4,8]The

proposed stoichiometry of ketone/allylindium (1:1) in the tran-

sition state is made on the basis of the studies done and the

transition state that was proposed by various groups, which are

working on indium-mediated allylation reactions. For details,

see ref.^[4,8]Furthermore, Baba et al. and other groups have iso-

lated or indicated the involvement of a monomeric indium(III)

species/intermediate from the reaction of In⁰with allyl brom-

ide, as the solvent employed and reaction conditions were con-

sidered.

[5] a) All the reactions were done with cyclic ketone (0.5 mmol),

allylic or propargyl halide (1.5 mmol), and In powder

(0.75 mmol) at room temp.; b) The stereochemistry was as-

signed on the basis of X-ray crystal structure analyses of the

key compounds (see Supporting Information for ORTEP dia-

grams); c) Compound 8g was isolated as a mixture of dia-

stereomers, and the stereochemistry of the major isomer is

shown on the basis of the X-structure crystal analysis of 8gB;

d) The mixture of diastereomers 8g (major) and 8gЈ (minor)

was subjected to the LiAlH₄-mediated reduction, which af-

forded diastereomers 8gA (major isomer) and 8gB (minor iso-

mer), respectively, in pure form; e) When compared to products

8a–8f, we observed a slightly lower dr for products 8g and 8h.

This is perhaps because of the involvement of the relatively less

rigid transition state, as substrate 6e has a Me group instead

of a COOEt group, which is present in substrates 6a–6d.

[6] For selected recent papers about the stereoselective syntheses

of lactones and their applications to natural products synthesis

see: a) H. Shi, L. Fang, C. Tan, L. Shi, W. Zhang, C.-C. Li, T.

Luo, Z. Yang, J. Am. Chem. Soc. 2011, 133, 14944; b) J. Xu,

L. Trzoss, W. K. Chang, E. A. Theodorakis, Angew. Chem.

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R. J. K. Taylor, Angew. Chem. 2008, 120, 1961; Angew. Chem.

Int. Ed. 2008, 47, 1935; d) see ref.^[1b]

.

[11] a) Freshly distilled anhydrous THF (over sodium wires) has

been used in all the reactions. The remaining solvents were used

after drying them over activated molecular sieves. For details,

see: D. B. G. Williams, M. Lawton, J. Org. Chem. 2010, 75,

8351; b) E. Vedejs, O. Daugulis, J. Org. Chem. 1996, 61, 5702;

c) R. Matovic, A. Ivkovic, M. Manojlovic, Z. Tokic-Vujosevic,

R. N. Saicic, J. Org. Chem. 2006, 71, 9411.

[7] a) CCDC-893884 (for 3a), -893886 (for 5a), -893887 (for 5i),

-893897 (for 5l), -894088 (for 5v), -893903 (for 5y), -893907 (for

5nC), -893900 (for 5tC), -895996 (for 5zb), -893901 (for 8cA),

-893905 (for 8gB), -893902 (for 10fA), -893906 (for 11f),

-893904 (for 11j), -893888 (for 12a), -893898 (for 12b), -893899

(for 23) contain the supplementary crystallographic data

for this paper. These data can be obtained free of charge

from The Cambridge Crystallographic Data Centre via

Received: October 18, 2012

Published Online: March 1, 2013

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Eur. J. Org. Chem. 2013, 2362–2380

Article Doi

Construction of functionalized carbocycles having contiguous tertiary carbinol and all-carbon stereogenic centers

DOI: 10.1002/ejoc.201201382

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Article abstract of DOI:10.1002/ejoc.201201382

Full text of DOI:10.1002/ejoc.201201382

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