Synthesis of natural oxygenated monocarbocyclic sesquiterpenoids from 6,7-epoxygeranyl acetate

TETRAHEDRON

Pergamon

Tetrahedron 56 (2000) 6099±6113

Synthesis of Natural Oxygenated Monocarbocyclic

Sesquiterpenoids from 6,7-Epoxygeranyl Acetate

*

Alejandro F. Barrero, Enrique J. Alvarez-Manzaneda, Rachid Chahboun, A. Rodriguez Rivas

and P. Linares Palomino

Â Â

Departamento de Quõmica Organica, Facultad de Ciencias, Instituto de Biotecnologia, Universidad de Granada, 18071 Granada, Spain

Received 15 March 2000; revised 19 May 2000; accepted 8 June 2000

AbstractÐNatural sesquiterpenes 5-(2⁰,5⁰-epoxy-2⁰,6⁰,6⁰-trimethyl)cyclohexyl-3-methyl-1-penten-3-ol (5), cis-3-[(E)-5⁰-hydroxy-3⁰-methyl-

3⁰-pentenyl]-2,2-dimethyl-4-methylenecyclohexanol (elegansidiol) (6), 4-(5⁰-acetoxy-2⁰,6⁰,6⁰-trimethyl)cyclohex-2⁰-enyl-3-methyl-1-

penten-3-ol (7) and 5-acetoxy-3-(3-hydroxy-3-methylpent-4-enyl)-2,4,4-trimethylcyclohex-2-enone (8) were prepared from 6,7-epoxyger-

anyl acetate (9), via (2⁰,5⁰-epoxy-2⁰,6⁰,6⁰-trimethyl)cyclohexylmethyl tosylate (10), for the ®rst time. 5 is an intermediate in the synthesis of

the sesquiterpene-coumarin ether (^)-farnesiferol C (1). The preparation of suitable intermediates for synthesising related natural farnesi-

Introduction

Natural oxygenated monocarbocyclic terpenoids are not

very common because biosynthetic processes usually

involve polycyclization. These compounds have a bicyclic

ether fragment, e.g. farnesiferol C (1)¹or a cyclohexanol

moiety, e.g. achilleol A (2)²and farnesiferol B (3) and D

(4).¹During the last few years the isolation of several mono-

carbocyclic compounds, such as 5, 7, 8^3,4and elegansidiol

(6),⁵have been reported, which suggests that they could be

more prevalent than it was presumed.

Several procedures have been described to create the bicyc-

lic system of 1. Mukaiyama et al. used a Diels±Alder asym-

metric reaction to prepare (1)-farnesiferol C.⁶More

recently, Demnitz et al. reported the formation of the

7-oxabicyclo[2.2.1]heptane ring system through an

unexpected rearrangement in the Baeyer±Villiger oxidation

of trans-3b-hydroxy-4,4,10b-trimethyl-9-decalone.⁷The

present authors have reported the preparation of the same

bicyclic ether system by selective electrophilic cyclization

of 6,7-epoxygeranyl acetate (9); as well as the obtention of

cyclohexanol type structures, such as elegansidiol (6), by

the Lewis acid-mediated opening of the bicyclic ether.^5,8

In this paper the synthesis of 5, 7 and 8, natural sesquiter-

penes isolated from Artemisia species,^3,4and elegansidiol

(6), a constituent from Santolina elegans,⁵via selective

electrophilic cyclization of 6,7-epoxygeranyl acetate (9) is

reported.

Keywords: terpenes; cyclization.

* Corresponding author. Tel.: 134-958-243318; fax: 134-958-243318;

e-mail: afbarre@goliat.ugr.es

PII: S0040-4020(00)00560-3

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A. F. Barrero et al. / Tetrahedron 56 (2000) 6099±6113

Scheme 1.

Results and Discussion

The second route in Scheme 1 involves the reversal of the

reactivity of the C₁of the tosyl derivative 10. Treatment of

10 with PhSH and KH afforded in quantitative yield the

sul®de 16, which was oxidised to the sulfone 17 with

MCPBA. The allylsulfone 18 was obtained by treating 17

with BuLi and HMPA in THF and then with allyl bromide.

Desulfonylation of 18 with 6% Na±Hg in a Na₂HPO₄

buffered solution yielded the allyl derivative 19, besides

signi®cant amounts of the diene derived from the sulfone

elimination (Scheme 3).

Two alternative routes to prepare the methylketone 22,

precursor of 5, from the tosyl derivative 10, which can be

easily synthesised from 9,⁸were proposed. In the ®rst the

side chain carbons are sequentially introduced (1C12C),

using cyanide and acetylide ions as synthons. In the second

route these carbons are simultaneously introduced through

an allyl halide (Scheme 1)

Heating of tosyl derivative 10 with KCN in DMSO yielded

the nitrile 11, which was reduced to the aldehyde 12 by

treating with DIBAL at 2808C in toluene under argon.

Further treatment with NaBH₄afforded the alcohol 13,

which after treating with TsCl and LiBr gave the bromide

14. The internal alkyne 15, instead of the terminal one, was

obtained when 14 was treated with lithium ethynyl±ethyl-

To prevent this problem an alternative route was estab-

lished. This involves the introduction of the side chain

oxygenated function, via epoxidation before reducing the

sulfone group. Treatment of 18 with MCPBA at room

temperature for 3 days yielded the epoxysulfone 20 as a

diastereomeric mixture. The ¹H NMR spectrum of the

crude shows signals due to three of the four possible isomers

in a 3:1:1 ratio. These can be satisfactorily resolved by

column chromatography. Treatment of 20 with LiAlH₄

under re¯ux allows the regioselective opening of the

epoxide and simultaneous desulfonylation, affording the

alcohol 21. This was oxidised with Jones reagent to give

22, which by treating with vinylmagnesium bromide gave 5,

which consists almost exclusively of an epimer. The

1

enediamine complex (Scheme 2). H NMR of 15 shows a

triplet (J2.5 Hz) at d 1.74 due to the Me±C₃. The quater-

nary carbons of the acetylenic group appears at d 75.8 and

79.5 in the ¹³C NMR spectrum. Rearrangement of carbon±

carbon triple bond from the C₃±C₄to the C₂±C₃position

under basic conditions is a known process.⁹15 could be

converted into the methylketone 22 by regioselective hydro-

boration using bulky reagents.

Scheme 2. (i) Ref. 8. (ii) KCN, DMSO, 1358C, 5 h (80%). (iii) DIBAL, Toluene, 2808 to 08C (70%). (iv) NaBH₄, MeOH, 2108C (70%). (v) TsCl, Py, DMAP,

OEt₂, 08C; LiBr, THF, 608C (71%). (vi) LiCCH, EDA, DMSO, 2.5 h (57%).

A. F. Barrero et al. / Tetrahedron 56 (2000) 6099±6113

6101

Scheme 3. (i) PhSH, KH, EtOH, re¯ux, 4 h (92%). (ii) MCPBA, CH₂Cl₂, 08C (98%). (iii) BuLi, HMPA, THF, 2788C; BrCH₂CHvCH₂, rt, Ar, 12 h (77%).

(iv) 6% Na±Hg, Na₂HPO₄, rt, 6 h (37%). (v) MCPBA, CH₂Cl₂, rt, 3 days (90%). (vi) LiAlH₄, THF, re¯ux, 80 h (98%). (vii) Jones, acetone, 08C (89%). (viii)

BrMgCHvCH₂, THF; ClNH₄, (85%).

spectroscopic properties of this compound were identical to

those reported for the natural sesquiterpene⁴(Scheme 3). 5

had been previously reported as an intermediate in the

synthesis of farnesiferol C (1).¹

regiosomers 24 and 25 (ratio 2:1), the combined yield being

higher than 60%. After isolation of the exo isomer and

protection of the secondary hydroxyl group, transformation

of 26 into 28 was achieved under standard conditions.

Nevertheless, all the attempts to condense this aldehyde

with nucleophiles such as 2-oxopropylidentriphenylphos-

phorane were unsuccessful. This dif®culty has also been

described in related structures,¹⁰and can be accounted for

by considering the steric hindrance exerted on the aldehyde

group by both the gem-dimethyl and the exocyclic double

bond.

The synthesis of compounds 6 and 7 was planned through

the cyclohexanol derivatives which result from the BBr₃-

mediated opening of the corresponding bicyclic ether

(Scheme 4).

The synthesis of 6 was ®rst approached by condensation of a

monocyclic synthon C₁₀with an acyclic synthon C₅. The

elaboration of the C₁₀moiety was carried out through elec-

trophilic cyclization of 6,7-epoxygeranyl acetate (9), on the

basis of previous studies by the present authors.⁸Scheme 5

depicts the ®rst synthetic approach using aldehyde 28 as the

C₁₀electrophile synthon. The ef®cient cyclization of 9 to 23

and subsequent opening of the bicyclic ether in anhydrous

conditions, which has been improved, led to a mixture of

The sulfone 29 was therefore studied as a new C₁₀nucleo-

philic synthon. This sulfone was formed starting from the

bicyclic ether 17, which after treating with BBr₃afforded a

mixture of the regioisomers 29 and 31 (ratio 1:1), which

were easily separated by column chromatography. After

protecting the hydroxyl group of 29 as its t-butyldimethyl-

silylether, alkylation of the carbanion generated from 30 by

Scheme 4.

Scheme 5. (i) Ref. 8. (ii) BBr₃, CH₂Cl₂, rt, 10 min; Collidine, CH₂Cl₂(72%). (iii) DHP, PPTS, CH₂Cl₂rt, 6h (85%). (iv) 2N KOH-MeOH, rt, 12 h (90%).

(v) PDC, CH₂Cl₂, rt, 24 h (80%).

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A. F. Barrero et al. / Tetrahedron 56 (2000) 6099±6113

Scheme 6. (i) BBr₃, CH₂Cl₂, rt, 15 min; Collidine (82%). (ii) TBSCl, imidazole, DMF, DMAP. rt, 10 h (87%). (iii) (a) n-BuLi, THF, 08C, 30 min; rt, 45 min.

(b) propylene oxide, rt, 1 h; 658C, 45 min. (c) 6% Na±Hg, Na₂HPO₄, EtOH, re¯ux, 6 h. (d) Jones, acetone, 08C, 30 min (70% overall yield). (iv) (a) n-BuLi,

THF, 08C, 30 min; rt, 45 min. (b) propylene oxide, rt, 1 h; 658C, 45 min. (c) Jones, acetone, 08C, 30 min (82% from 30). (v) Alumina, THF, rt, 2 h (95%). (vi)

Raney Ni, THF, rt, 30 min (92%). (vii) BrMgCHvCH2, THF, 08C, 30 min (95%). (viii) Ac₂O, Et₃N, DMAP, THF, re¯ux, 26 h (90%). (ix) PdCl₂(CH₃CN)₂,

THF, rt, 45 min (95%). (x) KOH, MeOH, rt, 45 min (94%). (xi) TBAF, THF rt, 6 h 89%).

treatment with butyllithium was attempted with a C₅allylic

bromide, the tetrahydropyranyl derivative of 4-bromo-3-

methyl-2(E)-butenol. Unfortunately, the use of the mono-

carbocycle as the nucleophile did not lead to a successful

reaction. In fact, at room temperature starting materials

remained unaltered and only decomposition of the allylic

derivative was observed after heating (Scheme 6).

amalgam and further oxidation of the hydroxyl group with

Jones reagent. In the second method oxidation of the

hydroxyl group was ®rst carried out, affording the ketosul-

fone 32, which was transformed into 34 by using a new

methodology developed by the present authors.¹¹Column

chromatography on alumina of 32 yielded the a,b-unsatu-

rated ketone 33, which was chemoselectively reduced with

Raney Ni to give 34. This ketone afforded the allylic alcohol

35 after being exposed to vinylmagnesium bromide. 35 is a

suitable intermediate for synthesizing (^)-farnesiferol B

(3).¹Acetate 36 underwent allylic rearrangement after treat-

ment with palladium dichloride bis acetonitrile to afford the

carbon skeleton of elegansidiol. Saponi®cation of the ester

This task could only be accomplished by treatment of the

sulfone anion with the much more stable propylene oxide at

658C to give a b-hydroxysulfone which was converted into

the ketone 34 following two alternative methods. The ®rst

involves the reduction of the sulfone group with sodium

Scheme 7. (i) BBr₃, CH₂Cl₂, rt, 1 h; Et₃N (87%). (ii) TBSCl, imidazole, DMF, DMAP, rt, 10 h (80%). (iii) (a) n-BuLi, THF, 08C, 30 min; rt, 45 min. (b)

propylene oxide, rt, 1 h; 658C, 15 min (85%). (iv) Jones, acetone, 08C, 30 min (90%). (v) Alumina, THF, rt, 4 h (98%). (vi) Raney Ni, THF, rt, 30 min (95%).

(vii) BrMgCHvCH₂, THF, 08C, 30 min (93%). (viii) TBAF, THF, rt, 4 h (81%). (ix) Ac₂O, Py, rt, 4 h (83%).

A. F. Barrero et al. / Tetrahedron 56 (2000) 6099±6113

6103

Scheme 8. (i) Ac₂O, Py, rt 6 h (95%). (ii) BBr₃, CH₂Cl₂, rt, 15 min; Collidine (89%). (iii) TBSCl, DMF, Imidazole, DMAP, rt, 44 h (95%). (iv) Na₂CrO₄,

NaOAc, Ac₂O, AcOH, Benzene, 658C, 3 h (88%).(v) K₂CO₃, MeOH, rt, 1 h (95%). (vi) 2 N KOH±MeOH, rt, 24 h (93%). (vii) Jones, acetone, 08C. (viii)

Jones, acetone, 2158C, 30 min (96%). (ix) BrMgCHvCH₂, THF, 2158C, rt, 45 min (87%). (x) TBAF, THF, 08C, rt, 2 h (81%). (xi) Ac₂O, Py, rt, 1 h (93%).

group and ¯uoride-induced cleavage of the silyl ether

completed the synthesis of 6, whose spectroscopic proper-

ties were identical to those of the natural product.⁵

obtained as a mixture of diastereomers. The spectroscopic

properties of 8 were identical to those of an authentic

sample (Scheme 8).

Sesquiterpene 7 was synthesised from sulfone 31, which

was obtained as the sole product when the BBr₃-induced

opening of 17 was quenched with Et₃N, following a similar

procedure to the above described for elegansidiol (6)

(Scheme 7). 44 could be easily converted into (^)-farnesi-

ferol D (4).¹At this time it should be pointed out that the

side chain carbon of endocyclic isomer 31 seems to be less

hindered than that of exocyclic compound 29. So, treatment

of the mixture of anions derived from regioisomers 29±31

with allyl bromide afforded the alkylated endo-alkene,

being 29 recovered unaltered. 44 was converted into the

mixture of diastereomers 7 after removal of the tert-butyl-

dimethylsilyl group and acetylation of the hydroxyl group.

The spectroscopic properties of the major epimer were

identical to those reported for the natural product.

In summary the monocarbocyclic terpenoids, 5±8, have

been synthesised from 6,7-epoxygeranyl acetate (9). The

key step in the synthesis of cyclohexenol derivatives, as

6±8, is the regioselective opening of the bicyclic ether

with BBr₃. The course of this reaction seems to depend on

the nature of the ether side chain as well as on the base used

to quench the reaction. Thus, bicyclic ethers having a polar

group at the carbon adjacent to the ring give mixtures of tri-

and disubstituted alkenes, when collidine is used as base;⁸

the use of the less hindered Et₃N affords the trisubstituted

carbon±carbon double bond almost exclusively (Scheme 7).

However, the tetrasubstituted alkene is obtained when the

side chain is longer and the polar group is distant from the

ring (Scheme 8).

Scheme 8 shows the synthetic sequence to 8. It is based on

the surprising behaviour of bicyclic ether 46 towards BrB₃,

which underwent regioselective opening to give the cyclo-

hexenol derivative 47. Oxidation at C₅was carried out after

protecting the hydroxyl group as a tert-buthyldimethylsilyl

ether. Treatment of 48 with Na₂CrO₄yielded the enone 49.

This compound is very reactive towards elimination

processes. When it was treated with 2N KOH±MeOH at

room temperature dienone 51 was obtained as the only

product. Its ¹H NMR spectrum shows two doublets

(J9.9 Hz) at d 6.19 and 6.72 due to the ole®nic protons.

Oxidation of 51 with Jones reagent gave the diketone 52,

which exhibited a simple spectrum. Treatment of 49 with

K₂CO₃in MeOH afforded the alcohol 50, which was

oxidized with the Jones reagent at 2158C to give the

diketone 53. When 53 was treated with vinylmagnesium

bromide in Et₂O at 2158C the allylic alcohol 54 was

obtained. Deprotection of the silyl ether with TBAF gave

the diol 55, which after acetylation was converted into 8,

Experimental

Melting points were determined with a Ko¯er hot stage

melting point apparatus and are uncorrected. IR spectra

were obtained on Perkin±Elmer Models 782 and 983G

spectrometers with samples between sodium chloride plates

or as potassium bromide pellets. Proton nuclear magnetic

resonance spectra were taken on a Bruker AMX 300

(300 MHz), Bruker ARX 400 (400 MHz) and Bruker

AMX 500 (500 MHz) spectrometers using CDCl₃, and

CD₃COCD₃as solvent and TMS or residual protic solvent

CHCl₃(d_H7.25 ppm) as internal reference, and the multi-

plicity of a signal is a singlet unless otherwise stated, when

the following abbreviations are used: s, singlet; bs, broad

singlet; d, doublet; bd, broad doublet; dd, double doublet; t,

triplet; m, multiplet. ¹³C NMR spectra were run on a Bruker

AMX 300 (75 MHz), ARX 400 (100 MHz) and AMX 500

(125 MHz) instruments. Chemical shifts are in ppm (d

scale) and the coupling constants are in Hertz. Carbon

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A. F. Barrero et al. / Tetrahedron 56 (2000) 6099±6113

substitution degrees were established by DEPT pulse

sequence. MS were recorded on a Hewlett±Packard

5988A spectrometer using an ionizing voltage of 70 eV.

HRMS were obtained on a trisector WG AutoSpecQ spec-

trometer. For analytical TLC Merck silica gel 60G in

0.25 mm thick layers was used. Chromatographic separa-

tions were carried out by conventional column on Merck

silica gel 60 (70±230 mesh) and by ¯ash column on Merck

silica gel 60 (230±400 mesh) using hexane±MeO^tBu (H±E)

mixtures of increasing polarity. Routinely, dry organic

solvents were stored under argon, over freshly activated

molecular sieves. Ether, benzene, and THF, were dried

over sodium-benzophenone ketyl, HMPA from Na,

dichloromethane over calcium hydride, and methanol

from magnesium methoxide. Where necessary reactions

were carried out under a nitrogen or argon atmosphere.

mixture was stirred at 08C for 70 min. Then it was diluted

with ether (100 ml), washed with water, sat. NaCl, and

dried, to yield after concentration 1.26 g of 13 (70%)

(colourless oil). IR (®lm): 3422 (OH), 2950, 2855,

1097 cm²¹. MS m/z (rel. int.): 184 [M¹] (1), 169

[M¹2Me](30), 166 [M¹2H₂O](2), 153 [M¹2Me±

H₂O](20). ¹H NMR (CDCl₃, 300 MHz): 3.65 (1H, d,

J5.5 Hz, H-5⁰), 3.50 (2H, m, H-1), 1.90 (1H, ddd,

J12.6, 8.7, 4.5 Hz, H-3⁰), 1.68±1.35 (4H, m), 1.25 (3H,

s, Me±C₂), 0.96 (3H, s, Me±C₆), 0.92 (3H, s, Me±C₆). ¹³C

NMR (CDCl₃, 75 MHz): 62.4 (1), 31.0 (2), 51.8 (1⁰), 86.6

(2⁰), 38.7 (3⁰), 25.6 (4⁰), 85.9 (5⁰), 45.0 (6⁰), 18.7 (7⁰), 23.6

(8⁰), 25.7 (9⁰). HREIMS m/z calcd for C₁₁H₂₀O₂M¹

184.1463, found 184.1472.

0

2-(2⁰,5⁰-Epoxy-2⁰,6⁰,6⁰-trimethyl)cyclohexyl-1-bromo-

ethane (14). To a stirred solution of 13 (1.125 g, 6.1 mmol)

in THF (3 ml), pyridine (7 ml), dimethylamino pyridine

(DMAP) (20 mg, 0.16 mmol) and TsCl (1.79 g,

8.65 mmol) were successively added at 258C and the

mixture was stirred at this temperature for 2 h 30 min. At

the end of this period a solution of lithium bromide (2.62 g,

30.5 mmol) in THF (26 ml) was added, and the mixture was

heated at 608C for 2 h. After dilution with ether (100 ml),

the mixture was successively washed with 5% NaHSO₄

solution, 5% NaHCO₃solution, water, sat. NaCl and then

dried. Concentration and chromatography (H±E 9:1) gave

1.07 g of 14 (71%) as a colourless oil. IR (®lm): 2925, 2850,

1085 cm²¹. MS m/z (rel. int.): 231, 233 [M¹2Me] (5, 5),

228(15), 230 [M¹2H₂O](1, 1), 167 [M¹2Br](3). ¹H NMR

(CDCl₃, 300 MHz): 3.73 (1H, d, J5.0 Hz, H-5⁰), 3.37 (2H,

m, H-1), 2.75±2.₀36 (4H, m, H-3⁰, H-4⁰, H-6⁰), 1.98±1.84

2-(2⁰,5⁰-Epoxy-2⁰,6⁰,6⁰-trimethyl)cyclohexyl acetonitrile

(11). To a solution of 10 (0.7 g, 2.18 mmol) in dimethylsulf-

oxide (DMSO) (30 ml), was added 0.79 g of KCN

(12.04 mmol) and the mixture was heated at 1358C for

5 h. The mixture was fractionated in H₂O±ether (100 ml)

and extracted with ether (3£50 ml). The dried organic

phases were evaporated and the residue was ®ltered through

silica gel to afford 0.31 g of 11 (79%) as a colourless oil. IR

(®lm): 2245(CN), 1024, 990 cm²¹. MS m/z (rel. int.): 179

1

[M¹] (6), 165 [M¹2N](8), 164 [M¹2Me](73). H NMR

(CDCl₃, 300 MHz): 3.79 (1H, d, J5.5 Hz, H-5⁰), 2.30

(1H, dd, J16.6, 7.2 Hz, H-2), 2.26 (1H, dd, J16.6,

8.6 Hz, H-2), 1.95 (1H, ddd, J12.7, 8.7, 4.5 Hz, H-3⁰),

1.80±1.50 (4H, m, H-3⁰, H-4⁰, H-6⁰), 1.38 (3H, s, Me±

C₂), 1.15 (3H, s, Me±C₆), 1.09 (3H, s, Me±C₆). ¹³C

NMR (CDCl₃, 75 MHz): 120.3 (1), 15.7 (2), 52.9 (1⁰),

85.9 (2⁰), 37.8 (3⁰), 25.9 (4⁰), 86.2 (5⁰), 45.1 (6⁰), 25.7

(7⁰), 23.3 (8⁰), 18.4 (9⁰). HREIMS m/z calcd for C₁₁H₁₇ON

M¹179.1310, found 179.1318.

0

(2H, m, H-2, H-3 ), 1.31 (3H, s, Me±C₂), 1.05 (3H, s, Me±

0

C₆), 0.99 (3H, s, Me±C₆). HREIMS m/z calcd for

C₁₁H₁₉OBr M¹246.0619, found 246.0627.

1-(2⁰,5⁰-Epoxy-2⁰,6⁰,6⁰-trimethyl)cyclohexyl-2-butyne (15).

A solution of lithium acetylide ethylenediamine complex

(0.49 g, 5.08 mmol) in anhydrous DMSO (20 ml) was

added to a solution of the bromide 14 (0.25 g, 1.02 mmol)

in DMSO (20 ml). The whole was heated at 408C and stirred

for 2 h 30 min, then it was quenched with water (20 ml), and

stirred for an additional 10 min. The mixture was extracted

with ether (25 ml£4) and the combined extracts were

washed with sat. NaCl, dried, and concentrated to give

after cromatography of the crude (H±E 7:3) 0.11 g of 15

(57%) as a colourless oil. IR (®lm): 1086, 908 cm²¹. MS m/z

(rel. int.): 192 [M¹] (7), 177 [M¹2Me](56), 162

[M¹22Me](22) [M¹2H₂O±Me](10). ¹H NMR (CDCl₃,

300 MHz): 3.56 (1H, d, J5.1 Hz, H-5⁰), 2.14 (2H, m, H-

1), 1.90 (1H, ddd, J12.6, 8.7, 4.5 Hz), 1.75±1.35 (4H, m),

2-(2⁰,5⁰-Epoxy-2⁰,6⁰,6⁰-trimethyl)cyclohexyl acetaldehyde

(12). DIBAH (1 M in hexane, 20 ml, 20 mmol) was added

to a solution of 11 (1.5 g, 8.37 mmol) in toluene (30 ml) at

2788C, and the whole mixture was slowly warmed to 08C

for 8 h, stirred at this temperature for an additional 5 h. 5%

NH₄Cl solution (25 ml) was added to the mixture and then

diluted with ether (100 ml). The organic layers were washed

with 1 M HCl, sat. NaCl and dried. Concentration gave a

crude which was directly puri®ed by ¯ash chromatography

(H±E 8:2) to yield 1.07 g of the aldehyde 12 (70%), as a

colourless oil, and 0.27 g (18%) of starting material. IR

(®lm): 2722, 1724, 1022 cm²¹. MS m/z (rel. int.): 182

1

[M¹] (2), 167 [M¹2Me](8), 164 [M¹2H₂O](2). H NMR

(CDCl₃, 300 MHz): 9.83 (1H, t, J1.3 Hz, H-1), 3.79 (1H,

d, J5.1 Hz, H-5⁰), 2.44 (1H, ddd, J18.2, 7.5, 1.3 Hz,

1.74 (3H, t, J2.5 Hz, Me-4), 1.31 (3H, s, Me±C₂), 1.08

0

H-2), 2.42 (1H, ddd, J18.2, 7.5, 1.3 Hz, H-2), 1.92 (1H,

(3H, s, Me±C₆), 1.07 (3H, s, Me±C₆). ¹³C NMR (CDCl₃,

75 MHz): 114.5 (1), 138.9 (2), 33.9 (3), 27.9 (4) 55.1 (1⁰),

86.7 (2⁰), 39.0 (3⁰), 25.8 (4⁰), 86.1 (5⁰), 45.3 (6⁰), 18.9 (7⁰),

23.4 (8⁰), 26.1 (9⁰). HREIMS m/z calcd for C₁₃H₂₀O M¹

192.1514, found 192.1522.

0

m, H-3 ), 1.75±1.42 (4H, m), 1.29 (3H, s, Me±C₂), 1.06

(3H, s, Me±C₆), 0.91 (3H, s, Me±C₆). ¹³C NMR (CDCl₃,

75 MHz): 202.5 (1), 43.1 (2), 50.3 (1⁰), 86.2 (2⁰), 37.9 (3⁰),

26.2 (4⁰), 86.1 (5⁰), 44.7 (6⁰), 18.9 (7⁰), 24.7 (8⁰), 25.7 (9⁰).

HREIMS m/z calcd for C₁₁H₁₈O₂M¹182.1307, found

182.1295.

0

(2⁰,5⁰-Epoxy-2⁰,6⁰,6⁰-trimethyl)cyclohexylmethyl phenyl

thioether (16). To a stirred suspension of KH (35% in oil,

1.45 g, 0.0126 mol) in ethanol (20 ml), thiophenol (1.33 g,

0.0126 mol) was added and the mixture was stirred for

15 min. Then a solution of 10 (1.95 g, 6.018 mmol) in

2-(2⁰,5⁰-Epoxy-2⁰,6⁰,6⁰-trimethyl)cyclohexyl ethanol (13).

NaBH₄(0.38 g, 10 mmol) was added to a solution of 12

(1.8 g, 9.9 mmol) in methanol (20 ml) at 2108C and the

A. F. Barrero et al. / Tetrahedron 56 (2000) 6099±6113

6105

ethanol (5 ml) was added, and the whole was heated under

re¯ux for 4 h. After removing the solvent, the residue was

taken up into ether, and the insoluble material was removed

by ®ltration. Concentration and column chromatography

(H±E 8:2) afforded 16 (1.45 g, 92%) (colourless oil). IR

(®lm): 2000, 1600, 1582, 1478, 1437, 1090, 937, 738,

690 cm²¹. MS m/z (rel. int.): 262 [M¹] (2), 153

(5H, m), 1.55±1.38 (2H, m), 1.61 (3H, s, Me-9⁰), 0.92

(3H, s, Me-8⁰), 0.76 (3H, s, Me-7⁰). ¹³C NMR (CDCl₃,

75 MHz): 116.8 (1), 135.9 (2), 41.2 (3), 66.3 (4), 53.9(1⁰),

87.3 (2⁰), 30.3 (3⁰), 25.7 (4⁰), 85.0 (5⁰), 47.9 (6⁰), 20.3 (7⁰),

24.9 (8⁰), 24.3 (9⁰), 139.1 (1⁰⁰), 129.3 (2⁰⁰-6⁰⁰), 128.9 (3⁰⁰-5⁰⁰),

133.7 (4⁰⁰). HREIMS m/z calcd for C₁₉H₂₆O₃S M¹

334.1602, found 334.1595.

1

[M¹2SPh] (100). H NMR (CDCl₃, 300 MHz): 7.22 (5H,

bs, Ph), 3.71 (1H, d, J7.0 Hz, H-5⁰), 2.95 (1H, dd, J12.0

and 7.0 Hz, H-1), 2.79 (1H, dd, J15.0 and 12.0 Hz, H-1),

1.95±1.40 (5H, m), 1.32 (3H, s, Me-9⁰), 1.1 (3H, s, Me-8⁰),

1.05 (3H, s, Me-7⁰). ¹³C NMR (CDCl₃, 75 MHz): 32.7 (1),

54.8 (1⁰), 86.8 (2⁰), 38.5 (3⁰), 25.7 (4⁰), 85.9 (5⁰), 45.7 (6⁰),

18.7 (7⁰), 22.9 (8⁰), 25.8 (9⁰), 137.6 (1⁰⁰), 128.5 (2⁰⁰), 128.8

(3⁰⁰), 125.6 (4⁰⁰), 128.8 (5⁰⁰), 128.5 (6⁰⁰). HREIMS m/z calcd

for C₁₆H₂₂OS M¹262.1391, found 262.1403.

4-(2⁰,5⁰-Epoxy-2⁰,6⁰,6⁰-trimethyl) cyclohexyl-1-butene (19).

To a solution of the sulphone 18 (0.7 g, 2.095 mmol) in

anhydrous ethanol (25 ml), Na₂HPO₄(1.2 g, 8.38 mmol)

and 6% Na±Hg (3.23 g, 8.43 mmol) was added and the

whole was heated under re¯ux for 6 h. It was cooled to

room temperature and the mixture poured into a 1 M HCl

solution, and extracted with ether (4£25 ml). The combined

extracts were washed with 10% NaHCO₃, water, sat. NaCl,

and then dried. Concentration and chromatography (hex-

ane±ether, 8:2) gave 0.15 g of 19 (36.9%) (colourless oil).

IR (®lm): 3070, 1638, 1081, 1005, 995, 910, 909 cm²¹. MS

m/z (rel. int.): 194 [M¹] (1), 179 [M¹2Me](5), 161

[M¹2Me-H₂O](4). ¹H NMR (CDCl₃, 300 MHz):, 4.97

(1H, ddt, J16.7, 9.0, 6.6 Hz, H-2), 5.02 (1H, dq, J16.7,

1.2 Hz, H-1trans), 4.97 (1H, dq, J9.0, 1.2 Hz, H-1cis),

3.74 (1H, d, J5.7 Hz, H-5⁰), 2.15±1.90 (m, 3H), 1.80±

1.60 (m, 2H), 1.60±1.20 (m, 4H), 1.34 (3H, s, Me-9⁰),

1.07 (3H, s, Me-8⁰), 1.03 (3H, s, Me-7⁰). ¹³C NMR

(CDCl₃, 75 MHz): 114.5 (1), 138.9 (2), 33.9 (3), 27.9 (4),

55.1(1⁰), 86.7 (2⁰), 39.0 (3⁰), 25.8 (4⁰), 86.1 (5⁰), 45.3 (6⁰),

18.9 (7⁰), 23.4 (8⁰), 26.1 (9⁰). HREIMS m/z calcd for

C₁₃H₂₂O M¹194.1670, found 194.1681.

(2⁰,5⁰-Epoxy-2⁰,6⁰,6⁰-trimethyl)cyclohexylmethyl phenyl

sulphone (17). A solution of 85% m-chloroperbenzoic

acid (MCPBA) (0.99 g, 5.72 mmol) in CH₂Cl₂(12 ml)

was slowly added at 08C to a solution of 16 (0.6 g,

2.3 mmol) in CH₂Cl₂(12 ml). After stirring at rt for 1 h,

the mixture was concentrated, and the residue was taken

up in CHCl₃(50 ml), washed successively with sat.

NaHCO₃and brine (2£30 ml). The ethereal phase was

dried over anh Na₂SO₄, ®ltered and evaporated under

vacuum to give a crude mixture which after chromatography

(H±E 1:9) yielded 17 (660 mg, 98%) as a colourless oil. IR

(®lm): 2000, 1600, 1589, 1307, 1150, 1070, 938, 738,

690 cm²¹. MS m/z (rel. int.): 294 [M¹] (1), 153

[M¹2SO₂Ph](100), 135 [M¹2SO₂Ph±H₂O](43). ¹H

NMR (CDCl₃, 300 MHz): 7.88 (2H, d, J8.3 Hz, H-3⁰⁰and

5⁰⁰), 7.64 (1H, d, J6.9 Hz, H-4⁰⁰), 7.54 (2H, d, J7.2 Hz,

H-2⁰⁰and 6⁰⁰), 3.79 (1H, d, J5.3 Hz, H-5⁰), 3.10 (2H, dd,

J4.5 and 1.5 Hz, H-1), 1.89 (2H, m), 1.70 (1H, m), 1.59

(1H, m), 1.47 (1H, m), 1.28 (3H, s, Me-9⁰), 1.08 (3H, s,

Me-8⁰), 1.05 (3H, s, Me-7⁰). ¹³C NMR (CDCl₃, 75 MHz):

55.1 (1), 49.9 (1⁰), 86.3 (2⁰), 38.5 (3⁰), 25.9(4⁰), 86.2 (5⁰),

45.6 (6⁰), 19.3 (7⁰), 24.7 (8⁰), 24.8 (9⁰), 140.2 (1⁰⁰), 129.4

(2⁰⁰), 127.9 (3⁰⁰), 133.7 (4⁰⁰), 127.9 (5⁰⁰), 129.4 (6⁰⁰). HREIMS

m/z calcd for C₁₆H₂₂O₃S M¹294.1289, found 294.1278.

4-(2⁰,5⁰-Epoxy-2⁰,6⁰,6⁰-trimethyl) cyclohexyl-4-phenyl-

sulphonyl-1,2-epoxybutene (20). A solution of allyl

sulphone 18 (2.56 g, 8 mmol) and 85% m-chloroperbenzoic

acid (MCPBA) (1.85 g, 10.4 mmol) in CH₂Cl₂(50 ml), was

stirred at room temperature for 77 h. After concentration,

the residue was taken up into ether (150 ml) and washed

successively with sat. NaHCO₃, sat. NaCl and dried.

Concentration and chromatography (H±E 1:1) of the

crude gave 1.3 g of the mixture of epoxysulphone 20a and

20b and 1.1 g of epoxysulphone 20c, as colourless oils.

20a±c IR (KBr): 1582, 1449, 1300, 1145, 1086,

876 cm²¹. 20a±c MS m/z (rel. int.) of 20a±c: 350. [M¹]

(0.02), 209 [M¹2SO₂Ph](75), 161 [M¹2SO₂Ph±H₂O](12).

4-(2⁰,5⁰-Epoxy-2⁰,6⁰,6⁰-trimethyl) cyclohexyl-4-phenyl-

sulphonyl-1-butene (18). n-Butyl lithium (2.26 M in

hexane, 11.3 ml, 2.94 mmol) and 5.2 ml of HMPA, was

added to a solution of 17 (0.83 g, 2.82 mmol) in 30 ml of

THF at 2788C, and the whole mixture was slowly warmed

to 08C and stirred for 1 h. A solution of allyl bromide

(3.41 g, 0.028 mol) was added at 2788C to this mixture

and stirred for 12 h. After addition of sat. NH₄Cl the mixture

was diluted with ether (100 ml), washed with 5% HCl,

water, sat. NaHCO₃, and sat. NaCl and the organic layer

was dried. Concentration and chromatography (H±E 1:1)

gave 0.73 g of 18 (77%) as a colourless oil. IR (®lm):

1639, 1584, 1303, 1146, 1085, 999, 918 cm²¹. MS m/z

(rel. int.): 334 [M¹] (1), 193 [M¹2SO₂Ph](100), 175

[M¹2SO₂Ph±H₂O](30). ¹H NMR (CDCl₃, 300 MHz):

7.87 (2H, d, J8.3 Hz, H-3⁰⁰and 5⁰⁰), 7.62 (1H, d,

J6.9 Hz, H-4⁰⁰), 7.54 (2H, dt, J7.2 Hz, H-2⁰⁰and 6⁰⁰),

5.44 (1H, ddd, J17.1, 10.1 and 5.6 Hz, H-2), 4.87 (1H,

dd, J17.1 and 1.6 Hz, H-1trans), 4.80 (1H, dd, J10.1

and 1.6 Hz, H-1cis), 3.81 (1H, d, J4.9 Hz, H-5⁰), 2.85

(1H, dddd, J7.5, 7.0, 5.7 and 1.4 Hz, H-4), 1.90±1.62

1

20a±b H NMR (CDCl₃, 300 MHz): Signals assignable to

20a 3.76 (1H, d, J4.9 Hz, H-5⁰), 3.73 (1H, dd, J4.7 and

4.2 Hz, H-1), 3.41 (1H, d, J10 Hz, H-4), 3.11 (1H, m,

H-2), 2.52 (1H, dd, J5.0 and 2.6 Hz, H-1), 2.12 (1H, dd,

J15.9 and 7.6 Hz, H-3), 1.87 (1H, s, H-1⁰), 1.60 (3H, s,

Me-9⁰), 0.99 (3H, s, Me-8⁰), 0.60 (3H, s, Me-7⁰). Signals

assignable to 20b: 3.80 (1H, d, J5.1 Hz, H-5⁰), 3.71 (1H,

dd, J10.3, 2.1 Hz, H-1), 2.42 (1H, dd, J4.9, 2.4 Hz, H-1),

2.00 (1H, d, J2.1 Hz, H-1⁰), 1.60 (3H, s, Me-9⁰), 0.99 (3H,

s, Me-8⁰), 0.60 (3H, s, Me-7⁰). 20a±b ¹³C NMR (CDCl₃,

75 MHz): 41.3 (1), 63.2 (2), 47.8 (3), 51.0 (4), 53.9(1⁰), 86.9

(2⁰), 28.2 (3⁰), 25.5 (4⁰), 84.8 (5⁰), 47.7 (6⁰), 20.1 (7⁰), 24.2

(8⁰), 25.1 (9⁰) 138.5 (1⁰⁰), 129.3 (2⁰⁰-6⁰⁰), 128.9 (3⁰⁰-5⁰⁰), 133.9

(4⁰⁰). 20c ¹H NMR (CDCl₃, 300 MHz): 3.80 (1H, d,

J5.0 Hz, H-5⁰), 3.20 (1H, d, J8.8 Hz, H-4), 2.90 (1H,

m, H-2), 2.75 (1H, ddd, J15.9, 8.8, 3.6 Hz, H-3), 2.72

(1H, t, J4.9 Hz, H-1), 2.60 (1H, dd, J4.9, 2.6 Hz, H-1),

2.21 (1H, dd, J15.9, 7.3 Hz, H-3), 1.54 (3H, s, Me-9⁰),

0.98 (3H, s, Me-8⁰), 0.73 (3H, s, Me-7⁰). ¹³C NMR

6106

A. F. Barrero et al. / Tetrahedron 56 (2000) 6099±6113

(CDCl₃, 75 MHz): 41.3 (1), 63.5 (2), 48.4 (3), 51.6 (4), 53.6

(1⁰), 86.8 (2⁰), 29.0 (3⁰), 25.4 (4⁰), 84.6 (5⁰), 47.6 (6⁰), 20.0

(7⁰), 23.6 (8⁰), 24.8 (9⁰) 138.4 (1⁰⁰), 129.2 (2⁰⁰-6⁰⁰), 128.5

(3⁰⁰-5⁰⁰), 133.6 (4⁰⁰). 20a±c HREIMS m/z calcd for

C₁₉H₂₆O₄S M¹350.1551, found 350.1543.

(rel. int.): 238 [M¹] (1), 195 [M¹2Me] (9), 220 [M¹2H₂O]

(1), 205 [M¹2H₂O±Me] (9), 43 [M¹2 C₂H₃O¹] (100). ¹H

NMR (CDCl₃, 300 MHz): 5.90 (1H, dd, J17.4, 10.8 Hz,

H-2), 5.20 (1H, d, J17.4 Hz, H-1), 5.05 (1H, d,

J10.8 Hz, H-1), 3.70 (1H, d, J5.4 Hz, H-5⁰), 1.90 (1H,

m), 1.68 (1H, m), 1.60±1.20 (6H, m), 1.28 (3H, s, Me-3),

1.31 (3H, s, Me-9⁰), 1.15 (1H, m), 1.03 (3H, s, Me-8⁰), 0.99

(3H, s, Me-7⁰). ¹³C NMR (CDCl₃, 75 MHz): 111.9 (1),

145.1 (2), 73.6 (3), 42.5 (4), 21.9 (5), 56.2(1⁰), 86.8 (2⁰),

39.0 (3⁰), 25.8 (4⁰), 86.1 (5⁰), 45.4 (6⁰), 19.0 (7⁰), 23.4 (8⁰),

26.2 (9⁰). HREIMS m/z calcd for C₁₅H₂₆O₂M¹238.1933,

found 238.1920.

4-(2⁰,5⁰-Epoxy-2⁰,6⁰,6⁰-trimethyl) cyclohexyl-2-butanol

(21). To a cold (08C) solution of epoxysulphone 20 (2.4 g,

7 mmol)) in THF (42 ml) lithium aluminium hydride

(2.68 g, 6 mmol) was added under argon atmosphere. The

reaction mixture was stirred for 72 h at room temperature

and further 12 h under re¯ux. This mixture was diluted with

ether (100 ml), and poured into water-ice. The mixture was

®ltered, and the ether layer separated and successively

washed with sat. NaCl and dried. Concentration and

chromatography (hexane±ether, 6:4) gave 1.47 g of 21a±b

(98%) (colourless oil). IR (®lm): 3406, 2871, 1071,

938 cm²¹. MS m/z (rel. int.): 212 [M¹] (4), 197 [M¹2

Me](19), 123 [M¹2C₅H₁₁O](18), 43 [M¹2C₂H₃O¹]

3-Acetyloxymethyl-2,2-dimethyl-4-methylenecyclohexa-

nol (24) and 3-acetyloxymethyl-2,2,4-trimethylcyclohex-

4-enol (25). To a stirred solution of 23 (1.27 g, 0.69 mmol)

in dry CH₂Cl₂(100 ml) a solution of freshly distilled BBr₃

(1.62 g, 6.46 mmol) in dry CH₂Cl₂(25 ml) was added drop-

wise. After stirring at room temperature under nitrogen for

10 min, the mixture was added to a 1 M solution of distilled

collidine in CH₂Cl₂(25 ml). The mixture was washed with

1 M HCl (3£50 ml) and saturated NaHCO₃(3£50 ml).

Organic layers were dried over anh. Na₂SO₄and evaporated

affording a crude (1.10 g), which after column chroma-

tography (H±E 1:1) yielded 0.91 g (72%) of a mixture of

regioisomers 24and 25 (ratio 2:1). Compounds 24 and 25

were further separated by AgNO₃±SiO₂1:5 column chro-

matography. 24 (colourless oil) IR (®lm): 3462, 1646, 1736,

1236 cm²¹. MS: m/z (%)153 (2), 137 (7), 123 (10), 119

(31), 107 (18), 93 (23), 57(6), 43(100). ¹H NMR

(300 MHz): 4.86 (1H, bs, H-9), 4.60 (1H, bs, H-9), 4.36

(1H, dd, J11.3, 9.1 Hz, H-1⁰), 4.30 (1H, dd, J11.3,

4.3 Hz, H-1), 2.38 (1H, ddd, J11.5, 5.6, 4.9 Hz, H-1),

2.20±2.02 (2H, m), 1.99 (3H, s, MeCOO), 1.85 (1H, m),

1.70 (1H, s, OH), 1.55 (1H, m), 1.04 (3H, s, Me-7), 0.82

(3H, s, Me-8). ¹³C NMR (75 MHz): 76.6 (1), 39.3 (2), 50.7

(3), 145.6 (4), 31.1 (5), 31.4 (6), 17.4 (7), 20.1 (8), 109.9 (9),

62.2 (1⁰), 171.3 (MeCOO), 21.1 (MeCOO). HREIMS m/z

calcd for C₁₂H₂₀O₃M¹212.1412, found 212.1421. 25

1

(100). H NMR (CDCl₃, 300 MHz): 1.70±1.15 (18H, m).

Signals assignable to 21a: 3.75 (1H, m, H-2), 3.69 (1H, d,

J5.3 Hz, H-5⁰), 1.31 (3H, s, Me-9⁰), 1.19 (3H, d,

J4.1 Hz, Me-1), 1.04 (3H, s, Me-8⁰), 0.99 (3H, s, Me-

7⁰).¹³C NMR (CDCl₃, 75 MHz): 19.9 (1), 68.4 (2), 39.6

(3), 23.5 (4), 56.1(1⁰), 86.8 (2⁰), 39.1 (3⁰), 25.6 (4⁰), 86.1

(5⁰), 39.7 (6⁰), 18.9 (7⁰), 23.3 (8⁰), 26.1 (9⁰). Signals assign-

able to 21b: 3.75 (1H, m, H-2), 3.69 (1H, d, J5.3 Hz, H-

5⁰), 1.31 (3H, s, Me-9⁰), 1.20 (3H, d, J4.1 Hz, Me-1), 1.04

(3H, s, Me-8⁰), 0.99 (3H, s, Me-7⁰).¹³C NMR (CDCl₃,

75 MHz): 19.9 (1), 68.3 (2), 39.4 (3), 23.6 (4), 55.9(1⁰),

86.7 (2⁰), 39.0 (3⁰), 25.6 (4⁰), 86.1 (5⁰), 39.7 (6⁰), 18.9

(7⁰), 23.4 (8⁰), 26.1 (9⁰). HREIMS m/z calcd for C₁₃H₂₄O₂

M¹212.1776, found 212.1785.

4-(2⁰,5⁰-Epoxy-2⁰,6⁰,6⁰-trimethyl) cyclohexyl-2-butanone

(22). A 3 M solution of Jones reagent (0.1 ml) was added

dropwise to a stirred solution of 21 (0.35 g, 2 mmol) in

acetone (15 ml) at 08C, and the mixture stirred at room

temperature for 30 min. It was diluted with water (10 ml)

and extracted with ether (3£20 ml). The combined layers

were washed with sat. NaCl (5£20 ml) and dried. Concen-

tration gave 0.31 g of 22 (89%) (colourless oil). IR (®lm):

2960, 2850, 1715, 1083 cm²¹. MS m/z (rel. int.): 210 [M¹]

(1), 195 [M¹2Me](6), 152 [M¹2C₃H₆O¹](14), 43 [M¹2

(colourless oil) IR (®lm): 3474, 1670, 1738, 1240 cm²¹

.

MS: m/z (rel. int.): 153 (6), 137 (26), 119(34), 107(51), 81

(50), 57(16), 43(100). ¹H NMR (300 MHz): 5.38 (1H, bs, H-

5), 4.44 (1H, dd, J11.8, 4.2 Hz, H-⁰1), 4.14 (1H, dd,

J11.8, 4.2 Hz, H-1⁰), 3.43 (1H, t, J5.4 Hz, H-1), 2.28

(1H, m, H-1), 2.10±1.90 (2H, m, H-4), 2.04 (3H, s,

MeCOO), 1.70 (3H, bs, Me-9), 1.00 (3H, s, Me-8), 0.95

(3H, s, Me-7). ¹³C NMR (75 MHz): 73.5 (1), 37.2 (2),

48.4 (3), 136.6 (4), 120.7 (5), 29.7 (6), 22.4 (7), 26.8 (8),

19.4 (9), 62.6 (1⁰), 170.7 (MeCOO), 21.2 (MeCOO).

HREIMS m/z calcd for C₁₂H₂₀O₃M¹212.1412, found

212.1408.

1

C₂H₃O¹] (100). H NMR (CDCl₃, 300 MHz):3.76 (1H, d,

J5.4 Hz, H-5⁰), 2.45 (2H, m, H-3), 2.17 (3H, s, Me±COO),

1.93 (1H, ddd, J12.5, 6.8, 4.5 Hz, H-3⁰), 1.80±1.40 (6H,

m), 1.37 (3H, s, Me-9⁰), 1.08 (3H, s, Me-8⁰), 1.04 (3H, s,

Me-7⁰). ¹³C NMR (CDCl₃, 75 MHz): 30.2 (1), 208.7 (2),

43.9 (3), 21.7 (4), 55.5(1⁰), 86.7 (2⁰), 39.0 (3⁰), 25.9 (4⁰),

86.2 (5⁰), 45.3 (6⁰), 19.0 (7⁰), 23.6 (8⁰), 26.3 (9⁰). HREIMS

m/z calcd for C₁₃H₂₂O₂M¹210.1619, found 210.1627.

(2⁰,2⁰-Dimethyl-3⁰-tetrahydropyranyloxy-6⁰-methylene)-

cyclohexylmethyl acetate (26). To a solution of 25 (0.38 g,

1.77 mmol) in dry CH₂Cl₂(10 ml) was added a solution of

freshly prepared pyridinium p-toluenesulphonate (PPTS)

(45 mg, 0.177 mmol) in dry CH₂Cl₂(7 ml) and then dihy-

dropyran (DHP) (0.22 g, 2.65 mmol) and the mixture was

stirred at room temperature for 5 h 30 min under argon.

After evaporating the solvent the residue was diluted with

Et₂O (60 ml) and the organic phase was washed with brine

(3£25 ml), dried over anh. Na₂SO₄and evaporated to yield a

crude (0.54 g), which after column chromatography (H±E

5-(2⁰,5⁰-Epoxy-2⁰,6⁰,6⁰-trimethyl) cyclohexyl-3-methyl-1-

penten-3-ol (5). A 1 M solution of vinylmagnesium bro-

mide in THF (0.95 ml) was added to a stirred solution of

22 (0.15 g, 0.63 mmol) in THF (4 ml) at 08C, and the whole

was stirred at 108C for 20 min, and then quenched with sat.

NH₄Cl. The mixture was extracted with ether (3£15 ml) and

the combined extracts were washed with sat. NaCl and

dried. Concentration and column chromatography (hex-

ane±ether, 7:3) gave 0.14 g of 5 (85%) (colourless oil). IR

(®lm): 3440, 3085, 1708, 1637, 1071, 918 cm²¹. MS m/z

A. F. Barrero et al. / Tetrahedron 56 (2000) 6099±6113

6107

9:1) afforded 26 (0.44 g, 85%) as a colourless oil. IR (®lm):

3005, 2942, 1738, 1675, 1230, 1201, 1154, 1117,

HREIMS m/z calcd for C₁₅H₂₄O₃M¹252.1725, found

252.1713.

1

1078 cm²¹. H NMR (CDCl₃, 300 MHz): 4.80 (1H, bs,

H-9⁰), 4.71 (1H, t, J3.0 Hz, H-2⁰⁰), 4.60 (1H, bs, H-9⁰),

4.58 (1H, m, H-2⁰⁰), 4.44 (1H, dd, J11.7, 4.5 Hz, H-1),

4.40 (1H, dd, J11.7, 4.5 Hz), 3.90 (2H, m, H-6⁰⁰), 3.50

(1H, dd, J4.0, 4.5 Hz, H-3⁰), 3.45 (2H, m, H-6⁰⁰), 3.26

(1H, dd, J3.0, 4.5 Hz, H-3⁰), 1. 98 (3H, s, MeCO), 1.01

Treatment of 28 with 2-oxopropylidenetriphenyl-

phosphorane

A mixture of 28 (0.4 g, 1.6 mmol) and the phosphorane

(0.57 g, 1.8 mmol) was re¯uxed in toluene (15 ml) over-

night. After cooling the mixture was passed through a silica-

gel column, and the eluate was evaporated affording

compound 26 unaltered.

0

(3H, s, Me±C₂), 1.00 (3H, s, Me±C₂), 0.95 (3H, s, Me±

C₂), 0.89 (3H, s, Me±C₂). ¹³C NMR (CDCl₃, 75 MHz):

63.1, 62.5 (1), 52.2, 51.9 (1⁰), 39.2, 38.5 (2⁰), 84.4, 77.3

(3⁰), 29.7 (4⁰), 31.2 (5⁰), 146.2, 146.1 (6⁰), 27.5, 26.6 (7⁰),

21.5, 21.1 (8⁰), 110.6, 110.3 (9⁰), 101.6, 94.5 (2⁰⁰), 30.7 (3⁰⁰),

29.7 (4⁰⁰), 25.5, 25.3 (5⁰⁰), 63.3, 62.2 (6⁰⁰), 171.0 (CO), 21.0,

20.5 (MeCO). HREIMS m/z calcd for C₁₇H₂₈O₄M¹

296.1987, found 296.1976.

0

Treatment of 17 with BBr₃

Synthesis of 2,2-dimethyl-4-methylene-3-phenylsulpho-

nylmethylcyclohexanol (29) and 2,2,4-trimethyl-3-

phenylsulphonylmethylcyclohex-4-enol (31). To a stirred

solution of 17 (0.5 g, 1.7 mmol) in dry CH₂Cl₂a solution of

BBr₃(0.52 g, 2.4 mmol) in CH₂Cl₂(4 ml) was added drop-

wise. After stirring at room temperature under argon for

15 min, the mixture was added to a 1 M solution of collidine

in CH₂Cl₂(5 ml), diluted with CHCl₃(75 ml) and succes-

sively washed with 5% NaHSO₄(4£25 ml), 5% NaHCO₃

(3£25 ml) and brine (4£25 ml). The organic phase was

dried over anh. Na₂SO₄and the solvent evaporated to afford

a crude that by column chromatography (MeOH±E 1:9)

gave 29 (0.20 g) and 31 0.21 g) (82%). 29 (colourless oil)

IR (®lm): 3530, 2935, 2856, 1651, 1495, 1469, 1446, 1145,

1024, 895 cm²¹. ¹H NMR (CDCl₃, 400 MHz): 7.88 (2H, d,

J7.1 Hz, H-3⁰⁰, H-5⁰⁰), 7.66±7.50 (3H, m, H-2⁰⁰, H-4⁰⁰,

H-6⁰⁰), 4.78 (1H, s, H-9), 4.62 (1H, s, H-9), 3.59 (1H, dd,

J15.1, 9.6 Hz, CH±SO₂Ph), 3.45 (1H, dd, J7.1, 3.6 Hz,

H-1), 3.37 (1H, dd, J15.1, 2.1 Hz, CH±SO₂Ph), 2.45 (1H,

d, J9.6, 2.1 Hz, H-3), 2.27 (1H, ddd, J13.2, 8.4, 4.9 Hz,

H-5), 1.92 (1H, ddd, J13.2, 7.7, 4.9 Hz, H-5), 1.76 (1H,

m), 1.50 (1H, m), 0.92 (3H, s, Me±C₂), 0.79 (3H, s, Me±C₂).

¹³C NMR (CDCl₃, 75 MHz): 75.6 (1), 39.9 (2), 46.3 (3),

144.5 (4), 31.3 (5), 29.2 (6), 26.0 (7), 19.1 (8), 111.5 (9),

57.0 (1⁰), 144.5 (1⁰⁰), 129.1 (2⁰⁰, 6⁰⁰), 128.2 (3⁰⁰, 5⁰⁰), 133.3

(4⁰⁰). HRFABMS m/z calcd for C₁₆H₂₂O₃S (M1Na)¹

317.1187, found 317.1196. 31 (colourless oil) IR (®lm):

3445, 3065, 2960, 1585, 1500, 1471, 1446, 1145, 1085,

(2⁰,2⁰-Dimethyl-3⁰-tetrahydropyranyloxy-6⁰-methylene)-

cyclohexylmethanol (27). 3N KOH in MeOH (8 ml) was

added to a solution of 26 (0.36 g, 1.21 mmol) in MeOH

(15 ml) and the mixture was re¯uxed for 2 h. After evapo-

ration of the solvent the crude was dissolved in Et₂O (60 ml)

and the organic phase was washed with H₂O (4£30 ml),

dried over anh. Na₂SO₄and evaporated to yield a crude

(0.3 g), which was chromatographed on silica gel (H±E

6:4) to give 27 (0.27 g, 91%) as a colourless oil. IR (®lm):

3449, 1645, 117, 814 cm²¹. EIMS m/z (rel. int.): 254 [M¹]

(1), 169 [M¹2THP] (1), 153 [M¹2THPO] (4), 85 [THP]

1

(100). H NMR (CDCl₃, 300 MHz): 4.87 (1H, bs, H-9⁰),

4.69 (1H, m, H-2⁰⁰), 4.68 (1H, bs, H-9⁰), 4.57 (1H, t,

J3.6 Hz, H-2⁰⁰), 3.86 (1H, m, H-1), 3.80 (2H, m, H-6⁰⁰),

3.58 (1H, ddd, J14.8, 7.4, 3.8 Hz, H-1), 3.46 (1H, t,

J4.3 Hz, H-3⁰), 3.43 (2H, m, H-6⁰⁰), 3.25 (1H, t,

0

J3.8 Hz, H-3 ), 1.07 (3H, s, Me±C₂), 0.98 (3H, s, Me±

C₂), 0.94 (3H, s, Me±C₂). ¹³C NMR (CDCl₃, 75 MHz):

62.4, 62.2 (1), 55.9, 55.8 (1⁰), 38.6, 37.9 (2⁰), 83.6, 76.7

(3⁰), 30.5, 30.4 (4⁰), 30.8, 30.7 (5⁰), 147.2, 147.1 (6⁰),

101.2, 93.8 (2⁰⁰), 29.1 (3⁰⁰), 195., 191. (4⁰⁰), 25.3, 24.7

(5⁰⁰), 61.3, 61.0 (6⁰⁰). HREIMS m/z calcd for C₁₅H₂₆O₃M¹

254.1882, found 254.1895.

0

(2⁰,2⁰-Dimethyl-3⁰-tetrahydropyranyloxy-6⁰-methylene)-

cyclohexylcarboxaldehyde (28). Pyridinium dichromate

(PDC) (0.55 g, 1.47 mmol) was added to a solution of 27

in dry CH₂Cl₂(5 ml) and the mixture was stirred at room

temperature under argon for 24 h. Then it was diluted with

Et₂O (50 ml), ®ltered and evaporated to yield a crude

(0.25 g) which by column chromatography (H±E 95:5)

gave 28 (0.22 g, 90%) (colourless oil). IR (®lm): 2740,

1714, 1645, 1118, 815 cm²¹. EIMS m/z (rel. int.): 252

1001, 916, 893, 880, 835 cm²¹

.

¹H NMR (CDCl₃,

300 MHz): 7.92 (2H, d, J7.1, H-2⁰⁰, H-6⁰⁰), 7.65±7.50

(3H, m, H-3⁰⁰, H-4⁰⁰, H-5⁰⁰), 5.26 (1H,bs, H-5), 3.81 (1H,

dd, J15.6, 3.6 Hz, CH±SO₂Ph), 3.50 (1H, t, J4.4 Hz,

H-1), 3.21 (1H, bs, OH), 3.00 (1H, dd, J15.6, 4.5 Hz,

CH±SO₂Ph), 2.32 (1H, d, J18.4 Hz, H-6), 1.98 (1H, d,

J18.4 Hz, H-6), 1.71 (3H, bs, Me±C₄), 0.96 (3H, s, Me±

C₂), 0.88 (3H, s, Me±C₂). ¹³C NMR (CDCl₃, 75 MHz): 73.0

(1), 36.6 (2), 41.6 (3), 134.1 (4), 118.7 (5), 23.2 (6), 21.2 (7),

25.6 (8), 25.6 (9), 55.1 (1⁰), 140.0 (1⁰⁰), 129.1 (2⁰⁰, 6⁰⁰), 127.9

(3⁰⁰, 5⁰⁰), 133.4 (4⁰⁰). HRFABMS m/z calcd for C₁₆H₂₂O₃S

(M1Na)¹317.1187, found 317.1196.

1

[M¹] (1), 234 [M¹2H₂O] (1), 151 [M¹2THPO] (2). H

NMR (CDCl₃, 300 MHz): 9.86 (1H, d, J3.5 Hz, H-1),

9.85 (1H, d, J3.5 Hz, H-1), 4.99 (1H, bs, H-9⁰), 4.81

(1H, t, J3.3 Hz, H-2⁰⁰), 4.74 (2H, bs, H-9⁰), 4.67 (1H, t,

J3.3 Hz, H-2⁰⁰), 3.85 (2H, m, H-6⁰⁰), 3.58 (1H, t, J2.5 Hz,

H-6⁰⁰), 3.52 (2H, m, H-6⁰⁰), 3.40 (1H, t, J3.4 Hz, H-3⁰),

(3⁰-tert-Butyldimethylsilyloxy-2⁰,2⁰-dimethyl-6⁰-methyl-

ene)cyclohexylmethyl phenyl sulphone (30). tert-Butyl-

dimethylsilyl chloride (1.08 g, 7.2 mmol) and imidazole

(0.5 g, 7.3 mmol) were added to a solution of 29 (1.32 g,

4.5 mmol) in DMF (15 ml) and the mixture was stirred for

10 h at room temperature. Then it was fractionated in ether

(100 ml)±brine (100 ml), and the organic phase was washed

with 1N HCl (3£25 ml), 5% NaHCO₃(3£25 ml) and brine

0

2.56 (1H, dd, J8.7, 3.0 Hz, H-1 ), 1.26 (3H, s, Me±C₂),

0

1.11 (3H, s, Me±C₂), 1.00 (3H, s, Me±C₂), 0.96 (3H, s,

0

Me±C₂). ¹³C NMR (CDCl₃, 75 MHz): 202.3, 202.1 (1),

66.3 (1⁰), 40.6, 29.9 (2⁰), 82.7, 81.0 (3⁰), 28.4, 28.2

(4⁰), 30.9, 30.7 (5⁰), 142.9, 142.8 (6⁰), 24.0, 23.8 (7⁰),

26.8 26.3 (8⁰), 113.6, 113.5 (9⁰), 101.7, 101.3 (2⁰⁰), 30.4,

29.0 (3⁰⁰), 19.7, 19.5 (4⁰⁰), 25.9, 25.5 (5⁰⁰), 62.6, 62.5 (6⁰⁰).

6108

A. F. Barrero et al. / Tetrahedron 56 (2000) 6099±6113

(4£25 ml). The ethereal solution was dried over anh. Na₂SO₄

and evaporated to give a crude mixture, that after column

chromatography (H±E 7:3) afforded 30 (1.55 g, 87%) as a

colourless oil. IR (®lm): 2957, 2924, 2856, 1668, 1490,

(3£30 ml). The organic phase was washed with brine

(3£30 ml), dried over anh. Na₂SO₄and the solvent evapo-

rated to give 140 mg of methylketone 34 (95%).

1450, 1080, 1026, 885 cm²¹

.

¹H NMR (CDCl₃,

Method B: 4-(3⁰-tert-Butyldimethylsilyloxy-2,2⁰-dimethyl-

6⁰-methylene)cyclohexyl-4-phenylsulphonyl-2-butanone

(32). Jones reagent (0.02 ml) was added to a solution of the

crude (0.1 g, 0.21 mmol), resulting of the reaction of anion

derived from 30 with propylene oxide, in acetone (5 ml)

cooled at 08, and the mixture was stirred at this temperature

for 20 min. Following the same procedure described for the

synthesis of 34, 95 mg of sulphonylketone 32 (95%) was

obtained as a colourless oil. IR (®lm): 3020, 2950, 2920,

2854, 1720, 1490, 1450, 1300, 1145, 1080, 950, 830 cm²¹.

¹H NMR (CDCl₃, 300 MHz): Signals corresponding to the

major diastereoisomer: 7.87 (2H, d, J8.6 Hz, PhSO₂), 7.63±

7.45 (3H, m, PhSO₂), 5.07 (1H, s, H-9⁰), 5.03 (1H, s, H-9⁰),

4.45 (1H, dt, J8.0, 2.1 Hz, H-4), 3.32 (1H, dd, J7.2,

3.2 Hz, H-3⁰), 3.22 (2H, m, H-3), 2.83 (1H, bs, H-1⁰), 2.28

300 MHz): 7.87 (2H, d, J8.3 Hz, H-2⁰⁰, H-6⁰⁰), 7.57 (1H,

t, J6.9 Hz, H-4⁰⁰), 7.48 (2H, t, J7.2 Hz, H-3⁰⁰, H-5⁰⁰), 4.71

(1H, s, H-9), 4.65 (1H, s, H-9), 3.66 (1H, dd, J7.5, 6.0 Hz,

CH-SO₂Ph), 3.48 (1H, dd, J7.0, 2.5 Hz, H-1), 3.40 (1H,

dd, J7.5, 2.0 Hz, CH±SO₂Ph), 0.84 (6H, s, Me±C₂), 0.80

(9H, s, Me±C±Si), 20.02 (6H, s, Me±Si). ¹³C NMR

(CDCl₃, 75 MHz): 56.1 (1), 46.7 (1⁰), 145.1 (6⁰), 30.9 (5⁰),

30.9 (4⁰), 75.9 (3⁰), 39.8 (2⁰), 25.8 (7⁰), 25.9 (8⁰), 112.3 (9⁰),

140.5 (1⁰⁰), 128.9 (2⁰⁰, 6⁰⁰), 128.1 (3⁰⁰, 5⁰⁰), 133.3 (4⁰⁰), 24.8

(Me±Si), 24.5 (Me±Si), 18.1 (Me±C±Si), 25.7 (Me±C±

Si). HRFABMS m/z calcd for C₂₂H₃₆O₃SSi (M1Na)¹

431.2052, found 431.2043.

Treatment of anion derived from 30 with 4-bromo-3-

methyl-2(E)-butenol

(1H, m, H-5⁰₀a), 2.11 (1H, m, H-5⁰b), 2.08 (3H, s, H-1), 1.69

0

(1H, m, H-4 b), 1.50 (1H, m, H-4 a), 0.87 (3H, s, Me±C₂),

0

0.81 (9H, s, Me₃C±Si), 0.67 (3H, s, Me±C₂), 0.00 (6H, s,

A 2.3 M solution of n-BuLi in hexane (0.3 ml) was added

under argon to a stirred solution of 30 (0.25 g, 0.61 mmol)

and HMPA (1.3 ml) in dry THF at 2788C and the mixture

was allowed to warm to 08C and further stirred for 1 h. Then

a solution of the allylic bromide (0.80 g, 3.23 mmol) in dry

THF (5 ml) was added and the mixture was stirred at room

temperature for 12 h. It was diluted with ether (100 ml) and

the organic phase was washed with 1 M HCl (3£25 ml), 5%

NaHCO₃(3£25 ml) and brine (3£50 ml), and dried over

anh. Na₂SO₄and evaporated, affording a residue which

consists of unaltered starting materials.

Me±Si). ¹³C NMR (CDCl₃, 75 MHz): 29.5 (1), 203.5 (2),

39.9 (3), 59.5 (4), 47.3 (1⁰), 40.3 (2⁰), 76.2 (3⁰), 31.1 (4⁰),

30.2 (5⁰), 142.4 (6⁰), 19.8 (7⁰), 26.9 (8⁰), 115.1 (9⁰), 128.5 (3⁰⁰,

5⁰⁰), 128.7 (2⁰⁰, 6⁰⁰), 133.2 (4⁰⁰), 139.3 (1⁰⁰), 25.6 (Me±C±Si),

25.0 (Me±Si), 24.9 (Me±Si), 17.8 (Me±C±Si). HRFABMS

m/z calcd for C₂₅H₄₀O₄SSi (M1Na)¹487.2314, found

487.2325.

4-(3⁰-tert-Butyldimethylsilyloxy-2,2⁰-dimethyl-6⁰-methyl-

ene)cyclohexyl-3-buten-2-one (33). Aluminium oxide

(10 g, 9.8 mmol) was added to a solution of 32 (0.15 g,

0.32 mmol) in THF (15 ml) and the mixture was stirred

for 2 h. Then it was ®ltered and the solvent was evaporated,

affording 0.095 g (95%) of 33 (colourless oil). IR (®lm):

2957, 2930, 2850, 1697, 1670, 1610, 1468, 1080, 1000,

Synthesis of 4-(3⁰-tert-butyldimethylsilyloxy-2,2⁰-dimethyl-

6⁰-methylene)cyclohexyl-2-butanone (34) from 30.

Method A: To a solution of n-butyllithium (1.8 M in hexane,

1.5 ml, 2.8 mmol) in THF (10 ml) cooled at 08 was added

HMPA (3 ml) and then a solution of sulphone 30 (0.99 g,

2.42 mmol) in THF (20 ml) under argon atmosphere. The

mixture was stirred for 30 min at 08C and it was allowed to

warm to room temperature and stirred for 45 min. Then

0.5 ml (7.26 mmol) of propylene oxide was added, the

mixture stirred at the same temperature for 1 h and further

heated at 658 for an additional 45 min. Then sat. aqueous

NH₄Cl (3 ml) and ether (100 ml) was added and the organic

solution was successively washed with 2N HCl (3£30 ml)

and brine (3£50 ml), dried over anh. Na₂SO₄and the solvent

evaporated to afford 0.85 g of crude.

875 cm²^{1 1}H NMR (CDCl₃, 300 MHz): 7.08 (1H, dd,

.

J15.9, 9.7 Hz, H-4), 5.99 (1H, d, J15.9 Hz, H-3), 4.80

(1H, s, H-9⁰), 4.56 (1H, s, H-9⁰), 3.44 (1H, dd, J7.6,

3.6 Hz, H-3⁰), 2.57 (1H, bd, J9.7 Hz, H-1⁰), 2.23 (3H, s,

H-1), 1.80±1.50 (4H, m, H-4⁰, H-5⁰), 0.89 (9H, s, Me₃C±

Si), 0.86 (Me±C₂), 0.85 (3H, s, Me±C₂), 0.05 (6H, s, Me±

Si). ¹³C NMR (CDCl₃, 75 MHz): 27.7 (1), 197.5 (2), 133.4

(3), 147.6 (4), 56.9 (1⁰), 40.3 (2⁰), 76.6 (3⁰), 31.3 (4⁰), 30.2

(5⁰), 148.2 (6⁰), 26.9 (7⁰), 27.1 (8⁰), 110.4 (9⁰), 26.0 (Me±C±

Si), 24.8 (Me±Si), 24.2 (Me±Si), 18.1 (Me±C±Si).

HRFABMS m/z calcd for C₁₉H₃₄O₂Si (M1Na)¹

345.2226, found 345.2218.

0

6% Na±Hg (0.79 g, 2.1 mmol) was added under argon to a

solution of the above crude (0.25 g) and disodium hydrogen

phosphate (0.29 g, 2.1 mmol) in EtOH cooled at 2108. The

mixture was stirred under re¯ux for 4 h, and then sat.

aqueous NH₄Cl (20 ml) was added and the mixture

extracted with OEt₂(3£30 ml). The organic phase was

washed with sat. aqueous NaHCO₃(3£30 ml) and H₂O

(3£40 ml), dried over anh. Na₂SO₄and evaporated to give

150 mg of crude.

4-(3⁰-tert-Butyldimethylsilyloxy-2,2⁰-dimethyl-6⁰-methyl-

ene)cyclohexyl-2-butanone (34). 1.4 g of an aqueous

suspension of Raney Nickel was added to a stirred solution

of 33 (0.15 g, 0.465 mmol) in THF (6 ml) and the mixture

was further stirred at room temperature for 30 min. Then it

was diluted with OEt₂and ®ltered through silicagel and the

solvent was evaporated to yield 0.138 g of 34 (92%) as a

colourless oil. IR (®lm): 2960, 2930, 2856, 1718, 1473,

1

1251, 109, 1006, 835 cm²¹. H NMR (CDCl₃, 300 MHz):

4.80 (1H, bs, H-9⁰), 4.48 (1H, bs, H-9⁰), 3.38 (1H, dd,

J7.1, 3.6 Hz, H-5⁰), 2.44 (1H, ddd, J17.1, 7.4, 7.1 Hz,

H-3), 2.30 (1H, m, H-5⁰a), 2.21 (1H, ddd, J17.1, 8.1,

4.6 Hz, H-3), 2.08 (3H, s, H-1), 1.96 (1H, m, H-5⁰b), 1.84

Jones reagent (0.03 ml) was added to a solution of the crude

(0.15 g, 0.46 mmol) in acetone (7 ml) cooled at 08C and the

mixture was stirred at this temperature for 30 min. H₂O

(5 ml) was added and the mixture was extracted with OEt₂

A. F. Barrero et al. / Tetrahedron 56 (2000) 6099±6113

6109

(1H, m, H-4⁰a), 1.65 (1H, m, H-4), 1.60 (1H, m, H-1⁰), 1.51

4-(3⁰-tert-Butyldimethylsilyloxy-2,2⁰-dimethyl-6⁰-methyl-

ene)cyclohexyl-3-methyl-2-penten-1-yl acetate (37).

Palladium (II) chloride bis acetonitrile complex (20 mg,

0.77 mmol) was added under argon atmosphere to a solution

of 36 (0.25 g, 0.634 mmol) in THF (10 ml) and the mixture

was stirred at room temperature for 45 min. The crude

obtained after evaporating the solvent was ®ltered through

silicagel to give 0.237 g (95%) of 37 (colourless oil). IR

0

(2H, m, H-4, H-4 b), 0.91 (3H, s, Me±C₂), 0.88 (9H, s,

0

Me₃C±Si), 0.81 (3H, s, Me±C₂), 0.02 (6H, s, Me±Si). ¹³C

NMR (CDCl₃, 75 MHz): 27.0 (1), 209.7 (2), 43.2 (3), 20.9

(4), 52.3 (1⁰), 40.4 (2⁰), 76.8 (3⁰), 20.7 (4⁰), 32.0 (5⁰), 148.1

(6⁰), 21.9 (7⁰), 25.9 (8⁰), 109.1 (9⁰), 26.0 (Me±C±Si), 24.9

(Me±Si), 24.1 (Me±Si), 17.8 (Me±C±Si). HRFABMS m/z

calcd for C₁₉H₃₄O₂Si (M1Na)¹345.2226, found 345.2232.

1

(®lm): 2955, 2932, 1739, 1640, 1095, 1020, 835 cm²¹. H

4-(3⁰-tert-Butyldimethylsilyloxy-2,2⁰-dimethyl-6⁰-methyl-

ene)cyclohexyl-3-methyl-1-penten-3-ol (35). 1 M vinyl-

magnesium bromide in THF (1 ml) was added to a

solution of 34 (0.3 g, 0.926 mmol) in THF (20 ml) at 08C

and the mixture was stirred at this temperature for 30 min;

then sat. NH₄Cl solution (1 ml) was added and the mixture

was diluted with OEt₂(50 ml). The organic phase was

washed with H₂O (3£30 ml), brine (3£30 ml), dried over

anh. Na₂SO₄and the solvent evaporated to give a residue,

which was chromatographed on silicagel (H±E 8:2) afford-

ing 0.31 g (95%) of 35 (colourless oil). IR (®lm): 2955,

NMR (CDCl₃, 300 MHz): 5.31 (1H, t, J7.1 Hz, H-2), 4.57

(2H, d, J7.1 Hz, H-1), 4.78 (1H, bs, H-9⁰), 4.54 (1H, bs,

H-9⁰), 3.37 (1H, dd, J7.1, 3.6 Hz, H-3⁰), 2.32 (1H, m,

H-5⁰), 2.04 (3H, s, AcO), 1.92 (1H, ddd, J12.4, 7.2,

4.3 Hz, H-4), 1.80±1.55 (7H, m), 1.67 (3H, s, Me±C₃),

0

0.90 (3H, s, Me±C₂), 0.88 (9H, s, Me₃C±Si), 0.78 (Me±

0

C₂), 0.03 (3H, s, Me±Si), 0.02 (3H, s, Me±Si). ¹³C NMR

(CDCl₃, 75 MHz): 61.6 (1), 117.8 (2), 142.2 (3), 38.8 (4),

24.7 (5), 16.6 (Me±C₃), 52.4 (1⁰), 40.4 (2⁰), 76.9 (3⁰), 32.1

(4⁰), 29.7 (5⁰), 148.3 (6⁰), 25.8 (7⁰), 27.1 (8⁰), 108.8 (9⁰),

26.0 (Me±C±Si), 24.7 (Me±Si), 24.1 (Me±Si), 18.1 (Me±

C±Si), 171.0 (MeCOO), 22.0 (MeCOO). HRFABMS m/z

calcd for C₂₃H₄₂O₃Si (M1Na)¹417.2801, found 417.2810.

1

2925, 1653, 1558, 1541, 1508, 885, 833 cm²¹. H NMR

(CDCl₃, 400 MHz): 5.90 (1H, dd, J17.3, 10.7 Hz, H-2),

5.18 (1H, dd, J173, 1.5 Hz, H-1), 5.02 (1H, dd, J10.7,

1.5 Hz, H-1), 4.79 (1H, d, J2.1 Hz, H-9⁰), 4.55 (1H, d,

J2.1 Hz, H-9⁰), 3.38 (1H, dd, J6.7, 3.5 Hz, H-3⁰), 2.33

(1H, m, H-5⁰), 1.91 (1H, ddd, J12.2, 7.6, 4.7 Hz, H-5⁰),

1.73 (1H, ddd, J13.1, 8.4, 4.5 Hz, H-4), 1.70±1.50 (6H,

m), 1.21 (3H, s, Me±C₃), 0.89 (9H, s, Me₃C±Si), 0.82 (3H,

4-(3⁰-tert-Butyldimethylsilyloxy-2⁰,2⁰-dimethyl-6⁰-methyl-

ene)cyclohexyl-3-methyl-2-pentenol (38). 2N KOH in

methanol (2 ml) was added to a solution of 37 (0.2 g,

0.507 mmol) in methanol (6 ml) and the mixture was stirred

for 45 min. After evaporating the solvent, the crude was

fractionated in Et₂O (50 ml)±H₂O (10 ml), and the organic

phase was washed with brine (3£30 ml), dried over anh.

Na₂SO₄and the solvent concentrated to afford 0.17 g

(94%) of 38 as a colourless oil. IR (®lm): 3560, 2960,

0

s, Me±C₂), 0.81 (Me±C₂), 0.05 (3H, s, Me±Si), 0.04 (3H,

s, Me±Si). ¹³C NMR (CDCl₃, 75 MHz): 111.6 (1), 145.4 (2),

73.6 (3), 41.9 (4), 21.0 (5), 28.1 (Me±C₃), 53.1 (1⁰), 40.5

(2⁰), 76.9 (3⁰), 32.1 (4⁰), 29.7 (5⁰), 148.4 (6⁰), 25.9 (7⁰), 27.4

(8⁰), 118.9 (9⁰), 26.0 (Me±C±Si), 24.8 (Me±Si), 24.1

(Me±Si), 18.1 (Me±C±Si). HRFABMS m/z calcd for

C₂₁H₄₀O₂Si (M1Na)¹375.2695, found 375.2703.

2925, 2856, 1645, 1097, 1022, 804 cm²¹

.

¹H NMR

(CDCl₃, 300 MHz): 5.38 (1H, t, J6.9 Hz, H-2), 4.80

(1H, s, H-9⁰), 4.54 (1H, s, H-9⁰), 4.12 (2H, d, J6.9 Hz,

H-1), 3.37 (1H, dd, J7.2, 3.6 Hz, H-5⁰), 2.34 (1H, ddd,

J12.3, 7.5, 4.7 Hz, H-5⁰), 1.90 (1H, ddd, J12.9, 8.3,

4.3 Hz, H-4), 1.80±1.45 (7H, m), 1.65 (3H, s, Me±C₃),

Acetylation of 35

Synthesis of 4-(3⁰-tert-butyldimethylsilyloxy-2⁰,2⁰-dimethyl-

6⁰-methylene)cyclohexyl-3-methyl-1-penten-3-yl acetate

(36). Acetic anhydride (1 ml), triethylamine (2 ml) and

dimethylaminopyridine (50 mg) was added to a solution

of 35 (0.25 g, 0.71 mmol) in THF (20 ml) and the mixture

was stirred under re¯ux for 26 h. It was diluted with Et₂O

(80 ml) and washed with 2N HCl (3£30 ml), sat. NaHCO₃

(3£30 ml) and brine (3£30 ml). After drying the organic

phase over anh. Na₂SO_4,the solvent was evaporated to

give, after chromatography on silicagel (H±E 9:1), 0.25 g

(90%) of 36 as a colourless oil. IR (®lm): 2960, 2856, 1741,

1508, 1473, 1259, 1095, 1022, 835 cm²¹. ¹H NMR (CDCl₃,

300 MHz): 5.96 (1H, dd, J17.6, 10.9 Hz, H-2), 5.10 (1H,

dd, J17.6, 1.3 Hz, H-1), 5.09 (1H, dd, J10.9, 1.3 Hz,

H-1), 4.78 (1H, s, H-9⁰), 4.53 (1H, s, H-9⁰), 3.37 (1H, dd,

J6.4, 3.5 Hz, H-3⁰), 2.33 (2H, m, H-5⁰), 1.92 (3H, s, AcO),

1.85±1.50 (8H, m), 1.50 (3H, s, Me±C₃), 0.88 (9H, s,

0

0.91 (3H, s, Me±C₂), 0.87 (9H, s, Me₃C±Si), 0.78 (Me±

0

C₂), 0.03 (3H, s, Me±Si), 0.02 (3H, s, Me±Si). ¹³C NMR

(CDCl₃, 75 MHz): 59.4 (1), 123.0 (2), 141.8 (3), 38.9 (4),

24.9 (5), 16.4 (Me±C₃), 52.4 (1⁰), 40.5 (2⁰), 77.1 (3⁰), 32.2

(4⁰), 29.5 (5⁰), 148.3 (6⁰), 25.9 (7⁰), 27.1 (8⁰), 108.7 (9⁰),

26.0 (Me±C±Si), 24.8 (Me±Si), 24.1 (Me±Si), 18.2 (Me±

C±Si). HRFABMS m/z calcd for C₂₁H₄₀O₂Si (M1Na)¹

375.2695, found 375.2701.

Elegansidiol (cis-3-[(E)-5-hydroxy-3-methyl-3-pentenyl]-

2,2-dimethyl-4-methylenecyclohexanol) (6). Tetrabutyl-

ammonium ¯uoride (0.1 g, 0.34 mmol) was added to a solu-

tion of 39 (0.1 g, 0.25 mmol) in THF (10 ml) and the

mixture was stirred at room temperature for 6 h. After

evaporating the solvent, the crude was chromatographed

on silicagel (H±E 4:6) to yield 54 mg (89%) of 6 (colourless

oil). IR (®lm): 3384, 2930, 2852, 1717, 1645, 1449, 1379,

1261, 1183, 1082, 1023, 890 cm²¹. EIMS m/z 238 [M¹],

(1), 220 (8), 205 (35), 187 (27), 175 (24), 159 (18), 134 (27),

119 (45), 107 (62), 96 (100), 81 (64), 67 (44), 55 (54), 43

0

Me₃C±Si), 0.86 (3H, s, Me±C₂), 0.81 (Me±C₂), 0.03

(3H, s, Me±Si), 0.02 (3H, s, Me±Si). ¹³C NMR (CDCl₃,

75 MHz): 113.1 (1), 142.1 (2), 83.4 (3), 39.7 (4), 20.8 (5),

23.6 (Me±C₃), 53.1 (1⁰), 40.4 (2⁰), 76.8 (3⁰), 32.0 (4⁰), 29.6

(5⁰), 148.4 (6⁰), 25.9 (7⁰), 27.3 (8⁰), 109.1 (9⁰), 26.0 (Me±C±

Si), 24.9 (Me±Si), 24.1 (Me±Si), 18.1 (Me±C±Si).

HRFABMS m/z calcd for C₂₃H₄₂O₃Si (M1Na)¹

417.2801, found 417.2814.

1

(85), 41 (83). H NMR (300 MHz, CDCl₃): 5.40 (1H, tq,

J6.9, H-4⁰), 4.88 (1H, bs, 1H, H-9), 4.60 (1H, bs, H-9),

4.15 (2H, d, J6.9 Hz, H-5⁰), 3.42 (1H, dd, J9.6, 4.2 Hz,

H-1), 2.32 (1H, dt, J13.1, 4.4 Hz, H-5a), 2.10 (1H, m, H-

2⁰), 2.00±1.85 (m, 2H, H-5b, H-6b), 1.75 (1H, m, H-2⁰),

6110

A. F. Barrero et al. / Tetrahedron 56 (2000) 6099±6113

0

1.68 (3H, s, Me±C₃), 1.65 (2H, m, H-3, H-1 ), 1.50 (2H, m,

H-6a, H-1⁰), 1.03 (3H, s, Me-8), 0.73 (s, 3H, Me-7). ¹³C

NMR (75 MHz, CDCl₃): 77.2 (1), 40.4 (2), 51.2 (3), 147.1

(4), 32.7 (5), 32.0 (6), 26.0 (7),₀16.2 (8), 108.3 (9), 23.8 (1⁰),

(CDCl₃, 300 MHz): 7.96 (2H, d, J8.6 Hz, Ph), 7.68±

7.54 (3H, m, Ph), 5.44 (1H, bs, H-3⁰), 3.88 (1H, m, H-2),

3.69 (1H, d, J6.3 Hz, H-4), 3.29 (1H, dd, J7.3, 5.8 Hz,

H-5⁰), 2.47 (1H, bs, H-1⁰), 2.27 (1H, ddd, J17.7, 9.2,

8.5 Hz, H-3), 2.05 (1H, m, H-4⁰), 1.97 (1H, m, H-4⁰), 1.87

(1H, bd, J17.7 Hz, H-3), 1.66 (3H, s, Me±C₃), 1.18 (3H, d,

J5.9 Hz, H-1), 0.82 (9H, s, Me₃C±Si), 0.64 (3H, s, Me±

0

38.7 (2 ), 140.1 (3 ), 123.1 (4 ), 59.3 (5 ), 15.7 (Me±C₃).

HRFABMS m/z calcd for C₁₅H₂₇O₂(M1H¹) 239.201105,

found 239.201432.

0

C₂), 0.38 (Me±C₂), 20.03 (3H, s, Me±Si), 20.05 (3H, s,

Me±Si). ¹³C NMR (CDCl₃, 75 MHz): 25.7 (1), 67.3 (2),

35.7 (3), 64.7 (4), 48.7 (1⁰), 139.7 (2⁰), 124.3 (3⁰), 32.2

(4⁰), 74.4 (5⁰), 39.3 (6⁰), 24.5 (7⁰), 24.7 (8⁰), 22.5 (9⁰),

138.5 (1⁰⁰), 129.6 (2⁰⁰), 129.3 (3⁰⁰), 132.4 (4⁰⁰), 26.0 (Me±

C±Si), 24.7 (Me±Si), 24.1 (Me±Si), 18.1 (Me±C±Si).

HRFABMS m/z calcd for C₂₅H₄₂O₄SSi (M1Na)¹

489.2471, found 489.2480.

2,2,4-Trimethyl-3-phenylsulphonylmethylcyclohex-4-enol

(31). To a stirred solution of 17 (0.42 g, 1.44 mmol) in dry

CH₂Cl₂a solution of BBr₃(0.44 g, 2.04 mmol) in CH₂Cl₂

(4 ml) was added dropwise. After stirring at room tempera-

ture under argon for 15 min, the mixture was added to 5 ml

of Et₃N, diluted with CHCl₃(75 ml) and was successively

washed with 5% NaHSO₄(4£25 ml), 5% NaHCO₃

(3£25 ml) and brine (4£25 ml). The organic phase was

dried over anh. Na₂SO₄and the solvent evaporated to afford

31 (0.37 g, 82%).

4-(5⁰-tert-Butyldimethylsilyloxy-2⁰,6⁰,6⁰-trimethyl)cyclo-

hex-2⁰-enyl-4-phenylsulphonyl-2-butanone (41). Jones

reagent (0.1 ml) was added to a solution of 40 (0.5 g,

1.07 mmol) in acetone (20 ml) cooled at 08C and the

mixture was stirred at this temperature for 30 min. Follow-

ing the same procedure described for 32, 0.45 g (90%) of 41

was obtained as a colourless oil. IR (®lm): 3015, 2955,

2926, 2856, 1724, 1492, 1448, 1186, 1084, 970,

Treatment of 31 with TBSCl

Synthesis of (5⁰-tert-butyldimethylsilyloxy-2⁰,2⁰,6⁰-tri-

methyl)cyclohex-2⁰-enylmethyl phenyl sulphone (39).

tert-Butyldimethylsilyl chloride (0.75 g, 5.04 mmol) and

imidazole (0.35 g, 5.11 mmol) was added to a solution of

31 (0.92 g, 3.15 mmol) in DMF (10 ml) and the mixture was

stirred for 10 h at room temperature. Then it was fractio-

nated in ether (70 ml)±brine (70 ml), and the organic phase

was washed with 1N HCl (3£20 ml), 5% NaHCO₃

(3£20 ml) and brine (4£20 ml). The ethereal solution was

dried over anh. Na₂SO₄and evaporated to give a crude, that

after column chromatography (H±E 7:3) afforded 39

(1.42 g, 80%) as a colourless oil. IR (®lm): 2950, 2920,

835 cm²^{1 1}H NMR (CDCl₃, 300 MHz): 7.88 (2H, d,

.

J7.5 Hz, Ph), 7.55 (3H, m, Ph), 5.47 (1H, bs, H-3⁰), 4.43

(1H, d, J9.4 Hz, H-4), 3.36 (1H, t, J5.4 Hz, H-5⁰), 3.23

(1H, dd, J18.9, 9.4 Hz, H-3), 2.74 (1H, bs, H-1⁰), 2.71

(1H, d, J18.9 Hz, H-3), 2.04 (3H, s, MeCOO), 2.20±

0

1.95 (2H, m, H-4 ), 1.85 (3H, s, Me±C₂), 0.79 (9H, s,

0

Me₃C±Si), 0.73 (3H, s, Me±C₆), 0.59 (3H, s, Me±C₆),

20.03 (3H, s, Me±Si), 20.05 (3H, s, Me±Si). ¹³C NMR

(CDCl₃, 75 MHz): 29.7 (1), 203.6 (2), 40.6 (3), 59.3 (4),

46.2 (1⁰), 132.5 (2⁰), 123.4 (3⁰), 32.4 (4⁰), 74.2 (5⁰), 39.0

(6⁰), 24.5 (7⁰), 26.5 (8⁰), 18.6 (9⁰), 139.9 (1⁰⁰), 129.0 (2⁰⁰),

128.7 (3⁰⁰), 133.5 (4⁰⁰), 26.0 (Me±C±Si), 24.6 (Me±Si),

24.4 (Me±Si), 18.3 (Me±C±Si). HRFABMS m/z calcd

for C₂₅H₄₀O₄SSi (M1Na)¹487.2314, found 487.2302.

2860, 1620, 1500, 1440, 1095, 1015, 870 cm²¹. H NMR

1

(CDCl₃, 300 MHz): 7.93 (2H, d, J7.1 Hz, H-2⁰⁰, H-6⁰⁰),

7.67±7.53 (3H, m, H-3⁰⁰, H-4⁰⁰, H-5⁰⁰), 5.24 (1H, bs, H-3⁰),

3.95 (1H, dd, J15.6, 3.5 Hz, H-1), 3.46 (1H, t, J4.1 Hz,

H-5⁰), 2.93 (1H, dd, J15.6, 4.5 Hz, H-1), 2.39 (1H, bs,

H-1⁰), 2.23 (1H, bs, J18.2 Hz, H-4⁰), 1.97 (1H, bd,

0

4-(5⁰-tert-Butyldimethylsilyloxy-2⁰,6⁰,6⁰-trimethyl)cyclo-

hex-2⁰-enyl-3-buten-2-one (42). Aluminium oxide (3 g,

0

J18.2 Hz, H-4 ), 1.73 (3H, s, Me±C₂), 0.98 (3H, s, Me±

0

C₆), 0.89 (3H, s, Me±C₆), 0.75 (9H, s, Me±C±Si), 0.05

(3H, s, Me±Si), 20.05 (3H, s, Me±Si). ¹³C NMR (CDCl₃,

75 MHz): 57.9 (1), 41.8 (1⁰), 134.5 (2⁰), 118.5 (3⁰), 32.3 (4⁰),

74.2 (5⁰), 37.1 (6⁰), 26.0 (7⁰), 25.7 (8⁰), 22.5 (9⁰), 140.6 (1⁰⁰),

129.2 (2⁰⁰, 6⁰⁰), 128.0 (3⁰⁰, 5⁰⁰), 133.4 (4⁰⁰), 25.7 (Me±C±Si),

25.0 (Me±Si), 24.4 (Me±Si), 17.8 (Me±C±Si).

HRFABMS m/z calcd for C₂₂H₃₆O₃SSi (M1Na)¹

431.2052, found 431.2064.

29.4 mmol) was added to

a solution of 41(0.5 g,

1.08 mmol) in THF (50 ml) and the mixture was stirred at

room temperature for 4 h. Following the same procedure

described for 33, 0.34 g (98%) of 42 (colourless oil) was

obtained. IR (®lm): 2957, 2930, 2856, 1697, 1676, 1618,

1471, 1084, 1005, 880 cm²¹. ¹H NMR (CDCl₃, 300 MHz):

6.83 (1H, dd, J16.1, 10.5 Hz, H-4), 6.00 (1H, d,

J16.1 Hz, H-3), 5.38 (1H, bs, H-3⁰), 3.48 (1H, t,

J5.1 Hz, H-5⁰), 2.37 (1H, d, J10.5 Hz, H-1⁰), 2.25 (3H,

4-(5⁰-tert-Butyldimethylsilyloxy-2⁰,6⁰,6⁰-trimethyl)cyclo-

hex-2⁰-enyl-4-phenylsulphonyl-2-butanol (40). A solution

of 39 (2.0 g, 4.9 mmol) and HMPA (5 ml) in THF (35 ml)

was added under argon atmosphere to a solution of n-butyl-

lithium (1.8 M in hexane, 2.8 ml, 5.2 mmol) in THF (20 ml)

cooled at 08C and the mixture was stirred at this temperature

for 30 min and it was allowed to warm to room temperature

and stirred for 45 min. Then propylene oxide (0.7 ml,

14.6 mmol) was added and the mixture was stirred at

room temperature for 1 h and heated at 658C for an

additional 15 min. Following the same work-up used for

30, 1.94 g (85%) of 40 was obtained as a mixture of dia-

stereomers. Colourless oil. IR (®lm): 3570, 2958, 2931,

s, H-1), 2.25 (1H, bd, J17.6 Hz, H-4⁰), 2.05 (1H, bd,

0

J17.6 Hz, H-4 ), 1.54 (3H, bs, Me±C₂), 0.88 (9H, s,

0

Me₃C±Si), 0.86 (3H, s, Me±C₆), 0.85 (3H, s, Me±C₆),

20.03 (3H, s, Me±Si), 20.04 (3H, s, Me±Si). ¹³C NMR

(CDCl₃, 75 MHz): 26.6 (1), 198.3 (2), 133.6 (3), 150.3 (4),

55.1 (1⁰), 131.9 (2⁰), 119.9 (3⁰), 32.4 (4⁰), 74.2 (5⁰), 37.9

(6⁰), 22.8 (7⁰), 26.5 (8⁰), 21.1 (9⁰), 26.0 (Me±C±Si), 24.7

(Me±Si), 24.3 (Me±Si), 18.2 (Me±C±Si). HRFABMS m/z

calcd for C₁₉H₃₄O₂Si (M1Na)¹345.2226, found 345.2237.

4-(5⁰-tert-Butyldimethylsilyloxy-2⁰,6⁰,6⁰-trimethyl)cyclo-

hex-2⁰enyl-2-butanone (43). An aqueous Raney Nickel

suspension (2.4 g) was added to a stirred solution of 42

1630, 1471, 1253, 1083, 1008, 835 cm²^{1 1}H NMR

.

A. F. Barrero et al. / Tetrahedron 56 (2000) 6099±6113

6111

(0.3 g, 0.93 mmol) in THF (10 ml) and the mixture was

further stirred at room temperature for 30 min. Following

the same procedure described for 34, 0.28 g (95%) of 43 was

obtained. Colourless oil. IR (®lm): 2960, 2930, 2856, 1734,

the mixture was stirred at room temperature for 4 h. After

work-up as for alcohol 35, 58 mg (83%) of 7 was obtained

as a colourless oil. IR (®lm): 3488, 2960, 2850, 1725, 1445,

1

1255, 1030, 1000, 918, 83, 760 cm²¹. H NMR (CDCl₃,

1618, 1471, 1257, 1107, 887 cm²¹

.

¹H NMR (CDCl₃,

300 MHz): 5.91 (1H, dd, J17.5, 10.7 Hz, H-2), 5.20 (1H,

dd, J17.5, 1.1 Hz, H-1), 5.05 (1H, dd, J10.7 Hz, 1.1H,

H-1), 5.08 (1H, dd, J10.7, 1.2 Hz, H-1), 4.65 (1H, t,

J6.4 Hz, H-5⁰), 2.25 (1H, dd, J18.0, 6.4 Hz, H-4⁰),

2.00 (1H, dd, J18.0, 6.4 Hz, H-4⁰), 1.99 (3H, s, OAc),

1.72 (1H, m, H-4), 1.70 (3H, bs, Me-9⁰), 1.67 (1H, m, H-

5), 1.50 (1H, m, H-4), 1.28 (1H, m, H-5), 1.25 (3H, s, Me±

C₃), 0.98 (3H, s, Me-7⁰), 0.85 (3H, s, Me-8⁰). ¹³C NMR

(CDCl₃, 75 MHz): 111.7 (1), 145.0 (2), 73.7 (3), 44.1 (4),

22.6 (5), 27.8 (Me±C₃), 49.5 (1⁰), 136.8 (2⁰), 117.3 (3⁰), 28.8

(4⁰), 76.5 (5⁰), 36.7 (6⁰), 25.5 (7⁰), 18.7 (8⁰), 22.8 (9⁰), 171.0

(MeCOO), 20.9 (MeCOO). HRFABMS m/z calcd for

C₁₇H₂₈O₃(M1Na)¹303.1936, found 303.1942.

300 MHz): 5.24 (1H, bs, H-3⁰), 3.39 (1H, dd, J8.1,

5.7 Hz, H-5⁰), 2.62 (1H, ddd, J16.3, 10.6, 5.5 Hz, H-3),

2.41 (1H, ddd, J15.9, 10.2, 5.5 Hz, H-3), 2.12 (3H, s, H-1),

2.10±1.90 (2H, m, H-4⁰), 1.70±1.25 (3H, m, H-4, H-1⁰),

0

1.65 (3H, s, Me±C₂), 0.91 (3H, s, Me±C₆), 0.87 (9H, s,

0

Me₃C±Si), 0.78 (3H, s, Me±C₆), 0.01 (6H, s, Me±Si). ¹³C

NMR (CDCl₃, 75 MHz): 30.0 (1), 202.4 (2), 45.2 (3), 22.3

(4), 49.1 (1⁰), 135.6 (2⁰), 119.9 (3⁰), 32.5 (4⁰), 75.1 (5⁰), 38.7

(6⁰), 22.6 (7⁰), 25.9 (8⁰), 16.7 (9⁰), 26.2 (Me±C±Si), 24.8

(Me±Si), 24.1 (Me±Si), 18.1 (Me±C±Si). HRFABMS m/z

calcd for C₁₉H₃₆O₂Si (M1Na)¹347.2382, found 347.2391.

4-(5-tert-Butyldimethylsilyloxy-2⁰,6⁰,6⁰-trimethyl)cyclo-

hex-2⁰-enyl-3-methyl-1-penten-3-ol (44). 1 M solution of

vinylmagnesium bromide in THF (3.2 ml) was added to a

solution of 43 (0.7 g, 2.16 mmol) in THF (50 ml) cooled at

08C and the mixture was stirred at this temperature for

30 min. Following the same procedure described for 35,

0.7 g (93%) of 44 was obtained as a colourless oil. IR

(®lm): 3480, 2962, 2930, 2856, 1471, 1085, 1000, 885,

Acetate of 4-(2⁰,5⁰-epoxy-2⁰,6⁰,6⁰-trimethyl)cyclohexyl-2-

butyl (46). Acetic anhydride (5 ml) was added to a solution

of 21 (1.3 g, 6.13 mmol) in pyridine (10 ml), and the

mixture was stirred at room temperature for 6 h. Then it

was diluted with ether (100 ml), and washed with 2N HCl,

sat. NaHCO₃, water, sat. NaCl and dried. Concentration

gave 1.47 g of 46 (95%) as a mixture of diastereomers.

Colourless oil. IR (®lm): 2874, 1736, 1060, 951 cm²¹. MS

m/z (rel. int.): 254. [M¹] (2), 239 [M¹2Me](8), 180

[M¹2C₃H₇O₂](11), 43 [M¹2C₂H₃O¹](100). ¹H NMR

(CDCl₃, 300 MHz): 1.73±1.14 (18H, m). Signals assignable

to 46a: 4.90 (1H, m, H-2), 3.70 (1H, d, J5.4 Hz, H-5⁰),

2.02 (3H, s, Me±COO), 1.30 (3H, s, Me-9⁰), 1.20 (3H, d,

J6.0 Hz, Me-2), 1.04 (3H, s, Me-8⁰), 0.98 (3H, s, Me-7⁰).

Signals assignable to 46b: 4.90 (1H, m, H-2), 3.70 (1H, d,

J5.4 Hz, H-5⁰), 2.03 (3H, s, Me±COO), 1.30 (3H, s, Me-

9⁰), 1.20 (3H, d, J6.0 Hz, Me-2), 1.06 (3H, s, Me-8⁰), 0.99

(3H, s, Me-7⁰). ¹³C NMR (CDCl₃, 75 MHz): Signals assign-

able to 46a: 19.9 (1), 71.3 (2), 36.1 (3), 23.4 (4), 55.8(1⁰),

86.7 (2⁰), 39.0 (3⁰), 25.8 (4⁰), 86.1 (5⁰), 45.2 (6⁰), 18.9 (7⁰),

23.4 (8⁰), 26.1 (9⁰), 170.8 (OAc), 21.4 (Me±COO). Signals

assignable to 46b: 19.8 (1), 71.2 (2), 36.1 (3), 23.4 (4),

55.6(1⁰), 86.7 (2⁰), 38.9 (3⁰), 25.8 (4⁰), 86.2 (5⁰), 45.2 (6⁰),

18.9 (7⁰), 23.2 (8⁰), 26.2 (9⁰), 170.8 (OAc), 21.4 (Me±COO).

HRFABMS m/z calcd for C₁₅H₂₆O₃(M1Na)¹277.1780,

found 277.1768.

770 cm²^{1 1}H NMR (CDCl₃, 300 MHz): 5.92 (1H, dd,

.

J16.3, 10.7 Hz, H-2), 5.20 (1H, d, J16.3 Hz, H-1),

5.19 (1H, bs, H-3⁰), 5.06 (1H, d, J10.7 Hz, H-1), 3.40

(1H, dd, J8.1, 5.6 Hz, H-5⁰), 2.10±1.90 (2H, m, H-4⁰),

2.00 (1H, m, H-4⁰), 1.70±1.30 (5H, m, H-4, H-5, H-1⁰),

0

1.67 (3H, s, Me±C₂), 1.29 (3H, s, Me±C₃), 0.90 (3H, s,

0

Me±C₆), 0.87 (9H, s, Me₃C±Si), 0.78 (3H, s, Me±C₆),

0.06 (3H, s, Me±Si), 0.01 (3H, s, Me±Si). ¹³C NMR

(CDCl₃, 75 MHz): 111.8 (1), 145.1 (2), 73.6 (3), 44.7 (4),

22.8 (5), 27.6 (Me±C₃), 49.9 (1⁰), 136.6 (2⁰), 118.9 (3⁰), 32.6

(4⁰), 75.2 (5⁰), 38.8 (6⁰), 22.6 (7⁰), 25.9 (8⁰), 16.5 (9⁰), 26.0

(Me±C±Si), 24.8 (Me±Si), 24.1 (Me±Si), 18.1 (Me±C±

Si). HRFABMS m/z calcd for C₂₁H₄₀O₂Si (M1Na)¹

375.2695, found 375.2684.

5-(5⁰-Hydroxy-2⁰,6⁰,6⁰-trimethyl)cyclohex-2⁰-enyl-3-methyl-

1-penten-3-ol (45). Tetrabutylammonium ¯uoride (0.13 g,

0.43 mmol) was added to a solution of 44 (0.14 g,

0.40 mmol) in THF (10 ml) and the mixture was stirred at

room temperature for 6 h. 76 mg (81%) of 45 was obtained

following the same procedure described for 38. Colourless

oil. IR (®lm): 3481, 2965, 2930, 2850, 1471, 1255, 1088,

3-(3⁰-Acetoxybutyl)-2,2,4-trimethylcyclohex-3-enol (47).

To a stirred solution of 46 (1.04 g, 4.1 mmol) in dry

CH₂Cl₂(45 ml), a 1 M solution of BBr₃in CH₂Cl₂

(4.9 ml) was added dropwise at 08C. After stirring for

15 min at room temperature a 1 M solution of collidine in

CH₂Cl₂(13.1 ml) was added at 08C and the mixture stirred

for 15 min at room temperature. Then, it was diluted with

CHCl₃(90 ml) and washed with 5% NaHSO₄(2£125 ml),

10% NaHCO₃(2£100 ml) and brine (2£100 ml). The

organic phase was dried over anh. Na₂SO₄and the solvent

evaporated to afford a crude reaction that by column chro-

matography (H±E 1:1) yielded 47 (927 mg, 89%) as a

1

1004, 918, 835, 758 cm²¹. H NMR (CDCl₃, 300 MHz):

5.94 (1H, dd, J18.6, 10.7 Hz, H-2), 5.24 (1H, bs, H-3⁰),

5.22 (1H, dd, J18.6 Hz, 1.2H, H-1), 5.08 (1H, dd, J10.7,

1.2 Hz, H-1), 3.47 (1H, dd, J8.1, 5.5 Hz, H-5⁰), 2.21 (1H,

m, H-4⁰), 1.99 (1H, m, H-4⁰), 1.75±1.30 (5H, m, H-4, H-5,

0

H-1 ), 1.71 (3H, bs, Me±C₂), 1.30 (3H, s, Me±C₃), 0.98

(3H, s, Me±C₆), 0.85 (3H, s, Me±C₆). ¹³C NMR (CDCl₃,

75 MHz): 112.0 (1), 145.1 (2), 73.6 (3), 44.6 (4), 22.7 (5),

26.0 (Me±C₃), 49.7 (1⁰), 136.9 (2⁰), 118.6 (3⁰), 31.9 (4⁰),

75.0 (5⁰), 38.6 (6⁰), 22.4 (7⁰), 25.6 (8⁰), 16.5 (9⁰).

HRFABMS m/z calcd for C₁₅H₂₆O₂(M1Na)¹261.1830,

found 261.1819.

0

1

colourless oil. IR (®lm): 3450, 2974, 1734, 1244 cm²¹. H

NMR (CDCl₃, 300 MHz): 4.87 (1H, tq, J6.2 Hz, H-3⁰),

3.45 (1H, dd, J9.3, 2.9 Hz, H-1), 2.10±1.90 (4H, m,

H-5, H-1⁰), 2.25 (1H, m, H-4⁰), 2.02 (3H, s, MeCO), 1.80

(1H, m), 1.70±1.50 (3H, m), 1.58 (3H, s, Me-9), 1.21 (3H, d,

J6.2 Hz, Me-4⁰), 1.03 (3H, bs, Me-8), 0.97 (3H, s, Me-7).

5-(5⁰-Acetoxy-2⁰,6⁰,6⁰-trimethyl)cyclohex-2⁰-enyl-3-methyl-

1-penten-3-ol (7). Acetic anhydride (1 ml) was added to a

solution of 45 (60 mg, 0.252 mmol) in pyridine (3 ml) and

6112

A. F. Barrero et al. / Tetrahedron 56 (2000) 6099±6113

¹³C NMR (CDCl₃, 75 MHz): 75.9 (1), 40.1 (2), 126.6 (3),

135.0 (4), 29.6 (5), 26.6 (6), 21.4 (7), 26.2 (8), 19.4 (9), 24.5

(1⁰), 36.4 (2⁰), 71.4 (3⁰), 19.8 (4⁰), 170.9 (MeCOO), 21.7

(MeCOO). HRFABMS m/z calcd for C₁₅H₂₆O₃(M1Na)¹

277.1780, found 277.1779.

Colourless oil. IR (®lm): 3460, 2950, 2862, 1668, 1160,

1070 cm²^{1 1}H NMR (CDCl₃, 300 MHz): 6.72 (1H, d,

.

J9.9 Hz), 6.19 (1H, d, J9.9 Hz), 3.88 (1H, tq,

J6.1 Hz, H-3⁰), 2.52 (1H, m, H-1⁰), 2.30 (1H, m, H-1⁰),

1.88 (3H, s, Me±C₄), 1.23 (3H, d, J6.1 Hz, H-4⁰), 1.22

(6H, s, Me±C₄). HRFABMS m/z calcd for C₁₃H₂₀O₂

(M1Na)¹253.1807, found 253.1803.

Treatment of 47 with TBSCl

TBSCl (0.17 g, 1.13 mmol), imidazole (0.08 g, 1.13 mmol)

and catalytic amount DMAP was added to a solution of 47

(0.18 g, 0.71 mmol) in anh. DMF (20 ml) and the mixture

stirred at room temperature for 44 h. Then it was diluted

with Et₂O and washed with 1N HCl (4£50 ml), 5%

NaHCO₃(4£50 ml) and brine (2£50 ml). The ethereal

phase was dried over anh. Na₂SO₄, ®ltered and evaporated

under vacuum to give a crude which after chromatography

(H±E 9:1) yielded 48 (1.07 g, 95 %). Colourless oil. IR

Reaction of 51 with Jones reagent

Preparation of 3-(3⁰-oxobutyl)-2,4,4-trimethylcyclohexa-

2,5-dienone (52). Jones reagent was added dropwise to a

solution of 51 (25 mg) cooled at 08C and the mixture stirred

for 15 min. After work-up as for alcohol 21, 52 (20 mg) was

obtained as a colourless oil. IR (®lm): 2962, 2931, 2858,

1716, 1660, 1628, 1604, 1471, 1371, 1257, 1163, 1089,

881 cm²^{1 1}H NMR (CDCl₃, 400 MHz): 6.71 (1H, d,

.

(®lm): 2969, 1745, 1242 cm²¹

.

¹H NMR (CDCl₃,

J9.9 Hz, H-5), 6.16 (1H, d, J9.9 Hz, H-6), 2.58 (4H, s,

H-1⁰, H-2⁰), 2.16 (3H, s, H-4⁰), 1.84 (3H, s, Me±C₂), 1.20

(6H, s, Me±C₄).¹³C NMR (CDCl₃, 100 MHz): 186.1 (1),

132.2 (2), 160.3 (3), 40.6 (4), 156.8 (5), 125.8 (6), 24.2

(7), 25.9 (8), 11.3 (9), 23.8 (1⁰), 42.1 (2⁰), 206.9 (3⁰), 29.7

(4⁰). HRFABMS m/z calcd for C₁₃H₁₈O₂(M1Na)¹

229.1204, found 229.1215.

300 MHz): 4.89 (1H, tq, J6.3 Hz, H-3⁰), 3.44 (1H, dd,

J7.4, 2.3 Hz, H-4), 2.04 (3H, s, AcO), 2.01±1.90 (4H,

m, H-6, H-1⁰), 1.70±1.50 (4H, m, H-5, H-2⁰), 1.56 (3H, s,

Me±C₁), 1.25 (3H, s, Me±C₃), 1.23 (3H, d, J6.3 Hz, H-4⁰),

0.91 (3H, s, Me±C₃), 0.89 (9H, s, Me±C±Si), 0.05 (3H, s,

Me±Si), 0.04 (3H, s, Me±Si). HRFABMS m/z calcd for

C₂₁H₄₀O₃Si (M1Na)¹391.2644, found 391.2649.

5-t-Butyldimethylsilyloxy-3-(3-hydroxybutyl)-2,4,4-tri-

methylcyclohex-2-enone (50). K₂CO₃(145 mg, 1.05

mmol) was added to a solution of 49 (300 mg, 0.78 mmol)

and the reaction mixture stirred for 1 h. After evaporating it

was diluted with H₂O (10 ml) and extracted with Et₂O

(3£30 ml). The combined organic phases were washed

with brine (3£30 ml), dried over anh. Na₂SO₄, ®ltered and

evaporated to afford a crude, which after chromatography

(H±E 7:3) gave 254 mg of 50 (95%). Colourless oil. IR

3-(3⁰-Acetoxybutyl)-5-t-butyldimethylsilyloxy-2,4,4-tri-

methylcyclohex-2-enone (49). To a solution of 48 (0.4 mg,

1.09 mmol) in dry benzene (14 ml), Na₂CrO₄(1.4 g,

8.6 mmol), NaOAc (1.06 g, 12.8 mmol), Ac₂O (4.2 ml)

and glacial AcOH (1.8 ml) was added and the reaction

mixture stirred at 658C for 3 h. Then it was poured into

ice and extracted with Et₂O (3£75 ml). The organic layer

was washed with 5% NaHCO₃(3£75 ml) and brine

(3£50 ml), dried and evaporated affording a crude which

after column chromatography (H±E 8:2), gave 366 mg of

49 (88%) as a colourless oil. IR (®lm): 2957, 2858, 1738,

1671, 1242, 1111 cm²¹. MS m/z (rel. int.): 383 [M11] (70),

325 (15), 251 (91), 191 (100). ¹H NMR (CDCl₃, 300 MHz):

4.95 (1H, tq, J6.2 Hz, H-3⁰), 3.76 (1H, dd, J10.0, 4.8 Hz,

H-5), 2.60 (1H, dd, J16.7, 4.7 Hz, H-6), 2.49 (1H, dd,

J16.7, 10.4 Hz, H-6), 2.25 (2H, m, H-1⁰), 2.06 (3H, s,

AcO), 1.76 (3H, s, Me-9), 1.67 (2H, m, H-2⁰), 1.26 (3H,

d, J6.3 Hz, Me-4⁰), 1.15 (3H, s, Me-8), 1.08 (3H, s, Me-7),

0.87 (9H, s, t-BuSi), 0.04 (3H, s, Me±Si), 0.03 (3H, s, Me±

Si). ¹³C NMR (CDCl₃, 75 MHz): 197.6 (1), 131.4 (2), 162.9

(3), 42.8 (4), 74.3 (5), 43.4 (6), 20.6 (7), 24.8 (8), 11.4 (9),

26.6 (1⁰), 34.6 (2⁰), 70.9 (3⁰), 19.9 (4⁰), 24.0 (Me±Si), 24.9

(Me±Si), 18.1 (Me±C±Si), 25.8 (Me±C±Si), 21.4 (Me±

CO), 170.8 (Me±CO). HRFABMS m/z calcd for

C₂₁H₃₈O₄Si (M1Na)¹405.2432, found 405.2437.

(®lm): 3450, 2958, 2857, 1665, 1112 cm²^{1 1}H NMR

.

(CD₃COCD₃, 500 MHz): 3.86 (1H, tq, J6.1 Hz, H-3⁰),

3.75 (1H, dd, J10.0, 4.7 Hz, H-5), 2.59 (1H, dd, J16.8,

4.7 Hz, H-6), 2.48 (1H, dd, J16.8, 10.0 Hz, H-6), 2.45±

2.20 (2H, m, H-1⁰), 1.76 (3H, s, Me-9), 1.59 (2H, m, H-2⁰),

1.23 (3H, d, J6.1 Hz, Me-4⁰), 1.16 (3H, s, Me-8), 1.08

(3H, s, Me-7), 0.86 (9H, s, t-Bu±Si), 0.04 (3H, s, Me±Si),

0.03 (3H, s, Me±Si). ¹³C NMR (CD₃COCD₃, 125 MHz):

197.8 (1), 131.0 (2), 163.9 (3), 42.8 (4), 74.3 (5), 43.4 (6),

19.8 (7), 24.8 (8), 11.5 (9), 27.0 (1⁰), 37.8 (2⁰), 68.4 (3⁰),

19.8 (4⁰), 24.0 (Me±Si), 24.9 (Me±Si), 18.1 (Me±C±Si),

25.9 (Me±C±Si). HRFABMS m/z calcd for C₁₉H₃₆O₃Si

(M1Na)¹363.2332, found 363.2331.

5-t-Butyldimethylsilyloxy-3-(3⁰-oxobutyl)-2,4,4-trimethyl-

cyclohex-2-enone (53). To a stirred solution of 50 (250 mg,

0.73 mmol) in acetone (8 ml), Jones reagent (0.3 ml) was

added dropwise at 2158C and the mixture was further

stirred for 30 min at this temperature. After work-up as

for alcohol 21, 53 (238 mg, 96%) was obtained as a colour-

less oil. IR (®lm): 2957, 2858, 1738, 1671, 1242,

Treatment of 49 with 2N KOH±MeOH

Preparation of 3-(3⁰-hydroxybutyl)-2,4,4-trimethylcyclo-

hexa-2,5-dienone (51). To a solution of 49 (50 mg,

0.13 mmol) in MeOH, a 2N KOH±MeOH solution (2 ml)

was added and the mixture stirred at room temperature for

24 h. After evaporating it was diluted with H₂O (10 ml) and

extracted with Et₂O (3£30 ml). The combined organic

phases were washed with brine (3£30 ml), dried over anh.

Na₂SO₄, ®ltered and evaporated to afford a crude, which

after chromatography (H±E 2:8) yielded 51 (25 mg, 93%).

1

1111 cm²¹. H NMR (CDCl₃, 400 MHz): 3.89 (1H, dd,

J9.4, 4.5 Hz, H-5), 2.68±2.41 (4H, m, H-6, H-2⁰), 2.13

(3H, s, Me±CO), 2.05 (2H, m, H-1⁰), 1.68 (3H, s, Me-9),

1.19 (3H, s, Me-8), 1.11 (3H, s, Me-7), 0.89 (9H, s, t-Bu±

Si), 0.09 (6H, s, Me±Si).¹³C NMR (CD₃COCD₃, 100 MHz):

196.3 (1), 131.6 (2), 162.3 (3), 43.3 (4), 75.5 (5), 43.8 (6),

21.2 (7), 25.1 (8), 11.3 (9), 24.7 (1⁰), 42.2 (2⁰), 206.0 (3⁰),

29.6(4⁰), 24.0 (Me±Si), 24.8 (Me±Si), 18.5 (Me±C±Si),

A. F. Barrero et al. / Tetrahedron 56 (2000) 6099±6113

6113

26.2 (Me±C±Si). HRFABMS m/z calcd for C₁₉H₃₄O₃Si

(M1Na)¹361.2173, found 361.2174.

was added to a solution of 55 (50 mg, 0.198 mmol) in pyri-

dine (2 ml), and the mixture was stirred at room temperature

for 1 h. After work-up as for alcohol 35, 8 was obtained

(54 mg, 93%). Colourless oil. IR (®lm): 3470, 1735, 1663,

924 cm²¹. MS m/z (rel. int.): 295 [M11] (1), 235 (20), 220

5-t-Butyldimethylsilyloxy-3-(3-hydroxy-3-methylpent-4-

enyl)-2,4,4-trimethylcyclohex-2-enone (54). Vinylmag-

nesium bromide (1 M in THF, 1 ml, 1 mmol) was added

to a stirred solution of 53 (200 g, 0.591 mmol) in THF

(8 ml) at 08C, and the whole was stirred at 08C for 45 min.

After work-up as for ketone 22, 54 (188 mg, 87%) was

obtained. Colourless oil. IR (®lm): 3426, 2929, 2856,

1655, 878 cm²¹.¹H NMR (CDCl₃, 400 MHz): 5.94 (1H,

dd, J17.5, 10.8 Hz, H-4⁰), 5.26 (1H, d, J17.3 Hz, H-5⁰

trans), 5.13 (1H, d, J10.7 Hz, H-5⁰cis), 3.76 (1H, dd,

J10.0, 4.8 Hz, H-5), 2.61 (1H, dd, J16.8, 4.8 Hz, H-6),

2.51 (1H, dd, J16.8, 10.0 Hz, H-6), 2.30 (2H, m, H-1⁰),

1.73 (3H, s, Me-9), 1.70±1.60 (2H, m, H-2⁰), 1.33 (3H, s,

1

(13), 149 (55). H NMR (CDCl₃, 300 MHz): 5.91 (1H, dd,

J17.3, 10.7 Hz, H-4⁰), 5.27 (1H, d, J17.3 Hz, H-5⁰

trans), 5.12 (1H, d, J10.7 Hz, H-5⁰cis), 5.04 (1H, dd,

J7.7 and 4.0 Hz, H-5), 2.75 (1H, dd, J16.9 and 4.1 Hz,

H-6), 2.54 (1H, dd, J16.9 and 7.8 Hz, H-6), 2.30 (2H, m,

H-1⁰), 2.03 (3H, s, Me±OAc), 1.77 (3H, s, Me-9), 1.75±1.65

0

(2H, m, H-2 ), 1.34 (3H, s, Me±C₃), 1.17 (3H, s, Me-8),

1.15 (3H, s, Me-7). ¹³C NMR (CDCl₃, 75 MHz): 195.7 (1),

131.3 (2), 162.1 (3), 40.5 (4), 75.7 (5), 39.1 (6), 25.1 (7),

21.8 (8), 11.6 (9), 25.1 (1⁰), 39.9 (2⁰), 73.3 (3⁰), 143.9 (4⁰),

0

112.6 (5 ), 28.1 (Me±C₃), 170.5 (MeCOO), 21.1 (MeCOO).

Me±C₃), 1.16 (3H, s, Me-8), 1.08 (3H, s, Me-7), 0.87 (9H,

HRFABMS m/z calcd for C₁₇H₂₆O₄(M1Na)¹317.1729,

found 317.1736.

0

s, t-Bu±Si), 0.05 (3H, s, Me±Si), 0.04 (3H, s, Me±Si).¹³C

NMR (CDCl₃, 100 MHz): 196.3 (1), 131.3 (2), 162.3 (3),

42.9 (4), 75.5 (5), 43.9 (6), 21.4 (7), 25.3 (8), 11.4 (9), 25.9

(1⁰), 41.3 (2⁰), 72.8 (3⁰), 146.3 (4⁰), 111.9 (5⁰), 24.0 (Me±

Acknowledgements

0

C±Si), 24.8 (Me±Si), 18.2 (Me±C±Si), 28.3 (Me±C₃),

25.9 (Me±C±Si). HRFABMS m/z calcd for C₂₁H₃₈O₃Si

(M1Na)¹389.2489, found 389.2487.

We should like to thank the CICYT (Projet PB 98-1365) for

®nancial support.

5-Hydroxy-3-(3⁰-hydroxy-3⁰-methylpent-4⁰-enyl)-2,4,4-

trimethylcyclohex-2-enone

(55).

TBAF

(158 mg,

References

0.5 mmol) was added at 08C to a solution of 54 (150 mg,

0.41 mmol) in THF (5 ml) and the mixture stirred at room

temperature for 2 h. The crude was diluted with Et₂O

(25 ml) and the organic phase washed with brine

(3£10 ml), dried and evaporated to yield 55 (83 mg, 81%)

1. Caglioti, L.; Naef, H.; Arigoni, D.; Jeger, O. Helv. Chim. Acta

1959, 42, 2557±2570.

2. Barrero, A. F.; Manzaneda, E. A.; Manzaneda, R. Tetrahedron

Lett. 1989, 30, 3351±3352.

as a colourless oil. IR (®lm): 3402, 2929, 1653, 803 cm²¹

.

3. Marco, J. A.; Sanz, J. F.; Morante, M. D.; Lliso, V. G.; Xirau,

J. V.; Jakupovic, J. Phytochemistry 1996, 41, 837±844.

4. Marco, J. A.; Sanz, J. F.; Yuste, A.; Jakupovic, J. Phyto-

chemistry 1991, 30, 3661±3668.

MS m/z (rel. int.): 253 [M11] (30), 235 (25), 217 (37), 149

1

(51). H NMR (CDCl₃, 300 MHz): 5.95 (1H, dd, J17.3,

10.7 Hz, H-4⁰), 5.28 (1H, d, J17.3 Hz, H-5⁰trans), 5.15

(1H, d, J10.7 Hz, H-5⁰cis), 3.83 (1H, dd, J9.2, 4.2 Hz,

H-5), 2.72 (1H, dd, J16.9, 4.1 Hz, H-6), 2.55 (1H, dd,

5. Barrero, A. F.; Manzaneda, E. A.; Herrador, M. M.; Manzaneda,

Â

R. A.; Quõlez, J.; Chahboun, R.; Linares, P.; Rivas, A. Tetrahedron

Lett. 1999, 40, 8273±8276.

J16.9 and 9.2 Hz, H-6), 2.30 (2H, m, H-1⁰), 1.77 (3H, s,

0

Me-9), 1.71±1.60 (2H, m, H-2 ), 1.34 (3H, s, Me±C₃), 1.15

6. Mukaiyama, T.; Iwasawa, N. Chem. Lett. 1981, 29±32.

7. Demnitz, F. W. J.; Philippini, C.; Raphael, R. A. J. Org. Chem.

1995, 60, 5114±5120.

(3H, s, Me-8), 0.87 (3H, s, Me-7). ¹³C NMR (CDCl₃,

75 MHz): 196.9 (1), 131.5 (2), 163.8 (3), 43.5 (4), 74.0

(5), 43.5 (6), ₀20.9 (7), 25.2 (8), 11.5 (9), 25.8 (1⁰), 41.3

8. Barrero, A. F.; Manzaneda, E. A.; Linares, P. Tetrahedron

1994, 50, 13239±13250.

0

(2 ), 72.2 (3 ), 146.8 (4 ), 111.9 (5 ), 28.4 (Me±C₃).

HRFABMS m/z calcd for C₁₅H₂₅O₃(M1Na)¹253.1807,

found 253.1803.

9. Pettit, G.; Herald, C.; Hallen, M.; Von Dreele J. Am. Chem. Soc.

1977, 262±270.

10. Armstrong, R. J.; Weiler, L. Can. J. Chem. 1986, 64, 584±596.

11. Barrero, A. F.; Manzaneda, E. A.; Chahboun, R.; Meneses, R.

Synlett 1999, 10, 1663±1666.

5-Acetoxy-3-(3⁰-hydroxy-3⁰-methylpent-4⁰-enyl)-2,4,4-

trimethylcyclohex-2-enone (8). Acetic anhydride (1 ml)

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Synthesis of natural oxygenated monocarbocyclic sesquiterpenoids from 6,7-epoxygeranyl acetate

DOI: 10.1016/S0040-4020(00)00560-3

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Article abstract of DOI:10.1016/S0040-4020(00)00560-3

Full text of DOI:10.1016/S0040-4020(00)00560-3

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