Total synthesis of (±)-infuscol A and (±)-cuprenenol

Article abstract of DOI:10.1081/SCC-200034755

Total synthesis of the nonaromatic cuparenoid sesquiterpenes (±)-infuscol A and cuprenenol, and (±)-infuscol B and neocuprenenol isolated from the Japanese liverwort Jungermannia infusca has been accomplished. Two ring-closing metathesis reaction based st

Full text of DOI:10.1081/SCC-200034755

This article was downloaded by: [Case Western Reserve University]
On: 04 November 2014, At: 22:22
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T
3JH, UK
Synthetic Communications:
An International Journal
for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Total Synthesis of (±)‐Infuscol
A and (±)‐Cuprenenol
A. Srikrishna a & G. Satyanarayana a
a Department of Organic Chemistry , Indian
Institute of Science , Bangalore, 560 012, India
Published online: 10 Jan 2011.
To cite this article: A. Srikrishna & G. Satyanarayana (2004) Total Synthesis of
(±)‐Infuscol A and (±)‐Cuprenenol, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 34:21, 3847-3864,
DOI: 10.1081/SCC-200034755
To link to this article: http://dx.doi.org/10.1081/SCC-200034755
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all
the information (the “Content”) contained in the publications on our
platform. However, Taylor & Francis, our agents, and our licensors
make no representations or warranties whatsoever as to the accuracy,
completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of
the authors, and are not the views of or endorsed by Taylor & Francis.
The accuracy of the Content should not be relied upon and should be
independently verified with primary sources of information. Taylor and
Francis shall not be liable for any losses, actions, claims, proceedings,
demands, costs, expenses, damages, and other liabilities whatsoever

or howsoever caused arising directly or indirectly in connection with, in
relation to or arising out of the use of the Content.
This article may be used for research, teaching, and private study
purposes. Any substantial or systematic reproduction, redistribution,
reselling, loan, sub-licensing, systematic supply, or distribution in any form
to anyone is expressly forbidden. Terms & Conditions of access and use
can be found at http://www.tandfonline.com/page/terms-and-conditions

SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 21, pp. 3847–3864, 2004
Total Synthesis of (+)-Infuscol A and
(+)-Cuprenenol
*
A. Srikrishna and G. Satyanarayana
Department of Organic Chemistry, Indian Institute of Science,
Bangalore, India
ABSTRACT
Total synthesis of the nonaromatic cuparenoid sesquiterpenes (+)-infus-
col A and cuprenenol, and (+)-infuscol B and neocuprenenol isolated
from the Japanese liverwort Jungermannia infusca has been accom-
plished. Two ring-closing metathesis reaction based strategies have
been developed for the generation of the key intermediate of the sequence.
Key Words: Claisen rearrangement; Cuparanes; Ring-closing meta-
thesis reaction; Terpene synthesis.
Liverworts are small plants, and are a rich source of unique, natural
products,[1] which are not found in higher plants. The Japanese and
*
Correspondence: A. Srikrishna, Department of Organic Chemistry, Indian
Institute of Science, Bangalore 560 012, India; Fax: þ91-80-23600529; 23600683;
E-mail: ask@orgchem.iisc.ernet.in.
3847
DOI: 10.1081/SCC-200034755
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

3848
Srikrishna and Satyanarayana
Taiwanese collections of the species Jungermannia infusca have yielded diter-
penoids, sesquiterpenoids, and aromatic compounds. Recently, Nagashima
and coworkers have reported isolation of several nonaromatic cuparenoid
sesquiterpenes, infuscols A–D 1–4, cuprenenol 5, neocuprenenol 6, endoper-
oxides 7 and 8, diepoxide 9, d-cuprenenol 10, and resulantol 11 along with
cuparene 12 from Jungermannia infusca collected at Tokushima.[2] Structures
of all these nonaromatic cuparenoids have been established based on the
spectral studies. Structures of infuscol A 1 and cuprenenol 5 were further
confirmed by X-ray crystal structures of the corresponding epoxides.[2a,c]
Absolute configuration was established by correlation to (S)-cuparene.
In contrast to the aromatic cuparenes, nonaromatic cuparenes have
received very little attention from synthetic chemists.[3] Herein we wish to
report the first total synthesis of the nonaromatic cuparenoids (+)-infuscol
A 1 and cuprenenol 5 along with infuscol B 2 and neocuprenenol 6.
Cyclohexenone 13 was readily identified as the appropriate precursor
for the synthesis of the infuscols 1, 2 and cuprenenols 5, 6. Based on the

Total Synthesis of (+)-Infuscol A and (+)-Cuprenenol
3849
Birch reduction-based protocol, the anisyl group was considered as a masked
cyclohexenone, and the norcuparene 14 was contemplated as the key inter-
mediate of the sequence. Two different methodologies, based on Claisen
rearrangement and ring-closing metathesis reaction (RCM) as key steps,
were developed for the synthesis of the norcuparane 14. The first method-
ology, based on the RCM reaction of the diene 15, is depicted in Sch. 1.
Thus, coupling of 4-bromoanisole with 2,2-dimethylpent-4-enal under
Barbier conditions followed by oxidation of the resultant benzylic alcohol
16 furnished the aryl ketone 17. As the conventional Wittig or Horner-
Wadsworth-Emmons reactions were not successful due to steric crowding, a
three-step strategy was employed for the conversion of the ketone 17 into
Scheme 1. Reagents, conditions, and yields: (a) Li, THF, 1 h, 85%. (b) PCC, silica
gel, CH2Cl2, rt, 3 h, 97%. (c) CH255CHMgBr, THF, 08C ! rt, 4 h, 70%. (d) PCC, silica
gel, CH2Cl2, rt, 30 h, 83%. (e) NaBH4, MeOH, 08C ! rt, 2 h, 70%. (f) CH3C(OEt)3,
EtCO2H, sealed tube, 1808C, 48 h, 47%. (g) PhCH55RhCl2(PCy3)2, CH2Cl2, rt, 8 h,
96%. (h) H2, 5% Pd/C, EtOH, 1 atm., 3 h, 100%. (i) LAH, Et2O, 08C ! rt, 1 h,
94%. (j) PCC, silica gel, CH2Cl2, rt, 0.5 h, 85%. (k) (PPh3)3RhCl, C6H6, sealed tube,
1208C, 24 h, 82%.

3850
Srikrishna and Satyanarayana
the allyl alcohol 18. Thus, addition of vinylmagnesium bromide to the ketone
17 followed by oxidation of the resultant allylic tertiary alcohol 19 with pyri-
dinium chlorochromate (PCC) and silica gel furnished the cinnamaldehyde 20
in a highly stereoselective manner, which on regioselective reduction with
sodium borohydride furnished the allyl alcohol 18. Since both E and Z
isomers of the alcohol 18 leads to the same ester 15 after Claisen rearrange-
ment, no attempt was made to establish the stereochemistry in the compounds
20 and 18, and was tentatively assigned as Z based on the steric reasons.
Johnson’s orthoester Claisen rearrangement[4] of the allyl alcohol 18 with
triethyl orthoacetate and a catalytic amount of propionic acid created the
second quaternary carbon atom and furnished the key intermediate 1,6-
diene 15. Treatment of the diene 15 with 5 mol% of Grubbs’ first generation
catalyst induced the RCM reaction[5] to generate the cyclopentene 21 in
near quantitative yield. Catalytic hydrogenation of the cyclopentene moiety
transformed the ester 21 into the ester 22. Reduction of the ester moiety in
22 with LAH followed by oxidation of the resultant primary alcohol 23
with PCC and silica gel transformed the ester 22 into the aldehyde 24.
Wilkinson catalyst-mediated decarbonylation transformed the aldehyde 24
into the norcuparane 14.
The second methodology is based on the RCM reaction of the diene 25
starting from the readily available[6] aldehyde 26, Sch. 2. Thus, the aldehyde
26 was prepared from 4-methoxyacetophenone employing the Claisen
rearrangement as the key step.[6] Addition of vinylmagnesium bromide to
the aldehyde 26 generated the RCM precursor, the diene 25 as a mixture of
diastereomers. RCM reaction of the diene 25 with first generation Grubbs’
catalyst furnished cyclopentenol 27 in near quantitative yield, which on
oxidation with PCC and silica gel generated the cyclopentenone 28. One step
dimethylation of the enone 28 with sodium hydride and iodomethane created
the second quaternary carbon atom and generated the cyclopentenone 29.
Catalytic hydrogenation transformed the enone 29 into the cyclopentanone
30. Thioketalization of the cyclopentanone 30 with ethanedithiol and boron
trifluoride etherate gave the thioketal 31. Desulfurization of the thioketal 31
with Raney nickel generated a mixture of the norcuparane 14 along with
varying amounts of the cyclopentene 32. Catalytic hydrogenation of a
mixture of 14 and 32 furnished the norcuparane 14.
After gaining access to the norcuparane 14, attention was turned towards
its conversion to nonaromatic cuparenoids 1, 2, 5, and 6, which is depicted
in Sch. 3. Thus, Birch reduction of the anisole moiety in 14 with lithium in
liquid ammonia and ethanol furnished the diene 33. Hydrolysis of the enol
ether in 33 with aqueous sulphuric acid furnished the enone 34, which
was found to be very sensitive to standard isomerization techniques. After
exploring various conditions, rhodium chloride trihydrate[7] was found to be

Total Synthesis of (+)-Infuscol A and (+)-Cuprenenol
3851
Scheme 2. Reagents, conditions, and yields: (a) reference 6. (b) CH255CHMgBr,
THF, 08C ! rt, 4 h, 77%. (c) PhCH55RuCl2(PCy3)2, CH2Cl2, 6 h, 97%. (d) PCC, silica
gel, CH2Cl2, 3 h, 96%. (e) NaH, CH3I, THF, DMF, RT, 12 h, 80%. (f) H2, 5% Pd/C,
EtOH, 5 h, 99%. (g) (CH2SH)2, BF3 . Et2O, 08C ! rt, 12 h, 93%. (h) Raney Ni, EtOH,
reflux, 2 h. (i) H2, 5% Pd/C, EtOH, 3 h; 80% from 31.
ideal for the isomerization of the olefin in 34 to furnish a 3 : 2 diastereomeric
mixture of the enone 13. Finally, addition of methylmagnesium iodide to
the diastereomeric mixture of the enone 13 followed by purification on a
silica gel column furnished infuscol A 1 and cuprenenol 5 as major products
(80%), and infuscol B 2 and neocuprenenol 6 as minor products (7%). The
1
synthetic compounds 1, 2, 5, and 6 exhibited the H and 13C NMR spectral
data identical to those of the natural compounds. To unambiguously establish
their identity, the mixture of infuscol A 1 and cuprenenol 5 was hydrogenated
with 5% palladium over carbon as the catalyst in ethanol to furnish a single
isomer of the dihydro derivative 35.
In conclusion, we have accomplished the first total synthesis of the
nonaromatic cuparenoid sesquiterpenoids infuscols A and B, cuprenenol and

3852
Srikrishna and Satyanarayana
Scheme 3. Reagents, conditions, and yields: (a) Li, liq. NH3, THF, EtOH, 2.5 h,
85%. (b) 10% aq. H2SO4, THF, 50 min., 90%. (c) 8 mol% RhCl3 . 3H2O, EtOH, reflux,
3 h, 90%. (d) CH3MgI, Et2O, 0–58C, 0.5 h, 86%. (e) 5% Pd/C, H2, EtOH, 6 h, 95%.
neocuprenenol isolated from the Japanese liverwort Jungermannia infusca.
Currently, we are investigating the extension of the methodologies for the
enantioselective synthesis of these nonaromatic cuparenoid sesquiterpenes.
EXPERIMENTAL SECTION
Melting points were recorded using Tempo and Mettler FP1 melting point
apparatus in capillary tubes and were uncorrected. IR spectra were recorded
1
on a Jasco FTIR 410 spectrophotometer. H (300 MHz) and 13C (75 MHz)
NMR spectra were recorded on JNM l-300 spectrometer, using 1 : 1
mixture of CDCl3 and CCl4 as solvent. The chemical shifts (d ppm) and
coupling constants (Hz) are reported in the standard fashion with reference
1
to either internal tetramethylsilane (for H) or the central line (77.0 ppm)
of CDCl3 (for 13C). In the 13C NMR spectra, the nature of the carbons

Total Synthesis of (+)-Infuscol A and (+)-Cuprenenol
3853
(C, CH, CH2, or CH3) was determined by recording DEPT-135 spectra, and
are given in parentheses. Low-resolution mass spectra were recorded using
a Shimadzu QP-5050A GCMS instrument using direct inlet mode. Relative
intensities are given in parentheses. High resolution mass spectra were
recorded on a Micromass Q-TOF micro mass spectrometer using electron
spray ionization mode.
1-(4-Methoxyphenyl)-2,2-dimethylpent-4-en-1-one (17): To a sono-
chemically irradiated suspension of lithium (375 mg, 53.5 mmol) in dry
THF (5 mL) in a round-bottom flask, placed in an ultrasonic cleaning
bath, was added a solution of 2,2-dimethylpent-4-enal (1 g, 8.9 mmol) and
4-bromoanisole (3.34 g, 17.8 mmol) in THF (2 mL) at 15–208C over a
period of 10 min, and sonochemically irradiated for 1 h. Then the reaction
mixture was decanted from the excess lithium, quenched with saturated
aqueous NH4Cl solution and extracted with ether (3 ꢀ 10 mL). The ether
extract was washed with brine and dried (Na2SO4). Evaporation of the
solvent and purification of the residue on a silica gel column using ethyl
acetate-hexane (1 : 20) as eluent furnished the alcohol 16 (1.67 g, 85%) as
1
oil. [IR (neat): vmax/cm21 3467, 914. H NMR (300 MHz, CDCl3 þ CCl4):
d 7.17 (2 H, d, J ¼ 8.4 Hz), 6.75 (2 H, d, J ¼ 8.4 Hz), 5.85 (1 H, t of dd,
J ¼ 16.2, 10.5 and 7.8 Hz), 5.14 (1 H, d, J ¼ 10.4 Hz), 5.13 (1 H, d,
J ¼ 16.8 Hz), 4.36 (1 H, s), 3.77 (3 H, s), 2.14 (1 H, dd, J ¼ 13.5 and
7.2 Hz), 1.97 (1 H, dd, J ¼ 13.5 and 7.2 Hz), 1.94 (1 H, br s), 0.86 (3 H, s),
0.79 (3 H, s). 13C NMR (75 MHz, CDCl3 þ CCl4): d 158.8 (C); 135.4 (CH),
134.0 (C), 128.7 (2 C, CH), 117.3 (CH2), 112.9 (2 C, CH), 80.4 (CH), 54.9
(CH3), 43.5 (CH2), 38.5 (C), 23.4 (CH3), 22.3 (CH3). Mass: m/z 243
(M þ Na, 88%), 220 (Mþ, 1), 137 (88), 135 (100), 121 (8), 109 (15), 107
(12)]. To a magnetically stirred solution of the secondary alcohol 16 (1.1 g,
5 mmol) in 5 mL of dry CH2Cl2 was added a homogeneous mixture of
PCC (3.23 g, 15 mmol) and silica gel (3.23 g) and stirred vigorously for 3 h
at RT. The reaction mixture was then filtered through a small silica gel
column and eluted the column with CH2Cl2. Evaporation of the solvent and
purification of the residue on a silica gel column using ethyl acetate-hexane
(1 : 40 to 1 : 20) as eluent furnished the ketone 17 (1.06 g, 97%) as oil. IR
1
(neat): vmax/cm21 1665, 918. H NMR (300 MHz, CDCl3 þ CCl4): d 7.76
(2 H, d, J ¼ 8.7 Hz), 6.83 (2 H, d, J ¼ 8.7 Hz), 5.64 (1 H, t of dd, J ¼ 16.8,
10.2 and 6.9 Hz), 4.97 (1 H, d, J ¼ 10.2 Hz), 4.94 (1 H, d, J ¼ 16.8 Hz),
3.81 (3 H, s), 2.47 (2 H, d, J ¼ 6.9 Hz), 1.30 (6 H, s). 13C NMR (75 MHz,
CDCl3 þ CCl4): d 204.5 (C), 161.9 (C), 134.3 (C, CH), 130.8 (2 C, CH),
130.6 (CH), 118.0 (CH2), 113.2 (2 C, CH), 55.1 (CH3), 47.3 (C), 45.5
(CH2), 26.2 (2 C, CH3). Mass: m/z 218 (Mþ, 4%), 136 (9), 135 (100), 107
(10), 92 (12). HRMS: m/z Calcd. for C14H19O2 (M þ 1): 219.1385. Found:
219.1388.

3854
Srikrishna and Satyanarayana
3-(4-Methoxyphenyl)-4,4-dimethylhepta-1,6-dien-3-ol (19): To a mag-
netically stirred solution of the ketone 17 (1 g, 4.6 mmol) in THF (3 mL) was
added a solution of vinylmagnesium bromide [prepared from magnesium
(550 mg, 22.9 mmol) and bromoethylene (1.94 mL, 27.5 mmol) in THF
(6 mL)] and stirred for 4 h at RT. The reaction was then quenched with
aqueous NH4Cl solution and extracted with ether (4 ꢀ 5 mL). The organic
layer was washed with water and brine, and dried (Na2SO4). Evaporation of
the solvent and purification of the residue on a silica gel column using ethyl
acetate-hexane (1 : 20) as eluent furnished the tertiary alcohol 19 (800 mg,
1
70%) as oil. IR (neat): vmax/cm21 3495, 913. H NMR (300 MHz, CDCl3 þ
CCl4): d 7.34 (2 H, d, J ¼ 8.7 Hz), 6.78 (2 H, d, J ¼ 8.7 Hz), 6.73 (1 H, dd,
J ¼ 17.0 and 10.8 Hz), 5.77 (1 H, m), 5.31 (1 H, d, J ¼ 17.0 Hz), 5.22 (1 H,
d, J ¼ 10.8 Hz), 5.02–4.80 (2 H, m), 3.77 (3 H, s), 2.10 (1 H, dd, J ¼ 13.5
and 6.9 Hz), 2.01 (1 H, dd, J ¼ 13.5 and 7.5 Hz), 1.74 (1 H, brs), 0.86
(6 H, s). 13C NMR (75 MHz, CDCl3 þ CCl4): d 158.3 (C), 142.0 (2 C, CH),
136.2 (CH), 128.6 (2 C, CH), 117.3 (CH2), 113.5 (CH2), 112.6 (2 C, CH),
80.77 (C), 55.0 (CH3), 41.7 (CH2), 41.2 (C), 22.5 (CH3), 21.9 (CH3). Mass:
m/z 163 (Mþ 2 C6H11, 100%), 135 (18), 91 (4). HRMS: m/z Calcd. for
C16H21O (M–OH): 229.1592. Found: 229.1602.
3-(4-Methoxyphenyl)-4,4-dimethylhepta-2,6-dienal (20): To a magne-
tically stirred suspension of PCC (8.2 g, 38.0 mmol) and silica gel (8.2 g) in
dry CH2Cl2 (7 mL) was added a solution of the tertiary alcohol 19 (780 mg,
3.17 mmol) in CH2Cl2 (2 mL) and stirred vigorously for 30 h at RT. The reac-
tion mixture was then filtered through a small silica gel column, and the
column eluted with more CH2Cl2. Evaporation of the solvent and purification
of residue on a silica gel column using ethyl acetate-hexane (1 : 20) as eluent
furnished the aldehyde 20 (643 mg, 83%) as oil. IR (neat): vmax/cm21 2747,
1675, 1638, 917. 1H NMR (300 MHz, CDCl3 þ CCl4): d 9.10 (1 H, d,
J ¼ 7.5 Hz), 7.04 (2 H, d, J ¼ 8.4 Hz), 6.87 (2 H, d, J ¼ 8.4 Hz), 6.09 (1 H,
d, J ¼ 7.5 Hz), 5.73 (1 H, t of dd, J ¼ 17.4, 10.2 and 6.9 Hz), 5.08 (1 H, d,
J ¼ 10.2 Hz), 5.03 (1 H, d, J ¼ 17.4 Hz), 3.82 (3 H, s), 2.17 (2 H, d,
J ¼ 6.9 Hz), 1.12 (6 H, s). 13C NMR (75 MHz, CDCl3 þ CCl4): d 193.7
(CH), 171.7 (C), 159.2 (C), 134.2 (CH), 130.2 (2 C, CH), 128.8 (CH),
128.4 (C), 118.2 (CH2), 113.2 (2 C, CH), 55.0 (CH3), 44.8 (CH2), 40.5 (C),
26.7 (2 C, CH3). Mass: m/z 244 (Mþ, 15%), 203 (100), 201 (40), 188 (96),
187 (34), 175 (35), 173 (35), 161 (22), 160 (22), 159 (25), 135 (75), 133
(25), 121 (50), 115 (20). HRMS: m/z Calcd. for C16H20O2Na (M þ Na):
267.1361. Found: 267.1380.
3-(4-Methoxyphenyl)-4,4-dimethylhepta-2,6-dien-1-ol (18): To an ice
cold, magnetically stirred solution of the aldehyde 20 (630 mg, 2.58 mmol)
in dry methanol (3 mL) was added NaBH4 (98 mg, 2.58 mmol) and stirred
for 2 h at the same temperature. The reaction was then quenched with water

Total Synthesis of (+)-Infuscol A and (+)-Cuprenenol
3855
(5 mL) followed by 3 N aqueous HCl (5 mL) and extracted with CH2Cl2
(5 ꢀ 6 mL). The combined CH2Cl2 extract was washed with brine and dried
(Na2SO4). Evaporation of the solvent and purification of the residue on a
silica gel column using ethyl acetate-hexane (1 : 30 to 1 : 10) as eluent
furnished the primary alcohol 18 (450mg, 70%) as oil. IR (neat): vmax/cm21
3353, 913. 1H NMR (300 MHz, CDCl3 þ CCl4): d 6.87 (2 H, d,
J ¼ 9.0 Hz), 6.78 (2 H, d, J ¼ 9.0 Hz), 5.76 (1 H, t of dd, J ¼ 16.8, 10.2
and 7.5 Hz), 5.67 (1 H, t, J ¼ 6.6 Hz), 5.01 (1 H, d, J ¼ 10.2 Hz), 4.96 (1 H,
J ¼ 16.8 Hz), 3.77 (3 H, s), 3.70 (2 H, d, J ¼ 6.6 Hz), 2.04 (2 H, d,
J ¼ 7.5 Hz), 1.23 (1 H, br s), 1.02 (6 H, s). 13C NMR (75 MHz, CDCl3 þ
CCl4): d 158.3 (C), 150.8 (C), 135.6 (CH), 131.2 (C), 130.3 (2 C, CH),
125.8 (CH), 117.1 (CH2), 113.2 (2 C, CH), 60.7 (CH2), 54.9 (CH3), 45.0
(CH2), 39.0 (C), 27.2 (2 C, CH3). Mass: m/z 246 (Mþ, 25%), 203 (30), 187
(75), 172 (50), 161 (90), 149 (35), 135 (37), 121 (75), 91 (100). HRMS:
m/z Calcd. for C16H22O2Na (M þ Na): 269.1517. Found: 269.1519.
Ethyl 3-(4-Methoxyphenyl)-4,4-dimethyl-3-vinylhept-6-enoate (15):
A solution of the allyl alcohol 18 (410 mg, 1.66 mmol), triethyl orthoacetate
(2.12 mL, 11.66 mmol), and a catalytic amount of propionic acid was placed
in a sealed tube and heated to 1808C for 2 days in an oil bath. The reaction
mixture was then cooled, diluted with ether (5 mL), washed with 3 N
aqueous HCl (5 mL) followed by saturated NaHCO3 solution (5 mL) and
brine, and dried (Na2SO4). Evaporation of the solvent and purification of
the residue on a silica gel column using ethyl acetate-hexane (1 : 40) as
eluent furnished the ester 15 (250 mg, 47%) as oil. IR (neat): vmax/cm21
1749, 1717, 913. 1H NMR (300 MHz, CDCl3 þ CCl4): d 7.23 (2 H, d,
J ¼ 9.3 Hz), 6.76 (2 H, d, J ¼ 9.3 Hz), 6.52 (1 H, dd, J ¼ 17.7 and
11.4 Hz), 5.66 (1 H, t of dd, J ¼ 17.4, 9.9 and 7.2 Hz), 5.32 (1 H, d,
J ¼ 11.4 Hz), 5.10 (1 H, d, J ¼ 17.4 Hz), 4.95 (1 H, d, J ¼ 10.2 Hz), 4.90
(1 H, d, J ¼ 17.4 Hz), 3.89 (2 H, q, J ¼ 6.9 Hz), 3.77 (3 H, s), 3.19 and
2.88 (2 H, AB q, J ¼ 16.5 Hz), 1.99 and 1.87 (2 H, 2 ꢀ dd, J ¼ 13.2 and
7.8 Hz), 1.06 (3 H, t, J ¼ 6.9 Hz), 0.82 (3 H, s), 0.79 (3 H, s). 13C NMR
(75 MHz, CDCl3 þ CCl4): d 170.9 (C), 157.6 (C), 139.4 (CH), 135.7 (CH),
133.0 (C), 130.1 (2 C, CH), 117.5 (CH2), 116.0 (CH2), 112.3 (2 C, CH),
59.6 (CH2), 54.8 (CH3), 52.2 (C), 42.0 (CH2), 40.4 (C), 36.7 (CH2), 22.5
(2 C, CH3), 14.2 (CH3). Mass: m/z 234 (Mþ 2 82, 16%), 233 (43), 187 (7),
160 (24), 159 (100), 145 (34), 115 (8). HRMS: m/z Calcd. for C20H28O3Na
(M þ Na): 339.1936. Found: 339.1928.
Ethyl 2-[1-(4-methoxyphenyl)-5,5-dimethylcyclopent-3-en-1-yl]ace-
tate (21): To a magnetically stirred solution of the dieneester 15 (150 mg,
0.7 mmol) in anhydrous CH2Cl2 (18 mL) was added a solution of Grubbs’
first generation catalyst (28 mg, 5 mol%) in anhydrous CH2Cl2 (15 mL) and
the reaction mixture was stirred at room temperature for 4 h. Evaporation of

3856
Srikrishna and Satyanarayana
the solvent under reduced pressure and purification of the residue on a silica
gel column using ethyl acetate-hexane (1 : 30) as eluent furnished the cyclized
1
compound 21 (134 mg, 98%) as oil. IR (neat): vmax/cm21 1734. H NMR
(300 MHz, CDCl3 þ CCl4): d 7.13 (2 H, d, J ¼ 9.0 Hz), 6.76 (2 H, d,
J ¼ 9.0 Hz), 6.26 (1 H, d, J ¼ 6.0 Hz), 5.85 (1 H, t of d, J ¼ 6.0 and
2.4 Hz), 3.87 (2 H, q, J ¼ 7.2 Hz), 3.76 (3 H, s), 3.03 and 2.47 (2 H, 2 ꢀ d,
J ¼ 15 Hz), 2.31 (1 H, m of d, J ¼ 15.6 Hz), 2.14 (1 H, m of d, J ¼ 15.6
and 3.0 Hz), 1.13 (3 H, s), 1.02 (3 H, t, J ¼ 7.2 Hz), 0.44 (3 H, s). 13C
NMR (75 MHz, CDCl3 þ CCl4): d 171.5 (C), 157.9 (C), 138.5 (CH), 134.4
(C), 129.4 (CH), 127.6 (2 C, CH), 113.2 (2 C, CH), 59.7 (CH2), 57.7 (C),
54.9 (CH3), 47.2 (CH2), 45.8 (C), 41.4 (CH2), 27.9 (CH3), 23.6 (CH3), 14.2
(CH3). Mass: m/z 288 (Mþ, 27%), 207 (24), 201 (100), 199 (28), 185 (19),
171 (51), 159 (23), 149 (23), 128 (12), 121 (23), 115 (17). HRMS: m/z
Calcd. for C18H24O3Na (M þ Na): 311.1623. Found: 311.1615.
Ethyl 2-[1-(4-methoxyphenyl)-2,2-dimethylcyclopentyl]acetate (22):
To freshly activated 5% Pd-C (7 mg) was added a solution of the ester 21
(108 mg, 0.57 mmol) in ethanol (3 mL). The reaction mixture was stirred for
3 h at RT in an atmosphere of hydrogen, created by evacuative replacement
of air (balloon), and then the catalyst was filtered off. Evaporation of the
solvent furnished the hydrogenated compound 22 (109 mg, 100%) as oil.
1
IR (neat): vmax/cm21 1731. H NMR (300 MHz, CDCl3 þ CCl4): d 7.15
(2 H, d, J ¼ 8.7 Hz), 6.74 (2 H, d, J ¼ 8.7 Hz), 3.82 (2 H, q, J ¼ 7.2 Hz),
3.75 (3 H, s), 2.94 and 2.41 (2 H, 2 ꢀ d, J ¼ 14.1 Hz), 2.62–2.45 (1 H, m),
2.26–2.12 (1 H, m), 1.90–1.75 (2 H, m), 1.60–1.45 (2 H, m), 1.05 (3 H, s),
0.95 (3 H, t, J ¼ 7.2 Hz), 0.58 (3 H, s). 13C NMR (75 MHz, CDCl3 þ CCl4):
d 171.7 (C), 157.5 (C), 135.7 (C), 128.2 (2 C, CH), 112.6 (2 C, CH), 59.4
(CH2), 54.7 (CH3), 52.5 (C), 45.5 (C), 40.7 (CH2), 39.1 (CH2), 34.2 (CH2),
25.9 (CH3), 24.4 (CH3), 20.1 (CH2), 14.0 (CH3). Mass: m/z 291 (Mþ þ 1,
13%), 290 (57), 220 (77), 207 (32), 203 (100), 165 (43), 159 (50), 149 (47),
148 (67), 147 (95), 121 (81). HRMS: m/z Calcd. for C18H26O3Na
(M þ Na): 313.1780. Found: 313.1772.
2-[1-(4-Methoxyphenyl)-2,2-dimethylcyclopentyl]ethanol (23): To a
cold (08C), magnetically stirred solution of the ester 22 (104 mg,
0.55 mmol) in 10 mL of dry ether was added LiAlH4 (21 mg, 0.55 mmol)
and stirred for 45 min. The reaction mixture was then diluted with ether
(5 mL) and carefully quenched with water (2 mL). The organic layer was
separated and the aqueous phase was extracted with ether (10 mL). The com-
bined organic phase was washed with brine and dried (Na2SO4). Evaporation
of the solvent and purification of the residue on a silica gel column using ethyl
acetate-hexane (1 : 10 to 1 : 5) as eluent furnished the primary alcohol 23
1
(84 mg, 94%). IR (neat): vmax/cm21 3355. H NMR (300 MHz, CDCl3 þ
CCl4): d 7.14 (2 H, d, J ¼ 8.7 Hz), 6.75 (2 H, d, J ¼ 8.7 Hz), 3.76 (3 H, s),

Total Synthesis of (+)-Infuscol A and (+)-Cuprenenol
3857
3.36 (1 H, d of t, J ¼ 9.9 and 5.4 Hz), 3.23 (1 H, d of t, J ¼ 9.9 and
5.4 Hz), 2.35–2.10 (2 H, m), 1.90–1.65 (5 H, m), 1.60–1.40 (2 H, m), 1.07
(3 H, s), 0.54 (3 H, s). 13C NMR (75 MHz, CDCl3 þ CCl4): d 157.4
(C), 136.3 (C), 128.3 (2 C, CH), 113.0 (2 C, CH), 60.7 (CH2), 54.9
(CH3), 52.0 (C), 45.2 (C), 39.3 (CH2), 37.6 (CH2), 33.3 (CH2), 26.2 (CH3),
24.5 (CH3), 20.1 (CH2). Mass: m/z 249 (Mþ þ 1, 6%), 248 (47), 203 (61),
178 (60), 173 (34), 165 (37), 147 (100), 135 (86), 121 (99), 115 (18), 91
(36). HRMS: m/z Calcd. for C16H24O2Na (M þ Na): 271.1674. Found:
271.1671.
4-(1,2,2-Trimethylcyclopentyl)anisole (14): To a magnetically stirred
suspension of PCC (139 mg, 0.65 mmol) and silica gel (139 mg) in dry
CH2Cl2 (0.5 mL) was added a solution of the primary alcohol 23 (32 mg,
0.13 mmol) in CH2Cl2 (0.5 mL) and stirred vigorously for 30 min at RT.
The reaction mixture was then filtered through a small silica gel column,
and the column eluted with more CH2Cl2. Evaporation of the solvent
furnished the aldehyde 24 (27 mg, 85%) as oil. [IR (neat): vmax/cm21 2733,
1
1719. H NMR (300 MHz, CDCl3 þ CCl4): d 9.24 (1 H, t, J ¼ 3.0 Hz), 7.20
(2 H, d, J ¼ 8.7 Hz), 6.80 (2 H, d, J ¼ 8.7 Hz), 3.77 (3 H, s), 2.99 (1 H, d,
J ¼ 15.0 Hz), 2.70–2.45 (1 H, m), 2.36 (1H, dd, J ¼ 15.0 and 3.0 Hz),
2.00–1.88 (3 H, m), 1.70–1.50 (2 H, m), 1.06 (3 H, s), 0.57 (3 H, s).
13C NMR (75 MHz, CDCl3 þ CCl4): d 203.0 (CH), 157.8 (C), 134.9 (C),
128.4 (2 C, CH), 113.3 (2 C, CH), 54.8 (CH3), 51.4 (C), 48.8 (CH2), 45.3
(C), 39.0 (CH2), 33.9 (CH2), 25.8 (CH3), 24.2 (CH3), 19.9 (CH2)]. Wilkinson
catalyst (28 mg, 0.03 mmol) was added to a solution of the aldehyde 24
(27 mg), obtained above, in dry benzene and heated at 120–1308C for 2
days in a sealed tube. Evaporation of the solvent under reduced pressure
followed by purification on a silica gel column using ethyl acetate-hexane
(1 : 30) as eluent furnished the decarbonylated compound 14 (14 mg, 82%
1
based on the recovered aldehyde 24) as oil. IR (neat): vmax/cm21 1514. H
NMR (300 MHz, CDCl3 þ CCl4): d 7.20 (2 H; d, J ¼ 8.4 Hz), 6.75 (2 H, d,
J ¼ 8.4 Hz), 3.76 (3 H, s), 2.55–2.35 (1 H, m), 1.80–1.45 (5 H, m), 1.24
(3 H, s), 1.04 (3 H, s), 0.55 (3 H, s). 13C NMR (75 MHz, CDCl3 þ CCl4): d
157.3 (C), 139.3 (C), 127.7 (2 C, CH), 112.7 (2 C, CH), 54.8 (CH3), 49.9
(C), 44.3 (C), 39.7 (CH2), 36.9 (CH2), 26.5 (CH3), 24.4 (CH3), 24.3 (CH3),
19.8 (CH2). Mass: m/z 218 (Mþ, 24%), 161 (50), 149 (30), 148 (100), 147
(28), 135 (65), 91 (23). HRMS: m/z Calcd. for C16H24O2Na (M þ 1):
219.1749. Found: 217.1742. Further elution of the column with CH2Cl2
furnished the unreacted aldehyde 24 (8 mg).
5-Methyl-5-(4-methoxyphenyl)hepta-1,6-dien-3-ol (25): To a magneti-
cally stirred solution of the aldehyde 26 (360 mg, 1.764 mmol) in THF (3 mL)
was added vinylmagnesium bromide [prepared from magnesium (210 mg,
8.82 mmol) and bromoethylene (0.746 mL, 10.6 mmol) in THF (5 mL)] and

3858
Srikrishna and Satyanarayana
stirred for 4 h at room temperature. The reaction was then quenched with
aqueous NH4Cl solution and extracted with ether (5 ꢀ 6 mL). The organic
layer was washed with water and brine, and dried (Na2SO4). Evaporation of
the solvent and purification of the residue over a silica gel column using
ethyl acetate-hexane (1 : 10) as eluent furnished a 1 : 1 diastereomeric
mixture of the dienol 25 (315 mg, 77%) as oil. IR (neat): vmax/cm21 3435,
1
917. H NMR (300 MHz, CDCl3þ CCl4, 1 : 1 diastereomeric mixture): d
7.21 and 7.20 (2 H, d, J ¼ 8.7 Hz), 6.79 and 6.78 (2 H, d, J ¼ 8.7 Hz), 6.10
(dd, J ¼ 17.1 and 10.8 Hz) and 6.05 (dd, J ¼ 17.4 and 10.8 Hz) [1 H],
5.85–5.60 (1 H, m), 5.15–4.90 (4 H, m), 4.20–4.00 (1 H, m), 3.75 (3 H, s),
2.04–1.87 (2 H, m), 1.46 & 1.43 (3 H, s). 13C NMR (75 MHz, CDCl3 þ CCl4,
1 : 1 diastereomeric mixture): d 157.8 (C), 147.7 and 147.1 (CH), 142.1 and
142.0 (CH), 138.7 (C), 127.7 and 127.6 (2 C, CH), 113.6 and 113.5 (2 C,
CH), 113.5 and 113.4 (CH2), 111.9 and 111.7 (CH2), 70.3 (CH), 55.0
(CH3), 48.3 (CH2), 43.2 (C), 25.9 and 25.7 (CH3). Mass: m/z 232 (Mþ,
20%), 162 (14), 161 (100), 146 (10), 121 (10), 91 (17). HRMS: m/z Calcd.
for C15H20O2Na (M þ Na): 255.1361. Found 255.1374.
4-Methyl-4-(4-methoxyphenyl)cyclopent-2-en-1-ol (27): To a magneti-
cally stirred solution of the dienol 25 (221 mg, 0.952 mmol) in anhydrous
CH2Cl2 (25 mL) was added a solution of Grubbs’ first generation catalyst
(39 mg, 5 mol%) in anhydrous CH2Cl2 (20 mL) and the reaction mixture
was stirred at room temperature for 6 h. Evaporation of the solvent under
reduced pressure and purification of the residue over a silica gel column
using ethyl acetate-hexane (1 : 5) as eluent furnished the cyclized compound
1
27 (189 mg, 97%) as oil. IR (neat): vmax/cm21 3362. H NMR (300 MHz,
CDCl3 þ CCl4, 1 : 1 diastereomeric mixture): d 7.19 and 7.11 (2 H, d,
J ¼ 8.7 Hz), 6.78 and 6.50 (2 H, d, J ¼ 8.7 Hz), 6.00–5.93 (1 H, m),
5.84–5.78 (1 H, m), 4.95–4.80 (1 H, m), 3.75 (3 H, s), 2.46–2.30 (1 H, m),
2.15 (1 H, s), 1.90–1.75 (1 H, m), 1.51 and 1.38 (3 H, s). 13C NMR
(75 MHz, CDCl3 þ CCl4): d 157.6 (C), 143.2 and 142.8 (CH), 141.4 and
140.8 (C), 132.1 (CH), 126.7 and 126.5 (2 C, CH), 113.6 and 113.5 (2 C,
CH), 77.2 and 77.1 (CH), 55.0 (CH3), 51.5 and 51.0 (CH2), 51.6 and 50.9
(C), 30.0 and 28.4 (CH3). Mass: m/z 204 (Mþ, 22%), 190 (13), 189 (100),
174 (19), 161 (27), 121 (17), 115 (15), 91 (15). HRMS: m/z Calcd. for
C13H16O2Na (M þ Na): 227.1048. Found: 227.1052.
4-Methyl-4-(4-methoxyphenyl)cyclopent-2-enone (28): To a magneti-
cally stirred solution of the secondary alcohol 27 (186 mg, 0.911 mmol) in
3 mL of dry CH2Cl2 was added a homogeneous mixture of PCC (589 mg,
2.735 mmol) and silica gel (589 mg) and stirred vigorously for 3 h at RT.
The reaction mixture was then filtered through a small silica gel column
and eluted the column with an excess of CH2Cl2. Evaporation of the
solvent and purification of the residue over a silica gel column using ethyl

Total Synthesis of (+)-Infuscol A and (+)-Cuprenenol
3859
acetate-hexane (1 : 40 to 1 : 20) as eluent furnished the cyclopentenone 28
(177 mg, 96%) as oil. IR (neat): vmax/cm21 1714. 1H NMR (300 MHz,
CDCl3 þ CCl4): d 7.58 (1 H, d, J ¼ 5.4 Hz), 7.13 (2 H, d, J ¼ 8.7 Hz),
6.80 (2 H, d, J ¼ 8.7 Hz), 6.14 (1 H, d, J ¼ 5.4 Hz), 3.76 (3 H, s), 2.52
(2 H, AB q, J ¼ 18.6 Hz), 1.60 (3 H, s). 13C NMR (75 MHz, CDCl3 þ CCl4):
d 208.7 (C), 170.9 (CH), 158.2 (C), 137.1 (C), 131.3 (CH), 126.6 (2 C,
CH), 114.0 (2 C, CH), 55.0 (CH3), 51.8 (CH2), 47.4 (C), 27.2 (CH3). Mass:
m/z 202 (Mþ, 30%), 188 (10), 187 (100), 159 (10), 144 (14), 128 (7),
115 (12). HRMS: m/z Calcd. for C13H15O2 (M þ 1): 203.1072. Found
203.1071.
4-(4-Methoxyphenyl)-4,5,5-trimethylcyclopent-2-enone (29): To a
magnetically stirred suspension of NaH (149 mg, 60% dispersion in oil,
3.71 mmol, washed with dry hexane) in THF (1 mL) was added a solution
of ketone 28 (150 mg, 0.74 mmol) in THF (1.5 mL) and DMF (0.5 mL), and
stirred for 40 min at RT. To the reaction mixture was then added iodomethane
(0.23 mL, 3.712 mmol) and stirred for 12 h at RT. It was then quenched
with water (3 mL) and extracted with ether (4 ꢀ 5 mL). The combined ether
extract was washed with brine and dried (Na2SO4). Evaporation of the
solvent and purification of the residue over a silica gel column by using
ethyl acetate-hexane (1 : 20) as eluent furnished the dimethylated ketone 29
1
(136 mg, 80%) as oil. M.p. 64–668C. IR (neat): vmax/cm21 1709. H NMR
(300 MHz, CDCl3 þ CCl4): d 7.67 (1 H, d, J ¼ 6.0 Hz), 7.04 (2 H, d,
J ¼ 8.4 Hz), 6.80 (2 H, d, J ¼ 8.4 Hz), 6.17 (1 H, d, J ¼ 6.0 Hz), 3.77 (3 H, s),
1.43 (3 H, s), 1.15 (3 H, s), 0.50 (3 H, s). 13C NMR (75 MHz, CDCl3 þ
CCl4): d 213.6 (C), 168.1 (CH), 158.3 (C), 135.3 (C), 129.3 (CH), 127.7
(2 C, CH), 113.6 (2 C, CH), 55.0 (CH3), 54.1 (C), 51.6 (C), 26.3 (CH3),
25.9 (CH3), 20.1 (CH3). Mass: m/z 230 (Mþ, 30%), 216 (10), 215 (100),
172 (19), 115 (8), 91 (4). HRMS: m/z Calcd. for C15H19O2 (M þ 1):
231.1385. Found: 231.1397.
3-(4-Methoxyphenyl)-2,2,3-trimethylcyclopentanone (30): To acti-
vated 5% Pd-C (25 mg) was added a solution the enone 29 (95 mg,
0.413 mmol) in ethanol (3 mL). The reaction mixture was stirred for 3 h at
RT in an atmosphere of hydrogen, created by evacuative replacement of
air (balloon) and then the catalyst was filtered off. Evaporation of the
solvent furnished the saturated ketone 30 (95 mg, 99%). M.p. 67–698C.
1
IR (neat): vmax/cm21 1737. H NMR (300 MHz, CDCl3 þ CCl4): d 7.25
(2 H, d, J ¼ 8.7 Hz), 6.82 (2 H, d, J ¼ 8.7 Hz), 3.78 (3 H, s), 2.70–2.30
(3 H, m), 1.88 (1 H, ddd, J ¼ 12.3, 9.0 and 2.0 Hz), 1.23 (3 H, s), 1.13 (3 H, s),
0.59 (3 H, s). 13C NMR (75 MHz, CDCl3 þ CCl4): d 221.2 (C), 158.0
(C), 136.9 (C), 127.4 (2 C, CH), 113.5 (2 C, CH), 54.9 (CH3), 53.2 (C),
48.0 (C), 33.6 (CH2), 29.9 (CH2), 25.5 (CH3), 22.2 (CH3), 18.5 (CH3).
Mass: m/z 233 (Mþ þ 1, 5%), 232 (36), 217 (12), 161 (100), 148 (42),

3860
Srikrishna and Satyanarayana
91 (18). HRMS: m/z Calcd. for C15H20O2Na (M þ Na): 255.1361. Found
255.1377.
7-(4-Methoxyphenyl)-6,6,7-trimethyl-1,4-dithiaspiro[4.4]nonane (31):
A solution of the ketone 30 (77 mg, 0.331 mmol), ethanedithiol (0.195 mL,
2.323 mmol), and BF3 . OEt2 (0.09 mL, 0.774 mmol) in dry benzene (1 mL)
was magnetically stirred at 08C to RT for 12 h. The reaction was then
quenched with aqueous NaHCO3 solution and extracted with ether. The
ether extract was washed with 5% aqueous NaOH solution and brine, and
dried (Na2SO4). Evaporation of the solvent and purification of the residue
over a silica gel column using ethyl acetate-hexane (1 : 50) as eluent furnished
the thioketal 31 (95 mg, 93%) as oil. IR (neat): vmax/cm21 1608, 1578,
1512. 1H NMR (300 MHz, CDCl3 þ CCl4): d 7.21 (2 H, d, J ¼ 8.7 Hz),
6.76 (2 H, d, J ¼ 8.7 Hz), 3.78 (3 H, s), 3.35–3.20 (4 H, m), 2.70–2.45
(3 H, m), 1.80–1.70 (1 H, m), 1.48 (3 H, s), 1.19 (3 H, s), 0.67 (3 H, s).
13C NMR (75 MHz, CDCl3 þ CCl4): d 157.5 (C), 139.8 (C), 127.8 (2 C,
CH), 113.0 (2 C, CH), 82.0 (C), 55.0 (CH3), 52.0 (C), 49.9 (C), 45.6 (CH2),
40.1 (CH2), 38.0 (CH2), 36.9 (CH2), 28.2 (CH3), 28.1 (CH3), 21.3 (CH3).
Mass: m/z 308 (Mþ, 2%), 233 (2), 199 (3), 190 (7), 177 (9), 175 (8), 149
(11), 148 (100), 133 (10), 121 (6). HRMS: m/z Calcd. for C17H24OS2Na
(M þ Na): 331.1166. Found 331.1176.
4-(1,1,2-Trimethylcyclopentyl)anisole (14): To a magnetically stirred
solution of the thioketal 31 (55 mg, 0.178 mmol) in dry ethanol (3 mL) was
added an excess of Raney nickel and refluxed for 2 h. The reaction mixture
was cooled and filtered through a short silica gel column to remove the
catalyst. Evaporation of the solvent and purification of the residue over a
silica gel column using ethyl acetate-hexane (1 : 50) as eluent furnished a
mixture of the cyclopentene and cyclopentane (31 mg). To activated 5%
Pd-C (15 mg) was added a solution of the mixture of 14 and 32 (31 mg) in
ethanol (3 mL). The reaction mixture was stirred for 3 h at RT in
an atmosphere of hydrogen, created by evacuative replacement of air
(balloon), and then the catalyst was filtered off. Evaporation of the solvent
furnished the saturated compound 14 (31 mg, 80%) as oil, which was ident-
ified by comparison of the spectral data with that of the sample obtained
earlier.
4-(1,2,2-Trimethylcyclopentyl)cyclohex-3-enone
(34):
Lithium
(350 mg, 50 mmol) was slowly added to a magnetically stirred solution of
the norcuparane 14 (179 mg, 0.82 mmol) in dry THF (6 mL) and freshly
distilled (over sodamide) liquid ammonia (100 mL) and absolute ethanol
(6 mL). The dark colored solution was stirred for 2.5 h and then quenched
with solid NH4Cl. Ammonia was slowly evaporated and the residue was
taken in water and extracted with ether (3 ꢀ 10 mL). The organic layer was
washed with saturated aq. NaCl solution and dried (Na2SO4). Evaporation

Total Synthesis of (+)-Infuscol A and (+)-Cuprenenol
3861
of the solvent furnished the diene 33 (175 mg), which was taken in THF
(3 mL) and 10% aq. H2SO4 (3 mL) was added. The mixture was stirred for
50 min at RT. It was then taken in ether (20 mL), washed with saturated aq.
NaHCO3 solution and brine, and dried (Na2SO4). Evaporation of the solvent
and purification of the residue over a silica gel column using ethyl acetate-
hexane (1 : 9) as eluent furnished the enone 34 (147 mg, 90% from 14)
1
as oil. IR (neat): vmax/cm21 1723. H NMR (300 MHz, CDCl3 þ CCl4): d
5.50 (1 H, t, J ¼ 3.6 Hz), 2.82 (2 H, d, J ¼ 3.6 Hz), 2.57–2.20 (4 H, m),
2.25–2.00 (1 H, m), 1.70–1.35 (5 H, m), 1.00 (6 H, s), 0.78 (3 H, s). 13C
NMR (75 MHz, CDCl3 þ CCl4): d 209.7 (C), 145.3 (C), 117.8 (CH), 51.5
(C), 43.7 (C), 40.5 (CH2), 39.9 (CH2), 38.8 (CH2), 36.9 (CH2), 26.8
(CH3), 26.4 (CH2), 25.2 (CH3), 22.2 (CH3), 19.4 (CH2). Mass: m/z 206
(Mþ, 18%), 136 (45), 123 (30), 109 (28), 107 (32), 93 (85), 91 (43), 69
(100). HRMS: m/z Calcd. for C14H22ONa (M þ Na): 229.1568. Found
229.1565.
4-(1,2,2-Trimethylcyclopentyl)cyclohex-2-enone (13): RhCl3 . 3H2O
(5 mg, 0.019 mmol) was added to a solution of the enone 34 (50 mg,
0.24 mmol) in absolute ethanol (1.6 mL) and heated at 100–1108C in a
sealed tube for 3 h. Evaporation of the solvent under reduced pressure and
purification of the residue on a silica gel column using ethyl acetate-hexane
(1 : 30) as eluent furnished a 3 : 2 diastereomeric mixture of the enone
1
13 (45 mg, 90%) as oil. IR (neat): vmax/cm21 1685. H NMR (300 MHz,
CDCl3 þ CCl4, 3 : 2 diastereomeric mixture): d 6.82 (d, J ¼ 10.2 Hz) and
7.07 (d, J ¼ 10.5 Hz) [1 H], 6.00–5.90 (1 H, m), 2.62–2.10 (4 H, m),
1.90–1.35 (7 H, m), 1.01 and 1.12 (3 H, s), 1.01 and 0.99 (3 H, s), 0.80 and
0.83 (3 H, s). 13C NMR (75 MHz, CDCl3 þ CCl4, 3 : 2 diastereomeric
mixture): d 198.6 and 198.4 (C), 154.8 and 152.8 (CH), 130.2 and 130.1
(CH), 47.8 and 47.5 (C), 45.2 and 43.1 (CH), 43.9 and 44.1 (C), 42.3 and
41.9 (CH2), 39.7 and 38.7 (CH2), 38.4 and 37.6 (CH2), 26.4 and 25.3
(CH2), 25.9 and 25.8 (CH3), 25.2 and 24.6 (CH3), 19.1 and 18.9 (CH2),
18.4 and 18.3 (CH3). Mass: m/z 207 (Mþ þ 1, 1%), 136 (4), 123 (17), 122
(15), 111 (63), 96 (68). HRMS: m/z Calcd. for C14H22ONa (M þ Na):
229.1581. Found: 229.1568.
Infuscol-A (1) and (1)-Cuprenenol (5): To a cold (08C), magnetically
stirred solution of methylmagnesium iodide (3.398 mmol), prepared from
magnesium (82 mg, 3.4 mmol) and iodomethane (0.21 mL, 3.4 mmol) and a
catalytic amount of iodine in 3 mL of dry ether, was added a solution of
the diastereomeric mixture of the enone 13 (70 mg, 0.34 mmol) in dry ether
(2 mL). The reaction mixture was slowly warmed up to RT and stirred for
0.5 h. It was then poured into saturated aq. NH4Cl solution and extracted
with ether (3 ꢀ 3 mL). The ether extract was washed with brine and dried
(Na2SO4). Evaporation of the solvent and purification of the residue on a

3862
Srikrishna and Satyanarayana
silica gel column using ethyl acetate-hexane (1 : 10) as eluent furnished first
a mixture of infuscol B (2) and neocuprenenol (6) (5 mg, 7%). IR (neat):
vmax/cm21 3371. 1H NMR (300 MHz, CDCl3 þ CCl4): d Peaks due to
infuscol B (2): 5.62 (2 H, m), 2.10 (1 H, m), 1.83–1.30 (11 H, m), 1.23
(3 H, s), 1.01 (3 H, s), 0.96 (3 H, s), 0.78 (3 H, s). Peaks due to neocuprenenol
(6): 5.87 (1 H, m of d, J ¼ 10.2 Hz), 5.62 (1 H, m), 2.13 (1 H, m), 1.83–1.30
(11 H, m), 1.24 (3 H, s), 1.08 (3 H, s), 0.95 (3 H, s), 0.80 (3 H, s). 13C NMR
(75 MHz, CDCl3 þ CCl4): d Peaks due to infuscol B (2): 134.2 (CH), 134.0
(CH), 66.4 (C), 47.6 (C), 44.4 (CH), 44.1 (C), 42.4 (CH2), 39.6 (CH2), 37.4
(CH2), 29.5 (CH3), 25.8 (CH3), 24.6 (CH3), 21.1 (CH2), 19.3 (CH2), 17.9
(CH3). Peaks due to neocuprenenol (6): 134.1 (CH), 132.5 (CH), 66.8 (C),
47.3 (C), 44.0 (C), 42.6 (CH), 42.2 (CH2), 38.8 (CH2), 38.0 (CH2), 29.9
(CH3), 26.2 (CH3), 25.3 (CH3), 22.0 (CH2), 19.2 (CH2), 17.7 (CH3). Further
elution of the column with the same solvent furnished a mixture of infuscol
A (1) and cuprenenol (5) (60 mg, 80%) as oil. IR (neat): vmax/cm21 3364.
1H NMR (300 MHz, CDCl3 þ CCl4): d Peaks due to infuscol A (1): 5.63–
5.53 (2 H, m), 2.32–2.18 (1 H, m), 1.87–1.31 (11 H, m), 1.23 (3 H, s),
0.98 (3 H, s), 0.95 (3 H, s), 0.75 (3 H, s). Peaks due to cuprenenol (5): 5.70
(1 H, t of d, J ¼ 10.5 and 1.2 Hz), 5.56 (1 H, t of d, J ¼ 10.5 and 2.4 Hz),
2.32–2.18 (1 H, m), 1.87–1.31 (11 H, m), 1.23 (3 H, s), 1.05 (3 H, s), 0.95
(3 H, s), 0.76 (3 H, s). 13C NMR (75 MHz, CDCl3 þ CCl4): d Peaks due to
infuscol A (1): 135.8 (CH), 131.2 (CH), 69.5 (C), 47.7 (C), 44.1 (C), 44.0
(CH), 42.2 (CH2), 39.6 (CH2), 38.7 (CH2), 28.2 (CH2), 25.2 (CH3), 24.6
(CH3), 23.8 (CH2), 19.3 (CH3), 17.6 (CH3). Peaks due to cuprenenol (5):
135.8 (CH), 129.7 (CH), 69.5 (C), 47.6 (C), 44.1 (C), 42.3 (2 C, CH2 and
CH), 39.4 (CH2), 39.0 (CH2), 28.4 (CH3), 26.1 (CH3), 25.8 (CH3), 24.6
(CH2), 19.2 (CH2), 17.8 (CH3). Mass: m/z 207 (Mþ 2 16, 3%), 137 (5),
123 (5), 119 (7), 111 (57), 94 (34), 69 (100).
trans-1-Methyl-4-(1,2,2-trimethylcyclopentyl)cyclohexanol (35): To
activated 5% Pd-C (10 mg) was added a solution of a mixture of infuscol A
(1) and cuprenenol (5) (6 mg, 0.027 mmol) in ethanol (3 mL). The reaction
mixture was stirred for 6 h at RT in an atmosphere of hydrogen, created by
evacuative replacement of air (balloon) and then the catalyst was filtered
off. Evaporation of the solvent furnished the saturated compound 35
(6 mg, 99%) as oil, which was solidified on standing. M.p. 83–858C. IR
1
(neat): vmax/cm21 3370. H NMR (300 MHz, CDCl3 þ CCl4): d 1.85–1.10
(16 H, m), 1.18 (3 H, s), 0.99 (3 H, s), 0.92 (3 H, s), 0.79 (3 H, s). 13C
NMR (75 MHz, CDCl3 þ CCl4): d 70.4 (C), 47.3 (C), 44.9 (CH), 44.0 (C),
42.3 (CH2), 41.2 (CH2), 40.7 (CH2), 40.0 (CH2), 26.8 (CH2), 25.6 (CH3),
25.4 (2 C, CH2 and CH3), 24.8 (CH3), 19.0 (CH2), 16.9 (CH3). Mass: m/z
206 (Mþ 2 H2O, 25%), 163 (13), 149 (14), 148 (13), 135 (31), 122 (30),
121 (75), 109 (28), 108 (100), 107 (31), 95 (66), 93 (43).

Total Synthesis of (+)-Infuscol A and (+)-Cuprenenol
3863
ACKNOWLEDGMENTS
We thank Professors Y. Asakawa and F. Nagashima for providing
the copies of the NMR spectra of natural infuscols A and B, cuprenenol,
and neocuprenenol; and C.S.I.R., New Delhi for the award of a research
fellowship to G.S.
REFERENCES
1. Asakawa, Y. Progress in the Chemistry of Organic Natural Products;
Herz, W., Kirby, G.W., Moore, R.E., Steglich, W., Tamm, Ch., Eds.;
Springer-Verlag: Wien, New York, 1995; Vol. 65.
2. (a) Nagashima, F.; Suzuki, M.; Takaoka, S.; Asakawa, Y. Sesqui- and
diterpenoids from the Japanese liverwort Jungermannia infusca. J. Nat.
Prod. 2001, 64, 1309–1317. For the first report on the isolation of cupre-
nenol from Jungermannia Rosulans, see: (b) Matsuo, A.; Terada, I.;
Nakayama, M.; Hayashi, S. Cuprenenol and rosulantol, new cuparane
class sesquiterpene alcohols from the liverwort Jungermannia rosulans.
Tetrahedron Lett. 1977, 3821–3824. For the isolation of cuprenenol
and neocuprenenols from Jungermannia infusca collected at different
locations, see: (c) Nagashima, F.; Tanaka, H.; Takaoka, S.; Asakawa, Y.
Sesqui- and diterpenoids from the Japanese liverwort Jungermannia
hattoriana. Phytochemistry 1997, 45, 353–363; (d) Nagashima, F.;
Suzuki, M.; Takaoka, S.; Asakawa, Y. New sesqui- and diterpenoids
from the Japanese liverwort Jungermannia infusca (Mitt) Steph. Chem.
Pharm. Bull. 1998, 46, 1184–1185; (e) Nagashima, F.; Suzuki, M.;
Takaoka, S.; Asakawa, Y. New acorane- and cuparane type sesqui and
new Labdane and secolabdane type diterpenoids from the Japanese
liverwort Jungermannia infusca (Mitt.) Steph. Tetrahedron 1999, 55,
9117–9132.
3. To the best of our knowledge, there is no report in the literature on the
synthesis of these nonaromatic cuparenoids infuscols A-D, cuprenenol,
and neocuprenenol.
4. Johnson, W.S.; Werthemann, L.; Bartlett, W.R.; Brocksom, T.J.; Li, T.-t.;
Faulkner, D.J.; Petersen, M.R. A simple stereoselective version of the
Claisen rearrangement leading to trans trisubstituted olefinic bonds.
Synthesis of squalene. J. Am. Chem. Soc. 1970, 92, 741–743.
5. (a) Grubbs, R.H.; Chang, S. Recent advances in olefin metathesis and its
applications in organic synthesis. Tetrahedron 1998, 54, 4413–4450;
(b) Fu¨rstner, A. Olefin metathesis and beyond. Angew. Chem., Int. Ed.
2000, 39, 3013–3043; (c) Trnka, T.M.; Grubbs, R.H. The development

3864
Srikrishna and Satyanarayana
of L2X2Ru=CHR olefin metathesis catalysts: An organometallic success
story. Acc. Chem. Res. 2001, 34, 18–29.
6. Srikrishna, A.; Reddy, T.J.; Kumar, P.P.; Vijaykumar, D. A methodology
for spirocyclopentannulation. Stereoselective total synthesis of tochuinyl
acetate and dihydrotochuinyl acetate. Synlett 1996, 67–68.
7. Grieco, P.A.; Nishizawa, M.; Marinovic, N.; Ehmann, W.J. Remote
double bond migration via rhodium catalysis: A novel enone transposi-
tion. J. Am. Chem. Soc. 1976, 98, 7102–7104.
Received in India June 14, 2004