The first total synthesis of (±)-laurokamurene B

Article abstract of DOI:10.1016/j.tet.2007.10.021

The first total synthesis of the rearranged aromatic sesquiterpene (±)-laurokamurene B, isolated from the Chinese red alga Laurencia okamurai Yamada, has been accomplished, confirming the structure of the natural product. A combination of Ireland-Claisen

Full text of DOI:10.1016/j.tet.2007.10.021

Tetrahedron 63 (2007) 12616–12620
The first total synthesis of ( )-laurokamurene B
*
A. Srikrishna, I. A. Khan, R. Ramesh Babu and A. Sajjanshetty
Department of Organic Chemistry, Indian Institute of Science, Bangalore, Karnataka 560012, India
Received 7 July 2007; revised 14 September 2007; accepted 4 October 2007
Available online 6 October 2007
Abstract—The first total synthesis of the rearranged aromatic sesquiterpene (Æ)-laurokamurene B, isolated from the Chinese red alga
Laurencia okamurai Yamada, has been accomplished, confirming the structure of the natural product. A combination of Ireland–Claisen
rearrangement and ring-closing metathesis was employed as key reactions.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Red algae of the genus Laurencia are found throughout the
world. Over the four decades, a significant number of cupar-
ene 1 and laurene 2 sesquiterpenoids have been isolated from
the genus Laurencia, which are characteristic of the genus.1
Recently, Mao and Guo in the course of their investigations
on the isolation of biologically active compounds from
Chinese marine organisms reported the isolation of two
new aromatic sesquiterpenes laurokamurenes A and B, 3
and 4, containing a new rearranged laurene skeleton, along
with known laurene sesquiterpenes 5–7.2 The structures of
laurokamurenes A and B, 3 and 4, were established on the
basis of 1 and 2D NMR spectra. A large number of bromi-
nated and nonbrominated sesquiterpenes, which can be clas-
sified into more than 20 sesquiterpenoid skeletons, are
known from the red algae of the genus Laurencia. However,
in most cases, three methyls in the aliphatic portion were
located at either positions 1,2,3 (laurene type) or 1,2,2
(cuparene type).3 Laurokamurenes 3 and 4 were the first
members of a new class of sesquiterpenes with three methyls
in the aliphatic ring arranged in a 2,2,3 fashion.
The presence of a new sesquiterpene carbon framework
prompted us to investigate the total synthesis of laurokamur-
ene B 4 to unambiguously establish the structure of the
marine natural product. It was contemplated, Scheme 1,
that a ring-closing metathesis (RCM) reaction4 of the diene
8 would generate an allyl alcohol, which can be reductively
deoxygenated to produce laurokamurene B 4. An Ireland–
Claisen rearrangement5 of the isobutyrate 9 was conceived
for the generation of the hydroxydiene 8 via the ester 10.
The synthetic sequence starting from isobutyric acid is de-
picted in Scheme 2. Thus, reaction of isobutyric acid with
potassium carbonate and E-crotyl chloride in refluxing
acetone generated the ester 9 in 80% yield. Ireland–Claisen
rearrangement of the ester 9 was explored via the cor-
responding trimethylsilyl (TMS) enol ether 11. Thus, gener-
ation of the TMS enol ether 11 of the ester 9 with LDA,
trimethylsilyl chloride and triethylamine in THF at À70 ꢀC
followed by heating the reaction mixture at reflux resulted
in the Ireland–Claisen rearrangement. Hydrolysis of the
Br
OH
laurokamurene B (4)
laurene (2)
laurokamurene A (3)
cuparene (1)
Br
H
O
O
HO
OH
5
6
7
Keywords: Laurenes; Cuparenes; Laurokamurenes A and B; Ring-closing metathesis; Ireland–Claisen rearrangement.
* Corresponding author. Tel.: +91 80 22932215; fax: +91 80 23600529; e-mail: ask@orgchem.iisc.ernet.in
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.10.021

A. Srikrishna et al. / Tetrahedron 63 (2007) 12616–12620
12617
O
ROOC
HO
O
4
8
10
9
Scheme 1.
O
a
b
O
COOH
O
MeOOC
c,d
80%
91%
9
OTMS
11
10
75%
O
OH
d
90%
e
84%
OHC
13
15
f
84%
14
OH
g
HO
HO
85%
8
16
17
d
86%
O
N
N
Cl
Cl
Ru
h
Ph
PCy3
86%
Grubbs II catalyst
4
18
Scheme 2. Reagents and conditions: (a) K2CO3, acetone, MeCH]CHCH2Cl reflux, 8 h; (b) (i) LDA, THF, TMSCl, NEt3, À70 ꢀC, 30 min, rt, 4 h, reflux, 4 h;
(ii) dil HCl, 40 min; (iii) CH2N2, Et2O, 0 ꢀC, 30 min; (c) LAH, Et2O, rt, 1 h; (d) PCC, silica gel, CH2Cl2, rt, 0.5 h; (e) Li, p-MeC6H4Br, THF,))), rt, 1 h; (f)
CH2]CHMgBr, THF, 0 ꢀC/rt, 4 h; (g) (i) Grubbs’ second generation catalyst (15 mol %), CH2Cl2, reflux, 4 h; (ii) moist CH2Cl2, silica gel, rt, 1 h; (h)
BF3$Et2O, NaCNBH3, THF, reflux, 1 h.
1
reaction mixture with dilute hydrochloric acid followed by
esterification with ethereal diazomethane furnished the ester
10 in 91% yield. The ester 10 was then converted into the
aldehyde6 13 by a two-step protocol, via reduction with
lithium aluminium hydride (LAH), followed by oxidation
of the resultant primary alcohol 12 with pyridinium chloro-
chromate (PCC) and silica gel in methylene chloride. Sono-
chemically accelerated Barbier reaction of the aldehyde 13
with lithium and 4-bromotoluene furnished the secondary
alcohol 14 in 84% yield, which on oxidation with PCC
and silica gel in methylene chloride at rt furnished the aryl
ketone 15 in 90% yield. Grignard reaction with vinylmagne-
sium bromide in THF transformed the aryl ketone 15 into
a 1:1 diastereomeric mixture of the hydroxydiene 8 in 84%
yield. RCM reaction of the hydroxydiene 8 with 15 mol %
Grubbs’ second generation catalyst in methylene chloride
at reflux for 4 h furnished the cyclopentenol 16, which was
found to be unstable. Hence, it was treated with silica gel
in moist methylene chloride to furnish an w2:1 epimeric
mixture of the rearranged alcohol 17 in 85% yield. Oxidation
of the allyl alcohol 17 with PCC and silica gel in methylene
chloride at rt furnished the enone 18 in 86% yield, whose
structure was established from its spectral data. An ionic
hydrogenation reaction7 was explored for the reductive
deoxygenation of the enone 18.8 Thus, refluxing a THF
solution of the enone 19 with boron trifluoride diethyl ether-
ate and sodium cyanoborohydride for 1 h furnished lauroka-
murene B 4 in 86% yield. Synthetic (Æ)-laurokamurene B 4
exhibited spectral data (IR, H and 13C NMR) identical to
that reported in the literature,2 confirming the structure of
the marine natural product.
In conclusion, we have accomplished the first total synthesis
of the sesquiterpene laurokamurene (Æ)-4, confirming the
structure of the natural product containing a new sesquiter-
pene carbon framework. A combination of an Ireland–
Claisen rearrangement and a RCM was employed as the
key reactions. Laurokamurene B 4 was obtained from iso-
butyric acid in 10 steps with an average yield of 86% in
each step.
3. Experimental section
3.1. General
IR spectra were recorded on Jasco FTIR 410 spectrophotom-
eter. H (300 MHz) and 13C (75 MHz) NMR spectra were
1
recorded on JNM l-300 spectrometer. The chemical shifts
(d ppm) and coupling constants (Hz) are reported in the
standard fashion with reference to either internal tetra-
methylsilane (for 1H) or the central line (77.0 ppm) of
CDCl3 (for 13C). In the 13C NMR spectra, the nature of the
carbons (C, CH, CH2 or CH3) was determined by recording
the DEPT-135 spectra, and is given in parentheses. High-
resolution mass spectra were recorded using Micromass

12618
A. Srikrishna et al. / Tetrahedron 63 (2007) 12616–12620
Q-TOF micro mass spectrometer using electrospray
ionisation.
for 1 h at rt. Ethyl acetate (0.5 mL) was added to the reaction
mixture to consume the excess reagent. The reaction was
then quenched with water (5 mL) and extracted with ether
(3Â5 mL). The combined ether extract was washed with
brine (5 mL) and dried (Na2SO4). Evaporation of the solvent
and purification of the residue on a silica gel column using
ethyl acetate/hexane (1:3) as eluent furnished the alcohol
12 (168 mg, 92%). To a magnetically stirred suspension of
PCC (539 mg, 2.5 mmol) and silica gel (539 mg) in
CH2Cl2 (1 mL) was added a solution of the alcohol 12
(160 mg, 1.25 mmol) in CH2Cl2 (1 mL) and stirred vigor-
ously at rt for 30 min. The reaction mixture was then filtered
through a silica gel column using CH2Cl2. Evaporation of
the solvent furnished the aldehyde 13 (130 mg, 82%) as
oil, which was found to decompose slowly on standing.6 Rf
(10% CH2Cl2/hexane) 0.8; IR (neat): nmax/cmÀ1 2704,
1732, 1639, 918; 1H NMR (300 MHz, CDCl3): d 9.37 (1H,
s, H-1), 5.60 (1H, ddd, J 18.3, 9.0 and 7.2 Hz, CH]CH2),
5.02–4.90 (2H, m, CH]CH2), 2.31 (1H, quintet, J 7.2 Hz,
CHCH]CH2), 0.91 (6H, s, 2Âtert-CH3), 0.88 (3H, d, J
7.2 Hz, sec-CH3); 13C NMR (75 MHz, CDCl3): d 205.6
(CH), 138.9 (CH), 116.2 (CH2), 48.3 (C), 42.8 (CH3), 19.7
(CH3), 17.9 (CH3), 14.9 (CH3).
3.2. E-But-2-enyl 2-methylpropionate 9
To a mixture of 2-methylpropanoic acid (1.27 g, 14.4 mmol)
and E-crotyl chloride (1.0 g, 11.1 mmol) in dry acetone
(8 mL) was added anhydrous K2CO3 (2.45 g, 17.77 mmol)
and the mixture heated at reflux for 8 h. The reaction mixture
was concentrated, poured onto crushed ice and extracted
with ether (3Â5 mL). The ether extract was washed with
brine (6 mL) and dried (Na2SO4). The solvent was evapo-
rated and the residue was purified on a silica gel column us-
ing hexane as eluent to furnish the isobutyrate 9 (1.26 g,
80%) as oil. Rf (5% CH2Cl2/hexane) 0.5; IR (neat): nmax
/
cmÀ1 1737; H NMR (300 MHz, CDCl3): d 5.77 (1H, dq,
J 15.3 and 6.0 Hz), 5.56 (1H, dt, J 15.3 and 6.9 Hz), 4.46
(2H, d, J 6.3 Hz, OCH2), 2.52 (1H, septet, J 6.9 Hz,
Me2CH), 1.71 (3H, d, J 6.0 Hz, ]CHCH3), 1.15 (6H, d, J
6.9 Hz, CH(CH3)2); 13C NMR (75 MHz, CDCl3): d 176.6
(C), 130.8 (CH), 125.3 (CH), 64.8 (CH2), 33.9 (CH), 19.0
(2C, CH3), 17.7 (CH3); HRMS (ESI): m/z for C8H14O2Na
(M+Na)+ calcd: 165.0891; found: 165.0892.
1
3.3. Methyl 2,2,3-trimethylpent-4-enoate 10
3.5. 2,2,3-Trimethyl-1-(4-methylphenyl)pent-4-
en-1-ol 14
To a pre-cooled (À70 ꢀC), magnetically stirred solution of
diisopropylamine (23.7 mmol) in anhydrous THF (10 mL)
was added a solution of n-BuLi (2.3 M in hexane, 9.2 mL,
21.1 mmol) and stirred for 10 min. To LDA thus formed
were added dropwise a solution of the ester 9 (1.2 g,
8.45 mmol) in anhydrous THF (10 mL), TMSCl (2.6 mL,
21.1 mmol) and Et3N (1.3 mL) and the reaction mixture
was stirred for 30 min at the same temperature. It was further
stirred at rt for 4 h and then heated at reflux for 4 h. The re-
action mixture was then cooled, diluted with ether (5 mL)
and 3 N HCl (1 mL) was added and stirred for 40 min. The
resulting biphasic mixture was separated, and the aqueous
layer was extracted with ether (3Â5 mL) and dried
(Na2SO4). Evaporation of the solvent furnished the acid,
which was dissolved in dry ether (5 mL), added dropwise
to a cold (0 ꢀC) solution of diazomethane (excess, prepared
from 1.4 g of N-nitroso-N-methylurea and 10 mL 60% aq
KOH solution and 10 mL of ether) and the reaction mixture
was stirred at rt for 30 min. Evaporation of the solvent on
a hot water bath and purification of the residue over a silica
gel column using CH2Cl2/hexane (1:9) as eluent furnished
the ester 10 (1.1 g, 91%) as oil. Rf (10% CH2Cl2/hexane)
To sonochemically activated lithium (22 mg, 3.2 mmol) in
dry THF (1 mL) in a round bottom flask was added slowly
a solution of the aldehyde 13 (80 mg, 0.63 mmol) and 4-bro-
motoluene (325 mg, 1.90 mmol) in THF (1 mL) over a pe-
riod of 5 min and the reaction irradiated sonochemically
for 1 h. The reaction mixture was decanted from excess lith-
ium, quenched with aq NH4Cl (5 mL) and extracted with
ether (3Â5 mL). The ether extract was washed with brine
(5 mL) and dried (Na2SO4). Evaporation of the solvent and
purification of the residue over a silica gel column using
CH2Cl2/hexane (1:5) as eluent furnished the alcohol 14
(115 mg, 84%) as oil. Rf (5% EtOAc/hexane) 0.5; IR
(neat): nmax/cmÀ1 3569, 3559, 1514, 913; 1H NMR
(300 MHz, CDCl3): (mixture of two isomers) d 7.20–6.95
(4H, m, Ar–H), 5.90–5.55 (1H, m, HC]CH2), 5.00–4.85
(2H, m, HC]CH2), 4.44 and 4.42 (1H, s, CHOH), 2.40–
2.20 (1H, m), 2.21 (3H, s, Ar–CH3), 1.68 (1H, br s), 0.92
and 0.89 (3H, d, J 7.2 Hz, sec-CH3), 0.73 and 0.72 (3H, s,
tert-CH3), 0.52 and 0.51 (3H, s, tert-CH3); 13C NMR
(75 MHz, CDCl3): d 142.1 and 142.0 (CH), 139.3 (C),
136.7 (C), 128.2 (2C, CH), 128.0 (2C, CH), 114.9 and
114.7 (CH2), 78.7 and 78.6 (CH), 44.0 and 43.9 (CH),
40.6 and 40.2 (C), 21.2 (CH3), 19.9 and 19.7 (CH3), 19.3
and 19.0 (CH3), 15.4 and 15.2 (CH3); HRMS (ESI): m/z
for C15H22ONa (M+Na)+ calcd: 241.1568; found: 241.1558.
1
0.6; IR (neat): nmax/cmÀ1 1733, 917; H NMR (300 MHz,
CDCl3): d 5.80–5.60 (1H, m, H-4), 5.05–4.95 (2H, m,
H-5), 3.64 (3H, s, OCH3), 2.46 (1H, quintet, J 6.9 Hz,
H-3), 1.10 (3H, s) and 1.08 (3H, s) [2Âtert-CH3], 0.93
(3H, d, J 6.9 Hz, sec-CH3); 13C NMR (75 MHz, CDCl3):
d 177.8 (C, OC]O), 139.6 (CH, C-4), 115.6 (CH2, C-5),
51.4 (CH3, OMe), 45.4 (C, C-2), 45.1 (CH, C-3), 22.9
(CH3), 21.0 (CH3), 15.2 (CH3); HRMS (ESI): m/z for
C9H17O2 (M+H)+ calcd: 157.1228; found: 157.1221.
3.6. 2,2,3-Trimethyl-1-(4-methylphenyl)pent-4-
en-1-one 15
To a magnetically stirred suspension of PCC (317 mg,
1.48 mmol) and silica gel (317 mg) in CH2Cl2 (1 mL) was
added a solution of the alcohol 14 (80 mg, 0.37 mmol) in
CH2Cl2 (0.5 mL). The reaction mixture was stirred at rt for
30 min and then filtered through a small bed of silica gel.
Evaporation of the solvent and purification of the residue
on a silica gel column using CH2Cl2/hexane (1:9) as eluent
3.4. 2,2,3-Trimethylpent-4-enal 13
To a cold (0 ꢀC) magnetically stirred solution of the pente-
noate 10 (200 mg, 1.40 mmol) in dry ether (3 mL) was
added LAH (107 mg, 2.82 mmol) and the mixture stirred

A. Srikrishna et al. / Tetrahedron 63 (2007) 12616–12620
12619
furnished the ketone 15 (71 mg, 90%) as oil. Rf (5% EtOAc/
hexane) 0.6; IR (neat): nmax/cmÀ1 1671, 1608, 915; 1H NMR
(300 MHz, CDCl3): d 7.61 (2H, d, J 8.4 Hz) and 7.18 (2H, d,
J 8.4 Hz) [Ar–H], 5.73 (1H, ddd, J 17.4, 10.8 and 8.1 Hz,
CH]CH2), 5.02 (1H, d, J 10.2 Hz) and 4.99 (1H, d, J
17.4 Hz) [CH]CH2], 2.89 (1H, quintet, J 7.2 Hz, CH–
CH]), 2.39 (3H, s, Ar–CH3), 1.26 (3H, s) and 1.21 (3H,
s) [2Âtert-CH3], 0.95 (3H, d, J 7.2 Hz, sec-CH3); 13C
NMR (75 MHz, CDCl3): d 207.8 (C), 141.1 (C), 139.7
(CH), 136.4 (C), 128.7 (2C, CH), 128.2 (2C, CH), 115.9
(CH2), 50.6 (C), 44.4 (CH), 24.2 (CH3), 21.6 (CH3), 21.5
(CH3), 15.3 (CH3); HRMS (ESI): m/z for C15H21O
(M+H)+ calcd: 217.1592; found: 217.1586.
2.4 Hz, C]CHCHOH), 4.48 (1H, dd, J 6.3 and 3.0 Hz,
CHOH), 2.34 (3H, s, Ar–CH3), 2.05–1.70 (3H, m), 1.14
(3H, s, tert-CH3), 1.06 (3H, d, J 6.9 Hz, sec-CH3), 1.05
(3H, s, tert-CH3); 13C NMR (75 MHz, CDCl3): (peaks due
to the major isomer) d 158.5 (C), 136.8 (C), 134.4 (C),
128.7 (2C, CH), 128.1 (CH, C-2), 127.7 (2C, CH), 76.4
(CH), 49.2 (CH), 47.9 (C), 26.1 (CH3), 25.6 (CH3), 21.3
(CH3), 8.9 (CH3); HRMS (ESI): m/z for C15H20ONa
(M+Na)+ calcd: 239.1412; found: 239.1423.
3.9. 4,4,5-Trimethyl-3-(4-methylphenyl)cyclopent-2-en-
1-one 18
To a magnetically stirred suspension of PCC (139 mg,
0.65 mmol) and silica gel (139 mg) in CH2Cl2 (1 mL) was
added a solution of the alcohol 17 (35 mg, 0.16 mmol) in
CH2Cl2 (0.5 mL). The reaction mixture was stirred at rt for
30 min and filtered through a small bed of silica gel column
using CH2Cl2. Evaporation of the solvent furnished the cy-
clopentenone 18 (30 mg, 86%) as oil. Rf (5% EtOAc/hexane)
0.45; IR (neat): nmax/cmÀ1 1705, 1611, 1587, 1509; 1H NMR
(300 MHz, CDCl3): d 7.36 (2H, d, J 8.1 Hz) and 7.20 (2H, d,
J 8.1 Hz) [Ar–H], 6.13 (1H, s, C]CHC]O), 2.40 (3H, s,
Ar–CH3), 2.35 (1H, q, J 7.5 Hz, CHMe), 1.35 (3H, s) and
1.23 (3H, s) [2Âtert-CH3], 1.14 (3H, d, J 7.5 Hz, sec-
CH3); 13C NMR (75 MHz, CDCl3): d 209.1 (C, C]O),
182.1 (C, C-3), 139.5 (C), 132.2 (C), 129.2 (2C, CH),
127.9 (CH, C-2), 127.8 (2C, CH), 54.6 (CH, C-5), 46.6 (C,
C-4), 26.5 (CH3), 24.7 (CH3), 21.4 (CH3), 9.8 (CH3);
HRMS (ESI): m/z for C15H19O (M+H)+ calcd: 215.1436;
found: 215.1436.
3.7. 4,4,5-Trimethyl-3-(4-methylphenyl)hepta-1,6-
dien-3-ol 8
To a cold (0 ꢀC) magnetically stirred solution of the ketone
15 (280 mg, 1.30 mmol) in THF (1 mL) was added dropwise
a solution of vinylmagnesium bromide [freshly prepared
from Mg (127 mg, 5.21 mmol) and vinyl bromide
(0.55 mL, 7.82 mmol) in THF (3 mL)] and stirred at rt for
4 h. The reaction was quenched with cold saturated aq
NH4Cl (10 mL) and extracted with ether (3Â5 mL). The or-
ganic 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
(1:19) as eluent furnished aw1:1 diastereomeric mixture of
the hydroxydiene 8 (267 mg, 84%) as oil. Rf (5% EtOAc/
hexane) 0.55; IR (neat): nmax/cmÀ1 3542, 1513, 918; H
1
NMR (300 MHz, CDCl3): (mixture of two isomers) d 7.31
and 7.27 (2H, d, J 8.4 Hz), 7.06 and 7.03 (2H, d, J
8.4 Hz), 6.80 and 6.66 (1H, dd, J 16.8 and 10.5 Hz), 6.10–
5.80 (1H, m), 5.40–4.90 (4H, m), 2.68 (1H, s, OH), 2.55–
2.45 (1H, m), 2.32 and 2.30 (3H, s), 0.95 and 0.93 (3H, d,
J 6.9 Hz), 0.90 and 0.88 (3H, s), 0.86 and 0.85 (3H, s); 13C
NMR (75 MHz, CDCl3): (mixture of two isomers) d 145.0
and 144.0 (CH), 142.6 and 142.0 (CH), 142.2 and 141.4
(C), 135.9 and 135.6 (C), 128.0 and 127.9 (2C, CH), 127.6
and 127.4 (2C, CH), 115.0 and 113.9 (CH2), 113.6 and
113.3 (CH2), 82.4 and 82.2 (C), 43.8 and 43.4 (C), 43.8
and 43.4 (CH), 23.3 and 21.4 (CH3), 21.0 (CH3), 18.1
(CH3), 17.7 and 17.0 (CH3); HRMS (ESI): m/z for
C17H24ONa (M+Na)+ calcd: 267.1725; found: 267.1722.
3.10. 4,5,5-Trimethyl-1-(4-methylphenyl)cyclopentene
(4, laurokamurene B)
Sodium cyanoborohydride (16 mg, 0.25 mmol) was added
to a magnetically stirred solution of the enone 18 (15 mg,
0.07 mmol) and boron trifluoride etherate (0.1 mL,
0.9 mmol) in 1 mL of dry THF and the reaction mixture
was heated at reflux for 1 h. After completion of the reaction
(monitored by TLC), saturated aq NaHCO3 (2 mL) was
added to the reaction mixture and extracted with ether
(3Â5 mL). The ether extract was washed with brine
(5 mL) and dried (Na2SO4). The solvent was evaporated
and the residue was purified on a silica gel column using
hexane as eluent to furnish laurokamurene B 4 (12 mg,
86%) as oil. Rf (hexane) 0.8; IR (neat): nmax/cmÀ1 1510,
3.8. 4,4,5-Trimethyl-3-(4-methylphenyl)cyclopent-2-
en-1-ol 17
1
828, 721; H NMR (300 MHz, CDCl3): d 7.18 (2H, d, J
To a diastereomeric mixture of the hydroxydiene 8 (50 mg,
0.21 mmol) in anhydrous CH2Cl2 (10 mL, 0.02 M) was added
Grubbs’ second generation catalyst (26 mg, 15 mol %) and
the mixture heated at reflux for 4 h. The solvent was then re-
moved under reduced pressure. The residue was then taken in
moist CH2Cl2 (2 mL), silica gel added (w1 g) and the mixture
magnetically stirred at rt for 1 h. The reaction mixture was
then filtered through a small pad of silica gel using CH2Cl2
as eluent. Evaporation of the solvent and purification of the
residue on a silica gel column using ethyl acetate/hexane
(1:19) as eluent furnished 1:3 epimeric mixture of the cyclo-
pentenol 17 (35 mg, 85%) as oil. Rf (5% EtOAc/hexane) 0.4;
IR (neat): nmax/cmÀ1 3376, 1510; 1H NMR (300 MHz,
CDCl3): (peaks due to the major isomer) d 7.19 (2H, d, J
8.1 Hz) and 7.08 (2H, d, J 8.1 Hz) [Ar–H], 5.85 (1H, d, J
8.0 Hz) and 7.07 (2H, d, J 8.0 Hz) [Ar–H], 5.67 (1H, br s,
HC]C), 2.50–2.30 (1H, m), 2.33 (3H, s, Ar–CH3), 2.10–
1.90 (2H, m), 1.09 (3H, s, tert-CH3), 1.00 (3H, d, J 6.6 Hz,
sec-CH3), 0.97 (3H, s, tert-CH3); 13C NMR (75 MHz,
CDCl3): d 152.9 (C, C-1), 136.0 (C), 135.5 (C), 128.6 (2C,
CH), 127.5 (2C, CH), 126.1 (CH, C-2), 47.8 (C, C-5), 45.8
(CH, C-4), 37.9 (CH2, C-3), 26.3 (CH3), 21.2 (CH3), 20.8
(CH3), 14.2 (CH3); HRMS (ESI): m/z for C15H19 (MÀH)+
calcd: 199.1482; found: 199.1478.
Acknowledgements
We thank the Indian Academy of Sciences and Indian Na-
tional Science Academy for providing summer fellowships

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A. Srikrishna et al. / Tetrahedron 63 (2007) 12616–12620
7. Srikrishna, A.; Viswajanani, R.; Sattigeri, J. A.; Yelamaggad,
C. V. Tetrahedron Lett. 1995, 36, 2347–2350.
to I.A.K. and A.S., and University Grants Commission, New
Delhi for the award of a research fellowship to R.R.B.
8. Initially, reductive deoxygenation of the allyl alcohol 17 was
attempted via ionoic hydrogenation to generate directly lauro-
kamurene B 4. However, treatment of the allyl alcohol 17 with
boron trifluoride diethyl etherate and sodium cyanoborohydride
in refluxing THF furnished laurokamuradiene I by rapid dehy-
dration, whose structure was established from its IR and NMR
References and notes
1. Martin, J. D.; Darias, J. Marine Natural Products; Scheuer, P. J.,
Ed.; Academic: New York, NY, 1978; Vol. 1, pp 151–161.
2. Mao, S.-C.; Guo, Y.-W. J. Nat. Prod. 2006, 69, 1209–1211.
3. Mao, S.-C.; Guo, Y.-W. Chin. Tradit. Herb. Drugs 2004, 35,
8–17.
4. (a) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413–4450;
(b) F€urstner, A. Angew. Chem., Int. Ed. 2000, 39, 3013–3043; (c)
Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18–29;
(d) Grubbs, R. H. Tetrahedron 2004, 60, 7117–7140.
5. (a) Ireland, R. E.; Mueller, R. H. J. Am. Chem. Soc. 1972, 94,
5897–5898; (b) Ireland, R. E.; Wipf, P.; Armstrong, J. D.
J. Org. Chem. 1991, 56, 650–657; (c) Gilbert, J. C.; Yin, J.;
Fakhreddine, F. H.; Karpinski, M. L. Tetrahedron 2004, 60,
51–60.
1
spectral data. IR (neat): nmax/cmÀ1 1508; H NMR (300 MHz,
CDCl3): d 7.38 (2H, d, J 8.1 Hz) and 7.11 (2H, d, J 8.1 Hz)
[Ar–H], 6.55 (1H, br s), 5.98 (1H, br s), 2.34 (3H, s, Ar–CH3),
1.92 (3H, s), 1.20 (6H, s, 2Âtert-CH3); 13C NMR (100 MHz,
CDCl3): d 155.5 (C), 153.6 (C), 135.6 (C), 133.7 (C), 129.0
(2C, CH), 126.0 (2C, CH), 125.3 (CH), 123.4 (CH), 53.0 (C),
29.8 (CH3), 22.6 (2C, CH3), 21.3 (CH3), 12.6 (CH3).
OH
BF3·Et2O
NaCNBH3
6. Bailey, P. D.; Harrison, M. J. Tetrahedron Lett. 1989, 30, 5341–
5344.
THF, reflux
17
I