Total synthesis of (±)-β-chamigrene and (±)-laurencenone C via Ireland ester Claisen rearrangement and an intramolecular type II carbonyl ene reaction sequence

Article abstract of DOI:10.1016/j.tet.2008.08.095

A combination of Ireland ester Claisen rearrangement and intramolecular type II carbonyl ene reactions were exploited for the total synthesis of chamigrenes containing a quaternary carbon atom next to the spirocentre in spiro[5.5]undecane.

Full text of DOI:10.1016/j.tet.2008.08.095

Tetrahedron 64 (2008) 10501–10506
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Total synthesis of (ꢀ)- -chamigrene and (ꢀ)-laurencenone C via Ireland
b
ester Claisen rearrangement and an intramolecular type II carbonyl
ene reaction sequence
*
A. Srikrishna , R. Ramesh Babu
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 July 2008
Received in revised form 29 August 2008
Accepted 29 August 2008
Available online 4 September 2008
A combination of Ireland ester Claisen rearrangement and intramolecular type II carbonyl ene reactions
were exploited for the total synthesis of chamigrenes containing a quaternary carbon atom next to the
spirocentre in spiro[5.5]undecane.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
Claisen rearrangement and intramolecular type II carbonyl ene
reactions for the construction of a spiro[5.5]undecane containing
Chamigrenes, containing a spiro[5.5]undecane carbon frame-
work incorporating two vicinal quaternary carbon atoms, are in-
teresting sesquiterpene natural products isolated from plant,
liverwort as well as marine sources. Chamigrenes appear to be the
more generalized metabolites in algae from the genus Laurencia,
and most of these are characterized by the predominant in-
a quaternary carbon atom adjacent to the spirocentre.
2. Results and discussion
The retrosynthetic sequence is depicted in Scheme 1. It was
conceived that intramolecular type II carbonyl ene reaction9 of the
aldehyde 7 would generate the spiro alcohol 8, which could be
corporation of chlorine and bromine atoms.1 Isolation of
b-chami-
grene 1 was first reported by Ito and co-workers2 in 1967 from the
leaf oil of Chamaecyparis taiwanensis, whereas the isolation of
converted to laurencenone C 5 or b-chamigrene 1 by oxidation or
reductive deoxygenation, respectively. The aldehyde 7 could be
generated from the ester 9. Ireland ester Claisen rearrangement10 of
the allyl ester 10 was contemplated for the generation of the ester 9
containing two vicinal quaternary carbon atoms.
The synthetic sequence starting from cyclohexane-1,4-dione 11
is depicted in Scheme 2. Controlled Horner–Wadsworth–Emmons
reaction of the dione 11 with sodium hydride and triethyl phos-
phonopropionate generated the keto ester 12 in 82% yield. Prior to
a
-chamigrene 2 was reported by Ohta and Hirose3 from the oil of
the fruits of Schisandra chinensis almost at the same time. Sub-
sequently, a variety of chlorine and bromine containing chami-
grenes were isolated from marine sources. Over 120 chamigrenes
were isolated from Laurencia species and sea hares grazing on
them. Thomson and co-workers reported4 the isolation of lau-
rencenones A–D 3–6 from Laurencia obtusa containing an enone
functionality in the A-ring of chamigrenes. Several of the haloge-
nated chamigrenes were shown to exhibit cytostatic activity and
remarkable antimicrobial activity on both Gram positive and Gram
negative bacteria.5 Recently, Cueto and co-workers reported the
isolation of several halogenated chamigrenes from Aplysia dacty-
lomela from Canary islands, some of which were shown to exhibit
cytotoxic activity against HeLa and Hep-2 cancer cell lines.6
the reduction of the a,b-unsaturated ester in the keto ester 12 into
an allyl alcohol, the keto group was protected as ethylene ketal by
refluxing with 1,2-ethanediol and a catalytic amount of p-tolue-
nesulfonic acid (PTSA) in benzene using a Dean–Stark water trap to
furnish the ketal ester 13 in 96% yield. Regioselective reduction
with lithium aluminum hydride (LAH) in ether at low temperature
transformed the ester 13 into the allyl alcohol 14 in 97% yield.11
Coupling of the allyl alcohol 14 with isobutyric acid in methylene
chloride in the presence of dicyclohexylcarbodiimide (DCC) and
4-N,N-dimethylaminopyridine (DMAP) produced the ester 15. Ire-
land-Claisen rearrangement of the ester 15 was then explored via
the corresponding trimethylsilyl (TMS) enol ether 16 for the gen-
eration of the requisite two vicinal quaternary carbon atoms. Thus,
generation of the TMS enol ether 16 of the ester 15 with LDA, tri-
methylsilyl chloride, and triethylamine in THF at ꢁ70 ꢂC followed
Synthesis of chamigrenes is challenging owing to the presence
of a quaternary carbon adjacent to the spirocentre.5,7,8 Herein, we
report a methodology for the synthesis of (ꢀ)-
b-chamigrene 1 and
(ꢀ)-laurencenone C 5 employing a combination of Ireland ester
* Corresponding author. Fax: þ91 80 23600529.
E-mail address: ask@orgchem.iisc.ernet.in (A. Srikrishna).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.08.095

10502
A. Srikrishna, R.R. Babu / Tetrahedron 64 (2008) 10501–10506
Cl
Cl
Br
HO
OHC
HO
Br
Cl
1
2
Cl
Cl
Cl
Cl
Br
Br
Br
Br
HO
HO
HO
HO
HO
Br
Br
O
O
O
O
Br
Cl
Cl
Cl
Br
3
4
5
6
by refluxing the reaction mixture for 4 h resulted in the Ireland
ester Claisen rearrangement. Hydrolysis of the reaction mixture
with dilute hydrochloric acid, which also led to the deprotection of
the ketal moiety, followed by esterification with ethereal diazo-
methane furnished the keto ester 17. Next, construction of the
second ring via an intramolecular ene reaction was investigated. In
order to avoid regiochemical problems, cyclohexanone in 17 was
converted into a methylcyclohexene moiety by employing a Wittig
reaction followed by olefin isomerization. Thus, reaction of the keto
ester 17 with methylenetriphenylphosphorane in benzene fur-
nished the methylene compound 18, which on isomerization with
PTSA in methylene chloride furnished the cyclohexene 19. For the
conversion of the ester 19 into the homologated aldehyde 7,
a Wittig reaction based methodology was contemplated. First, the
ester 19 was converted in to the aldehyde 20 employing a two-step
protocol, via reduction with lithium aluminum hydride (LAH) in
ether, followed by oxidation of the resultant primary alcohol 21
with pyridinium chlorochromate (PCC) and silica gel in methylene
chloride. Wittig reaction of the aldehyde 20 with methoxy-
methylenetriphenylphosphorane furnished the enol ether 22.
Attempted hydrolysis of the enol ether 22 under a variety of acid
conditions directly generated the spiro[5.5]undecanes 8 and 23 in
varying proportions12 instead of the aldehyde 7. It is interesting to
note that the enol ether 22 underwent competitive cyclization
leading to the methoxy spiro compound 23, even before the hy-
drolysis to the aldehyde 7. It was found that the best results were
obtained on treatment of the enol ether 22 with 10 mol % of tri-
fluoroacetic acid in 2:1 acetic acid and water at 70 ꢂC leading to the
by an intramolecular type II carbonyl ene reaction generates the
alcohol 8. Whereas, initial protonation of the enol ether 22 gener-
ates the oxonium ion 24, which on cyclization generates the
methoxy compound 23.
Barton’s free radical mediated deoxygenation13 was employed
for the conversion of the alcohol 8 into
b-chamigrene 1. Thus,
treatment of the alcohol 8 with sodium hydride, carbon disulfide,
and methyl iodide in the presence of imidazole furnished the
dithiocarbonate 25. Reaction of the dithiocarbonate 25 with trib-
utyltin hydride and a catalytic amount of azobisisobutyronitrile
(AIBN) in refluxing benzene furnished
On the other hand oxidation of the spiro alcohol 8 with PCC and
silica gel in methylene chloride for 1 h furnished the -un-
b-chamigrene 1 in 76% yield.
b,g
saturated enone 26. Isomerization of the exo-methylene group in
26 with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in methylene
chloride at rt for 2.5 h furnished laurencenone C 5. Both b-chami-
grene 1 and laurencenone C 5 exhibited spectral data identical to
those of the authentic compounds reported5,7 in the literature.
Conversion of either
b-chamigrene 1 or laurencenone C 5 into
a-chamigrene 2 has already been reported in the literature.
3. Conclusions
In summary, we have accomplished total syntheses of (ꢀ)-lau-
-chamigrene 1. A combination of Ireland
rencenone C 5 and (ꢀ)-
b
ester Claisen rearrangement and an intramolecular type II carbonyl
ene reactions were employed for the efficient construction of the
requisite two vicinal quaternary carbon atoms.
formation of a 11:6 mixture of hydroxy-b-chamigrene 8 and
methoxy- -chamigrene 23 in 87% yield, which were separated by
b
4. Experimental section
4.1. General
column chromatography on silica gel, and their structures were
established from their spectral data. Formation of the spiro com-
pounds 8 and 23 could be explained as depicted in Scheme 3. Acid
catalyzed hydrolysis of the enol ether 22 to the aldehyde 7 followed
Melting points are recorded using Mettler FP1 melting point
apparatus in capillary tubes and are uncorrected. IR spectra were
recorded on Jasco FTIR 410 spectrophotometer. 1H (300 MHz) and
13C (75 MHz) NMR spectra were recorded on JNM
l
-300 spectrom-
CHO
OH
1 and 5
eter. The chemical shifts (
d ppm) and coupling constants (Hz) are
reported in the standard fashion with reference to either internal
tetramethylsilane (for 1H) or the central line (77.0 ppm) of CDCl3 (for
13C). In the 13C NMR, the nature of carbons (C, CH, CH2, CH3) was
determined by recording the DEPT-135 spectra, and is given in pa-
rentheses. High-resolution mass spectra were recorded using
Micromass Q-TOF micro mass spectrometer using electron spray
ionization mode. Elemental analyses were carried out using Carlo
Erba 1106 CHN analyzer at the Department of Organic Chemistry,
Indian Institute of Science, Bangalore. Thin-layer chromatographies
8
7
O
COOR
O
O
O
X
X
11
10
Scheme 1.
9

A. Srikrishna, R.R. Babu / Tetrahedron 64 (2008) 10501–10506
10503
O
O
O
OEt
OEt
O
O
OH
O
O
a
b
O
c
82%
96%
97%
O
11
12
13
14
d
99%
O
O
O
O
O
O
O
e
OTMS
OMe
O
O
90%
17
16
15
f
88%
O
O
CHO
OH
OMe
OMe
i
g
h
90%
87%
91%
20
j
81%
19
21
18
OMe
k
OMe
OH
+
87%
( 6 : 11 )
23
8
79%
22
l
n
72%
OCSSMe
O
O
m
o
76%
70%
( )-1
( )-5
26
25
Scheme 2. Reagents: (a) (EtO)2P(O)CH(Me)CO2Et, NaH, THF; (b) (CH2OH)2, PTSA, C6H6; (c) LiAlH4, Et2O; (d) DCC, DMAP (catalytic), Me2CHCOOH, CH2Cl2; (e) (i) LDA, THF, TMSCl,
NEt3; (ii) dil HCl; (iii) CH2N2, Et2O; (f) Ph3P]CH2, C6H6; (g) PTSA, CH2Cl2; (h) LiAlH4, Et2O; (i) PCC, silica gel, CH2Cl2; (j) Ph3P]CHOMe, THF; (k) TFA, AcOH, H2O; (l) NaH, CS2, MeI,
THF, imidazole; (m) nBu3SnH, AIBN, C6H6; (n) PCC, silica gel, CH2Cl2; (o) DBU, CH2Cl2.
(TLC) were performed on glass plates (7.5ꢃ2.5 cm and 7.5ꢃ5.0 cm)
coated with Acme’s silica gel G containing 13% calcium sulfate as
binder and various combinations of ethyl acetate, methylene chlo-
ride, and hexane were used as eluent. Visualization of spots was
accomplished by exposure to iodine vapor or anisaldehyde–H2SO4
or MeOH–H2SO4 spray followed by heating. Acme’s silica gel (100–
200 mesh) was used for column chromatography (approximately
15–20 g per 1 g of the crude product).
a period of 15 min and stirred for 3 h at ice temperature. The re-
action was then quenched by careful addition of saturated aq NH4Cl
(2 mL) solution and extracted with ether (3ꢃ5 mL). The combined
ether extract was washed with brine (2 mL) and dried (Na2SO4).
Evaporation of the solvent and purification of the residue over
a silica gel column using ethyl acetate–hexane (1:6) as eluent fur-
nished the keto ester 12 (1.43 g, 82%) as oil. Rf (1:6 EtOAc–hexane)
0.4; IR (liquid film): nmax/cmꢁ1 2980, 2906, 1716, 1628, 1446, 1304,
1284, 1246, 1204, 1105, 1022, 774; 1H NMR (300 MHz, CDCl3):
(2H, q, J 6.9 Hz, OCH2CH3), 2.95 (2H, t, J 6.3 Hz), 2.64 (2H, t, J 6.3 Hz),
2.60–2.30 (4H, m),1.90 (3H, s, olefinic-CH3),1.32 (3H, t, J 6.9 Hz); 13
d 4.18
4.1.1. Ethyl 2-(4-oxocyclohex-1-ylidene)propionate 12
A suspension of sodium hydride (392 mg, 60% dispersion in oil,
9.81 mmol) in hexanes under nitrogen atmosphere was magneti-
cally stirred for 10 min and the solvent was syringed out. The oil
free NaH was then suspended in dry THF (8 mL) and cooled in an ice
bath. Triethyl phosphonopropionate (2.3 mL, 10.7 mmol) was
added dropwise and the reaction mixture was stirred for 30 min at
rt. The above reagent was transferred to a pressure equalizer funnel
and added dropwise to a solution of cyclohexane-1,4-dione 11
(1.0 g, 8.92 mmol) in dry THF (2 mL) at ice temperature over
C
NMR (75 MHz, CDCl3): d 209.7 (C, C]O), 168.3 (C, OC]O), 144.0 (C,
C-10), 123.2 (C, C-2), 60.0 (CH2, OCH2), 38.9 (CH2), 38.5 (CH2), 28.0
(CH2), 27.7 (CH2), 15.3 (CH3, C-3), 14.3 (CH3, OCH2CH3); HRMS: m/z
calcd for C11H16O3Na (MþNa): 219.0997, found: 219.0998.
4.1.2. Ethyl 2-(4,4-ethylenedioxycyclohexylidene)propionate 13
A magnetically stirred solution of the keto ester 12 (1.0 g,
5.1 mmol), ethylene glycol (0.85 mL, 15.3 mmol), and PTSA (70 mg,
OMe
H3O+
OH
O
8
H
7
22
H+
O+Me
OMe
H
23
24
Scheme 3.

10504
A. Srikrishna, R.R. Babu / Tetrahedron 64 (2008) 10501–10506
10 mol %) in 10 mL of dry benzene was refluxed using a Dean–Stark
water separator for 4 h. Benzene was distilled off, saturated aq
NaHCO3 (5 mL) solution was added to the residue and extracted
with ether (3ꢃ5 mL). The ether layer was washed with water
(5 mL) and brine (4 mL), and dried (Na2SO4). Evaporation of the
solvent under reduced pressure and purification of the residue on
a silica gel column using ethyl acetate–hexane (1:19) as eluent
furnished the ketal ester 13 (1.18 g, 96%) as oil. Rf (1:9 EtOAc–hex-
ane) 0.4; IR (liquid film): nmax/cmꢁ1 2952, 2883, 1714, 1636, 1446,
1366, 1312, 1283, 1206, 1126, 1095, 1034, 945, 913, 886, 775, 752,
for 10 min. To LDA thus formed were added dropwise a solution of
the ester 15 (1.0 g, 3.73 mmol) in anhydrous THF (1 mL), TMSCl
(1.1 mL, 8.58 mmol), and NEt3 (0.5 mL), and stirred the reaction
mixture for 30 min at the same temperature. It was further stirred
at rt for 4 h and then refluxed for 4 h. The reaction mixture was
then cooled, diluted with ether (2 mL), and 3 N HCl (3 mL) was
added and stirred for 45 min. The resulting biphasic mixture
was separated and the aqueous layer was extracted with ether
(3ꢃ3 mL). The ether extract was dried (Na2SO4). Evaporation of the
solvent furnished the acid, which was taken in dry ether (2 mL),
added dropwise to a cold (0 ꢂC) solution of diazomethane (excess,
prepared from 2 g of N-nitroso-N-methylurea and 20 mL of 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 water bath
and purification of the residue over a silica gel column using ethyl
acetate–hexane (1:9) as eluent furnished the ester 17 (797 mg, 90%)
as oil. Rf (1:7 EtOAc–hexane) 0.55; IR (liquid film): nmax/cmꢁ1 3086,
2974, 2954,1721, 1631, 1457, 1433,1391, 1340, 1266,1190, 1142, 1104,
1015, 995, 961, 900, 828, 776, 759; 1H NMR (300 MHz, CDCl3):
693; 1H NMR (300 MHz, CDCl3):
d 4.17 (2H, q, J 7.2 Hz, OCH2CH3),
3.94 (4H, s, 2ꢃOCH2), 2.59 (2H, t, J 6.3 Hz), 2.37 (2H, t, J 6.3 Hz), 1.87
(3H, s, olefinic-CH3), 1.90–1.65 (4H, m), 1.30 (3H, t, J 7.2 Hz); 13C
NMR (75 MHz, CDCl3): d 169.7 (C, OC]O), 144.9 (C), 121.1 (C), 108.3
(C), 64.3 (2C, CH2, OCH2CH2O), 60.0 (CH2, OCH2CH3), 35.6 (CH2),
35.3 (CH2), 28.6 (CH2), 27.8 (CH2), 15.4 (CH3, C-3), 14.4 (CH3,
OCH2CH3); HRMS: m/z calcd for C13H20O4Na (MþNa): 263.1259,
found: 263.1250.
4.1.3. 2-(4,4-Ethylenedioxycyclohexylidene)propanol 14
d
5.38 (1H, s) and 4.98 (1H, s) [C]CH2], 3.65 (3H, s, OCH3), 2.50–2.15
(6H, m), 2.00–1.75 (2H, m), 1.86 (3H, br s), 1.22 (6H, s, 2ꢃtert-CH3);
13C NMR (75 MHz, CDCl3):
211.7 (C, C]O), 176.8 (C, OC]O), 142.0
To a cold (ꢁ50 ꢂC) magnetically stirred solution of the keto ester
13 (600 mg, 2.5 mmol) in dry ether (4 mL) was added LAH (143 mg,
3.75 mmol) and stirred at the same temperature for 2 h. Ethyl ac-
etate (0.5 mL) was added to the reaction to consume the excess
LAH. The reaction was then quenched with water (5 mL) and
extracted with ether (3ꢃ5 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 (1:9) as eluent furnished the alcohol 14
(481 mg, 97%) as oil. Rf (1:3 EtOAc–hexane) 0.5; IR (liquid film):
nmax/cmꢁ1 3423 (OH), 2946, 2882, 1663, 1444, 1367, 1281, 1237,
1125, 1105, 1064, 1033, 944, 909, 864; 1H NMR (300 MHz, CDCl3):
d
(C, C]CH2), 118.1 (CH2, C]CH2), 51.5 (CH3, OCH3), 48.8 (C), 46.7 (C),
38.1 (2C, CH2, C-30 and C-50), 30.2 (2C, CH2, C-20 and C-60), 22.2 (2C,
CH3), 21.4 (CH3, olefinic-CH3); HRMS: m/z calcd for C14H22O3Na
(MþNa): 261.1467, found: 261.1454.
4.1.6. Methyl 2-(1-isopropenyl-4-methylenecyclohexyl)-
2-methylpropanoate 18
To
a
freshly prepared tAmOK [from potassium (100 mg,
t
t
2.52 mmol) and AmOH (3 mL) followed by evaporation of AmOH
under vacuum] in dry benzene (10 mL) was added methyl-
triphenylphosphonium bromide (1.125 g, 3.15 mmol) and the
resulting yellow solution was stirred for 30 min at rt. The solution
was allowed to settle for 30 min. The dark yellow solution of
methylenetriphenylphosphorane was added to a magnetically
stirred solution of the keto ester 17 (300 mg, 1.26 mmol) in dry
benzene (1 mL) at rt and stirred for 1 h. Saturated aq NH4Cl solution
(2 mL) was added to the reaction mixture and extracted with ether
(3ꢃ4 mL). The combined ether extract was washed with brine
(3 mL) and dried (Na2SO4). Evaporation of the solvent and purifi-
cation of the residue over a silica gel column using methylene
chloride–hexane (1:9) as eluent furnished the ester 18 (262 mg,
88%) as oil. Rf (1:4 CH2Cl2–hexane) 0.4; IR (liquid film): nmax/cmꢁ1
3071, 2976, 2949, 2847, 1727, 1651, 1630, 1470, 1449, 1434, 1389,
1377, 1261, 1219, 1191, 1140, 1111, 1095, 993, 886, 826; 1H NMR
d
3.99 (2H, s, CH2OH), 3.86 (4H, s, OCH2CH2O), 2.44 (1H, br s), 2.30–
2.15 (4H, m), 1.69 (3H, s, olefinic-CH3), 1.60–1.50 (4H, m); 13C NMR
(75 MHz, CDCl3):
134.0 (C), 125.9 (C), 108.6 (C, C-40), 64.0 (2C, CH2,
d
OCH2CH2O), 62.7 (CH2, CH2OH), 35.8 (CH2), 35.3 (CH2), 27.0 (CH2),
26.3 (CH2), 16.2 (CH3). HRMS: m/z calcd for C11H18O3Na (MþNa):
221.1154, found: 221.1158.
4.1.4. 20-[4,4-Ethylenedioxycyclohexylidene]propyl
2-methylpropanoate 15
To a magnetically stirred solution of isobutyric acid (0.2 mL,
2.20 mmol) in dry CH2Cl2 (3 mL) were added a solution of the al-
cohol 14 (250 mg, 1.26 mmol) in anhydrous CH2Cl2 (2 mL), DCC
(390 mg, 1.89 mmol), and a catalytic amount of DMAP and stirred at
rt for 5 h. The reaction mixture was then concentrated under re-
duced pressure and filtered through a short silica gel column using
ethyl acetate. Evaporation of the solvent and purification of the
residue over a silica gel column using ethyl acetate–hexane (1:19)
as eluent furnished the ester 15 (335 mg, 99%) as oil. Rf (1:19
EtOAc–hexane) 0.6; IR (liquid film): nmax/cmꢁ1 2973, 2947, 2879,
1732, 1471, 1388, 1367, 1343, 1273, 1251, 1190, 1155, 1107, 1069, 1035,
(300 MHz, CDCl3): d 5.20 (1H, s), 4.82 (1H, s), 4.48 (2H, s), 3.57 (3H,
s, OCH3), 2.25–1.98 (6H, m), 1.72 (3H, s, olefinic-CH3), 1.50–1.30 (2H,
m), 1.11 (6H, s, 2ꢃtert-CH3); 13C NMR (75 MHz, CDCl3):
d 177.1 (C,
OC]O), 148.7 (C), 143.3 (C), 117.2 (CH2), 106.2 (CH2), 51.3 (CH3,
OCH3), 49.1 (C), 47.4 (C), 31.7 (2C, CH2), 31.5 (2C, CH2), 22.3 (2C,
CH3), 21.9 (CH3); HRMS: m/z calcd for C15H24O2Na (MþNa):
259.1674, found: 259.1668.
945, 912; 1H NMR (300 MHz, CDCl3): 4.58 (2H, s, H-10), 3.94 (4H, s,
d
OCH2CH2O), 2.53 (1H, sep, J 6.9 Hz, H-2), 2.45–2.25 (4H, m), 1.73
(3H, s, olefinic-CH3), 1.70–1.55 (4H, m), 1.16 (6H, d, J 6.9 Hz,
4.1.7. Methyl 2-(1-isopropenyl-4-methylcyclohex-3-enyl)-
2-methylpropanoate 19
HC(CH3)2); 13C NMR (75 MHz, CDCl3):
d
176.6 (C, OC]O), 137.0 (C),
121.3 (C), 108.4 (C, C-400), 64.8 (CH2, C-10), 64.1 (2C, CH2, OCH2CH2O),
35.8 (CH2), 35.4 (CH2), 33.9 (CH, C-2), 27.2 (CH2), 26.8 (CH2), 19.0
(2C, CH3, HC(CH3)2), 16.5 (CH3); HRMS: m/z calcd for C15H24O4Na
(MþNa): 291.1572, found: 291.1572.
To a magnetically stirred solution of the compound 18 (60 mg,
0.254 mmol) in CH2Cl2 (1.5 mL) was added PTSA (25 mg, 50 mol %)
and the reaction mixture was stirred for 3.5 h at rt. It was neu-
tralized with saturated aq NaHCO3 solution (2 mL) and extracted
with CH2Cl2 (3ꢃ4 mL). The organic layer was washed with brine
(4 mL) and dried (Na2SO4). Evaporation of the solvent and purifi-
cation of the residue on a silica gel column using methylene chlo-
ride–hexane (1:9) as eluent furnished the isomerized ester 19
(52 mg, 87%) as oil. Rf (1:4 CH2Cl2–hexane) 0.45; IR (liquid film):
nmax/cmꢁ1 3084, 3002, 2964, 2909, 2838, 1727, 1629, 1473, 1448,
4.1.5. Methyl 2-[1-isopropenyl-4-oxocyclohexyl]-
2-methylpropanoate 17
To a cold (ꢁ70 ꢂC) magnetically stirred solution of diisopropyl-
amine (1.2 mL, 8.58 mmol) in anhydrous THF (8 mL) was added
a solution of nBuLi (2.4 M in hexane, 3.1 mL, 7.46 mmol) and stirred

A. Srikrishna, R.R. Babu / Tetrahedron 64 (2008) 10501–10506
10505
1434, 1389, 1372, 1258, 1192, 1160, 1085, 1068, 1029, 1010, 988, 900,
840, 805, 775, 744, 697; 1H NMR (300 MHz, CDCl3):
5.29 (1H, d,
residue over a silica gel column using hexanes as eluent furnished
the enol ether 22 (100 mg, 81%) as oil. Rf (hexane) 0.65; IR (liquid
film): nmax/cmꢁ1 3082, 2961, 2927, 2865, 1657, 1626, 1453, 1435,
1396, 1378, 1299, 1102, 895, 744, 696; 1H NMR (300 MHz, CDCl3):
d
J 5.1 Hz, H-30), 5.10 (1H, s) and 4.72 (1H, s) [C]CH2], 3.62 (3H, s,
OCH3), 2.45–1.50 (6H, m), 1.74 (3H, s) and 1.57 (3H, s) [2ꢃolefinic-
CH3], 1.18 (3H, s) and 1.17 (3H, s) [2ꢃtert-CH3]; 13C NMR (75 MHz,
d
5.69 (1H, d, J 7.2 Hz, H-1), 5.30 (1H, d, J 5.1 Hz, H-30), 5.08 (1H, s)
CDCl3):
d
177.3 (C), 144.5 (C, C]CH2), 133.9 (C), 120.2 (CH, C-30),
and 4.68 (1H, s) [C]CH2], 4.10 (1H, d, J 7.2 Hz, H-2), 3.49 (3H, s,
OCH3), 2.40–1.00 (6H, m), 1.78 (3H, s) and 1.56 (3H, s) [2ꢃolefinic-
CH3], 1.09 (3H, s) and 1.07 (3H, s) [2ꢃtert-CH3]; 13C NMR (75 MHz,
115.9 (CH2, C]CH2), 51.3 (CH3, OCH3), 49.2 (C), 45.8 (C), 30.0 (CH2),
28.7 (CH2), 27.5 (CH2), 23.2 (CH3), 22.9 (CH3), 22.4 (CH3), 22.0 (CH3);
HRMS: m/z calcd for
259.1674.
C
15H24O2Na (MþNa): 259.1674, found:
CDCl3): d
145.5 (C, C-100),145.1 (CH, C-1),133.5 (C, C-40),121.2 (CH, C-
30), 115.0 (CH2, C]CH2), 114.5 (CH, C-2), 59.5 (CH3, OCH3), 47.5 (C),
41.7 (C), 29.8 (CH2), 28.7 (CH2), 27.1 (CH2), 25.4 (CH3), 25.2 (CH3),
24.0 (CH3), 23.4 (CH3); HRMS: m/z calcd for C16H26ONa (MþNa):
257.1881, found: 257.1883.
4.1.8. 2-(1-Isopropenyl-4-methylcyclohex-3-enyl)-
2-methylpropanol 21
To a magnetically stirred solution of the ester 19 (60 mg,
0.254 mmol) in dry ether (2 mL) was added LAH (20 mg,
0.51 mmol) in one portion. The reaction mixture was stirred at rt for
45 min. Ethyl acetate (0.2 mL) was added to consume excess LAH
and the reaction was then quenched with water (2 mL) and
extracted with ether (3ꢃ4 mL). The ether extract was washed with
brine (2 mL) and dried (Na2SO4). Evaporation of solvent and puri-
fication of the residue over a silica gel column using ethyl acetate–
hexane (1:9) as eluent furnished the primary alcohol 21 (48 mg,
91%) as oil. Rf (1:7 EtOAc–hexane) 0.5; IR (liquid film): nmax/cmꢁ1
3378, 3081, 2962, 2925,1626,1476,1476,1446,1372,1158, 1031, 897,
4.1.11. 3-Methoxy-1-methylene-5,5,9-trimethylspiro[5.5]
undec-8-ene 23 and 1-methylene-5,5,9-trimethylspiro[5.5]
undec-8-en-3-ol 8
A solution of the enol ether 22 (158 mg, 0.67 mmol) in
CH3CO2H–H2O (2:1, 3 mL) and TFA (8 mg, 10 mol %) was magneti-
cally stirred at 70 ꢂC for 2 h. The reaction mixture was diluted with
water (4 mL) and extracted with CH2Cl2 (3ꢃ5 mL). The combined
organic layer was washed with aq NaHCO3 (3 mL) and brine (4 mL),
and dried (Na2SO4). Evaporation of the solvent and purification of
the residue over a silica gel column using ethyl acetate–hexane
804; 1H NMR (300 MHz, CDCl3):
d
5.28 (1H, d, J 5.1 Hz, H-30), 5.14
(1:19) as eluent furnished a diastereomeric mixture of methoxy b-
(1H, s) and 4.79 (1H, s) [C]CH2], 3.52 and 3.40 (2H, 2ꢃd, J 11.1 Hz,
CH2OH), 2.45–1.00 (7H, m), 1.83 (3H, s) and 1.56 (3H, s) [2ꢃolefinic-
CH3], 0.93 (3H, s) and 0.90 (3H, s) [2ꢃtert-CH3]; 13C NMR (75 MHz,
chamigrene 23 (48 mg, 31%) as oil. Rf (1:19 EtOAc–hexane) 0.5; IR
(liquid film): nmax/cmꢁ1 3085, 2945, 2875, 2824, 1652, 1465, 1455,
1386, 1371, 1190, 1118, 1094, 974, 890; 1H NMR (300 MHz, CDCl3,
CDCl3):
d
146.9 (C, C]CH2), 133.7 (C, C-40), 120.6 (CH, C-30), 115.6
w1:1 mixture of epimers): d 5.29 (1H, br s, H-8), 4.96 and 4.95 (1H,
(CH2, C]CH2), 69.4 (CH2, CH2OH), 45.4 (C), 41.1 (C), 29.6 (CH2), 28.4
(CH2), 27.0 (CH2), 23.7 (CH3), 23.2 (CH3), 21.3 (CH3), 21.2 (CH3);
HRMS: m/z calcd for C14H24ONa (MþNa): 231.1725, found: 231.1734.
s) and 4.68 and 4.61 (1H, s) [C]CH2], 3.50–3.20 (1H, m), 3.33 and
3.28 (3H, s, OCH3), 2.60–1.00 (10H, m), 1.58 (3H, s, olefinic-CH3),
0.94 and 0.92 (3H, s) and 0.86 and 0.82 (3H, s) [2ꢃtert-CH3]; 13C
NMR (75 MHz, CDCl3, w1:1 mixture of epimers): d 146.6 and 145.8
4.1.9. 2-(1-Isopropenyl-4-methylcyclohex-3-enyl)-
2-methylpropanal 20
(C), 132.6 and 132.5 (C), 119.9 and 119.8 (CH, C-8), 113.3 and 112.9
(CH2, C]CH2), 76.7 and 76.6 (CH, C-3), 55.7 and 55.6 (CH3, OCH3),
44.5 (C), 42.7 and 39.7 (CH2), 38.1 and 36.7 (CH2), 37.4 and 37.2 (C),
28.9 and 28.8 (CH2), 28.2 and 27.9 (CH2), 26.1 and 25.9 (CH2), 25.3
and 25.2 (CH3), 25.1 (CH3), 24.1 (CH3), 23.3 (CH3); HRMS: m/z calcd
for C16H26ONa (MþNa): 257.1881, found: 257.1870.
To a magnetically stirred solution of the primary alcohol 21
(200 mg, 0.96 mmol) in anhydrous CH2Cl2 (1 mL) was added a ho-
mogeneous mixture of PCC (415 mg, 1.92 mmol) and silica gel
(415 mg), and stirred at rt for 45 min. The reaction mixture was
then filtered through a small silica gel column using CH2Cl2 as el-
uent. Evaporation of the solvent and purification of the residue on
a silica gel column using ethyl acetate–hexane (1:19) as eluent
furnished the aldehyde 20 (168 mg, 90%) as oil. Rf (1:4 CH2Cl2–
hexane) 0.5; IR (liquid film): nmax/cmꢁ1 3084, 2964, 2717, 1723,
Further elution of the column with ethyl acetate–hexane (1:4) as
eluent furnished an epimeric mixture of hydroxy-b-chamigrene 8
(83 mg, 56%) as a white solid. Mp: 77–79 ꢂC; [found: C, 81.61; H,
11.03. C15H24O requires: C, 81.76; H, 10.98%]; Rf (1:7 EtOAc–hexane)
0.45; IR (liquid film): nmax/cmꢁ1 3374, 3087, 2956, 2922, 2878, 1637,
1460, 1438, 1387, 1367, 1046, 1024, 897, 887, 817, 803; 1H NMR
1629, 1468, 1447, 1373, 899, 804; 1H NMR (300 MHz, CDCl3):
d 9.70
(1H, s, H-1), 5.29 (1H, d, J 5.1 Hz, H-30), 5.16 (1H, s) and 4.76 (1H, s)
[C]CH2], 2.40–1.50 (6H, m), 1.77 (3H, s) and 1.58 (3H, s)
[2ꢃolefinic-CH3], 1.07 (3H, s) and 1.04 (3H, s) [2ꢃtert-CH3]; 13C
(400 MHz, CDCl3, w1:3 mixture of epimers): d 5.25 (1H, br s, H-8),
4.99 and 4.94 (1H, s), 4.73 and 4.58 (1H, s) [C]CH2], 4.00–3.90 and
3.80–3.60 (1H, m, CHOH), 2.58 and 2.38 (1H, dd, J 12.4 and 4 Hz),
2.25–1.00 (10H, m), 1.56 (3H, s, olefinic-CH3), 0.95 and 0.90 (3H, s)
and 0.86 and 0.80 (3H, s) [2ꢃtert-CH3]; 13C NMR (100 MHz, CDCl3,
NMR (75 MHz, CDCl3): d 206.6 (C, C]O), 144.3 (C, C]CH2), 134.1 (C,
C-40), 119.7 (CH, C-30), 116.4 (CH2, C]CH2), 50.6 (C, C-2), 45.6 (C, C-
10), 29.7 (CH2), 28.0 (CH2), 27.2 (CH2), 23.2 (2C, CH3), 18.9 (CH3), 18.7
(CH3); HRMS: m/z calcd for C14H22ONa (MþNa): 229.1568, found:
229.1578.
signals due to the major isomer):
d 145.8 (C, C-1), 132.7 (C, C-9),
119.9 (CH, C-8), 113.4 (CH2, C]CH2), 67.9 (CH, C-3), 46.2 (CH2), 44.0
(C), 41.9 (CH2), 37.6 (C), 28.9 (CH2), 27.9 (CH2), 26.3 and 26.2 (CH2),
25.1 (CH3), 24.1 (CH3), 23.4 (CH3).
4.1.10. 3-[(1-Isopropenyl)-4-methylcyclohex-3-enyl]-1-methoxy-
3-methylbut-1-ene 22
4.1.12. Methyl 3-(1-methylene-5,5,9-trimethylspiro[5.5]undec-8-
enyl)dithiocarbonate 25
To
a
magnetically stirred solution of methoxymethyl-
triphenylphosphonium chloride (454 mg, 1.33 mmol) in THF (2 mL)
To a magnetically stirred suspension of NaH (60% in oil, 14 mg,
0.36 mmol, washed with hexane) in dry THF (2 mL) was added
a solution of the alcohol 8 (53 mg, 0.24 mmol) in dry THF (0.5 mL)
followed by a catalytic amount of imidazole (4 mg). The reaction
mixture was heated to 60 ꢂC for 15 min. It was cooled to rt, CS2
(0.02 mL, 0.36 mmol) was added and refluxed for 15 min. It was
recooled to rt, MeI (0.06 mL, 0.96 mmol) was added and refluxed
for 4 h. It was then cooled to rt, diluted with water (2 mL), and
extracted with ether (3ꢃ4 mL). The combined organic layer was
n
was added BuLi (2.4 M, 0.4 mL, 1.07 mmol) at 0 ꢂC, and the
resulting wine red colored solution was stirred for 25 min at rt. The
Wittig reagent thus formed was added to a magnetically stirred
solution of the aldehyde 20 (110 mg, 0.53 mmol) in dry THF (1 mL)
and stirred at rt for 30 min. Saturated aq NH4Cl solution (2 mL) was
added to the reaction mixture and extracted with ether (2ꢃ5 mL).
The combined organic layer was washed with brine (4 mL) and
dried on Na2SO4. Evaporation of the solvent and purification of the

10506
A. Srikrishna, R.R. Babu / Tetrahedron 64 (2008) 10501–10506
washed with brine (2 mL) and dried (Na2SO4). Evaporation of the
solvent and rapid purification of the residue on a silica gel column
using hexane as eluent furnished the dithiocarbonate 25 (59 mg,
79%) as yellow oil. Rf (hexane) 0.45; IR (liquid film): nmax/cmꢁ1
3089, 2959, 2831, 1639, 1439, 1390, 1371, 1224, 1163, 1128, 1054,
963, 899, 804; 1H NMR (300 MHz, CDCl3, mixture of epimers):
4.1.15. 1,5,5,9-Tetramethylspiro[5.5]undeca-1,8-dien-3-one
(laurencenone C 5)
To a magnetically stirred solution of the enone 26 (15 mg,
0.068 mmol) in anhydrous CH2Cl2 (0.5 mL) was added a catalytic
amount of DBU (ca. 50 mL) and stirred for 2.5 h at rt. The reaction
mixture was then diluted with CH2Cl2 (5 mL), washed with 1 N aq
HCl, and brine, and dried (Na2SO4). Evaporation of the solvent and
purification of the residue on a silica gel column using ethyl ace-
tate–hexane (1:9) as eluent furnished laurencenone C 5 (8.5 mg,
53%) as oil. Rf (1:5 EtOAc–hexane) 0.55; IR (liquid film): nmax/cmꢁ1
3016, 2962, 2927, 2876, 2855, 1667, 1610, 1447, 1390, 1376, 1320,
d
5.76 and 5.70 (1H, m), 5.29 (1H, br s, H-8), 5.05 and 5.00 (1H, s),
4.70 and 4.73 (1H, s), 2.80–2.30 (2H, m), 2.54 and 2.51 (3H, s, SCH3),
2.25–1.40 (8H, m), 1.58 (3H, s, olefinic-CH3), 0.94 (3H, s) and 0.91
(3H, s) [2ꢃtert-CH3]; 13C NMR (75 MHz, CDCl3, mixture of epimers):
d
214.9, 144.3, 143.5, 132.8, 132.7, 119.7, 114.9, 114.4, 80.8, 80.5, 44.6,
44.3, 41.1, 39.8, 38.1, 37.1, 36.0, 28.9, 28.8, 28.2, 27.9, 26.1, 25.4, 25.1,
24.9, 23.7, 23.3, 18.9, 18.6; HRMS: m/z calcd for C17H26OS2Na
(MþNa): 333.1323, found: 333.1329.
1282,1257,1021; 1H NMR (300 MHz, CDCl3):
d 5.87 (1H, s, H-2), 5.51
(1H, s, H-8), 2.62 (1H, br d, J 18.3 Hz), 2.24 (1H, br d, J 18.3 Hz), 2.10–
1.70 (6H, m), 1.98 (3H, s, C1-CH3), 1.68 (3H, s, C9-CH3), 1.03 (3H, s)
and 0.95 (3H, s) [2ꢃtert-CH3]; 13C NMR (75 MHz, CDCl3):
d 198.7 (C,
4.1.13. 1-Methylene-5,5,9-trimethylspiro[5.5]undec-8-ene (
b-
C]O), 170.5 (C, C-1), 134.2 (C, C-9), 127.0 (CH, C-3), 121.6 (CH, C-8),
49.0 (CH2, C-4), 43.4 (C, C-6), 40.4 (C, C-5), 28.2 (2C, CH2), 28.0
(CH2), 24.8 (CH3), 24.3 (CH3), 23.9 (CH3), 23.3 (CH3).
chamigrene 1)
A solution of the dithiocarbonate 25 (51 mg, 0.173 mmol),
nBu3SnH (0.1 mL, 0.346 mmol), and a catalytic amount of AIBN
(5 mg, 20 mol %) in dry benzene (1 mL) was refluxed for 2 h. The
reaction mixture was cooled, diluted with ether (5 mL), washed
successively with 1% aq NH4OH solution (2ꢃ3 mL), water (2 mL),
and brine (3 mL), and dried (Na2SO4). Evaporation of the solvent
and purification of the residue on a silica gel column using hexane
Acknowledgements
We thank the University Grants Commission, New Delhi for the
award of a research fellowship to R.R.B.
as eluent furnished b-chamigrene 1 (27 mg, 76%) as colorless oil. Rf
References and notes
(hexane) 0.95; IR (liquid film): nmax/cmꢁ1 3086, 2951, 2930, 2868,
1636, 1452, 1384, 1367, 1157, 1129, 890; 1H NMR (300 MHz, CDCl3):
1. Dorta, E.; Diaz-Marrero, A. R.; Cueto, M.; D’Croz, L.; Mate, J. L.; Darias, J. Phy-
tochemistry 2004, 45, 7065–7068.
d
5.30 (1H, br s, H-8), 4.86 (1H, s) and 4.50 (1H, s) [C]CH2], 2.24
2. Ito, S.; Endo, K.; Yoshida, T.; Yatagai, M.; Kodama, M. J. Chem. Soc., Chem.
Commun. 1967, 186–188.
3. Ohta, Y.; Hirose, Y. Tetrahedron Lett. 1968, 2483–2485.
4. Kennedy, D. J.; Selby, I. A.; Thomson, R. H. Phytochemistry 1988, 27, 1761–1766;
For the isolation of laurencenone C from the German liverwort Marchantia
polymorpha, see: Asakawa, Y.; Tori, M.; Masuya, T.; Frahm, J.-P. Phytochemistry
1990, 29, 1577–1584.
5. Martin, J. D.; Perez, C.; Ravelo, J. L. J. Am. Chem. Soc. 1986, 108, 7801–7811.
6. Dias, T.; Brito, I.; Moujir, L.; Paiz, N.; Darias, J.; Cueto, M. J. Nat. Prod. 2005, 68,
1677–1679.
(1H, td, J 12.6 and 5.4 Hz), 2.20–2.00 (2H, m), 2.00–1.90 (2H, m),
1.85–1.65 (4H, m), 1.58 (3H, s, olefinic-CH3), 1.60–1.30 (2H, m), 1.15
(1H, m of d, J 13.5 Hz), 0.87 (3H, s) and 0.82 (3H, s) [2ꢃtert-CH3]; 13
C
NMR (75 MHz, CDCl3):
d 149.1 (C, C-1), 132.7 (C, C-9), 119.9 (CH, C-
8), 110.5 (CH2, C]CH2), 44.7 (C, C-6), 37.2 (C, C-5), 37.0 (CH2), 32.2
(CH2), 28.9 (CH2), 27.9 (CH2), 25.9 (CH2), 25.0 (CH3), 23.8 (CH2, C-3),
23.2 (CH3), 23.0 (CH3).
7. Ireland, R. E.; Dow, W. C.; Godfrey, J. D.; Thaisrivongs, S. J. Org. Chem. 1984, 49,
1001–1013; Adams, J.; Lepine-Frenette, C.; Spero, D. M. J. Org. Chem. 1991, 56,
4494–4498; Hatsui, T.; Wang, J.-J.; Takeshita, H. Bull. Chem. Soc. Jpn. 1994, 67,
2507–2513; Srikrishna, A.; Lakshmi, B. V.; Mathews, M. M. Tetrahedron Lett.
2006, 47, 2103–2106; Chen, Y.-J.; Wang, C.-Y.; Lin, W.-Y. Tetrahedron 1996, 52,
13181–13188 and references cited therein.
4.1.14. 1-Methylene-5,5,9-trimethylspiro[5.5]undec-8-en-3-one 26
To a magnetically stirred solution of the spiro alcohol 8 (30 mg,
0.136 mmol) in anhydrous CH2Cl2 (0.5 mL) was added a homoge-
neous mixture of PCC (147 mg, 0.68 mmol) and silica gel (147 mg),
and stirred for 45 min at rt. The reaction mixture was then filtered
through a small silica gel column using CH2Cl2 as eluent. Evapo-
ration of the solvent and purification of the residue on a silica gel
column using ethyl acetate–hexane (1:9) as eluent furnished the
ketone 26 (26 mg, 88%) as oil. Rf (1:9 EtOAc–hexane) 0.6; IR (liquid
film): nmax/cmꢁ1 3070, 2946, 2853, 1720, 1651, 1635, 1452, 1373,
8. A very short approach to
Plamondon and Canonne. However, 1H and 13C spectral data for synthetic
-chamigrene reported by these authors is quite different from that re-
a-chamigrene via spiroalkylation was reported by
(ꢀ)-a
ported by others. See, Plamondon, J.; Canonne, P. Tetrahedron Lett. 1991, 32,
589–592.
9. Clarke, M. L.; France, M. B. Tetrahedron 2008, 64, 9003–9031; Oppolzer, W.;
Snieckus, V. Angew. Chem., Int. Ed. Engl. 1978, 17, 476–486; Taber, D. F. Intra-
molecular Diels–Alder and Alder Ene Reactions; Springer: Berlin, 1984.
10. (a) Ireland, R. E.; Mueller, R. H. J. Am. Chem. Soc. 1972, 94, 5897–5898; (b) Ire-
land, 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.
11. Srikrishna, A.; Ramesh Babu, R. Tetrahedron Lett. 2007, 48, 6916–6919.
12. For example, 3 N HCl and CH2Cl2 (1:1) under sonochemical irradiation gave 72
and 24% of 23 and 8, respectively, whereas 3 N HCl and THF (1:10) gave 32 and
36%, respectively. 20 mol % of TFA in 2:1 THF–water at rt gave 35 and 33% of 23
and 8, respectively.
1306, 1261, 1230, 1054, 886; 1H NMR (300 MHz, CDCl3):
d 5.34 (1H,
br s, H-8), 4.96 (1H, s) and 4.70 (1H, s) [C]CH2], 3.27 and 2.92 (2H,
2ꢃd, J 15.3 Hz), 2.68 (1H, d, J 14.7 Hz), 2.40–1.00 (7H, m), 1.61 (3H,
s), 1.02 (3H, s) and 0.81 (3H, s) [2ꢃtert-CH3]; 13C NMR (75 MHz,
CDCl3):
d 207.6 (C, C]O), 143.5 (C), 132.7 (C), 119.4 (CH, C-8), 114.4
(CH2, C]CH2), 52.5 (CH2), 49.0 (CH2), 44.3 (C), 39.3 (C), 28.8 (CH2),
28.1 (CH2), 25.8 (CH2), 24.2 (CH3), 24.1 (CH3), 23.3 (CH3); HRMS: m/z
calcd for C15H22ONa (MþNa): 241.1568, found: 241.1560.
13. Barton, D. H. R.; Mc Combie, S. W. J. Chem. Soc., Perkin Trans. 1 1975, 1574–1585;
Barton, D. H. R.; Crich, D.;Lobberding, A.; Zard, S. Z. Tetrahedron 1986, 42, 2329–2338.