Enantiospecific construction of the BC-ring system of taxanes

Article abstract of DOI:10.1016/j.tetlet.2004.02.075

Two alternative approaches to the BC-ring system of taxanes, suitable for generating both enantiomeric forms of taxanes, starting from the readily and abundantly available monoterpene (R)-carvone employing a ring-closing metathesis reaction as key step, are described.

Full text of DOI:10.1016/j.tetlet.2004.02.075

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 2939–2942
Enantiospecific construction of the BC-ring system of taxanesq
A. Srikrishna,* Dattatraya H. Dethe and P. Ravi Kumar
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
Received 7 January 2004; revised 2 February 2004; accepted 12 February 2004
Abstract—Two alternative approaches to the BC-ring system of taxanes, suitable for generating both enantiomeric forms of taxanes,
starting from the readily and abundantly available monoterpene (R)-carvone employing a ring-closing metathesis reaction as key
step, are described.
Ó 2004 Elsevier Ltd. All rights reserved.
Paclitaxel (1, Taxol),1 by virtue of its complex and den-
sely functionalised structure, coupled with its novel
mechanism of action, potent antitumour activity and its
clinical use as a powerful anticancer drug has attracted
the attention of many synthetic chemists. Indeed, only
very few molecules in the last two decades have stirred as
much imagination and activity among synthetic chemists
as the taxanes.2 While a few groups have addressed the
total synthesis of 1, a larger number have confined
themselves to the development of methodologies towards
various segments of 1 as well as analogues of taxanes.3
One of the most difficult tasks in the synthesis of the
taxane framework is the construction of the B-ring,
because of the well known2i complications associated
with the formation of an eight-membered ring. In this
context, we have developed two simple and efficient
routes for the enantiospecific generation of the BC-ring
system of taxanes employing (R)-carvone 2 as the C-ring
of taxanes, and a ring-closing metathesis (RCM)4 strat-
egy for the formation of the C-10–C-11 bond of the
eight-membered B-ring of taxanes. The present
methodology also provides access to both enantio-
meric forms of the BC-ring system of taxanes starting
from a single enantiomer of carvone.
We envisaged two appropriate side arms, with terminal
olefins suitable for forming the B-ring by a RCM reac-
tion, could be attached to carvone 2 either at (i) C-2 and
C-3 or (ii) C-3 and C-4 positions, and that the ketone
and isopropenyl groups could be considered as hydroxy
group equivalents at the C-5 and C-7 positions of tax-
anes (Scheme 1). For the construction of the B-ring via
formation of the C-10–C-11 bond, in addition to the
high activation energy for the formation of eight-mem-
bered ring, it would also be necessary to overcome steric
crowding at the C-11 olefinic carbon in the precursor,
and moreover, the product would be neopentylic in
nature. Hence, to begin with, a synthesis of the BC-ring
system without the gem dimethyl group was investigated
by following the first option via 6-methylcarvone 3.
Kinetic alkylation of (R)-carvone 2 using lithium diiso-
propylamide (LDA) and methyl iodide furnished a 3:2
diastereomeric mixture of 6-methylcarvone 3, which on
low temperature crystallisation provided the major iso-
mer trans-6-methylcarvone 3t in stereochemically pure
form.5 An alkylative 1,3-enone transposition method-
ology6 followed by a reductive allylation sequence was
contemplated for the introduction of the five- and three-
carbon side-chains at the C-3 and C-2 positions
O
AcO
O
O
OH
O
Ph
NH O
OH
18
13
19
9
11
7
R
O
15
R
B
Ph
O
A
C
3
Carvone
OH
7
10
H
HO
5
1
O
14
11
H
AcO
Ph
R = Me or H
B
C
20
15
1 (Taxol)
O
5
OH
q Chiral Synthons from Carvone, Part 63. For Part 62, see: Srikrishna,
A.; Dethe, D. H. Org. Lett. 2004, 6, 165–168.
R
R
O
O
* Corresponding author. Tel.: +91-80-2932215; fax: +91-80-23600683/
23600529; e-mail: ask@orgchem.iisc.ernet.in
Scheme 1.
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.02.075

2940
A. Srikrishna et al. / Tetrahedron Letters 45 (2004) 2939–2942
(Scheme 2). Thus, sonochemically accelerated reaction
of the enone 3t with pent-4-enyl bromide and lithium
under Barbier conditions followed by oxidation of the
resultant tertiary alcohol 4 with pyridinium chloro-
chromate (PCC) and silica gel furnished the enone 5.
Reductive allylation of the enone 5 with lithium in liquid
established on the basis of the spectral data and litera-
ture precedents.7 Contrary to our expectations,8 the
RCM reaction of the compound 6 was found to be very
efficient even with the first generation GrubbsÕ catalyst
7a. Treatment of the dienone 6 with 10 mol % of the
catalyst 7a in 0.005 M methylene chloride solution at
room temperature for 2 h resulted in the efficient closure
of the eight-membered ring to give the bicyclic com-
pound 9 in near quantitative yield. Compound 9 rep-
resents a typical BC-ring system of taxane containing
both the C-19 and C-20 methyl groups, with the natural
configuration at the C-3 and C-8 positions and a trans-
BC ring junction.
ammonia and allyl bromide generated the RCM pre-
24
D
selective manner. The stereochemistry of
cursor 6, ½aꢀ ꢁ10.0 (c 6.6, CHCl3), in a highly stereo-
6 was
O
b
c
HO
O
a
After successfully generating the BC-ring system 9 via
the first option, we then investigated the second option,
Scheme 3. Since the isopropenyl group is a masked
ketone, it was conceived that generation of the two 6,6-
dialkylated carvones 10a and 10b would give access to
both enantiomeric forms of BC-taxanes. Generation of
the kinetic enolate of 6-methylcarvone 3 with LDA and
treatment with allyl bromide generated the alkylated
product (4S,5S)-10a. Reversal of the alkylation
sequence, namely first allylation of carvone followed by
methylation, gave the compound (4R,5S)-10b.9 Cou-
pling of the dialkylated compounds 10a,b with pent-4-
R
2 R = H
3t R = Me
4
5
O
O
d
e
H
9
H
6
Scheme 2. Reagents and conditions: (a) (i) LDA, THF, ꢁ70 °C; MeI,
!rt, 12 h, 95%; (ii) crystallisation from hexane; (b) Li,
CH2@CH(CH2)3Br, THF, ))), 15 °C ! rt, 0.5 h; (c) PCC, silica gel,
CH2Cl2, rt, 4 h; 85% from 3t; (d) Li, liquid NH3, THF, ꢁ33 °C, allyl
bromide, 80%; (e) 10 mol % 7a, CH2Cl2, rt, 2 h, >95%.
All compounds exhibited spectral data consistent with their structures. Yields (unoptimised) refer to isolated and chromatographically pure
22
compounds. Selected spectral data for 9: Mp: 86–88 °C. ½aꢀ ꢁ4.5 (c 1.8, CHCl3). IR (neat): mmax/cmꢁ1 1708. 1H NMR (300 MHz, CDCl3þCCl4):
D
d 5.73 (1H, ddd, J ¼ 10:5, 7.8, 7.8 Hz), 5.59 (1H, ddd, J ¼ 10:5, 10.5, 6.6 Hz), 4.74 (2H, s), 2.64 (1H, t, J ¼ 13:5 Hz), 2.45 (1H, dd, J ¼ 12:9, 6.6 Hz),
2.20–1.90 (5H, m), 1.80–1.50 (5H, m), 1.67 (3H, s, olefinic-CH3), 1.40–1.10 (1H, m), 1.14 (3H, s, tert-CH3), 0.87 (3H, d, J ¼ 5:4 Hz, sec-CH3). 13
C
NMR (75 MHz, CDCl3þCCl4): d 212.6 (C, C@O), 146.1 (C, C@CH2), 131.5 (CH), 129.1 (CH), 112.7 (CH2, C@CH2) 53.6 (CH), 52.7 (C, C-8), 48.8
(CH), 42.7 (CH2), 34.8 (CH), 33.6 (2 C, CH2), 29.0 (CH2), 27.6 (CH2), 21.0 (CH3), 18.2 (CH3), 17.2 (CH3). Anal. Calcd for C17H26O: C, 82.87; H,
23
10.64. Found: C, 82.47; H, 10.64. For 12a: ½aꢀ þ135.4 (c 2.6, CHCl3). IR (neat): mmax/cmꢁ1 1665, 1605. 1H NMR (300 MHz, CDCl3þCCl4): d 5.85–
D
5.65 (2H, m, H-3 and 4), 5.02 (1H, br s) and 4.87 (1H, s) [C@CH2], 2.86 (1H, dd, J ¼ 14:7, 3.6 Hz), 2.64–2.46 (3H, m), 2.30–2.16 (4H, m), 2.07 (1H,
dd, J ¼ 13:8, 5.4 Hz), 2.00–1.85 (1H, m), 1.84 (3H, s), 1.74 (3H, s) [2 ꢂ olefinic-CH3], 1.58–1.44 (1H, m), 1.09 (3H, s, tert-CH3). 13C NMR (75 MHz,
CDCl3þCCl4): d 197.9 (C, C@O), 164.5 (C, C-8), 144.9 (C, C@CH2), 132.8 (C, C-9), 132.5 (CH), 128.8 (CH), 115.7 (CH2, C@CH2), 47.5 (C), 45.7
(CH), 39.3 (CH2), 34.7 (CH2), 31.5 (CH2), 28.2 (CH2), 27.8 (CH2), 23.0 (CH3), 20.7 (CH3), 11.6 (CH3). HRMS (QTOF): m=z calcd for C17H24ONa
23
D
22
D
(MþNa): 267.1725. Found: 267.1750. For 12b: ½aꢀ þ177.0 (c 1.3, CHCl3). For 13: ½aꢀ )83.3 (c 1.2, CHCl3). IR (neat): mmax/cmꢁ1 1670, 1615. 1H
NMR (300 MHz, CDCl3þCCl4): d 5.77 (1H, t of dd, J ¼ 16:8, 10.2, 6.6 Hz, CH@CH2), 5.19 (1H, s, H-8), 5.02 (1H, d, J ¼ 16:8 Hz) and 4.98 (1 H,
d, J ¼ 10:2 Hz) [CH@CH2], 2.60–2.00 (9H, m), 1.73 (3H, s) and 1.67 (3H, s) [2 ꢂ olefinic-CH3], 1.53 (1H, quintet, J ¼ 7:5 Hz), 1.29–1.25 (1H, m),
1.28 (3H, s, tert-CH3). 13C NMR (75 MHz, CDCl3þCCl4): d 198.1 (C, C@O), 160.1 (C, C-5), 142.3 (C, C-9), 137.7 (CH, CH@CH2), 130.9 (C, C-4),
122.0 (CH, C-8), 115.8 (CH2, CH@CH2), 52.8 (CH, C-1), 48.2 (C, C-6), 43.3 (CH2), 37.8 (CH2), 34.6 (CH2), 31.5 (CH2), 28.1 (CH2), 26.6 (CH3),
23
D
15.2 (CH3), 12.2 (CH3). HRMS (QTOF): m=z calcd for C17H24ONa (MþNa): 267.1725. Found: 267.1723. For 16a: ½aꢀ þ5.8 (c 1.8, CHCl3). IR
(neat): mmax/cmꢁ1 1667, 1644, 1613. 1H NMR (300 MHz, CDCl3þCCl4): d 5.75 (1H, dd, J ¼ 17:1, 10.5 Hz, CH@CH2), 5.41 (1H, s, H-8), 4.98 (1H,
d, J ¼ 10:5 Hz) and 4.96 (1H, d, J ¼ 17:1 Hz) [CH@CH2] 2.75 (1 H, d, J ¼ 14:8 Hz), 2.56 (1H, dd, J ¼ 17:1, 3.6 Hz), 2.38 (1H, dd, J ¼ 17:1,
15.0 Hz), 2.42-2.00 (5H, m), 1.71 (6H, s) [2 ꢂ olefinic-CH3], 1.43 (1H, dd, J ¼ 9:9, 7.5 Hz) 1.05 (6H, s), 1.00 (3H, s) [3 ꢂ tert-CH3]. 13C NMR
(75 MHz, CDCl3þCCl4): d 199.4 (C, C@O), 166.2 (C, C-5), 147.2 (CH, CH@CH2), 140.8 (C, C-9), 130.5 (C, C-4), 123.6 (CH, C-8), 111.6 (CH2,
C@CH2) 52.5 (CH, C-1), 49.6 (C, C-6), 40.8 (CH2), 40.7 (CH2), 37.1 (C, C-3), 36.0 (CH2), 27.0 (CH2), 26.6 (CH3), 26.5 (CH3), 22.2 (CH3), 14.6
23
D
(CH3), 11.5 (CH3). HRMS (QTOF): m=z calcd for C19H28ONa (MþNa): 295.2038. Found: 295.2050. For 16b: ½aꢀ )83.9 (c 1.55, CHCl3). For 19a:
23
Mp: 123–125 °C. ½aꢀ þ41.4 (c 1.4, CHCl3). IR (neat): mmax/cmꢁ1 1665, 1605. 1H NMR (300 MHz, CDCl3þCCl4): d 5.47 (1H, d, J ¼ 11:7 Hz, H-4),
D
5.40 (1H, ddd, J ¼ 11:7, 11.7, 7.2 Hz, H-3), 2.79, 2.63 (2H, 2 ꢂ d, J ¼ 4:8 Hz, O-CH2), 2.71 (1H, dd, J ¼ 15:0, 10.5 Hz), 2.60–2.30 (4H, m), 2.26
(1H, dd, J ¼ 15:0, 6.6 Hz), 1.98 (1H, dd, J ¼ 10:5, 6.6 Hz), 1.75 (3H, s, olefinic-CH3), 1.70–1.60 (1 H, m), 1.62 (1H, dd, J ¼ 10:5, 3.3 Hz), 1.35 (3H,
s), 1.25 (3H, s), 1.13 (3H, s) and 1.05 (3H, s) [4 ꢂ tert-CH3]. 13C NMR (75 MHz, CDCl3þCCl4): d 197.0 (C, C@O), 165.6 (C, C-8), 142.5 (CH, C-4),
132.4 (C, C-9), 126.4 (CH, C-3), 57.2 (C, C-O), 54.2 (CH2, CH2-O), 47.1 (C), 44.5 (CH, C-12), 42.1 (CH2), 36.6 (CH2), 35.7 (CH2), 35.4 (C), 35.3
(CH3), 26.0 (CH2), 25.7 (CH3), 21.5 (CH3), 20.5 (CH3), 11.8 (CH3). HRMS (QTOF): m=z for C19H28O2Na (MþNa), calcd: 311.1987. Found:
23
311.1993. For 19b: ½aꢀ )102.0 (c 1.4, CHCl3). Crystal data for 19a: X-ray data were collected at 293 K on a SMART CCD-BRUKER
D
ꢀ
diffractometer with graphite monochromatic Mo-Ka radiation (k ¼ 0:7107 A). Structure was solved by direct methods (SIR92). Refinement was by
full-matrix least-squares procedures on F 2 using SHELXL-97. The nonhydrogen atoms were refined anisotropically whereas hydrogen atoms were
ꢀ
refined isotropically. C19H28O2, MW ¼ 288.41, colourless crystal, Crystal system: monoclinic, space group: P2(1), cell parameters: a ¼ 8:470 (4) A,
3
b ¼ 10:268 (5) A, c ¼ 10:497 (5) A, b ¼ 112:44° (1), V ¼ 843:89 A , Z ¼ 2, Dc ¼ 1:135 gcmꢁ3, F (0 0 0)¼ 316:0, l ¼ 0:07 mmꢁ1. Total number of l.s.
parameters ¼ 195, R1 ¼ 0.0581 for 1647 Fo > 4r(Fo) and 0.1193 for all 2828 data. WR2 ¼ 0.2328, GOF ¼ 0.748, restrained GOF ¼ 0.748 for all data.
Crystallographic data (without structure factors) have been deposited with the Cambridge Crystallographic Data Centre and the depository
number is CCDC 226177.
ꢀ
ꢀ
ꢀ

A. Srikrishna et al. / Tetrahedron Letters 45 (2004) 2939–2942
2941
7a
7a
CH2=CH2
12b
13
13
X
Me
Me
i.
Br
ref. 9
Li, THF, )))
ii. PCC, silica gel
CH2Cl2
O
O
O
Next, attention was turned towards the synthesis of the
BC-ring system of taxanes also containing the C-15 gem
dimethyl group, starting from the dialkylated carvones
10a,b (Scheme 4). Bromide 14 was obtained in three steps
from dimethylallyl alcohol. Coupling the bromide 14
2
10a α-Me
10b β-Me
75-80%
11aα-Me
11b β-Me
7a
CH2Cl2
90%
O
with 10a,b followed by oxidation resulted in the forma-
O
23
D
tion of the RCM precursors 15a, ½aꢀ þ2.0 (c 2.65,
11a
12a
23
D
CHCl3), and 15b, ½aꢀ þ50.9 (c 1.2, CHCl3). Interest-
H
7a
CH2Cl2
ingly, RCM reaction of the compounds 15a and 15b with
the catalyst 7a in 0.005 M methylene chloride solution
for 15 minutes furnished only the hydrindanes trans-16a
and cis-16b, respectively, in near quantitative yields. No
detectable amounts of the cyclooctene compounds 17a,b
(BC-ring system of taxanes) were found in either of these
reactions, even when the reaction was stopped after ca.
3 min, indicating that the hydrindanes 16a,b were formed
directly and not via cyclooctene intermediates. The
reluctance of the formation of the B-ring of taxane in
the compounds 15a,b is clearly a reflection of the effect of
the steric crowding due to the neopentylic nature of the
second olefin partner.9 The RCM of 15a,b with 5 mol %
of the second generation GrubbsÕ catalyst 8 for 15 min
also produced the same result.
+
Me
O
O
O
11b
12b
13
time % yield of
PCy3
Cl
Mes
N
N
Mes
12b
13
39
50
56
64
Ru
0.5 h 56
Cl
Ph
Cl
R
PCy3
Ru
1 h
2 h
4 h
45
36
28
Cl
PCy3
7a R = Ph
7b R = H
8
Scheme 3.
enyl bromide under Barbier conditions followed by
oxidation of the resultant tertiary alcohols furnished the
It seemed that in order to prevent formation of the
hydrindanes, the isopropenyl group in 15a,b needed to
be masked. Thus, regio- and stereoselective epoxidation
23
D
RCM precursors 11a, ½aꢀ þ9.7 (c 1.75, CHCl3), and
23
D
11b, ½aꢀ þ64.5 (c 3.1, CHCl3). The RCM reactions of
both the isomers 11a,b were found to be very rapid and
efficient.8 Thus, treatment of the 4S,5S isomer 11a with
10 mol % of the catalyst 7a in 0.005 M methylene chlo-
ride solution at room temperature for 30 min furnished
12a in near quantitative yield. In contrast, under the
same conditions, reaction of the 4R,5S isomer 11b with
10 mol % of 7a for 30 min gave a mixture of the desired
12b (56%) and the hydrindane 13 (39%), which were
separated on a silver nitrate impregnated silica gel col-
umn. The structures of 12a,b and 13 were established
from their spectral data. As the formation of trisub-
stituted olefin 13 in the RCM reaction by first genera-
tion GrubbsÕ catalyst 7a is unusual, the reaction was
further probed to discover the origin of the hydrindane
13. Extending the reaction time increased the yield of the
hydrindane 13 at the expense of the cyclooctene product
12b as shown in Scheme 3. This result indicated that the
initial product of the RCM reaction is the cyclooctene
12b, which isomerised to the hydrindane 13 with time,
perhaps via the ring-opening metathesis (ROM) fol-
lowed by RCM. The cyclooctene 12b was resubjected to
RCM conditions using the catalyst 7a, but was found to
be stable and no detectable amount of 13 was observed,
probably because of the absence of the reactive RCM
catalyst 7b in the medium. On the other hand, treatment
of 12b with catalyst 7a in methylene chloride containing
ethylene (thereby generating the reactive catalyst 7b in
the medium) for 1 h furnished a ꢃ1:2 mixture of the
hydrindane 13 and 12b, confirming that the hydrindane
13 was formed via a RCM–ROM–RCM pathway. A
similar result employing the more reactive GrubbsÕ sec-
ond generation catalyst 8 was observed by Meng and
Parker.10
of 15a,b with 1 equiv of m-chloroperbenzoic acid
24
D
(MCPBA) furnished the epoxides 18a, ½aꢀ ꢁ64.6 (c 1.3,
25
D
CHCl3), and 18b, ½aꢀ þ40.6 (c 1.8, CHCl3). Though no
reaction was observed with the catalyst 7a, gratifyingly
RCM of the trienones 18a,b with GrubbsÕ second gen-
eration catalyst 8 in refluxing methylene chloride fur-
nished 19a,b in excellent yields. In order to rule out the
possibility of olefin isomerisation during or after RCM
reaction,8 the structures were confirmed by single crystal
X-ray diffraction analysis of the epoxide 19a (Fig. 1),
which also established the stereochemistry of the epoxy
carbon.
Me
OH
c,d
a
b
O
COOEt
Br
15a α-Me
15b -Me
14
β
Me
e
H
X
>95%
Me
16a,b
O
O
O
a. α-Me
15a,b
17a,b
β
b. -Me
Scheme 4. Reagents and conditions: (a) MeC(OEt)3, EtCO2H, sealed
tube, 160 °C, 2 d, 80%; (b) (i) LAH, ꢁ70 °C ! rt, Et2O, 2 h, 95%; (ii)
CBr4, PPh3, CH2Cl2, rt, 10 h, 90%; (c) Li, 10a or 10b, THF, ))),
10 °C ! rt, 0.5 h; (d) PCC, silica gel, CH2Cl2, 4 h; 70% from 10a or 10b;
(e) 10 mol % of 7a or 5% mol of 8, CH2Cl2, 0.25 h.

2942
A. Srikrishna et al. / Tetrahedron Letters 45 (2004) 2939–2942
2. (a) Swindell, C. S. Org. Prep. Proced. Int. 1991, 23, 465–
543; (b) Kingston, D. G. I.; Molinero, A. A.; Rimoldi, J.
M. In Prog. Chem. Org. Nat. Prod.; Springer: New York,
1993; Vol. 61; (c) Guenard, D.; Gueritte-Voegelein, F.;
Potier, P. Acc. Chem. Res. 1993, 26, 160–167; (d) Boa, A.
N.; Jenkins, P. R.; Lawrence, N. J. Contemp. Org. Synth.
1994, 1, 47–75; (e) Nicolaou, K. C.; Dai, W. M.; Guy, R.
K. Angew. Chem., Int. Ed. 1994, 33, 15–44; (f) Georg, G.
I.; Chen, T. T.; Ojima, I.; Vyas, D. M. Eds., Taxane
Anticancer Agents: Basic Science and Current Status, ACS
Symposium Series 583; American Chemical Society:
Washington, DC, 1995; (g) Taxol Science and Applica-
tions; Suffness, M., Ed.; CRC: Boca Raton, FL, 1995; (h)
Wender, P. A.; Natchus, M. G.; Shuker, A. J. In TaxolR
Science and Applications; Suffness, M., Ed.; CRC: New
York, 1995; pp 123–187; (i) Mehta, G.; Singh, V. Chem.
Rev. 1999, 99, 881–930; (j) Kingston, D. G. I. Chem.
Commun. 2001, 867–880; (k) Kingston, D. G. I.; Jagtap, P.
G.; Yuan, H.; Samala, L. In Prog. Chem. Org. Nat. Prod.,
Herz, W., Falk, H., Kirby, G. W., Eds., 2002; Vol.
84.
Figure 1. ORTEP diagram of 19a.
O
O
Me
H
Me
H
a
65%
b
92%
15a,b
O
a.α-Me
O
b.β -Me
18a,b
19a,b
Reagents and conditions: (a) MCPBA, CH2Cl2, 0 °C, 1 h; (b) 5 mol %
8, CH2Cl2, reflux, 3 h.
3. For the total synthesis of taxol, and the recent approaches
to taxanes, see: Uttaro, J.-P.; Audran, G.; Galano, J.-M.;
Monti, H. Tetrahedron Lett. 2002, 43, 2757–2760, and
references cited therein.
In conclusion, we have developed two very convenient,
short and efficient RCM-based enantiospecific routes for
the construction of the complete BC-ring system of
taxanes. Generation of either enantiomeric form further
enhances the synthetic potential of this strategy. Cur-
rently, we are investigating the extension of this meth-
odology for the enantiospecific synthesis of the ABC ring
system of taxanes by incorporating suitable substituents
at the C-1 and C-11 positions of the BC-ring system.
4. (a) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413–
€
4450; (b) Furstner, A. Angew. Chem., Int. Ed. 2000, 39,
3013–3043; (c) Trnka, T. M.; Grubbs, R. H. Acc. Chem.
Res. 2001, 34, 18–29.
5. (a) Gesson, J.-P.; Jacquesy, J.-C.; Renoux, B. Tetrahedron
1989, 45, 5853–5866; (b) Gesson, J.-P.; Jacquesy, J.-C.;
Renoux, B. Tetrahedron Lett. 1986, 27, 4461–4464; (c)
Srikrishna, A.; Vijaykumar, D. J. Chem. Soc., Perkin
Trans. 1 2000, 2583–2589.
6. Buchi, G.; Egger, B. J. Org. Chem. 1971, 36, 2021–2023.
7. (a) Srikrishna, A.; Reddy, T. J. Arkivoc 2001, viii, 9–19; (b)
Srikrishna, A.; Reddy, T. J. J. Chem. Soc., Perkin Trans. 1
2001, 2040–2046.
Acknowledgements
8. For example, Prunet and co-workers have reported that
after 6 days in refluxing benzene with the catalyst 7a a
yield of 10% was obtained in their synthesis of the BC-ring
system of taxanes via C-9–C-10 bond formation by an
RCM reaction. Even with the more reactive Schrock
catalyst the reaction required 3 days in refluxing benzene.
See: Bourgeois, D.; Pancrazi, A.; Ricard, L.; Prunet, J.
Angew. Chem., Int. Ed. 2000, 39, 726–728; Bourgeois, D.;
Mahuteau, J.; Pancrazi, A.; Nolan, S. P.; Prunet, J.
Synthesis 2000, 869–882.
We thank the CCD facility of the Indian Institute of
Science for providing the single crystal X-ray diffraction
analysis and the Council of Scientific and Industrial
Research, New Delhi for the award of a research fellowship
to P.R.K.
References and notes
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