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An Approach to Epothilones Based on Olefin Metathesis.

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(d). 144.67 (d). 137.54 (d), 128.94 (d). 127.89 (d), 115.37 (t), 97.68 (s), 89.78 (d),
78.13 (d). 34.97 (t), 32.82 (t), 30.29 (s). 26.05 (4).
An Approach to Epothilones Based on
Olefin Metathesis**
CL-15. 'H NMR (360 MHz, CDCI,): 6 = 6.76 (dd. J =10.2. 2.9 Hz, HC=CHC=O. lH),6.19(dd,J=10.0,2.3H~,HC=CH-C=O,1H),6.13(dd,J=10.2,
K. C.
2.2 Hz, H C = C H C=O, 2 H ) , 5.85 (dddd. J = 1 7 . 2 , 10.2, 7.0. 6.3 Hz, H,C=CH),
Nicolaou,* Yun He, Dionisios Vourloumis,
5.06(dm.J=17.2Hz.HHC=CH),502(dm,J=10.2Hz,HHC=CH),4.29-4.21Hans Vallberg, and Zhen Yang
(m. 0 - C H - CH,). 3.92 (d. J = 5.3 Hz. !Bu-CH), 2.36-2.28 (m. H,C=CHC H H ) . 2.17 2.05 (m. H,C=CH-CHH). 1.76-1.65 (m. 0-CH--CH,), 1.06 (s,
Epothilones A and B (1 and 2, respectively; Scheme 1) repretBu). ' " C NMR (50.3 MHz, CDCI,): 6 =185.35 (s), 145.71 (d). 143.49 (d), 137.63
(d).129.52(d).12784(d),115.40(t),96.73(s),86.81(d),79.19(d).32.7l(t),31.21
(s). 30.12 (t). 26.99 (q). Mixture of didstereoisomers. Anal. calc. for C,,H,,O,
(262.35): C 73 25. H 8.45: found- C 73.20, H 8.42.
Received- April 26. 1996 [Z9072IE]
German version: Angew. Chem. 1996, 108, 2523-2525
Keywords: asymmetric induction
hydrostannylations * radicals
-
chelate control
*
diols
-
[l] P. Renaud. M. Gerster, J. Am. Chein. Soc. 1995, f17, 6607-6608.
121 Since the publication of our preliminary results [l], we have discovered that it
is more convenient to use Me,AI instead of Et,AICI/Na,CO, to prepare the
aluminum alkoxide.
[3] Reviews on the stereoselectivity of radical reactions: N. A. Porter, B. Giese,
D. P. Curran. Ace. Chem. Res. 1991, 24, 296-304; W. Smadja, S.ynletr 1994,
1 - 1 6 ; D. P. Curran. N. A. Porter, B. Giese, Srereorhemisrry of Rudicul Reucrions. VCH, Weinheim, 1996
For stereoselective reactions based on 1-oxy radicals, see: B. Giese, W. Damm,
J. Dickhaut. F. Wetterich, S. Sun, D. P. Curran. Terruhedron Let!. 1991, 32.
6097 6100: B . Giese. B. Carboni, T. Gobel. R Muhn, F. Wetterich, ibid. 1992,
33. 2673 -2676.
For chelation control in radical reactions. see: Y Guindon, J.-F. Lavallee. M.
Llinas-Brunet. G. Horner. J. Rancourt. J. Am. Chem. Sac. 1991. 113, 97019702: Y. Guindon. B. Guirin, C. Chabot, N. Mackintosh, W. W. Ogilvie. Svnle// 1995.449 451 ;H. Nagano, Y. Kuno, J. Chem. Sor. Chem. Commun. 1994.
987- 988: T. Toru. Y. Wdtanabe. M. Tsusaka, Y. Ueno, J. Am. Chem. S o ( . 1993,
115. 10464 - 10465: M. Kito, T.Sdkai, K. ydmada. F.Matsuda, H. Shiramana.
S.vnh,r! 1993. 158 -162; T. Gillmann, Tetruhedron Lett. 1993, 34, 607-610; Y.
Yamamoto. S. Onuki, M. Yumoto, N. Asao, J. Am. Chem. Soc. 1994, ff6,
421 -422: M. Kawatsura. F Matsuda. H. Shirahama. J. Org. Chem. 1994, 59,
6900 - 6901: A. G. Molander, J. A. McKie. ibid. 1995,60.872-882; H. Urabe,
K. Yamashita. K. Suzuki, K Kobayashi, F. Sato, ibtd. 1995.60. 3576-3577; J.
Hongliu. R. Radinov. N. A. Porter, J Am. Chem. Soc. 1995, 117. 1102911030; M. P. Sibi, C. J Jasperse, J. Ji. ihid. 1995, 117, 10779-10780; H.
Stadtmiiller. P Knochel, Synlerr 1995,463-464. M. P. Sibi, J. Ji. Angew. Chem.
1996. 108, 198 200; Angen. Cliern. Int. Ed. Engl. 1996, 35, 190-192.
K. S . Feldman. H M. Berven, P. H. Weinreb, J. Am. Chem. Soc 1993, 115,
11364- 11369.
R.N. Saisic. R. Matovic. Z. Cekovic, Guzz Chim. Iml. 1991, f2f.325-328.
Crystallographic data (excluding structure factors) for the structure reported in
this paper have been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication no. CCDC-179-89. Copies of the data can
be obtained free of charge on application to The Director, CCDC, 12 Union
Road. Cambridge CB2 IEZ, U K (fax: Int. code +(1223) 336-033; e-mail.
teched(a chemcryscdm ac.uk).
The preliminary " C N M R study supports the formation of a chelate. Details
will be published in a forthcoming full paper.
The reaction with like(lk) topicity affords the unlike(u) product and vice versa.
J. E. Eksterowicz. K. N. Houk, Tetrahedron Lert. 1993, 34, 427-430; W.
Damm, J. Dickhaut, F.Wetterich, B. Giese. ibid. 1993, 34. 431-434.
R. D. McKelvey. T. Sugarawa, H . Iwamura, Mugn. Reson. Chem. 1985, 23,
330-334: Y.-D. Wu. K. N. Houk, J. Am. Chem. SOC.1992. 114, 1656-1661.
Very recently i t was found that the stereoselectivity of 1-amino-substltuted
cyclic radicals was strongly dependent of the nature of the R group attached at
the radical center. An explanation based on pyramidalization of the reactive
center in the transition state was proposed: D. Crich, S. Natarajan, J. Org.
Chcm. 1995, 60. 6237-6241.
[14] D. J. Cram. F. A. A. Elhafez. J. Am. Chem. SOC.1952, 74, 5828-5835; D. J.
Cram. K . R. Kopecky, ihid. 1959,81, 2748-2755; D. J. Cram, D. R. Wilson,
ihrd 1963. 85. 1245-1249: J. H. Stocker, P. Sidisunthorn. B. M. BenJamin,
C. J. Collins. ihid. 1960. 82, 3913-3918: for a review. see: E. L. Eliel, S. H.
r r ~Organic Compounds. Wiley. New York, 1994.
Wilen. S t e r r o ~ h e i t ~ o of
[15] Preliminary experiments have shown that the 2-rerr-butyl-1 -methyloxiranyl
radical reacts preferentially with ul topicity that is syn to the /err-butyl group.
For reaction with monosubstituted oxiranyl radicals, see: F. E. Ziegler, P. G.
Harrdn. Terruh~&on Lert. 1993, 34, 4505-4508.
[16] Syn bromination of 2-substituted aziridinyl radicals has been reported. F. E.
Ziegler, M.Belena. J. Org. Chem. 1994, 59, 7962-7967.
[17] For a recent result that may l i t in this category, see- H. Urabe, K . Kobayashi.
F Sato. J. Cfiem. SOC. Chem. Commun. 1995, 1043-1044. See also J. 0
Metzger. K. Schwarzkopf, W. Saak, S. Pohl, Chem. Ber. 1994,127,1069- 1073.
A n o , , ~ . . C/wm h r r
FA Fnnl
1996 ? 5
No. 20
sent a new class of natural products with interesting molecular
architecture and considerable potential in medicine. Originally
isolated by Hofle et al.['] from myxobacteria Sorangium cellulosum strain 90, these compounds possess striking biological
properties, for example potent antifungal activity['] against
oomyceten (Plasmopara viticola, Phytopthora infkstans) both in
vitro and in the greenhouse as well as cytotoxic activity against
mouse fibroblasts [cell line L929, IC,, 2 mgmL-' for
epothilone B (2)]. Most importantly, the epothilones exhibit
significant in vitro selectivity against breast and colon cell
lines;[*,31 they exert their cytotoxicity by the same mechanism as
tax01,[~]namely by stabilization of microtubules. The latter observation made by Merck scientists, who also discovered the
epothilones inde~endently,~~]
is both exciting and intriguing in
view of taxol's success as an anticancer agent and the absence
of any apparent structural similarity between taxol and
epothilones. The structures of these compounds have recently
been established by Hofle and his groupc2]with spectroscopic
1: epothilone A (R = H)
2: epothilone B (R = CH,)
Q
olefin
7
metathesis
a
HO
0
3
aldoi
._
0
0
4
a
Q
OR
o
0
'
esterification
5
Scheme 1. Structures and retrosynthetic analysis of epothilones A (1) and B (2).
I*] Prof. Dr. K . C. Nicolaou, Y He, Dr. D. Vourloumis, Dr. H. Vallberg.
Dr. Z. Yang
Department of Chemistry and
The Skaggs Institute of Chemical Biology
The Scripps Research Institute
10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA)
Fax: Int. code +(619)784-2469
and
Department of Chemistry and Biochemistry
University of California San Diego
9500 Gilman Drive, La Jolla, CA 92093 (USA)
[**I This work was financially supported by The Skaggs Institute of Chemical
Biology and the National Institutes of Health (USA).
cs? VCH Verlaasaesellschuft mbH, 0.69451 Weinheim. 1996
0570-083319613520-2399$15.00+ .2Si0
2399
COMMUNICATIONS
techniques and X-ray crystallographic analysis of epothilone B
(2). In this communication we report a olefin metathesis based
approach to the macrocyclic skeleton of the epothilones that
may be used to construct not only the natural substances, but
also a library of analogs for biological screening.
A plausible retrosynthetic strategy for epothilones is illustrated in Scheme 1. According to this metathesis-based approach,
the epothilone structure is traced back to the 16-membered ring
skeletons 3 or 4, which lack, besides the side chain, a number of
oxygen atoms. Further disconnection of 3 or 4 by a retro
metathesis reaction reveals the open chain compound 5 as a
potential precursor. Disassembly of 5 can easily be envisioned
as indicated in Scheme 1, leading to three simple building
blocks. Thus, though the exact sequence will have to await experimentation, the strategy evolved from this analysis will involve rapid assembly of 5, ring closure by olefin metathesis,[5.6l
introduction of the required oxygen functions, and side chain
attachment. Conformational effects of the 16-membered ring as
well as neighboring group participation are expected to play
important roles in setting the proper stereorelationships within
the target molecules. Most importantly, the scheme is flexible
enough to allow entry to all possible stereoisomers of the
epothilones.
Since the stereochemical details of the epothilones A (I) and
B (2) were at first unknown, we initially focused on a flexible
sequence aimed at exploring a general strategy capable of delivering all possible stereoisomers and, eventually, an epothilone
library of maximum diversity. To this end, the three requisite
fragments 6-8 were synthesized as shown in Scheme 2. Con-
7
+cop
0
12 0
O t 3
13
14
15
16
0
1
7
1
10
The assembly of the epothilones skeleton from buidling
blocks 6-8 is shown in Scheme 3. Coupling of 7 and 8 with
dicyclohexylcarboiimide (DCC) led to 12 (99 YOyield) whose
enolate, generated by the action of lithium diisopropylamide
(LDA). reacted with aldehyde 6 to afford a mixture of diastereo-
0
0
0
ia
17
Scheme 3. Synthesis of the epothilone cyclic framework by olefin metathesis:
a) 1.5 equiv DCC. 1.5 equiv 4-dimethylaminopyridine,toluene, 25 " C , 8 h, 99%;
b)1.2equivLDA. - 7 8 "C . TH F, 0 . 5 h ; t h e n 6 i n TH F, -78'C,0.5h,13(29%).
14 (60%); c) SUbStrdte concentration: 0 . 0 0 6 ~ in CH,CI,, 5-10mol%
[RUCI,(=CHP~)(PC~,),].
25°C. 4-12 h, 80-82%.
11
Scheme 2. Construction of the building blocks 6-8. a) 3.0 equiv SO, Pyr. 5 equiv
Et,N, CH,CI,:DMSO (4:1), O'C. 2 h, 88%: b) 1.5 equiv Ph,P=CH, THF, 0 'C,
2 h, 9 4 % ; c) 2.4equiv DIBAL. CH,CI,, -78 + 25'C. 20 h. 83%; d) 5.0equiv
NaIO,, CH,CI,:H,O (4: 1). 25°C. 20 h, 81 %: e) 1.1 equiv TPSCI. 1.2 equiv imidazole. CH,CI,. 25 'C. 100%: f ) 1.1 equiv 1,3-dithiane. 1.1 equiv nBuLi. THF.
-30-25 'C. 84%: g) 1.1 equiv Hg(CIO,),, 1.2equiv CaCO,, THF:H,O (1O:l).
12 h. 85%; h) 2.5equiv Ph,P=CH,, THF, 0 C. 1 h, 8 3 % ; 1.6equiv NaH, THF,
0+25'C, 1 h, 87%: J) CF,COOH:CH,CI, ( l : l ) , 25 C, O S h , 100%. TPS=
SiPh,tBu: Piv = COtBu.
struction of building block 6 involved oxidation of alcohol 9[']
to the corresponding aldehyde, Wittig olefination, DIBAL-induced removal of the pivaloate groups, and sodium periodate
cleavage of the resulting 1.2-diol (56 YOoverall yield). Preparation of 7 proceeded smoothly from (R)-(+)-glycidol (10)
through silyl ether formation, epoxide opening with the lithio
derivative of dithiane, liberation of the aldehyde, and olefin
formation (59 YOoverall yield). Synthesis of 8 required selective
phosphonate condensation with readily available ketoaldehyde
l1Js1followed by acidic cleavage of the fert-butyl ester (87 Yo
overall yield, Scheme 2).
2400
C, VCH
Verlug.wesellschufi mhH. 0-69451 Weinheim. 1996
isomers, 13 (29% yield) and 14 (60% yield). After chromatographic separation (silica, 20 YOethyl acetate in hexanes), pure
13 was subjected to the Grubbs conditions for olefin metathesis
with a [RuCI,(=CHPh)(PCy,)J catalyst[51 (Cy = cyclohexyl)
and furnished the 16-membered macrolide ring 1519' in 80%
yield. Under similar conditions, diastereoisomer 14 led to cyclic
system 16cg1in 82% yield. The diastereomeric macrolide systems 17rg1and 18[91were also synthesized in similar yields starting with the enantiomer of 10 and following the same sequence.
The use of the enantiomer of 6 is expected to allow entry to yet
another series of stereoisomers of the epothilone skeleton.
In conclusion, we have demonstrated the viability of a convergent and highly efficient approach to the epothilone cyclic
framework through the olefin metathesis reaction. This strategy, and its many imaginable variants, pave the way for the total
synthesis of both natural and designed members of this new
class of compounds for biological investigations and possible
therapeutic
Received: August 7, 1996 [Z94301EJ
German version: AnXrw Chcm. 1996, 108. 2554-2556
0570-OX3319613520-24UU$' tS.00t.1sLLj
APXWW
r17vm Inr Fd Fnol 1996 35
NO
w
COMMUNICATIONS
Keywords: cyclizations - epothilones . natural products * olefin
metathesis synthetic methods
-
[l] a) C. Hofle. N. Bedorf, K. Gerth, H. Reichenbach, DE-4138042, 1993 [Chem.
Ahstr. 1993. 130, 528411, b) K. Gerth, N. Bedorf. G Hofle, H. Irschtk. H.
Reichenbach, J. Antihior. 1996. 49, 560-563.
[2] G. Hofle, N . Bedorf, H. Steinmetz, D. Schomburg, K. Gerth, H. Reichenbach,
Angew. Cheiii. 1996, 108. 1671-1673; Angew. Chem. In!. Ed. Engl. 1996. 3s.
1567- 1569.
[3] M. R. Grevel-. S . A. Schepartz, B. A. Chabner, Semin. Oncol. 1992, 19, 622638.
[4] D. M. Bollag, P. A. McQueney, J. Zhu, 0. Hensens, L. Koupal, J. Liesch, M.
Goetz, E Ldzdrldes, C. M. Woods, Cancer Res. 1995, 55, 2325-2333.
[5] For the development of the olefin metathesis as a ring forming reaction, see
a) W. J. Zuercher. M. Hashimoto, R. H. Grubbs, J Am. Chem. Sac. 1996, 118,
6634 -6640, h) P. Schwab, R. H. Grubbs, J. W. Ziller. ibid. 1996,118,100-110;
c ) R . H Grubbs. S . J. Mil1er.G. C. Fu. Arc. Chem. Res. 1995.28.446-452. and
reference$ therein.
[6] Applications of the olefin metathesis reaction in medium and large ring synthesis. see a) A. Furstner. K. Langemann, J. Org. Chem. 1996.61.3942-3943; b)
S . F. Martin. H -3. Chen, A. K. Courtney, Y. Liao. M. Patzel, M. N. Ramser.
A. S . Wagman. Tctruhedron 1996. 52, 7251-7264; c) T. D. Clark, M. R.
Ghadiri. J Am. Cheni. Sot. 1995, 117, 12364-12365; d) A. F. Houri, Z. Xu.
D. A Cogdn. A . H. Hoveyda, ibid. 1995, 117, 2943-2944; e) B. C. Borer. S.
Deerenberp. H Bieraugel. U. K. Pandlt, Tetrahedron Left. 1994. 35.
3191 -3194
[7] Compound 9 was synthesized from geraniol by standard chemistry: D. F.
Taber. K . K . You, J. Am. Cheni. Soc. 1995, 117, 5157-5762. and references
thertm. Both enantiomers of 6 may also be reached by asymmetric synthesis
with chiral auxiliaries.
[XI Ketoaldehyde 11 was prepared from propionyl chloride according to a published procedure: T. Inukai, R. Yoshizawa, J. Org. Chem. 1967, 32, 404-407.
[9] Selected physical properties of compounds: 15: R, = 0.29 (silica, 20% ethyl
acetate in hexanes): IR (film): ,F = 3522 (br. OH), 1718 (C(O)O), 1698
(COC). 1646 (CH=CHCO); 'H NMR (400 MHz, CDCI,): b =7.67-7.35 (m.
10H. SiPh,). 7.07 (d, I H, J =16.0 Hz, =CHCOO). 5.85 (d, 1 H, J =16.0 Hz,
(CH,),CH=). 5 29 (m. 2H. CH=CHCH,), 5.23 (m. 1 H, COOCH), 3.76 (dd.
1 H. J, = 6.3 Hz. J, =10.6 Hz, CH,OSi), 3.69 (dd. 1 H. J , = 5.2Hz.
CH(CH3)CO), 0.96 (d, 3H. J = 6.6 Hz, CH(OH)CH(CH,)); HRMS for
C,,H,oO,SiCs (M+CsC):calcd 723.2482, found 723.2506 16: R, = 0.20 (silica. 20% ethyl acetate in hexanes); 1R (film): C,, = 3520 (br, OH), 1711
(C(0)O). 1705 (COC), 1646 (CH=CHCO); 'HNMR (400 MHz, CDCI,):
b=7.68-~7.35(m,10H,SiPI~,),6.78(d.lH,J=15.8Hz,=CHCOO),5,98(d,
1H. J=15.8Hz, (CH,),CH=). 5.40 (m, 2H, CH=CHCH,). 5.20 (m, I H ,
COOCH), 3.75 (dd, 1H, Jl = 6.0 Hz, Jz =10.7 Hz, CH,OSi), 3.68 (dd, 1 H.
J, = 5.8 Hz, J, =10.7 Hz, CH,OSi). 3.57 (m, 1H. CH(OH)), 3.05 (m, 2H,
(CH,)CHCO, CH(0H)). 2.42 (m, 1H. CH,CH=CHCH,). 2.21 (m. 1H.
CH,CH=CHCH,), 2.08 (m. l H , CH,CH=CHCH,). 1.98 (m. l H ,
CH2CH=CHCH,), 1.44 (m, 2H. CH(CH,)CH,CH,). 1.36 (s. 3H, C(CH,),).
1.25 (m. 1 H, CH(CH,)CH,CH,), 1.20 (s, 3H, C(CH,),), 1.15 (m, 2H,
CH(CH,)CH,CH,), 1.04 (s, 9H. C(CH,),). 1.02 (d. 3H. J = 6.9 Hz,
CH(CH,)CO), 0.90 (d, 3H, J = 6.5 Hz, CH(OH)CH(CH,)); HRMS for
C,,H,,O,SiCs (M+Cs+): calcd 723.2482. found 723.2508. 17: R, = 0.34 (silica, 20% ethyl acetate in hexanes); IR (film): v,*. = 3524 (broad, OH), 1722
(-C(O)-0). 1699 (COC), 1648 (CH=CHCO); 'HNMR (400 MHz, CDCI,):
6=7.67-7.35(m,10H,SiPh2),6.90(d,1H,J=15.8Hz.=CHCOO),5.98(d,
l H , J=15.8Hz. (CH,),CH=),5.35(m,2H,CH=CHCH2),
5.20(m, l H ,
COOC H i , 3.73 (dd, 1 H, J, = 5.7 Hz, Jz =10.7 Hz, CH,OSI), 3.69 (dd, 1 H,
JI = 5.8 Hz. J, =10.7 Hz. CH,OSi). 3.14 (4%1 H, J = 6 9 Hz. (CH,)CHCO).
3.10 (d, 1H, J = 9 . 6 H z , O H ) , 2.96 (s, I H , (Off)). 2.42 (m. I H ,
CH,CH=CHCH,), 2.27 (m, 1H. CH,CH=CHCH,), 2.14 (m, I H ,
CH,CH=CHCH,), 1.97 (m. l H , CH,CH=CHCH,), 1.44 (m, 2H,
CH(CH,)CH,CH,). 1.19 (m, l H , CH(CH,)CH,CH,), 1.15 (m, 2H,
CH(CH,)CH,CH,). 1.33(s.3H,C(CH3),). 1.22(s,3H,C(CH3),). 1.04(s,9H,
C(CH,),). 1.02 (d, 3H, J = 6.9 Hz. CH(CH3)CO), 0.96 (d, 3H. J = 6.5 Hz,
CH(OH)CH(CH,)); HRMS calcd for C,,H,,O,SiCs ( M + Cs'): 723 2482.
found: 723.2508.18: R, = 0.18(silica. 20% ethyl acetatein hexanes); IR(fi1m).
v,,, = 3523 (broad, OH), 1719 (C(O)O), 1699 (COC), 1646 (CH=CHCO),
'HNMR (400MHz, CDCI,): 6 =7.68-7.32 (m, 10H, SiPh,), 7.01 ( I H ,
J =16.0 Hz, =CHCOO). 5.83 (d, 1 H. J =16.0 Hz, (CH,),CH =), 5.33 (m,
2H. CH=CHCH,), 5.22 (m. 1 H, COOCH). 3.73 (dd. 1 H. J, = 5.5 Hz,
J2 =11.4 Hz. -CH,OSi), 3.69 (dd, 1 H, J, = 4.3 Hz, J2 = 11.4 Hz. CH,OSi),
3.57 (m. l H , CHOH), 3.04 (m, 2H, (CH,)CHCO, CH(0H)). 2.42 (m, 1 H,
CH,CH=CHCH,), 2.27 (m, 1H. CH,CH=CHCH,), 2.14 (m, l H ,
CH,CH=CHCH,).
1.97 (m, l H , CH,CH=CHCH,), 1.44 (m, 2H,
CH(CH,)CH,CH,), 1-19 (m, l H , CH(CH,)CH,CH,). 1.15 (m, 2H.
CH(CH,)CH,CH,). 1.33fs,3H,C(CH3),). 1.22(s.3H,C(CH3),), 1.04(s,9H,
J2=10.6H~.CH,OSi).3.26(d,1H,J=9.1H~,CH(OH)).3.13(q,1H,J=
C(CHd3). 1.02 (d, 3H, J = 6.9 Hz, -CH(CH,)CO), 0.96 (d, 3H, J = 6.5 Hz,
7.0 Hz.(CH,)CffCO),2.87 (s, 1H. CHOH), 2.47 (m, 1 H, CH,CH=CHCH,),
CH(OH)CH(CH,)); HRMS calcd for C,,H,,O,SiCs (hl + Cs'): 723.2482.
found 1 723.2506.
2.30 (m. 1 H. CH,CH=CHCH,), 2.09 (m, 1 H, CH,CH=CHCH,), 1.96 (m.
I H . CH,CH=CHCH,). 1 5 0 (m. 2H, CH(CH,)CH,CH,). 1.37 (m, IH,
[lo] All new compounds exhibited satisfactory spectral and analytical and/or exact
CH(CH,)CH,CH,). 1.35(m. 2H, CH(CH,)CH,CH,), 1.33 (s. 3H, C(CH,),),
mass data. Yields refer to chromatographically and spectroscopically homoge1.24 ( 8 . 3H. C(CH,)2). 1.04 ( s . 9H. C(CH,),). 1.02 (d, 3H. J = 6 9 Hz.
neous materials.
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