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Organic Synthesis workbook li - Bittner C.

Bittner C. Organic Synthesis workbook li - John Wiley & Sons, 2001. - 292 p.
ISBN: 3-527-30415-0
Download (direct link): bittnerorganicsynthesisworkbook2001.pdf
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14 W. R. Roush, T. D. Bannister, Tetrahedron Lett. 1992, 33, 3587-3590.
15 For a review see: M. Schroder, Chem. Rev. 1980, 80, 187-213.
16 R. Criegee, L. Kraf t, B. Rank, Liebigs Ann. Chem. 1933, 507, 159-167.
17 K. Takai, K. Nitta, K. Utimoto, Tetrahedron Lett. 1988, 29, 5263-5266.
18 a) J. C. Gilbert, U. Weerasooriya, J. Org. Chem. 1979, 44, 4997-4998; b) D. Seyferth, R. S. Marmor, P.Hilbert, J. Org. Chem. 1971,56, 1379-1386
19 N. Miyaura, K. Yamada, H. Suginome, H. Suzuki, J. Am. Chem. Soc. 1985, 107, 972-980.
20 J. Uenishi, J.-M. Beau, R. W. Armstrong, Y. Kishi, J. Am. Chem. Soc. 1987,109, 4756-4758.
21 J. Inanaga, K. Hirata, H. Saeki, T. Katsuki, M. Yamagushi, Bull. Chem. Soc. Jpn. 1979, 52, 1989-1993.
22 T. Mukaiyama Org. React. 1982, 28, 238-248.
23 D. A. Evans, M. J. Dart, J. L. Duffy, M. G. Yang, J. Am. Chem. Soc. 1996,118, 4322-4343.
24 a) M. Cherest, H. Felkin, N. Prudent, Tetrahedron Lett. 1968, 2199-2204; b) N. T. Anh, O. Eisenstein, Nouv. J. Chem. 1977,
1, 61-70.
25 K. A. Scheidt, H. C. Chen, . C. Follows, S. R. Chemler, D. S. Coffey, W. R. Roush, J. Org. Chem. 1998, 63, 6436-6437.
26 M. Gingras, Tetrahedron Lett. 1991, 32, 7381-7384.
27 A. S. Pilcher, P. DeShong, J. Org. Chem. 1996, 61, 6901-6905.
Organic Synthesis Workbook II
C. Bittner, A. S. Busemann, U. Griesbach, F. Haunert, W.-R. Krahnert, A. Modi, J. Olschimke, P. L. Steck
Copyright 2001 Wiley-VCH Verlag GmbH ISBNs: 3-527-30415-0 (Softcover); 3-527-60013-2 (Electronic)
3
Curacin A (Wipf 1996)
3.1 Introduction
Marine cyanobacteria offer a wide range of biologically active metabolites, some of which display high potential in treating human diseases.1 One of these compounds is curacin A (1) from Lyngbya majuscala collected off the coast of Curaijao and isolated by Gerwick et al. in 1994.2 By inhibiting the microtubule assembly by compound 1 cells are prevented from dividing and growing - the fundamental requirement for an anticancer drug. As well as its promising antiproliferative effects; curacin A (1) also inhibits the binding of colchicine (2) to tubulin as a consequence of its high binding affinity to the colchicine site of tubulin.3
Other remarkable facts are the structural features of compound 1. It contains a vinyl and cyclopropyl substituent at C-7 and C-5 which makes 1 an unusual example among natural products with a thiazoline ring. Furthermore, three of the four stereogenic centers are included in this moiety.4 Both biological activity and structural features motivated several research groups to find synthetic routes toward l,5 whose first total synthesis was published by White and co-workers in 1995.6 The same group determined the absolute configuration via comparison of products obtained from asymmetric preparation with those acquired by degradation of the natural material. In 1996 Wipf e,t al. reported an interesting synthetic approach to curacin A (1) by use of modern organometallic chemistry.4
OMe
1
curacin A
MeO.
MeO
OMe
2
colchicine
3 Curacin A
3.2 Overview
1. TPSCI, Im, DMF, r. t 24 h, 99 %
2. Cp2Zr(H)CI, CH2CI2, r. t., 40 min, then
3. ZnEtg, -60 C, 1.5 h, then
4. E-2-methyl-2-butenal, 0 C, 6 h 94 % (over three steps)
5. Mn02, hexane, r. t., overnight, 90 % _
4
1. Cp2Zr(H)CI, CH2CI2, 40 C, overnight, then
2. /?BuNC, 0 C ^ r. t
4 h, then
3. HCI, -78 0 C 54 % (from 5)
OTPS
1. NaH, Mel, THF, r.t.,
6 h, 90 %
2. TBAF, THF, r.t.,3h,
3. MsCI, NEt3, r. t overnight, 95 %
4. Nal, acetone, reflux,
2 h, 99 %
5. PPh3, MeCN, 90 C,
24 h, quant.
3 Curacin A
2.
1. L-Serine-OMe, DCC, DMAR CH2CI2, r. t., overnight, 71 %
2.TBSCI, Im, DMAP, CH2CI2, r. t., overnight, 89 %
3. LiCI, NaBH4, THF, EtOH, r. t., overnight, 88 %
4. (COCI)2, DMSO, NEt3, CH2CI2> -60 C, 20 min, quant.
8 + 11
1.
2.
OMe
38
3 Curacin A
3.3 Synthesis
Problem
1.TPSCI, Im, DMF, r. t 24 h, 99 %
2. Cp2Zr(H)CI, CH2CI2, r. t., 40 min, then
3. ZnEt2, -60 C, 1.5 h, then
4. ?-2-methyl-2-butenal 14, 0 C, 6 h,
94 % (over three steps)
5. Mn02, hexane, r. t., overnight, 90 %

H
Hints The first step adds a protecting group.
In the second step the triple bond is attacked.
An organozirconium species is formed via hydrometalation.
What are the positions of the zirconium and the hydrogen in the substrate?
What happens to the organozirconium species on treatment with ZnEt2?
A transmetalation takes place.
Compound 14 represents a Michael system. Does a 1,2- or a 1,4-addition occur?
Manganese dioxide is often used for the mild oxidation of special types of alcohol.
Solution
TPSO
14
Discussion
Zr
4j| xci 16
Schwartz reagent
First conversion of primary alcohol 3 to the r e /7 - b u t Idiphe n I s i l l ether 15 occurs. In the field of silyl ethers the TPS group as well as the triisopropylsilyl (TIPS) group are the most stable protecting groups against a large variety of reaction conditions - consequently they are frequently used in organic synthesis (see Chapter 2).7 Generation of organozirconium species 18 follows the hydrozirconation of the triple bond using zirconocene hydrochloride (,Schwartz reagent) 16. This 16-electron, d Zr(IV) complex is coordinatively unsaturated, so alkyne 15 coordinates to the electrophilic Zr center followed by insertion of the triple bond into the Zr-H bond. The resulting o-vinyl-Zr(IV)-species 18 is formed with a high f/.v-selectivity and regioselectivity, such that the bulky zirconocene moiety always adds end-on to the terminal multiple bond.
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