- Magnesium bromide diethyl etherate mediated highly diastereoselective aldol reaction between an aldehyde and a silyl enol ether
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High yield and excellent diastereoselectivity in the formation of methyl (2R,3R,5R,6S)-2,6-dibenzyloxy-7-(t-butyldimethylsiloxy)-3-hydroxy-5-(4-methoxybe nzyloxy)-4,4-dimethylheptanoate 3 and methyl (2R,3R,4S)-2,4-dibenzyloxy-3-hydroxypentanoate 7 are achieved by aldol reaction between (Z)-2-benzyloxy-1-methoxy-1-(trimethylsiloxy)ethene 1 and chiral alkoxy aldehydes using three equivalents of MgBr2·OEt2. The following mechanism of the above aldol reaction proposes that MgBr2·OEt2 activated both chiral alkoxy aldehydes and silyl enolate, that is, magnesiumu enolate, formed by transmetalation from silyl enolate and MgBr2·OEt2, reacted with MgBr2·OEt2-chelated alkoxy aldehydes via the six-membered cyclic transition state.
- Fujisawa, Hidehiko,Sasaki, Yasuhiro,Mukaiyama, Teruaki
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- An effective method for the preparation of chiral polyoxy 8-membered ring enone corresponding to the B ring of taxol
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An effective method for the preparation of 8-membered ring enone, (4S,5R,7R,8R)-4,8-bis(benzyloxy)-7-(t-butyldimethylsiloxy)-5- (4-methoxybenzyloxy)-2,6,6-trimethylcyclooct-2-enone (1), in sufficient quantities was developed. Optically active trioxy aldehyde, (3R,4S)-4-benzyloxy-5-(t-butyldimethylsiloxy)-3-(4-methoxybenzyloxy)- 2,2-dimethylpentanal (3), was prepared first by diastereoselective dihydroxylation of (2R,4S)-2-(4-methoxyphenyl)-5,5-dimethyl-4-vinyl-1,3-dioxane derived from D-pantolactone. Next, 8-chloro-7-oxoaldehyde, (2R,3R,5R,6R)-2,6-bis(benzyloxy)-5-(t-butyldimethylsiloxy)-8-chloro-3- (4-methoxybenzyloxy)-4,4-dimethyl-7-oxononanal (30), was newly synthesized by the following reactions: i) MgBr2·OEt2-mediated diastereoselective aldol reaction of the aldehyde 3 with (Z)-2-benzyloxy-1-methoxy-1-(trimethylsiloxy)ethene and ii) reaction of methyl (2R,3R,5R,6S)-2,6-bis(benzyloxy)-3,7-bis(t-butyldimethylsiloxy)-5- (4-methoxybenzyloxy)-4,4-dimethylheptanoate with 1,1-dichloroethyllithium, followed by successive reductive dehalogenation of thus formed 1,1-dichloroethyl ketone with 1,1-dichloroethyllithium. Then, the chiral 8-chloro-7-oxoaldehyde 30 was converted to the 8-membered ring enone 1 by SmI2-mediated aldol cyclization.
- Shiina,Shibata,Ibuka,Imai,Mukaiyama
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p. 113 - 122
(2007/10/03)
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- An effective method for the preparation of optically active polyoxy 8-membered ring enone corresponding to the B ring of taxol
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An effective method for the preparation of 8-membered ring enone 1 in sufficient quantities was developed. First, optically active trialkoxyaldehyde 3 was prepared by diastereoselective dihydroxylation of olefin 7 derived from D-pantolactone. Secondly, 8-
- Shiina, Isamu,Shibata, Jun,Imai, Yumiko,Ibuka, Ryoutarou,Fujisawa, Hidehiko,Hachiya, Iwao,Mukaiyama, Teruaki
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p. 1145 - 1146
(2007/10/03)
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- Asymmetric total synthesis of Taxol
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The asymmetric total synthesis of Taxol was achieved by way of B to BC to ABC to ABCD ring construction. Optically active 8-membered ring enones 1 and 2 corresponding to the B ring of Taxol have been synthesized in high yields from the linear precursors 28 and 32, respectively, by intramolecular aldol cyclization using SmI2. The optically active linear polyoxy compounds 28 and 32 were obtained by way of diastereoselective aldol reaction between aldehyde 4 and ketene silyl acetal 8 catalyzed by MgBr2 · OEt2. The chiral pentanal 4 was synthesized either by asymmetric aldol reaction of achiral aldehyde 7 and ketene silyl acetal 8 by means of a chiral Lewis acid or by diastereoselective aldol reaction between the chiral aldehyde 16, derived from L-serine, and the lithium enolate derived from methyl isobutyrate. Optically active bicyclo[6.4.0]dodecanone 38β, corresponding to the BC ring system of Taxol, was prepared from 8-membered ring enone 2 in high yield by stereoselective Michael addition and successive intramolecular aldol cyclization. Furthermore, baccatin III, the ABCD ring system of Taxol, was efficiently synthesized from the BC ring system 38β by successive construction of the A and D rings by intramolecular pinacol coupling cyclization, introduction of the C-13 hydroxyl group and an oxetane-forming reaction. Finally, the total synthesis of Taxol was accomplished by dehydration condensation between a protected N-benzoylphenylisoserine 70 or 75 and 7-TES baccatin III, prepared from baccatin III. Taxol side chains 70, 73, 75, and 77, optically active protected N-benzoylphenylisoserines, were synthesized by enantioselective aldol reaction from two achiral starting materials, benzaldehyde and an enol silyl ether 65 derived from S-ethyl benzyloxyethanethioate.
- Mukaiyama, Teruaki,Shiina, Isamu,Iwadare, Hayato,Saitoh, Masahiro,Nishimura, Toshihiro,Ohkawa, Naoto,Sakoh, Hiroki,Nishimura, Koji,Tani, Yu-Ichirou,Hasegawa, Masatoshi,Yamada, Koji,Saitoh, Katsuyuki
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p. 121 - 161
(2007/10/03)
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- A Novel Approach to the Synthesis of Taxol. A Synthesis of Optically Active 3,7-dibenzyloxy-4,8-di-t-butyl-dimethylsiloxy-5,5-dimethyl-6-p-methoxybenzyloxy-2-octanone by Way of Stereoselective Aldol Reactions
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Optically active 3,7-dibenzyloxy-4,8-di-t-butyldimethylsiloxy-5,5-dimethyl-6-p-methoxybenzyloxy-2-octanone (2) has been synthesized by way of diastereoselective aldol reaction between 4-benzyloxy-5-t-butyldimethylsiloxy-2,2-dimethyl-3-p-methoxy-benzyloxypentanal (3) and ketene silyl acetal 4 using MgBr2*OEt2 as a catalyst.The chiral pentanal 3 was synthesized either by asymmetric aldol reaction of both prochiral aldehyde 5 and ketene silyl acetal 4 using a chiral Lewis acid or by diastereoselective aldol reaction between the chiral aldehyde 6 derived from L-serine andthe lithium enolate derived from methyl isobutyrate.
- Mukaiyama, Teruaki,Shiina, Isamu,Sakata, Kaku,Emura, Takayuki,Seto, Keitarou,Saitoh, Masahiro
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p. 179 - 180
(2007/10/02)
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