Intramolecular Cyclization of 2,7- or 2,8-Bis-unsaturated Esters Mediated by (2-Propene)Ti(O-i-Pr)2. Faci
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- 作者：Hirokazu Urabe ; Ken Suzuki ; and Fumie Sato
- 刊名：Journal of the American Chemical Society
- 出版年：1997
- 出版时间：October 22, 1997
- 年：1997
- 卷：119
- 期：42
- 页码：10014 - 10027
- 全文大小：705K
- 年卷期：v.119,no.42(October 22, 1997)
- ISSN：1520-5126
文摘
tert-Butyl 2-en-7-ynoate 6 wastreated with(
2-propene)Ti(O-i-Pr)2(3), generated in situ fromTi(O-i-Pr)4 or Ti(O-i-Pr)3Cl andi-PrMgCl, in ether at -50 to -20 
C to afford theproduct 8 in good yield. The presenceof the intermediate titanabicycle 7 was verified bybis-deuterolysis with excess D2O. When thetitanabicycle 7 wastreated with 1.1 equiv of i-PrOD and then worked up asusual, the monodeuterated product 10 was obtainedwithhigh site selectivity and stereoselectivity. Other electrophilessuch as aldehydes and ketones also reacted with thetitanabicycle in a highly stereoselective manner to give cyclopentaneshaving a stereo-defined side chain. On thecontrary, treatment of the corresponding ethyl ester, ethyl8-(trimethylsilyl)-(E)-2-octen-7-ynoate (28),with 3 underthe same conditions followed by the addition of 1.1 equiv ofs-BuOH afforded2-(trimethylsilyl)-1-bicyclo[3.3.0]octen-3-one (32) in 80% yield. Quenching the samereaction mixture with i-PrOD, EtCHO, andEt2CO in place ofs-BuOH gave 4-deuterio (with exclusive deuteriumincorporation), 4-(1-hydroxypropyl), and4-(1-ethyl-1-hydroxypropyl) derivatives of the above bicyclic ketone (34,35, and 36) in good yields. Theseelectrophiles were alwaysintroduced from the convex face of the bicyclic skeleton. Thestereochemistry of the cyclization could be controlledby an allylic substituent such as(tert-butyl)dimethylsiloxy or butyl group to a highdegree yet with a reversaldiastereoselection to give 45 or 47. Thereaction of ethyl 7-octen-2-ynoate (56) and 3 at-50 to 0 C took place ina quite different way to afford1-[(ethoxycarbonyl)methyl]bicyclo[3.1.0]hexane(64) in 74% yield after hydrolysis.If the simple hydrolysis is replaced by deuterolysis or the actionof diethyl ketone,1-[(ethoxycarbonyl)dideuteriomethyl](with 99% deuterium incorporation), or1-[(ethoxycarbonyl)(3-pentylidene)methyl] derivative of theabove product(65 or 66) was obtained in good yields. A7-en-2-ynoate having an internal Z-double bond such as80 afforded asingle stereoisomer 82 with the substituent at theendo position of the bicyclic skeleton, suggesting thatthestereochemical integrity of the Z-double bond of thestarting material was retained in the product. An alkylsubstituentat the allylic position of the substrates like 74 and76 nicely controlled the stereochemistry of the cyclizationtoafford single products 75 and 77 with thesubstituent being placed in the exo orientation of thebicyclic structure.This high diastereoselectivity was successfully applied to anenantioselective synthesis of d-sabinene from anopticallyactive enynoate via nearly complete chirality transfer.
2-propene)Ti(O-i-Pr)2(3), generated in situ fromTi(O-i-Pr)4 or Ti(O-i-Pr)3Cl andi-PrMgCl, in ether at -50 to -20 C to afford theproduct 8 in good yield. The presenceof the intermediate titanabicycle 7 was verified bybis-deuterolysis with excess D2O. When thetitanabicycle 7 wastreated with 1.1 equiv of i-PrOD and then worked up asusual, the monodeuterated product 10 was obtainedwithhigh site selectivity and stereoselectivity. Other electrophilessuch as aldehydes and ketones also reacted with thetitanabicycle in a highly stereoselective manner to give cyclopentaneshaving a stereo-defined side chain. On thecontrary, treatment of the corresponding ethyl ester, ethyl8-(trimethylsilyl)-(E)-2-octen-7-ynoate (28),with 3 underthe same conditions followed by the addition of 1.1 equiv ofs-BuOH afforded2-(trimethylsilyl)-1-bicyclo[3.3.0]octen-3-one (32) in 80% yield. Quenching the samereaction mixture with i-PrOD, EtCHO, andEt2CO in place ofs-BuOH gave 4-deuterio (with exclusive deuteriumincorporation), 4-(1-hydroxypropyl), and4-(1-ethyl-1-hydroxypropyl) derivatives of the above bicyclic ketone (34,35, and 36) in good yields. Theseelectrophiles were alwaysintroduced from the convex face of the bicyclic skeleton. Thestereochemistry of the cyclization could be controlledby an allylic substituent such as(tert-butyl)dimethylsiloxy or butyl group to a highdegree yet with a reversaldiastereoselection to give 45 or 47. Thereaction of ethyl 7-octen-2-ynoate (56) and 3 at-50 to 0 C took place ina quite different way to afford1-[(ethoxycarbonyl)methyl]bicyclo[3.1.0]hexane(64) in 74% yield after hydrolysis.If the simple hydrolysis is replaced by deuterolysis or the actionof diethyl ketone,1-[(ethoxycarbonyl)dideuteriomethyl](with 99% deuterium incorporation), or1-[(ethoxycarbonyl)(3-pentylidene)methyl] derivative of theabove product(65 or 66) was obtained in good yields. A7-en-2-ynoate having an internal Z-double bond such as80 afforded asingle stereoisomer 82 with the substituent at theendo position of the bicyclic skeleton, suggesting thatthestereochemical integrity of the Z-double bond of thestarting material was retained in the product. An alkylsubstituentat the allylic position of the substrates like 74 and76 nicely controlled the stereochemistry of the cyclizationtoafford single products 75 and 77 with thesubstituent being placed in the exo orientation of thebicyclic structure.This high diastereoselectivity was successfully applied to anenantioselective synthesis of d-sabinene from anopticallyactive enynoate via nearly complete chirality transfer.