2026-09-20T14:47:43Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/287002022-01-13T07:54:21Zcom_1721.1_7582com_1721.1_7581col_1721.1_131022
Gregory C. Fu.
Mermerian, Ara Haig, 1976-
Massachusetts Institute of Technology. Dept. of Chemistry.
Massachusetts Institute of Technology. Department of Chemistry
2005-09-27T17:51:18Z
2005-09-27T17:51:18Z
2004
2004
http://hdl.handle.net/1721.1/28700
59133141
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2004.
Vita.
Includes bibliographical references.
(cont.) imine.
The enantioselective C-acylation of cyclic silyl ketene acetals was achieved catalytically by employing planar-chiral heterocycles derived from 4-(pyrrolidino)pyridine. Key mechanistic features of this process involve activation of both the electrophile (acylating agent --> acylpyridinium) and the nucleophile (silyl ketene acetal --> enolate). This process accomodates a wide variety of aryl- and heteroaryl-substituted silyl ketene acetals, furnishing quaternary stereocenters with enantioselectivities up to 99%. Further investigation of this process revealed that acyclic disubstituted silyl ketene acetals can also participate in this nucleophile-catalyzed process, furnishing enantioselectivities up to 97%. Isomeric mixtures of silyl ketene acetals are efficiently converted into the same enantiomer of the product β-ketoester, rendering this a stereoconvergent catalytic C-acylation process. Silyl ketene imines were also shown to be suitable reaction partners in this catalytic enantioselective C-acylation reaction, affording nitriles bearing an adjacent quaternary stereocenter with enantioselectivies up to 83%. This process is also believed to proceed via activation of the electrophile (acylating agent --> acylpyridinium) and the nucleophile (silyl ketene imine --> nitrile anion), which is in direct analogy to the process developed for silyl ketene acetals. Application of this transformation to the enantioselective total synthesis of (S)-Verapamil was successfully achieved in 8 steps and 25% overall yield from commercially available 3,4-dimethoxyphenylacetonitrile. The key bond construction in this total synthesis involved enantioselective construction of the quaternary stereocenter via a catalytic C-acylation of a silyl ketene
by Ara Haig Mermerian.
Ph.D.
298 p.
10544370 bytes
10584253 bytes
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Massachusetts Institute of Technology
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http://dspace.mit.edu/handle/1721.1/7582
Chemistry.
Enantioselective reactions of silyl ketene acetals and silyl ketene imines catalyzed by planar-chiral heterocycles
Thesis
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<Abstract>The enantioselective C-acylation of cyclic silyl ketene acetals was achieved catalytically by employing planar-chiral heterocycles derived from 4-(pyrrolidino)pyridine. Key mechanistic features of this process involve activation of both the electrophile (acylating agent --> acylpyridinium) and the nucleophile (silyl ketene acetal --> enolate). This process accomodates a wide variety of aryl- and heteroaryl-substituted silyl ketene acetals, furnishing quaternary stereocenters with enantioselectivities up to 99%. Further investigation of this process revealed that acyclic disubstituted silyl ketene acetals can also participate in this nucleophile-catalyzed process, furnishing enantioselectivities up to 97%. Isomeric mixtures of silyl ketene acetals are efficiently converted into the same enantiomer of the product β-ketoester, rendering this a stereoconvergent catalytic C-acylation process. Silyl ketene imines were also shown to be suitable reaction partners in this catalytic enantioselective C-acylation reaction, affording nitriles bearing an adjacent quaternary stereocenter with enantioselectivies up to 83%. This process is also believed to proceed via activation of the electrophile (acylating agent --> acylpyridinium) and the nucleophile (silyl ketene imine --> nitrile anion), which is in direct analogy to the process developed for silyl ketene acetals. Application of this transformation to the enantioselective total synthesis of (S)-Verapamil was successfully achieved in 8 steps and 25% overall yield from commercially available 3,4-dimethoxyphenylacetonitrile. The key bond construction in this total synthesis involved enantioselective construction of the quaternary stereocenter via a catalytic C-acylation of a silyl ketene</Abstract>
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