Enantioenriched allenylsilanes as building blocks for stereocontrol in organic synthesis
Brawn, Ryan Alton
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Allenylsilanes have recently emerged as a potent nucleophiles for additions to C=X pi bonds. A limiting factor in the development of allenylsilane reagents has been the lack of procedures for a reliable, multi-gram synthesis of highly enantioenriched reagents. A lipase mediated kinetic resolution/Claisen rearrangement strategy was used for the synthesis of allenysilanes, forming the reagents in high yields with high levels of enantioselectivity on a multi-gram scale. The chiral allenes were used for additions to oxonium ions in a three-component reaction with aldehydes and silyl ethers, forming homopropargylic ethers. The desired products were formed in high yields and diastereoselectivities for a variety of reaction partners. C-glycosidation reactions with glycals led to the stereoselective formation of carbohydrate derivatives with a side chain containing an internal alkyne. Additions of enantioenriched allenylsilanes to iminium ions provided a variety of enantioenriched reaction products. Reactions with N-acyl iminium ions formed from tertbutyl carbamate resulted in the stereoselective formation of 4,5-cis dihydropyrroles, in moderate yields and very high levels of disatereoslectivity. Switching the nitrogen source to methyl carbamate led to the selective formation of dihydrooxazines, again formed in very high levels of selectivity and moderate yields. Iminium ions derived from sulfonamides lead to acyclic homopropargylic sulfonamides, with a mechanistically interesting lactone byproduct formed when aryl aldehydes were used. The homopropargylic ether reaction products were used as a template for diversity oriented synthesis. When an azide functionality was imbedded on either the aldehyde or silyl ether reaction partner a dipolar cycloaddition could occur, leading to highly functionalized fused ring systems containing a 1 ,2,3-triazole functionality. A range of aldehyde and silyl ethers with imbedded azides led to a high level of high structural and stereochemical diversity in these reactions. Conversion of the ester functionality to a sulfamate ester, followed by metallonitrene formation, resulted in a cycloadditon cascade terminated by a dearomative cyclopropanation. The products of these reactions were structurally uniquering systems containing stable norcaradienes.
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