Syntheses of Dihydroconduramines (卤)-B-1, (卤)-E-1, and (卤)-F-1 via Diastereoselective Epoxidation of N-Protected 4-Aminocyclohex-2-en-1-ols

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• 作者：M茅abh B. Brennan ; Krist铆na Csatayov谩 ; Stephen G. Davies ; Ai M. Fletcher ; William D. Green ; James A. Lee ; Paul M. Roberts ; Angela J. Russell ; James E. Thomson
• 刊名：Journal of Organic Chemistry
• 出版年：2015
• 出版时间：July 2, 2015
• 年：2015
• 卷：80
• 期：13
• 页码：6609-6618
• 全文大小：509K
• ISSN：1520-6904

文摘

Diastereoselective syntheses of dihydroconduramines (卤)-B-1, (卤)-E-1, and (卤)-F-1 have been achieved from N-protected 4-aminocyclohex-2-en-1-ols via two complementary procedures for epoxidation as the key step. Treatment of either trans- or cis-4-N-benzylaminocyclohex-2-en-1-ol with Cl₃CCO₂H and then m-chloroperoxybenzoic acid (m-CPBA) resulted in initial formation of the corresponding ammonium species, followed by epoxidation on the face syn to the ammonium moiety exclusively; chemoselective N-benzylation then provided either (1RS,2SR,3RS,4RS)- or (1RS,2RS,3SR,4SR)-2,3-epoxy-4-N,N-dibenzylaminocyclohexan-1-ol, respectively. Treatment of either trans- or cis-4-N,N-dibenzylaminocyclohex-2-en-1-ol with m-CPBA resulted in initial formation of the corresponding N-oxide, followed by epoxidation on the face syn to the hydroxyl group exclusively; reduction then provided either (1RS,2RS,3SR,4RS)- or an alternative route to (1RS,2RS,3SR,4SR)-2,3-epoxy-4-N,N-dibenzylaminocyclohexan-1-ol, respectively. In all cases, S_N2-type ring opening of these epoxides upon treatment with aqueous H₂SO₄ proceeded by nucleophilic attack with inversion at C(2) preferentially, distal to the in situ formed ammonium moiety. Hydrogenolytic N-deprotection then gave the corresponding dihydroconduramines (卤)-B-1, (卤)-E-1, and (卤)-F-1.