Ring Opening of Aziridines by Pendant Silanols Allows for Preparations of (±)-Clavaminol H, (±)-Des-Acetyl-Clavaminol H, (±)-Dihydrosphingosine, and (±)-N-Hexanoyldihydrosphingosine

Abstract

We present a unique strategy for the synthesis of vicinal amino alcohols. Ring opening of aziridines with pendant silanols is compatible with a range of substrates. To engage productively in ring opening, the aziridine must be at least mildly activated, and a variety of such N-substituents are tolerated. The utility of this methodology is highlighted in facile preparations of the natural products (±)-Clavaminol H, (±)-dihydrosphingosine, and (±)-N-hexanoyldihydrosphingosine as well as a natural product analogue (±)-des-acetyl-Clavaminol H.

Substrate-Directed Enantioselective Aziridination of Alkenyl Alcohols Controlled by a Chiral Cation

“…Mitsunobu cyclization of the hydrogenation products then provides ready access to enantioenriched pyrrolidine and azetidine heterocycles ( 49 , 50 ), and the N -sulfonyl azetidine could be ring-opened with thiophenolate in tandem with N -deprotection ( 51 ). We also investigated the ability of the terminal hydroxyl group to selectively deliver reagents to the proximal and less electronically activated carbon of these aziridines . This started with a directed reduction of 9a using Red-Al in which a proposed pre-complexation between the alcohol and the reducing agent results in excellent regioselectivity for the formation of protected benzylic amine 52 .…”

Dancing silanols: stereospecific rearrangements of silanol epoxides into silanoxy-tetrahydrofurans and silanoxy-tetrahydropyrans

“…Our laboratory has a programmatic focus on the development of the di-tert-butyl silanol moiety [16][17][18][19][20] into a synthetically useful auxiliary. [21][22][23][24][25][26][27][28] During our exploration of epoxide opening reactions by pendant silanols, 24 we serendipitously discovered an unprecedented rearrangement reaction of silanol epoxides into 1′-silanoxy-tetrahydrofurans. The uniqueness of this transformation prompted us to further explore its scope, mechanism, and potential applications.…”

Ring Opening of Aziridines by Pendant Silanols Allows for Stereospecific Preparations of 1’-Amino-Tetrahydrofurans

“…Our laboratory has a program of developing cyclization technology using the ditert-butyl silanol auxiliary (Scheme 1A). [1][2][3][4][5][6][7][8] We have recently investigated the ring-opening of epoxides at varying distances from the pendant silanol tether. 5 When the epoxide is located at carbons 4 and 5 relative to the silanol, silanoxytetrahydrofurans form from a tandem SN2 attack and silyl shift.…”