Lewis Acid Mediated Asymmetric [2,3]-Sigmatropic Rearrangement of Allylic Amines. Scope and Mechanistic Investigation

Abstract

The first asymmetric [2,3]-sigmatropic rearrangement of achiral allylic amines has been realized by quaternization of the amines with an enantiomerically pure diazaborolidine and subsequent treatment with Et3N. The resultant homoallylic amines were obtained in good yields and excellent ee's. The observed diastereo- and enantioselectivities were rationalized by invoking a kinetically controlled process, and support for this model was obtained from an NMR spectroscopic investigation of the chiral Lewis acid-substrate complex. The structure of the Lewis acid-product complex was established by X-ray crystallographic analysis and supported the proposed mechanism.

Asymmetric Sommelet–Hauser Rearrangement of N‐Benzylic Ammonium Salts

“…In conclusion, we have reported the asymmetric rearrangement of N-benzylic ammonium ylides that undergo exclusively the Sommelet-Hauser rearrangement ( [2,3] sigmatropic shift). The rearrangement of an ammonium salt derived from N-benzylic proline or N-benzylic glycine (À)-8-phenylmenthol ester is shown to proceed with remarkably high levels of stereoselectivity.…”

“…Interestingly, the [2,3] rearrangement products 7 a and 7 b were obtained in excellent yields with high levels of diastereoselectivity, and the other [2,3] rearrangement product 8 was not detected.…”

“…[2b] However, when the rearrangement was performed in THF at À40 8C using potassium tert-butoxide (1.5 equiv) as a base, the Sommelet-Hauser rearrangement (concerted [2,3] sigmatropic process) proceeded exclusively to give the corresponding a-aryl proline [6] derivative 3 in 96 % yield. The 1 H NMR analysis of 3 showed a new singlet peak from benzylic methyl protons (d = 2.27 ppm in CDCl 3 ), three proton signals from aromatic protons, and the disappearance of the benzylic methylene protons.…”

“…The enantiomeric excess was determined to be greater than 99 % by chiral HPLC analysis after reduction of 3 to the amino alcohol with lithium aluminum hydride. [7] The R configuration of 3 was assigned by analogy with the reported examples of [2,3] Stevens rearrangement of proline-derived ammonium salts. [2d, e] With this method in hand, we carried out the rearrangement of various types of ammonium bromide 4 [8] , derived from N-benzylic-N,N-dimethylglycine (À)-8-phenylmenthol ester, that might afford the a-aryl glycine derivative 5 ( Table 1).…”

“…

The Stevens and Sommelet-Hauser rearrangements of ammonium ylides are known as useful transformations for organic synthesis because they convert a readily accessible CÀN bond into a new CÀC bond.[1] The Stevens rearrangement has been widely used for the asymmetric synthesis of aamino acid derivatives, [2,3] whereas the Sommelet-Hauser rearrangement is much less common because it usually competes with the [1,2] Stevens rearrangement.[4] For example, the base-induced rearrangement of carbonyl-stabilized ammonium ylides such as those derived from N-benzylic aamino esters almost exclusively undergoes the [1,2] Stevens rearrangement to give the a-benzylated amino acid derivatives. For these reasons, synthetic applications of the Sommelet-Hauser rearrangement and its asymmetric versions have been limited.

[5] Herein, we report a unique example of a Sommelet-Hauser rearrangement of carbonyl-stabilized ammonium ylides that is not accompanied by the [1,2] Stevens rearrangement to a detectable extent.

Recently, we reported that the [1,2] Stevens rearrangement of ammonium salt 1, which is derived from (2S)-N-(4-tert-butoxycarbonyl)benzyl proline tert-butyl ester, proceeds with a perfect level (greater than 99 %) of N-to-C chirality transfer to give the a-benzylated proline tert-butyl ester 2 (Scheme 1).

[2b] However, when the rearrangement was performed in THF at À40 8C using potassium tert-butoxide (1.5 equiv) as a base, the Sommelet-Hauser rearrangement (concerted [2,3] sigmatropic process) proceeded exclusively to give the corresponding a-aryl proline [6] derivative 3 in 96 % yield.

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