Asymmetric Sommelet–Hauser Rearrangement of N‐Benzylic Ammonium Salts

Abstract

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. 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]

Controlling Selectivity by Controlling the Path of Trajectories

“…Attempts at control through changes in reaction conditions have most often met with little success, peppered with occasional results that are spectacular but enigmatic. 4 , 6 − 8…”

Recent Advances in the Base‐Induced Sommelet–Hauser Rearrangement of Amino Acid Derived Ammonium Ylides

“…Interestingly, when the rearrangement was performed with solid t BuOK in THF at room temperature, the α‐arylproline 7b was obtained as the corresponding S–H rearrangement product in a low yield (27%) along with 6b . The S–H rearrangement proceeded exclusively with a perfect level (>99%) of N‐to‐C chirality transmission at −40°C to give 7b . This result was the first successful example of a base‐induced asymmetric S–H rearrangement.…”

Synthesis of 2‐Aryl‐N‐(EWG‐methyl)‐N‐methylpyrrolidinium Salts as Precursors of Ylides Entering the [1,2] Stevens Rearrangement

“…Other quaternary proline derivatives find application as reagents in organic synthesis. N-Benzylproline (S)-proline t-butyl [12][13][14][15] or methyl [12,[15][16][17][18] ester quaternary derivatives are used in the synthesis of 2-substituted (R)-proline respective esters derivatives. Corresponding ylides generated in the presence of bases undergo the asymmetric [1,2] Stevens [12,13,16] or [2,3] Sommelet-Hauser [12,[14][15][16][17][18] rearrangements.…”

“…Selected examples of prolines C,D obtained from salts A,B are presented in Scheme 1. [13,16] Moreover, the [2,3] Sommelet-Hauser rearrangement of ylides generated from proline derived N-(substituted)allyl ammonium salts is one of the steps in the synthesis of stemofoline derivatives, [19] amathaspiramide F, [20] cephalotaxine, [21] (�)-strictamine [22] and (À )-cephalezomine G. [23] What is important, in all cases rearrangement of ylides generated from proline-derived ammonium salts affords derivatives of proline esters, substituted at C-2 with benzyl, [12,13,16] allyl [12,[15][16][17][18] or aryl [12,14] group. To the best of our knowledge, there are no examples of the rearrangements of these ylides that occur via ring-enlargement.…”