The Aza-[2,3]-Wittig Sigmatropic Rearrangement of Acyclic Amines:  Scope and Limitations of Silicon Assistance

Abstract

The inclusion of a C-2 trialkylsilyl substituent into allylic amine precursors allows the base-induced aza-[2,3]-Wittig sigmatropic rearrangement to proceed in excellent yield and diastereoselectivity. The rearrangement precursors require a carbonyl-based nitrogen protecting group that must be stable to the excess of strong base required for the reaction. The N-Boc and N-benzoyl group are very good at stabilizing the product anion and initiating deprotonation. The migrating groups (G) need to stabilize the intial anion by resonance and require G-CH(3)() pK(a) > 22 in order for the initial anion to be reactive enough for rearrangement. Products 7, 20b-d,f,g, and 23 are formed with high (10-20:1) anti diastereoselectivity. Product 23 containing the morpholine amide group is useful for preparing other carbonyl derivatives.

Asymmetric aza-[2,3]-Wittig sigmatropic rearrangements: chiral auxiliary control and formal asymmetric synthesis of (2S, 3R, 4R)-4-hydroxy-3-methylproline and (–)-kainic acid

“…The major diastereoisomer from the rearrangement of 14 has been inferred as anti by us previously. 2 Therefore rearrangement of (−)-8phenylmenthyl ester 12 gives only the anti-2,3-diastereoisomer, with the observed diastereoisomeric ratio by 1 H NMR being equal to the diastereoselectivity exerted by the chiral auxiliary (3 : 1).…”

“…1 In addition, we have defined the limits of activation and control of diastereoselectivity imparted by the dimethylphenylsilyl group. 2 However, all our studies to date have been racemic, and we wish to report in this paper out first attempts at achieving asymmetric rearrangements, culminating in the use of a chiral auxiliary.…”

“…Good enantioselectivities were obtained from the rearrangement of enantiomerically enriched vinylaziridines that were independently reported by the groups of Somfai 8 and Coldham. 9 The use of configurationally defined lithio carbanions derived from enantiomerically enriched tributylstannyl-Ntert-butoxycarbonyl pyrrolidine gave complicated results, due to epimerisation of the chiral lithio carbanion and also a mixture of competing [1,2] and [2,3] rearrangement pathways. 10 This work, from Gawley et al, verified that the [2,3] rearrangement proceeded with complete inversion of configuration at the lithiumbearing carbanion centre, in accord with precedent in the oxygen series.…”

“…9 The use of configurationally defined lithio carbanions derived from enantiomerically enriched tributylstannyl-Ntert-butoxycarbonyl pyrrolidine gave complicated results, due to epimerisation of the chiral lithio carbanion and also a mixture of competing [1,2] and [2,3] rearrangement pathways. 10 This work, from Gawley et al, verified that the [2,3] rearrangement proceeded with complete inversion of configuration at the lithiumbearing carbanion centre, in accord with precedent in the oxygen series. 11 We were intrigued by the possibilities of a chiral † Electronic supplementary information (ESI) available: Synthesis and characterisation of chiral auxiliary rearrangement precursors.…”

Phosphite‐Catalyzed C−H Allylation of Azaarenes via an Enantioselective [2,3]‐Aza‐Wittig Rearrangement

“…Subsequent elimination of the chiral phosphite from rearranged product 5 would reestablish aromaticity in the final product (6). [9] N-allyl isoquinoline 1a was selected as the substrate for the initial development of the stereoselective CÀHallylation of azaarenes (Table 1). [9] N-allyl isoquinoline 1a was selected as the substrate for the initial development of the stereoselective CÀHallylation of azaarenes (Table 1).…”