Allylic amination/ -Stevens rearrangement

The key step of the synthesis was palladium -catalyzed allylic amination/[2,3]-Stevens rearrangement. Amathaspiramides A-F (129-134) were synthesized by Chiyoda et al. [67]. They started the synthesis by taking 3-methoxyphenacyl bromide and the key step was the reduction of lactam moiety to the cyclic imine by Schwartz s reagent, [Cp2Zr(H)Cl]. 

Scheme 15.35 Mechanism of the palladium-catalyzed tandem allylic aminatinn/r2.31-Stevens rearrangement of tertiary amines.

To address the need for a more general catal)Tic method of s)mthesizing allylic ammonium ylides for [2,3]-rearrangements that is amenable to enantioselective catalysis, our group recently developed a palladium-catalyzed tandem allylic amination/[2,3]-Stevens rearrangement of tertiary amines that proceeds through a palladium-n-allyl intermediate rScheme 15.34T Metal-catalyzed allylic aminations between primary or secondary amines... 

Chiral auxiliary approaches have been examined for the production of enantioenriched products through [2,31-rearrangements. For example, Sweeney and coworkers treated N,N-dimethylammonium salts 186 with sodium hydride to generate ammonium ylides bearing Oppolzer s camphorsultam, which underwent diastereoselective [2,31-Stevens rearrangements to enantioenriched products 187 [Scheme 1S.44. Eq. Oppolzer s camphorsultam was also compatible with our group s palladium-catalyzed tandem allylic amination/[2,31-Stevens rearrangement of tertiary amines [Scheme 1S.44. Eq. 2) ... 

In a total synthesis of ( )-amathaspiramide F, via a tandem palladium-catalysed allylic amination/[2,3]-Stevens rearrangement, the unexpected diastereoselectivity of the [2,31-rearrangement has been reported to be controlled by substitution patterns of the aromatic ring (Scheme 55)7 ... 

A two-step stereoselective strategy for converting glycine-derived aminoesters into unnatural cyclic amino acids has been reported. The process involves a palladium-catalysed tandem allylic amination/[2,3]-Stevens rearrangement followed by a ruthenium-catalysed ring-closing metathesis (Scheme 175). " ... 

The [2,3]-Stevens rearrangement is a thermal sigmatropic rearrangement of an ammonium ylide (38) to form unnatural amino acid derivatives 39 (Scheme 12). Traditionally, the ammonium ylides have been formed through alkylation of aminoesters 36 with aUcyl halides 37 to form quaternary salts followed by treatment with base. Although effective, the harsh conditions lead to side products and limited substrate scope. More recently, the coupling of diazoesters 40 and allylic amines 41 in the presence of metals like copper, rhodium, and palladium has been developed for the direct constmction of ammonium ylides 38 via metal carbenoid intermediates. " Although this approach represented an advance over the traditional alkylation chemistry, the use of diazoesters still limits the synthetic utility of these reactions. 

Stevens rearrangement. We envisioned that a palladium-catalyzed ally lie amination of a tertiary aminoester 42 with an allylic carbonate 43 in the presence of base should directly provide ammonium ylide 38 and subsequent thermal rearrangement product 39 (Scheme 13). Although primary and secondary allylic amines have extensively been used in allylic amination chemistry, tertiary amines are not considered competent substrates for this mode of reactivity. Despite the lack of literature precedent, Arash was determined to develop this reaction. 

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