Rearrangement allylhydroxylamines

In 1950, Cope and coworkers unsuccessfully attempted to use the well-known Meisenheimer rearrangement of 7V-allylamine oxides to 0-allylhydroxylamines in performing the formally analogous rearrangements of allyl aryl sulfoxides to allyl arenesulfenates and of allyl aryl sulfones to allyl arenesulfinates (equations 11-13). 

A new [2,3]-sigmatropic rearrangement of the lithium salt 192 of the Af-benzyl-0-allylhydroxylamines (191) affording Af-benzyl-A-allylhydroxylamines (193) in moderate yields was reported (equation 56). The absence of crossover products confirms the intramolecular character of the transformation and an envelope transition state is proposed. The rearrangement proceeds via a transition state where facial selectivity is determined by stereoelectronic effects. 

Furthermore, the rearrangement of ( )-A-allylhydroxylamines into ( )-0-allylhydrox-ylamines at room temperature was reported . An aminoxyl radical was detected by EPR and its participation in a Meisenheimer [2,3]-rearrangement was proposed. 

Meisenheimer rearrangement. Allylic amines are oxidized to give A-oxides at low temperatures. On warming up 0-allylhydroxylamines are generated, which can be cleaved by Zn-HOAc. ... 

N-Allylhydroxylamines can be prepared from nitrone hydrochlorides, which are produced by the reaction of nitroso compounds with alkenes, in an ene-type mechanism (Scheme 188). Analogues of potent dopaminomimetic ergot derivatives have been prepared, in which of a (5R,8S,10R)-6-allylergoline N -oxide was converted into a substituted hydroxylamine function. The key step is a Meisenheimer [3,2] sigmatropic rearrangement of the N6-oxide (Scheme 189). 413... 

Linalool 54 was similarly synthesized through a [2,3]-Meisenheimer rearrangement by taking advantage of the facile cleavage of N—O bonds in the O-allylhydroxylamine rearrangement products (Scheme 15.111. Aminoalcohol 51 was converted to amine iV-oxide 52, which was transformed to O-allylhydroxylamine 53 under thermal conditions. This intermediate was subjected to reductive conditions, which selectively cleaved the N—O bond to unveil linalool 54. 

The [2,3]-rearrangement of amine iV-oxides was utilized in an efficient S5mthesis of 2,6-dimethyl-l,5-heptadien-3-ol acetate 61, a pheromone of the insect Pseudococcus comstocki tScheme lS.12id Dimethylpyridine 55 was converted in two steps into silylated piperidine 56, which was oxidized with m-CPBA to generate cyclic amine A-oxide 57. Sila-Cope elimination furnished O-silylhydroxylamine 58, which was methylated and desilylated in the presence of Mel and CsF to yield acyclic amine A-oxide 59. Heating this ammonium zwitterion facilitated the [2,3]-Meisenheimer rearrangement to O-allylhydroxylamine 60, which was transformed to the desired pheromone 61 in three steps. 

Similarly, Reetz and Lauterbach studied the diastereoselective [2,3]-rearrangement of chiral amine iV-oxides 71, which were generated from enantioenriched chiral allylic amines 70 tScheme These sigmatropic rearrangements generated O-allylhydroxylamine... 

An alternative strategy for the development of a catalytic enantioselective Meisenheimer rearrangement is based on the conversion of achiral amine IV-oxide 111 into chiral O-allylhydroxylamine 112 via an enantioselective [2,3]-rearrangement (Scheme 1S.26. Eq. 2). A chiral catalyst would govern the conversion of achiral 111 into enantioenriched 112. 

Based on the ability of Pd(OAc)2 to accelerate the [2,3]-rearrangement of amine iV-oxide 114, we explored chiral palladium(ll) salts to catalyze the enantioselective rearrangement. When we treated amine iV-oxides 116 with Pd(OAc)2 and chiral phosphoramidite 118, chiral O-allylhydroxylamines 117 were isolated in 80-85% ee (Scheme 1S.28V Subsequent optimization revealed the beneficial effect of methanol and meta-chlorobenzoic acid (m-CBA) as additives, allowing the isolation of chiral nonracemic O-allylhydroxylamines 117 with greater than 90% enantioenrichment. This palladium-catalyzed enantioselective [2,31-rearrangement can tolerate a wide variety of functional groups in the amine N-oxide substrate. For example, we can synthesize chiral allylic hydrojq lamine products with reactive functional groups such as alcohols and aldehydes, which are inconpatible with many other methods for the synthesis of chiral alcohol derivatives. 

As a preliminary mechanistic proposal, we hypothesize that the palladimn(ll)-phosphoramidite catalyst acts as a chiral n-acid to activate the amine iV-oxide substrate (Scheme 1S.291. similar to the mechanism proposed for the Overman rearrangement of allylic trichloroacetimidates. While it is not clear whether the reactive species is oxide-bound complex 119a or olefin-bound complex 119b, we propose heterocycle 120 as an intermediate in this cyclization-induced mechanism Grob-type fragmentation eventually reveals O-allylhydroxylamine 117 and the palladium(n)-phosphoramidite catalyst, which can reenter the catalytic cycle. 

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