Asymmetric reactions allyl amine derivatives

Attempts to achieve asymmetric nitrene insertion reactions catalyzed by chiral transition metal complexes have also been performed [41,42]. The reaction of the nosyl-imine derivative as the nitrene donor with indane 61 catalyzed by the chiral rhodium complex 63 gave the optically active allyl amine 62 in good yield and moderate ee (Eq. (15)) [41],... 

An asymmetric variant of this kind of allylic amination, based on their phenylcyclohexanol-derived chiral N-sulfinyl carbamates, was developed by Whitesell et al. (see also Sect. 3.2) (Scheme 34) [85]. After the asymmetric ene reaction with Z-configured olefins (not shown) had occurred, nearly di-astereomerically pure sulfinamides 127 were obtained which were found to be prone to epimerization. Their rapid conversion via O silylation and [2,3]-a rearrangement dehvered the carbamoylated allyhc amines 128 with around 7 1 diastereoselectivity as crystalline compounds that can be recrystallized to enhance their isomeric purity to 95 5. Obviously the imiform absolute configuration at Cl in the ene products 127 was difficult to transfer completely due to the already mentioned ease of epimerization. Unhke the sulfonamides of Delerit (Scheme 33) [84], the carbonyl moiety can easily be cleaved by base treatment. 

The various possibilities for the preparation of chiral allylic amines or a aryl substituted amines are outlined in Figure 1.9. Although the addition reaction of a carbon nucleophile to an imine derived from an aryl substituted aldehyde is very efficient (B), the related addition to an a,p unsaturated imine (A) can sometimes proceed via a 1,4 addition pathway. Similarly, the asymmetric C=N reduction reaction (C and D) is sometimes hampered by the possibility of either obtaining conjugate reduction (in the case of C) or low enantioselectivities (in D when R = aryl). The addition of sp hybridized carbanions to imines (E) is a particularly effective... 

The Petasis reaction is a mild multicomponent reaction that allows the conden sation of a boronic acid, an amine, and a carbonyl derivative to generate an allylic amine. Although several diastereoselective Petasis reactions have been reported [106], the first catalytic asymmetric reaction was described in 2008 (Scheme 1.29) [107]. It was shown that the condensation proceeds in high yields and enantiomeric excesses, affording the corresponding protected a vinylglycine derivatives. 

Nemoto and Hamada [50] has described the development of a new class of chiral phosphorus ligand - aspartic acid-derived P-chirogenic diaminophosphine oxides, DIAPHOXs - and their application to several Pd-catalyzed asymmetric allylic substitution reactions. Pd-catalyzed asymmetric allylic alkylation was initially examined in detail using diaminophosphine oxides 77, resulting in the highly enantioselective construction of quaternary stereocenters. With the use of the Pd-DIAPHOX catalyst system, asymmetric allylic alkylation, asymmetric allylic amination, and enantioselective construction of quaternary carbons were achieved with high ee (up to 97-99% in many cases) (Scheme 24). 

Asymmetric allylic amination of allylic carbonates, prepared from racemic MBH adducts, proceeds in the presence of the Pd catalyst chiral diamino-phosphine oxide (DIAPHOX) (292) and BSA to afford the corresponding chiral aza-MBH adduct derivatives 293 in excellent yield with up to 99% ee. The cyclic reaction products could be converted into various synthetically useful compounds, such as chiral cyclic p-amino acids (Scheme 3.119). ... 

Since its discovery in 1974, more than 180 papers have been published on the use of the Overmann rearrangement to prepare allylic amines and their analogs from their allylic alcohols. For example, a recent synthesis of the fluoroalkene peptidomimetic precursor of A -acetyl-Z,-glutamyI-Z.-alanine involves the Overman rearrangement of the imidate derived from the allylic alcohol 60. ° This alcohol is readily prepared through Evans asymmetric aldol reaction of oxozolidinone with an aldehyde. 

A remarkable increase in catalyst selectivity was observed as a function of the dendrimer generation. This steady increase in enantiomeric excess values for the allylic amination was less pronounced for the PPI-derived catalysts (40% ee for PPI(PyrphosPdCl2)54) than for the palladium-PAMAM dendrimer catalysts for which an increase in selectivity from 9% ee for the mononuclear complex to 69% ee for PAMAM(PyrphosPdCl2)54 was found. The same general trend was observed in the asymmetric allylic alkylation of 1,3-diphenyl-l-acetatopropene with sodium dimethylmalonate, which indicates that the results of the amination reaction may be typical for allylic substitutions in general. 

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