Chiral allylic amines

Anderson CE, Donde Y, Douglas CJ, Overman LE (2005) Catalytic asymmetric synthesis of chiral allylic amines. Evaluation of ferrocenyloxazoline palladacycle catalysts and imidate motifs. J Org Chem 70 648-657... 

Overman LE, Owen CE, Pavan MM, Richards CJ (2003) Catalytic asymmetric rearrangement of allylic N-aryl trifluoroacetimidates. A useful method for transforming prochiral allylic alcohols to chiral allylic amines. Org Lett 5 1809-1812... 

Chiral allylic amines are isolated with high enantiomeric excess (ee), by submitting chiral ferrocenyltellurides to the above-described protocol. 

Aminocarbonylation has been combined with the Pauson-Khand reaction to construct fused tricyclic alkaloid skeletons (see 00154). The tandem aminocarbonylation/Pauson-Khand reaction of haloalkynes with a chiral allylic amine promoted by Co2(CO)8 gave angular triquinanes as exemplified in Scheme 25. Thus, the reaction of l-chloro-2-phenylethyne 175 with Co2(CO)8 at 0°C gave alkyne-dicobalt complex 176, which was converted to enoyl-dicobalt complex 177 upon warming to 25 °C. The reaction of enoyl-dicobalt complex 177 with cyclopente-nylmethyl(l-phenylethyl)amine 179 yielded Pauson-Khand reaction product, angular triquinane 180, via A -allylic aminocarbonylated alkyne-dicobalt complex 178 (Scheme 25). ... 

Intermolecular alkyl radical addition to imine derivatives proceeds in aqueous media when indium is used as an SET radical initiator. The one-pot reaction based on radical addition to glyoxylic hydrazone provides an a-amino acid (Scheme 8.94) [126]. A similar indium-mediated radical addition to an electron-deficient C-C bond gives the corresponding adduct. Chiral allylic amines are synthesized in high yields by treatment of 2-iodomethyl N-tosyl aziridines with indium in MeOH under reflux (Scheme 8.95) [127]. 

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... 

Synthesis of chiral allylic amines by substitution reaction has many choices of protocol, in terms of metal complexes and ligands. Pd catalysts having pairing with a C2-s)mimetric mthenocene (32) are quite novel among other mote conventional P,N-Ugands that include... 

Synthesis of chiral allylic amines from alkynes and A -sulfonylaldimines involves reductive activation of the alkynes. The metal atom of iridacyclopropene intermediates also gathers the sulfonylimine as a bidentate ligand prior to bonding reorganization within the coordination sphere. The absolute stereochemical sense is governed by the chiral ligand employed (such as a member of the BIPHEP series). 

Aziridine cleavage. Cob(I)alamin is prepared in situ by Zn reduction of hy-droxocob(III)alamin HCl in the presence of NH4CI. Fused mcso-aziridines are cleaved to chiral allylic amines. 

Simple reflux of chiral 5-iodomethyl-2-oxazolidinoncs 211 in methanol with indium metal (2 equivalents) afforded chiral allylic amines 212 in excellent yields (80-96%) <01TL6385>. The use of Pd(dba)j with posphine ligands as DPPF or Xantphos catalysed the A(-arylation of 2-oxazolidinones 213 <01OL2539,01TL3681>. 

Cobalt Oxazoline Palladacycles (COPs) are organocobalt-palladium complexes which catalyse the asymmetric rearrangements of non-chiral allylic trichloroacetamidates with very high enantiomeric selectivity (>90%) to provide chiral allylic amines [it is an aza-Claisen rearrangement, The Overman Rearrangement Overman Carpenter Org React 66 2005, Kirsch, Overman and Watson J Org Chem 69 8101 2004] and in the presence of phenols stereospecific cross-couphng also occurs to provide chiral phenoxyallyl ethers with veiy high (>90%) enantiomeric selectivity [Kirsch, Overman and White Org Lett 9 911 2007, Overman Carpenter Org React 66 2005]. 

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... 

Pd(0)-catalyzed rearrangement of allylic sulfoximines to sulfinamides has been developed recently and appears to be an efficient route to chiral allylic amines (Scheme 22). This reaction is also known to occur thermaUyt but only for y-phenyl-substituted... 

Hydroboration of Chiral Allyl Amines and Chiral Allyl Alcohols... 

Chiral allylic amines constitute key synthetic intermediates, auxiliaries, and resolving agents in the synthesis of both natural and nonnatural products. In 2004, Jamison and Patel reported the first highly enantioselective catalytic synthesis of allylic amines from alkynes, imines, and organobo-ranes such as triethylborane. Catalysed by a chiral complex derived from Ni(cod)2 and chiral ferrocenylphosphine [R)-27, this novel three-component process provided chiral tetrasubstituted allylic amines in good yields in one-pot (Scheme 4.27). These products were obtained in moderate to very good enantioselectivities of up to 89% ee. Both symmetrical and... 

Hartwig has reported the use of chiral iridium complexes derived from ligand 123 in the formation of chiral allylic amines. The branched amines 122 were isolated in moderate to good yield and excellent enantiomeric purity (> 94% ee). 

The stereoselectivity of cyclopropanation is highly affected by the stereogenic centers close to the alkene unit. Aggarwal et al. reported that A -chiral allylic amine 96 underwent stereoselective cyclopropanation to give 97 in 95% yield (Scheme 1.50) [85]. The obtained product 97 was almost a single isomer. 

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