Enecarbamates, amination

A catalytic asymmetric amination of enecarbamates has been attained using a chiral Cu(II) complex of diamine (210) as catalyst. Thus, azodicarboxylates have been shown to react with various enecarbamates (208) derived from aromatic and aliphatic ketones and aldehydes to provide acylimines (209) in good yields with high enantioselectivity (<99% ee). The catalyst loading required for high enantioselectivity was generally low (0.2 mol% in some cases).259... 

As described above, the carbon-carbon bond formation at the a-position of amines using anodically a-methoxylated carbamates as the starting compounds is highly useful for the synthesis of alkaloid type compounds, however, this method is limited only to the bond formation at the a-position. On the other hand, it has been found that the elimination of methanol from the a-methoxylated carbamates 47 yields the corresponding enecarbamates 48 in high yields 30). 

The formation of a carbon-carbon bond at the p-position of amines is made possible by the reaction of these enecarbamates with electrophiles. The acylation, Vilsmeyer reaction and hydroboration at the P-position of carbamates have been achieved by using this technique31. The syntheses of a derivative of hydrolulolidine 49 and nicotin-aldehyde 50 are shown below as typical examples. 

A chiral ligand mediated approach to lithiation-substitutions of allylic amines has also been well developed. Weisenburger and Beak demonstrated that lithiation of doubly protected allylic amines 141 in the presence of the chiral ligand (-)-sparteine (5), and substitution with a variety of electrophiles provided highly enantioenriched enecarbamate products 142 (Scheme 44) [100]. The authors demonstrated that the intermediate organolithium could be viewed as either an aldehyde P-homoenolate or y-lithioamine synthetic equivalent by hydrolysis or reduction and deprotection of the enecarbamates, respectively. 

The Homer-Wadsworth-Emmons (HWE) reaction of a lithiated (diphenylphosphinoyl)methyl amine with a biaryl aldehyde furnishes the corresponding enecarbamates, which serve as key intermediates for the synthesis of the Amaryllidaceae alkaloid buflavine (eq 44). ... 

Treatment of enecarbamate 344 with sodium azide and ceric ammonium nitrate (CAN) in acetone furnished azidocarbazole 345. The low yield in this oxidative cychzation reaction is due to formation of the diastereomer consisting of stereochemical inversion at the azide-substituted carbon. At this point, azide reduction employing the Staudinger conditions of triphenyl-phosphine in a mixture of water and THF led to an amine, which was subjected to trichloroacetyl chloride in a solution of dichloromethane and triethylamine to yield amide 346 (Scheme 49). 

N-acyl imines [144]. A slightly modified chiral Br0nsted acid 185 was found to catalytically induce addition of indoles to N-Boc-protected enecarbamates ISK) in high yields and enantioselectivities (Scheme 8.51) [145]. In a related study, Zhou demonstrated the use of a-aryl enamides to obtain optically enriched tertiary amine products [146]. 

An efficient enantioselective reductive amination of a-branched aldehydes (90) via d5namic kinetic resolution catalyzed by (89) has been described (Scheme 26). Reductive coupling of 1,3-enynes to heterocyclic aromatic aldehydes use an achiral rhodium-catalyst with a chiral Bronsted acid (89) as co-catalyst (Scheme 27). A highly efficient enantioselective aza-ene-type reaction of N-benzoylimines (91) with enecarbamates (92) has been achieved. The reaction can be performed at extremely low loading of the catalyst (93) without notable loss of enantioselectivity of P-aminoimines obtained (Scheme 28). ... 

Despite their scarcity, asyrmnetric additions to electron-rich alkenes have also appeared in the literature. For example, Terada and coworkers [48a] reported the first enantioselective Friedel-Crafts reaction of enecarbamates 141 catalyzed by (R)-BINOL-derived monophosphoric acid 142 [49] (Scheme 10.28). This method provided an efficient access to highly enantioenriched 1-indolyl-l-alkylamine derivatives that have pharmaceutical and biological importance. Notably, the geometric isomers 141(Z) and 141( ) afforded the optical active amine 143 with the almost same... 

Their reaction setup requires the conversion of aldehyde 122 and aromatic amine 123 into the imine prior to treatment with catalyst 99c (a phosphoric acid) and enecarbamate (and a final reduction of the hemiaminal intermediate 125). This three-component reaction can thus be classified as a sequential reaction. Notably, the authors also used aliphatic aldehydes successfully. Using substituted enecarbamates gave 1,2-disubstituted 1,3-diamines 126 with excellent anti-selectivity. They proposed a transition state in which the chiral phosphoric acid activates not only the imine as a Bronsted acid, but also the (i )-enecarbamate as Bronsted base, resulting in a pseudo-intramolecular Si-face attack to the imine [69]. 

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