1,4-Conjugate addition aldimines

The reaction of butyllithium with 1-naphthaldehyde cyclohexylimine in the presence of (/C )-l,2-diphenylethane-1,2-diol dimethyl ether in toluene at —78 °C, followed by treatment with acetate buffer, gave 2-butyl-1,2-dihydronaphthalene-l-carbaldehyde, which was then reduced with sodium borohydride in methanol to afford (1 R,2.S)-2-butyl-1 -hydroxymcthyl-1,2-dihydronaphthalene in 80% overall yield with 91 % ee83. Similarly, the enantioselective conjugate addition of organolithium reagents to several a,/J-unsaturated aldimines took place in the presence of C2-symmetric chiral diethers, such as (/, / )-1,2-butanediol dimethyl ether and (/, / )- ,2-diphenylethane-1,2-diol dimethyl ether. 

Except for the well-documented conjugate additions of diethylaluminum cyanide,92 triethylaluminum-hydrogen cyanide and Lewis acid-tertiary alkyl isonitriles,93 examples of Lewis acid catalyzed conjugate additions of acyl anion equivalents are scant Notable examples are additions of copper aldimines (233),94, 94b prepared from (232), and silyl ketene acetals (234)940 to a,(3-enones which afford 1,4-ketoal-dehydes (235) and 2,5-diketo esters (236), respectively (Scheme 37). The acetal (234) is considered a glyoxylate ester anion equivalent. 

Conjugate addition of RLi to an a,fi-unsaturated aldimine.1 This chiral diether is a catalyst for this reaction and also controls the enantioselectivity. It is more... 

Activation by TMSCl has also been applied to the allylstannane allylation of aldimines ", the copper-catalysed conjugate addition of organoaluminium reagents to enones, and in the uncatalysed conjugate addition of organozincs in THF/iV-methylp3Trofidone. Its involvement in the conjugate addition of stabilized... 

The addition of BF3 improves some of the usual organocop-per reactions, enables some unprecedented ones, e.g. the direct alkylation of allylic alcohols. It also favors 1,4- over 1,6-addition to methyl sorbate 1,6-addition predominates with Bu2CuLi-LiI, and also with BuMgBr/CuCl, but 1, 4-addition is observed for BuCu-BFs. One particularly interesting application of the BF3 procedure is the conjugate addition of Cu aldimines to a./S-unsaturated carbonyl compounds (eq 1), which after hydrolysis gives 1,4-diketones. ... 

A dihydroquinidine-derived chiral thiourea (DHQD-30), which demonstrated significantly better stereocontrol than other cinchona alkaloids, was utilized in the aza-Henry reaction with nitroalkanes and aldimines by Schaus and coworkers (Scheme 13.8) [26]. The utility of the nitroethane pronucleophile conveniently offers a tertiary stereogenic center in the P-nitroamine product 32. The methodology is also conveniently applicable to novel a,P-unsaturated aliphatic imines 29, which are difficult substrates in asymmetric conjugate addition reactions. Similar reaction conditions can be appHed towards to the use of dimethyl malonates as pronucleophiles that generate adducts in high enantioselectivity, which then convert smoothly into P-amino esters under the Nef conditions. 

Many other functional groups are reduced by Sml. For example, sulfonyl halides are converted to disulfides. The reduction of nitro compounds by this reagent enables synthesis of 1,2-diamines based on a reaction sequence initiated by nitronate addition to aldimines, and in the presence of nitriles it furnishes amidines, and that of isothiocyanates in the presence of conjugated esters, the half thioamide derivatives of succinic esters. 

Activated imines and atninal derivatives react with malonic esters to give precursors of p-amino acids, while conjugated aldimines undergo 1,4- and 1,2-additions, both induced by TiCl47... 

Addition to the N=X bonds. Amine synthesis, particularly from chiral hydra-zones, using RCeCL as nucleophiles is well established. " The reagent formed from 1 1 RLi and CeClj is superior to RLi alone or RMgX. For conjugated aldimines, enantioselective 1,2-addition predominates. Allylcerium halide reagents can be pre-... 

Schiff base formation between pyridoxal (140) and amino acids leads to complexes of type (141) which are in tautomeric equilibrium with (142). This tautomeric equilibrium leads to transamination, thus the same metal complexes can be obtained when either pyridoxal and alanine or pyridoxamine and pyruvic acid are allowed to react together in the presence of a metal ion. Hopgood" has studied the rates of transamination of 15 amino acids in the presence of zinc(II) and pyridoxal 5-phosphate (143). On mixing the reagents zinc(II)-aldimine complexes are rapidly formed (ca. 5 min) and these species subsequently transaminate in a slow second step. Ai" and Zn" systems have been particularly well studied.The role of the metal ion seems to involve both stabilization or trapping of the Schiff base, and in addition it also ensures the planarity of the conjugated ir-system. In the case of the aldimine tautomer, extensive H NMR studies have shown that formation of the ternary complex results in activation at the amino acid 2-carbon. At room temperature the reaction occurs without incorporation of into the aldehyde methine position indicating that the primary mechanism is carbanion formation rather than tautomerism. 

The rhodium-catalyzed addition of aryl- and 1-alkenylboronic acids tooc, unsaiurated ketones, aldehydes, esters, and amides gave the conjugate 1,4-addition products in high yidds. The ifaodium(I) complexes also catalyzed the 1,2-addition of organoboronic acids to aldehydes or N-sulfonyl aldimines. The dficiency of protocol was demonstrated in the asymmetric addition reactions of organoboronic acids in the presoice of a rhodium(acacV BINAP complex. 

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