Aldimines chiral

The preparation of optically active analogues of the natural amino acids has proven reasonable using the reaction of tris(trimethylsilyl) phosphite with chiral aldimines prepared from optically active amines.225 The asymmetric induction has been observed to be as high as 80%, a significant competitive process compared to the multistep approaches available.226227 An alternative one-step approach involving asymmetric induction upon addition to an aldimine derived from a chiral N-substituted urea provided a product with less desirable optical purity.228... 

Asymmetric reactions have also been developed. The reactions of allyltitaniums with chiral aldimines derived from optically active 1-phenylethylamine afford optically active homoallylic amines with excellent diastereofacial selectivities. Thus, the Cram syn addition products are obtained highly predominantly when using crotyltitanium reagent 33, as exemplified in Scheme 13.30 [61]. 

Scheme 13.30. Addition of crotyltitanium reagents to a chiral aldimine.

Table 5. a-Alkylated Aldehydes by Alkylation of Chiral Aldimines, Followed by Hydrolysis2... 

The reaction of chiral aldimines with 2-silyloxybutadienes in the presence of triflic acid affords novel Mannich-type products with high diastereoselectivity986 [Eq. (5.357)]. 

The approach of leveraging chirality at the imine nitrogen to impart enantioselectivity has also been used to advantage in the preparation of chiral heterosubstituted aziridines. Thus, when 2-(l-chloroethyl)-4-methyl-thiazole 671 is deprotonated with lithium diisopropylamide (LDA) and treated with the chiral aldimine 670, the aziridinyl thiazole derivative 672 is produced in excellent yield and diastereoselectivity (Scheme 164) <2004T1175>. 

The chiral allylzinc complex also reacts with chiral aldimines to afford allylated secondary amines in high enantioselectivity. For the acyclic (E)-benzaldehyde IV-phenylimine, the amine was... 

The complexes (5,5)-(Phebox)Pt(OTf) and [(5,5)-(Phebox)Pt(H20)](BF4) react with A -phenylbenzaldimine to afford the corresponding chiral aldimine complexes. Addition of organolithium reagents gives, after work-up, the corresponding enantio-merically enriched amines (Sch. 34) [145],... 

Radical anions of carbonyl groups and imines also seem to be produced in the presence of titanium (IV) chloride in methanol as solvent. Consecutive oxidation and deprotonation of methanol leads to hydroxymethyl radicals which combine with the carbonyl radical anions to give 1,2-diols and 1,2-aminoalcohols, respectively. The synthesis of the pheromone frontalin has been achieved in a one-pot reaction by hydroxy-methylation of a diketone [127-129]. Likewise triplet sensitizers [130] can be used for direct excitation of the substrate in methanol [131]. Chiral aldimines can be conveniently hydroxymethylated with moderate diastereoselectivity by irradiation of methanolic solutions in the presence of an excess TiCU (Scheme 34) [132]. 

A two step synthesis of the first p-aminophosphotyrosyl mimetic (360) was carried out. Addition of (—)(R)-tert-butanesulfinylamide to 4-phosphonome-thyl benzaldehyde (361) gave chiral aldimine (362) which under treatment with the titanium enolate of methyl acetate produced the target compound with high diastereoselectivity (Figure 60). ... 

Table 3 The Reaction of Organometallic Reagents with Chiral Aldimines (8) R ...

The method may be of interest because it uses the least expensive chiral ammonia equivalent available (Table 8.2) in essentially equimolar quantities (1.05 equiv) as compared to the limiting reagent, the aldehyde. Additionally, this one-pot process has significant yield advantages over the two-step process (formation of the (R)- or (S)-N-a-methylbenzyl aldimine, isolation of this chiral aldimine, followed by carbanion addition). The reactions are fast (3 h at -78°C), but the low temperature requirements, low reactor volume to product ratio, and the need for 3 equiv of a cuprate (CuBr based) will be considered restrictive. Many times the cuprate can be reduced to 2.0 equiv... 

Loh et al. found a tritlic acid-catalyzed 2-oxonia Cope rearrangement, which was used in the stereocontrolled synthesis of linear 22i -homoallylic sterols (eq 48). Interestingly, poor stereoselectivity was observed when In(OTf)3 was employed as the catalyst for this reaction. Stereoselective Mannich-type reaction of chiral aldimines with 2-silyloxybutadienes in the presence of triflic acid gives the corresponding products with 70-92% de in 62-74% chemical yield, which are not obtained by general Lewis acid-promoted methods (eq 49). ... 

A major synthetic effort, however, has been focused on asymmetric induction resulting from the addition of organometallic reagents to aldimines/aldimine derivatives derived h om chiral amines/hydrazines. A variety of chiral aldimines (8), nitrones (9) and hydrazones (all of which contain as part of... 

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