N-phosphinoyl imines

Employing a similar strategy, y-lactams could be synthesized by addition of the homoenolate equivalent to an appropriate imine (Scheme 9.20) [61]. A variety of functionalized a,/ -unsaturated aldehydes 62 and N-4-methoxybenzenesulfonyl imines 70 produced disubstituted y-lactams 71 in good yields and with a preference for the cis diastereomer. One crucial point is the reversibility of the addition of the catalyst to the imine to enable a reaction with the aldehyde. N-Aryl, N-alkyl, N-tosyl and N-phosphinoyl imines where either unreactive or inhibited any catalytic reaction due to the formation of a stable adduct with the catalyst. 

Both Me-DuPHOS (483) and Me-DuPHOS monoxide (484) have been successfully used as chiral ligands in the copper catalysed highly enantio-selective addition of dialkylzinc to N-phosphinoyl imines (485). A simple deprotection of N-protecting group from (486) provided a-chiral amines (Figure 91). ... 

R SO2P-TOI hCOOH, H2O Scheme 1.6 Most widely described methods for the preparation of N phosphinoyl imines. 

Tlie Kresze reaction has also been used in the synthesis of N phosphinoyl imines derived from nonenolizable aldehydes, although usually in modest yields [25, 26]. The N phosphinoyl imine derived from trifluoromethyl ketones can be prepared via the ethanolate intermediate (Scheme 1.7) [27]. This adduct is directly used in the subsequent nucleophilic addition reaction. 

Since the stability of N phosphinoyl imines derived from enolizable aldehydes can be problematic, an in situ formation of the N phosphinoyl imine from its... 

Table 1.6 Selected examples of catalytic asymmetric addition of diorganozinc reagents to N phosphinoyl imines.

Table 1.7 Enantioselective addition to alkyl substituted N phosphinoyl imines.

Scheme 1.33 Addition of a lboronic acid to N phosphinoyl imines.

Even the very efficient enantioselective catalysts used in organozinc addition reactions to carbonyl compounds failed to catalyze the corresponding addition reactions to nonactivated imines such as N-silyl-, N-phenyl-, or A-benzyl-imines. However, enantioselective additions of dialkylzinc compounds to more activated imines, like A7-acyl- or N-phosphinoyl-imines, in the presence of catalytic or stoichiometric amounts of chiral see Chiral) aminoalcohols, have been recently reported. For example, in presence of 1 equiv of (N,N-dibutylnorephedrine) (DBNE) diethylzinc reacts with masked N-acyl imines like A7-(amidobenzyl)benzotriazoles, to give chiral N- -phenylpropyl) amides with up to 76% e.e. (equation 68). 

Addition to C=N bond. Strecker-type synthesis, the addition of MesSiCN to imines, on extending to AT-phosphinoyl ketimines is enantioselective in the presence of 86, and the optimal conditions involve the addition of 10 mol% of MCPBA. ... 

P ligand first by adding one C-NH bond in a reductive amination process, and then forming the second C=N bond and finally the third-generation complex 14 (Fig. 40). This new class of catalyst was effective in the rapid reduction of N-diphenylphosphinoyl-activated imines containing phosphinoyl groups in >99 % e.e. (Fig. 41) [126, 127]. 

---