Phosphinoyl imines

Takemoto and co-workers communicated that bifunctional organocatalyst 166 would promote aza-Henry reactions of phosphinoyl imines with nitroalkanes (Scheme 52) [104]. The catalytic additions provided high selectivities and yields... 

Table 5.11 The /MCD-mediated aza-MBH reaction of diphenyl-phosphinoyl imines and HFPA.

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. 

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 A-silyl-, A-phenyl-, or iV-benzyl-imines. However, enantioselective additions of diaUcylzinc compounds to more activated imines, like iV-acyl- or iV-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 (A,A-dibutylnorephedrine) (DBNE) diethylzinc reacts with masked A-acyl imines like A-(amidobenzyl)benzotriazoles, to give chiral A-(l-phenylpropyl)amides with up to 76% e.e. (equation 68). 

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.

Soai and co-workers have continued their studies as described in two recent communications. One report details the synthesis of enantiomerically enriched ferrocenylamines by the catalytic, asymmetric dialkylzinc alkylation of a ferro-cenylimine [35b], and the other report introduces the use of heterogeneous chiral catalysts in the enantioselective diethylzinc alkylation of a phosphinoyl imine [35c]. 

All of catalytic enantioselective alkylations of imines that have been described up to this point used homogeneous chiral catalysts. In an effort to facilitate the separation process of the product from the reaction mixture, Soai and co-workers have employed copolymers of norephedrine for the enantioselective addition of diethylzinc to a phosphinoyl imine [35c]. 

Substrate Preferred Metab Oxime Phosphinoyl Imine Phosphinoyl Amine Primary Amine... 

Refers to the enantioselective step (reduction of the phosphinoyl imine), requires 24 equiv of Et3N/HC02H (2 5 ratio), reactions performed at room temperature. 

Reduction products of phosphinoyl imines formed using iPrOH, AiMes, and (S)-BiNOL (toiuene, 60 °C)... 

A new class of chiral bifunctional thiourea catalysts derived from trans-2-amino-l-(diphenylphosphino)cyclohexane was developed by Jacobsen and Fang in order to be applied to a highly enantioselective synthesis of a wide range of 2-aryl-2,5-dihydropyrrole derivatives. This strategy was based on a [3-1-2] cycloaddition between an A-phosphinoyl imine and an allene in the presence of TEA and water as additives. High yields combined with excellent enantioselectivities of up to 98% ee were observed in all cases of substrates, as shown in Scheme 6.19. 

Scheme 6.19 [3 -E 2] Cycloadditions of allenes with iV-phosphinoyl imines.

Scheme 5.93 Mukaiyama-Mannich reaction of phosphinoyl imines 346 and 350, mediated with copper complexes of ligands 348 and 351, respectively.

Scheme 13 Alkynyl addition to (a) sulfinyl and (b) phosphinoyl imines...

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