Prochiral nitroalkanes

In 2010, Du reported the use of chiral squaramides as catalyst for the Michel addition of nitroalkanes to chalcones with excellent results in terms of yields and enantioselectivities [97]. However, when cyclic enones were used the enantioselec-tivity dropped dramatically and when prochiral nitroalkanes were used the diastereoselectivity was very low. 

To overcome the low diastereoselectivities reported in the Michael addition of prochiral nitroalkanes to enones, Maruoka and coworkers reported the use N-spiro quaternary ammonium salt (108) as phase-transfer catalysts [98a]. As shown in Scheme 33.30, the results in terms of yields and diastereo- and enantioselectivities were excellent. A year later, the same research group expanded the scope of the reaction with the use of silylnitronates instead of nitroalkanes [98b]. 

Yamaguchi and coworkers have found that proline rubidium salts catalyze the asymmetric Michael addition of nitroalkanes to prochiral acceptors. When (25)-L-prolines are used, acyclic ( )-enones give (S)-adducts. Cyclic (Z)-enones give (R)-adducts predominantly (Eq. 4.139).203 Recently, Hanessianhas reported that L-proline (3 7% mol equiv) and 2,5-dimethylpiperazine are more effective to induce catalytic asymmetric conjugate addition of nitroalkanes to cycloal-kanones.204... 

Nitroalkanes react with allylic carbonates in the presence of iridium catalysts [83]. However, nitroalkanes are prochiral, and products are formed with poor diastereo-selectivity. Nitroalkanes and other prochiral nucleophiles are discussed further in Sect. 6. 

In a series of reports between 1991 and 1997 Yamaguchi showed that rubidium salts of L-proline (9) catalysed the conjugate addition of both nitroalkanes [29, 30] andmalonates [31-33] to prochiral a,p-unsaturated carbonyl compounds in up to 88% ee (Scheme 1). Rationalisation of the selectivities observed involved initial formation of an iminium ion between the secondary amine of the catalyst and the a,p-unsaturated carbonyl substrate. Subsequent deprotonation of the nucleophile by the carboxylate and selective delivery using ion pair... 

Chiral crown ether phosphine-palladium complexes have been used to catalyse the alkylation of carbanions derived from a-nitro ketones and a-nitro esters,63 and proline rubidium salts have been used to catalyse asymmetric Michael addition of nitroalkanes to prochiral acceptors 64 80% enantioselectivity can be achieved in each case. 

A rubidium salt of proline (5-10 mol%) has been reported to catalyse the asymmetric Michael addition of nitroalkanes to prochiral acceptors. When L-proline was used, acyclic (I )-enones produced (.S )-adducts. whereas cyclic (Z)-enones gave (R )-adducts.88... 

Apart from linear unfunctionahzed nitroalkanes, various other prochiral nitro-aUcanes bearing aryl, alcohol, ether, and ester groups also participate effectively in reactions promoted by 25, producing sy -P-nitroamines in good yields and high enantiomeric excesses [32]. The utihty of this methodology was demonstrated by the synthesis of the neurokinin-1 receptor antagonist CP-99,994 (Scheme 29.14). 

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