Enamines nitroalkene acceptor reactions with

Nitroalkene acceptors in reactions with enamines Dihydrooxazine oxides (406) have now been identified as stable, key intermediates in the Michael addition of aldehydes to nitroalkenes, catalysed by pyrrolidines (405) (Scheme 15). Theoretical calculations suggest that these intermediates are protonated directly (e.g. by p-nitrophenol), without the formation of the zwitterion species. The latter protonation accounts for both the role of the acid cocatalyst and the stereochemistry.257 Theoretical studies of the proline-catalysed Michael addition of aldehydes and ketones to 0-nitrostyrene (MP2/6-311-l-G //M06-2X/6-31G ) suggest that, contrary to the... 

A high degree of syn selectivity can be obtained from the addition of enamines to nitroalkenes. In this case, the syn selectivity is largely independent of the geometry of the acceptor, as well as the donor, double bond. Next in terms of selectivity, are the addition of enolates. However, whether one obtains syn or anti selectivity is dependent on both the geometry of the acceptor and the enolate double bond, whereas anti selectivity of a modest and unreliable level is obtained by reaction of enol silyl ethers with nitroalkenes under Lewis acid catalysis. 

Bronsted acid (Scheme 2.42) [26-28]. (For experimental details see Chapter 14.9.4). These catalysts mediate the addition of ketones to nitroalkenes at room temperature in the presence of a weak acid co-catalyst, such as benzoic acid or n-butyric acid or acetic acid. The acid additive allows double alkylation to be avoided, and also increases the reaction kinetic. The Jacobsen catalyst 24 showed better enantio- and diastereoselectivity with higher n-alkyl-ethyl ketones or with branched substrates (66 = 86-99% dr = 6/1 to 15/1), and forms preferentially the anti isomer (Scheme 2.42). The selectivity is the consequence of the preferred Z-enamine formation in the transition state the catalyst also activates the acceptor, and orientates in the space. The regioselectively of the alkylation of non-symmetric ketones is the consequence of this orientation. Whilst with small substrates the regioselectivity of the alkylation follows similar patterns (as described in the preceding section), leading to products of thermodynamic control, this selectivity can also be biased by steric factors. 

As has already been mentioned, the low reactivity of enamine nucleophiles needs a highly electrophilic Michael acceptor for the reaction to proceed with good conversions in an acceptable time. In this context, the Michael reaction of aldehydes and ketones with nitroalkenes can be regarded as one of the most studied transformations in which the enamine activation concept has been applied. This reaction furnishes highly functionalized adducts with remarkable potential in organic synthesis, due to the synthetic versatility of the nitro group and the presence of the carbonyl moiety from the donor reagent. 

Interesting examples for conjugate additions mediated by chiral amines have been described by Alexakis et al. (Scheme 36), who used the nitroalkene 151 as a Michael acceptor in organocatalytic enamine-catalyzed conjugate addition reactions 149, 150, 153). Michael reaction of 151 with propionaldehyde 60 in the presence of the diamine catalyst 152 (15 mol%) gave 153 as a mixture of four diastereomers in good yield. Subsequent aldehyde protection and conversion of the... 

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