Addition, conjugate of amines

The effect of the solvent on the product distribution is observed in the conjugate addition of amines to 1-bromo-l-(phenylsulfonyl)alkenes (54) (equation 54)46. When the reaction is conducted in benzene at room temperature for 4 days, the adduct 55 is formed in good yield. On the other hand, the reaction in DMSO at 80-90 °C for 2.5 h affords 2-(phenylsulfonyl)aziridines (56) and no adduct (55) is isolated. 

While sluggish under thermal conditions,274-275 the asymmetric conjugate addition of amines to alkyl crotonates is achieved at room temperature under high pressure (15 kbar).276 Thus, benzylamine can be added to the crotonate derived from 8-p-naphthyl menthol, with virtually complete diastereoselectivity. A related intramolecular 1,4-addition of an amine to a chiral enoate was used in a total synthesis of the alkaloid (-)-tylophorine.277 Additions of amines to chiral iron complexes of type (116) proceed with excellent selectivity and allow the preparation of homochiral p-lactams.l27128,l3() l32 In contrast, the addition of amine nucleophiles to chiral vinylic sulfoxides278-2811 and to chiral vinylsulfoximines281 proceeds with comparably low selectivities. 

Conjugate addition of amines to ct,P-enones (10,9).8 This reaction had been used to effect addition of aziridine to withaferin A (1). The product (2) has significant nnlitumor activity. 

Conjugate additions of thiols to N-enoyloxazolidinones E- or Z-7.42 derived from 1.116 [415] or to lactone derivative 1.31 [66] take place with a good selectivity. After removal of the chiral auxiliary, the corresponding adducts are readily obtained. Conjugate additions of amines to lactone 1.36 (G = menthyl) [66, 1396] are also highly selective. Reduction of the resulting adducts with LAH provides... 

There is a remarkable effect of water as the solvent on the rate of the conjugate addition of amines to a/l-unsaturated nitriles. The lack of apparent reactivity of a,/3-unsaturated esters comes from the reverse reaction, which is particularly accelerated in water [74]. 

DBU also promotes conjugate addition of amines to a, 3-unsaturated esters, nitriles, and ketones. ... 

A similar situation prevails in the conjugate addition of amines to a,yS-ethylenic esters yielding yff-aminoesters (Scheme 10.9). 

One of the simplest methods of obtaining 6-amino-esters is by the conjugate addition of amines to a,6-unsaturated esters. At high pressures the addition is efficient, and the use of a p-substituted 8-phenylmenthy1 group as a chiral auxiliary attached to the... 

Alcohol-substituted thioureas also catalyse the Petasis-type reaction of quinolines [39] and conjugate addition of amine [40]. 

The asymmetric intramolecular conjugate addition of amines to optically active a,p-unsaturated sulfoxides has been studied [111-115], For example, the (Rs)-(E)-a,P-unsaturated sulfoxide (141), upon basic hydrolysis with lithium hydroxide, gave a mixture of the diastereoisomeric isoquinolines (143) and (144) in the ratio 63 37, An enhanced diastereoselectivity was observed upon basic hydrolysis of the (i s)-(2)-a,P-unsaturated sulfoxide (142) with benzyltriethylammonium hydroxide, giving (143) and (144) in the ratio 16 84 (note that the major product... 

Diastereocontrolled conjugate additions of amines to a,B-unsaturated iron acyls where the n -CpFe(CO)(PPh ) moiety directed the addition have been achieved. Addition of the amine occurred away from the bulky phosphine ligand. Oxidative cleavage of the iron moiety allowed preparation of the corresponding esters (and also B-lactams)... 

Nitrogen nucleophiles The conjugate addition of amines to electron-deficient alkenes has been shown to be complete in several minutes when carried out in the ionic liquid [H03S-biPy][FeCl4]. ... 

The Evans mechanism for the Lewis acid-catalysed Michael addition to chiral oxa-zoUdinones and related systems has been challenged rather than chelation, open-chain mono- and bis-coordinated complexes with antiparaUel carbonyls (120) have been proposed, based on the NMR and DFT computational studies. This new mechanism is consistent with the experimental results reported for the conjugate addition of amines to a,j8-unsaturated acylimidazolidinones (119) with aluminium, boron, or zinc Lewis acids. ... 

Figure 7.1. Synthesis of poly(beta-amino ester)s by the conjugate addition of amines (numbers) to diacrylates (letters).

Figure 7.6. Lipidoid synthesis by the conjugate addition of amines to alkyl-acrylates and alkyl-acrylamides. [Reproduced with permission from Ref. 63.1...

Table 3.1. Conjugate addition of amines to Michael receptors.

A last example shows the reaction of a vinyl chloride such as 3.30 with ethylamine (see reaction 7). Addition of the amine generated the usual enolate anion intermediate, which displaced the P-chlorine to give a new conjugated ester. In this case, the product was ethyl 3-(N,N-diethylamino)but-2-enoate (3.57).23 The yield was relatively poor, but this example illustrates that conjugate addition of amines can lead to either the normal saturated product or, as in this case, an unsaturated amino acid. 

There are other types of conjugate addition reactions that do not readily fit into Table 3.1. Conjugate addition of amines to alkynyl esters or acid, for example, illustrate this point since they give 3-aminopropenoic acid derivatives. When 3.32... 

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