Conjugate Addition of Nitrogen Nucleophiles

Dondoni, A, Fantin, G, Fogagnolo, M, Merino, P, Regio- and stereoselective conjugate addition of nitrogen nucleophiles to 2-alkenyl iV-methylthiazolium iodides. Synthesis of 3-epi-daunosamine and some lincosamine analogues. Tetrahedron, 46, 6167-6184, 1990 see also Ref. [97b]. 

Reactions of chiral allylic boranes with carbonyl compounds Reactions of chiral allyl boranes with imines Asymmetric Addition of Carbon Nucleophiles to Ketones Addition of alkyl lithiums to ketones Asymmetric epoxidation with chiral sulfur ylids Asymmetric Nucleophilic Attack by Chiral Alcohols Deracemisation of arylpropionic acids Deracemisation of a-halo acids Asymmetric Conjugate Addition of Nitrogen Nucleophiles An asymmetric synthesis of thienamycin Asymmetric Protonation... 

Metal salt catalyzed conjugate addition of nitrogen nucleophiles has attracted considerable interest as means to access valuable intermediates for the preparation of P-amino acid, P-lactams, isoxazolidinones, aziridines, and so on. However, enantios-elective Cu(II)-catalyzed reactions of this type are limited. Cardillo and coworkers reported the Cu(OTf)2/Bn-BOX (32)-catalyzed additions of O-benzylhydroxylamine (230) and N,0-bis(trimethylsilyl)hydroxylamine (232) to alkylidene malonates (219) (Scheme 17.49) [68]. Yields and enantioselectivities ofthedesired P-amino carbonyl compounds (231) and (233) are moderate to good under optimized conditions. In the latter case the conjugate addition products are readily converted to enantiomerically enriched aziridines (234) in good yields. 

The introduction of a chiral auxiliary on the nitrogen of an azaenolate offers the capability to perform asymmetric conjugate additions of chiral nucleophiles to achiral acceptors. This is in contrast to the typical asymmetric conjugate addition of achiral nucleophiles to chiral acceptors.137 For example, the con-... 

These reactions are characterized by a two step process in which conjugate addition of nitrogen or carbon nucleophiles 408a e to 4-(substituted methylene)-pyrazol-3-ones 409a e, is followed by the elimination of a small molecule from... 

The enantioselective conjugate addition of nitrogen-based nucleophiles provides products useful in the synthesis of 3-amino acids, and this reaction proceeds with high ee using both enantiomerically pure Lewis acidic metal-based catalysts and organocatalysts. 

The organocatalytic asymmetric conjugate addition of heteroatom nucleophiles to different electrophilic olefins has become a very popular reaction during the last few years. Different nitrogen, oxygen, sulfur, and selenium nucleophilic species have been successfully used leading to enantiomerically emiched heterofunctionalized derivatives. 

Using the achiral lithium amide derived from Af-trimethylsilylbenzylamine, an enantioselective conjugate addition followed by alkylation has been realized by Tomioka and coworkers by using the chiral additive 1,2-diphenyl-1,2-dimethoxyethane [149]. Various enantioselective conjugate additions of nitrogen, oxygen, and sulfur nucleophiles under in situ protonation of the intermediate enolate, without trapping with other electrophiles have been described [144]. 

Diastereoselective conjugate addition of oxygen and nitrogen- centered nucleophiles to nitroalke-nes derived from (+)-camphoisulfonic acid and ozonolysis give a-hydroxy and a-amino thiol acid derivatives (Eq. 4.39). In all cases, the (/ )-diasteromer is formed as the major component.49... 

The conjugate addition of activated nitrogen nucleophiles, such as hydroxylamine and hydrazine derivatives, to a,/3-unsaturated bicyclic lactam 284 gave the corresponding /3-amino product 285 in good yield and excellent diastereoselectivity. These products can be manipulated to afford enantiopure /3-aminopyrrolidinones of potential application as conformationally constrained, substituted glutamate templates (Equation 45) <2001J(P1)2997>. 

Diastereoselective tandem conjugate addition of both oxygen- and nitrogen-centred nucleophiles (potassium phthalimide, TsNHK, MeONa, and MesSiOK) to the novel (IN)-lO-camphorsulfonic acid-derived nitroalkenes (139 R = Me, Pr, and... 

Preliminary mechanistic studies show no polymerization of the unsaturated aldehydes under Cinchona alkaloid catalysis, thereby indicating that the chiral tertiary amine catalyst does not act as a nucleophilic promoter, similar to Baylis-Hilhnan type reactions (Scheme 1). Rather, the quinuclidine nitrogen acts in a Brpnsted basic deprotonation-activation of various cychc and acyclic 1,3-dicarbonyl donors. The conjugate addition of the 1,3-dicarbonyl donors to a,(3-unsaturated aldehydes generated substrates with aU-carbon quaternary centers in excellent yields and stereoselectivities (Scheme 2) Utility of these aU-carbon quaternary adducts was demonstrated in the seven-step synthesis of (H-)-tanikolide 14, an antifungal metabolite. 

During our investigations on asymmetric C—C bond formation reactions via conjugate addition of SAMP hydrazones to various a,(3-unsaturated Michael acceptors, it occurred to us to use the chiral hydrazine auxiliary S AM P as a nitrogen nucleophile and a chiral equivalent of ammonia in aza-Michael additions. Thus, we developed diastereo- and enantioselective 1,4-additions for the synthesis of P-amino acids and P-aminosulfonates [14, 15]. 

Nitroalkenes can serve as the two-carbon fragment of a [3 + 2] cyclization involving enamines as nucleophiles (equation 86) (81LA1534). This reaction is presumably initiated by a conjugate addition of the enamine to the nitroalkene (equation 87). The most attractive formulation of the cyclization is via an intramolecular nucleophilic addition to the aci-form of the nitronate anion. This provides a reduced nitrogen substituent which could be eliminated to complete aromatization. This procedure has provided quite satisfactory yields over a range of structural types. 

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