Nitrogen nucleophiles, conjugate

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>. 

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]. 

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]. 

The palladium forms the usual allyl cation complex and the nitrogen nucleophile attacks the ler hindered end also retaining the conjugation. Attack at the triple bond would give an allene. 

Conjugated dienes coordinated to palladium(Il) undergo nucleophilic addition of oxygen and nitrogen nucleophiles from the opposite side of the palladium center to give Ti-allylpalladium complexes. Subsequent reaction of the 7C-allyl complexes with another molecule of nucleophile results in the 1.4-addition of two kinds of nucleophiles to dienes. The direction of the second nucleophilic attack is dependent on the nature of the nucleophiles as well as the reaction conditions. Representative examples... 

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... 

The application of chiral sulfoxides to the asymmetric synthesis of biologically active compounds has recently been reviewed [3]. Conjugate addition to chiral vinyl sulfoxides has been used by several research groups to achieve the enantioselective synthesis of natural products. For example, intramolecular asymmetric conjugate addition of a nitrogen nucleophile to a chiral vinyl sulfoxide (Scheme 3) was studied by Pyne and applied to the enantioselective synthesis of (-R)-carnegine and other alkaloid systems (Scheme 3) [10]. 

Because nitrogen nucleophiles can complex with palladium(O) and thereby deactivate the catalyst, it appeared necessary to study the palladium(0)-catalyzed reaction of allyl carbonates with amines. Without deactivation of the catalyst, the reaction of [11a,b] with piperidine led to the piperidine conjugate [39] in a yield of 73% as a mixture of regioisomers (Eq. 19). 

---