Phosphonate-substituted pyrrolidines

The scope of the silver-catalyzed [3+2] cycloaddition is not limited to amino acid-derived iminoesters. Grigg has reported the use of aminophosphane-derived azomethine ylides in the cycloaddition to afford the corresponding phosphonate-substituted pyrrolidines (Scheme 2.36).62 The diastereoselectivity of these cycloadditions is not inferior to those of standard amino acid-derived imines. 

Stereoselective alkylation of chiral oxazolopyrrolidine phosphonate (458) occurred with a complete retention of stereochemistry on the a-stereogenic center. Removal of the chiral auxiliary from the resultant diastereomeri-cally pure phosphonates (459) by catalytic hydrogenolysis gave rise to enantiomerically homogenous cx-substituted pyrrolidin-2-yl-phosphonates (460) (Scheme 106). ° ... 

Intramolecular displacement of benzylic chlorides by nitrile anions was previously demonstrated as an efficient method making substituted pyrrolidines " however, the question of enanti-oselectivity was not addressed. Recent works on the synthesis of substituted cyclopentane showed that intramolecular enolate displacement of benzylic phosphate proceeded in clean inversion. Thus, it was envisioned that an appropriately substituted cyano phosphonate could be used to construct the pyrrolidine ring (Scheme 5.23). This intermediate could potentially be produced by the addition of a fert-butylamine to acrylonitrile. The desired amine could be produced via reaction... 

The regiospecific nucleophilic displacement of 1,2-cyclic sulfamidates 130 with methyl thioglycolate or a-amino esters 130 can be accompanied by lactamization (thermal, base mediated, or cyanide catalyzed) to give thiomorpho-lin-3-ones and piperazin-2-ones 131 (Scheme 19) <20030L811>. If malonate esters, phosphonate-stabilized esters, or aryl-substituted enolates were used as nucleophiles in this reaction, trisubstituted pyrrolidines were obtained in high yield <2004OL4727>. 

The pyrrolidine phosphonate 125 does much the same thing in one step but the real virtue of these methods is that the enamines 123 and 126 are reactive enough to combine with various electrophiles, particularly allylic halides, a-halo-carbonyl compounds and Michael acceptors (see chapter 10) to give substituted homologous aldehydes or ketones28 127. 

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