Piperidinones, alkylation with

An access to spiro-2-aminopyrimidinones 184 was reported by Balalaie et al. in 2008 by reacting N-substi-tuted 4-piperidinones 182 with guanidinium carbonate 183 and alkyl 2-cyanoacetates 181 in refluxing methanol (Scheme 13.43) [76], The desired products 184 were obtained in short reaction times and high to excellent yields (70-96%). 

Bicyclic alkaloids. Nagao et al. have developed a general synthesis of chiral bicyclic alkaloids with a nitrogen atom at the ring juncture, such as pyrrolizidines [5.5], quinolizidines [6.6], and indolizidines [6.5], based on a highly diastereose-lective alkylation of 3-a>-chloroacyl-(4S)-isopropyl-l,3-thiazolidine-2-thiones (1, m = 1,2) with 5-acetoxy-2-pyrrolidinone (2, n = 1) or 6-acetoxy-2-piperidinone (2, n = 2). Thus the tin enolate of 1 (m = 1), prepared with Sn(OTf) and N-... 

In a similar manner to l-benzyl-5-ethoxy-2-pyrrolidone (y-lactam, vide supra), treatment of l-benzyl-6-ethoxy-2-piperidinone (1, Rl = Bn R2 = OC2H5) with 1.2 equivalents of lithium diisopropylamide at —78 °C in tetrahydrofuran gives the enolate which, when treated with 1.3 equivalents of iodoalkane, furnishes 60 40 ratios (by NMR) of the 3-alkylated diastereomers 2 with unidentified stereochemistry in good yields (75 — 85%)17 ls. 

Akiyama et al. reported on the chiral Br0nsted-acid-cat-alyzed aza-Diels-Alder reaction of aldimines 237 with Brassard s diene 238. After the C N alkylative cyclization, piperidinone derivatives 239 were formed with high yield and excellent enantioselectivity. " They used pyridinium salt of chiral phosphoric acid as the chiral Br0nsted acid (Scheme 40.52). 

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