4-Phenylperhydropyrido optically active

Perhydro derivatives of pyrido[l,2-7)][l,2]oxazines are frequently applied in the total synthesis of various alkaloids to control the stereochemistry, and pyrido[l,2-c][l,3]oxazines and [l,3]oxazino[3,4-u]quinolines were also used in the stereoselective syntheses of different alkaloids. Perhydropyrido[l,2-c][l,3]oxazines and their benzologs are formed form 2-(2-hydroxyethyl) piperidines and from their benzologs to justify the stereochemistry of 2-(2-hydroxyethyl) derivatives. Different optically active pipecolic acids can be prepared via 4-phenylperhydropyrido[2,l-c][l,4]oxazin-l-ones. 

Optically active pipecolic acids, and their 2-substituted derivatives were prepared by the catalytic hydrogenation of the respective optically active 4-phenylperhydropyrido[2,l-c][l,4]oxazin-l-ones and their 9a-substituted derivatives over Pearlman s catalyst in good yields (05TA3858). 

Cyclization of the optically active enantiomers of methyl a-(2-carba-moylpiperidinyl)-a-phenylacetate 332 with 1.0 equiv. of NaOH in EtOH provided almost pure optically active l-phenylperhydropyrido[l,2-a]pyr-azine-2,4-diones 333 (09TA1759). 

Cyclocondensation of optically active (S)-pipecolinamide 389 and enantiomers of methyl 2-(4-methylphenylsulfonyloxy)phenylacetates 390 in the presence of an excess of K2CO3 in MeCN led to 67-81 33-19 mixture of (4R,9aS)- and (4S,9aS)-4-phenylperhydropyrido[l,2-a]pyra-zine-l,3-diones 391, regardless of whether (S)-390, (R)-390, or rac-390 was used as starting material (09TA1759). 

Reactions of 3-substituted 2-(lV-phenylaminomethyl)piperazines with a slight excess of ethyl 2-chloroacetate under reflux afforded mixtures of 9-substituted 2-phenylperhydropyrido[l,2-a]pyrazin-3- and -4-ones, which could be separated by column chromatography [72JCS(P2)1374], When 2-[(3-trifluoromethylphenyl)aminomethyl]piperidine was heated with optically active ethyl 2-chloropropionate (87MIP1 91TA231), or lactic acid ethyl ester methanesulphonate (91TA231), the product was a C-9a epimeric mixture of 2-(3-trifluoromethylphenyl)-4-methylperhydropyrido[l,2-fl]-pyrazin-3-ones. The reaction between yV-methyl-2-piperidine-carboxamide and hydroxymaleic anhydride in pyridine resulted in 2,3-dimethyl-3-hydroxyperhydropyrido[l,2-a]pyrazine-l,4-dione (74CB2804). 

---