2.3.4.6.7.116- Hexahydro isoquinolin-4-ones, oxidation

Reaction of iV-aminocarbonyl-2-phenylethylamines with mesityl oxide and 2-butenal afforded l,2,3,6,7,llb-hexahydro-477-pyrimido[6,l- ]isoquinoline-4-ones <2003MC278>. 9,10-Dimethoxy-l,2,3,6,7,llb-... 

Oxidation of 2-(3-aminopropyl-l,2,3,4-tetrahydroisoquinoline with mercuric acetate in 4% aqueous acetic acid at 50°C for 6 h, and then at room temperature overnight followed by the treatment of the filtered solution with 20% potassium hydroxide solution, yielded 1,3,4,6,7,llb-hexahydro-2//-pyrimido[2,l-a]isoquinoline (16, R = R1 = H) in 27% yield (73JOC437). 1,3,4,6,7,llb-Hexahydro-2//-primido[2,l-a]isoquinolines (16, R = H, MeO, R1 = H) and their 2-oxo derivatives (18, R = H, MeO, R1 = H) were obtained from 2-(3-aminopropyl)- and 2-(2-aminocarbonylethyl)-3,4-dihydroisoquinolinium salts (17 and 19, R = H, MeO, R1 = H) by treatment with a base (62CB2122,62MI1). The adjustment of the pH value of a solution of l-methyl-2-(2-aminocarbonylethyl)-3,4-dihydroisoquinolinium perchlorate (19, R = H, R1 = Me, X = C104) in 10% aqueous acetic acid with sodium carbonate to 9 yielded 1 lb-methyl-1,3,4,6,7,1 lb-hexahydro-2//-primido[2,l-a]isoquinolin-2-one (111) (93KGS499). 

Oxidation of 6-oxopyrido[2,l-h][l,3]thiazine-4,9-dicarboxylates (85 n = 0, R = H, phthalamido) with 1 mol eq of 3-chloroperoxybenzoic acid yielded sulfoxides (85 n = 1, R = H, phthalamido) [83JCS(CC)199 92JCS(P1)621]. Oxidation of 2,3,4,6,7,llh-hexahydro[l,3]thiazino[2,3-a]-isoquinolin-4-ones with 3-chloroperoxybenzoic acid in dichloromethane gave sulfones (69FRP1552211). The appropriate sulfone was also prepared from perhydropyrido[2,l-h][l,3]thiazine (59AP165) and 3,4,7,8, 9,10-hexahydro-2//,6//-[ 1,3]thiazino[3,2-h] isoquinolin-6-one [79JAP(K)79/ 92996 81USP4284778]. 

Dess-Martin oxidation of 1,3,4,6,7,1 lfr-hexahydro[l,4Joxazino[3,4-aJ isoquinolin-4-ones 189 in CH2C12, or their oxidation with Cr03 in the presence of pyridine and Ac20 in a mixture of CH2C12 and DMF provided l,3,4,6,7,llMiexahydro[l,4]oxazino[3,4-a]isoquinoline-l,4-ones 190 (08T2321). 

Krapcho decarbomethoxylation of diester 216 provided monoester 217 (06SL1691). Chemoselective Swern oxidation of 3-(3-hydroxypropyl)-1,2,3,4,11, 1 lrt-hexahydro-6/T-pyrazino[l,2-fr]isoquinolin-4-ones 203 followed by silyl enol ether formation with TIPSOTf and Et3N in Et20 for 12 h at room temperature gave compounds 218 as a single isomer in excellent yields (08JA7148,09JOC2046). 

Swern oxidation of 3-hydroxymethyltetrahydroisoquinoline 358, followed by the treatment of the reaction mixture with BU4NF gave a mixture of 3-formyltetrahydroisoquinoline 252 and 2,3,4,6/11,1 la-hexahydro-lH-pyrazino[l,2-fc]isoquinolin-4-one 253 (07AGE3962). That of 3-hydroxy-methyltetrahydroisoquinolines 359 afforded a 3 2 mixture of epimeric mixture of 1-hydroxy derivatives 202 in excellent yields (08JA7148, 09JOC2046). 

Hydroxy-1, 2,3,4,11/1 lfl-hexahydro-6H-pyrazino[l,2- ]isoquinolin-4-one 204 was obtained in 83% overall yield, when tetrahydroisoquinoline-3-carboxylate 360 was reduced with LiBH4 in a mixture of MeOH and EtaO at room temperature for 4 h, followed by Swern oxidation (08JA7148). 

Oxidation of 8,9-dihydroxy-l, 3,4,6,11,1 la-hexahydro [1,4]oxazino[4,3-6]isoquinolin-l-one with Se02 in hot AcOH afforded 8,9-dihydroxy-l-oxo-... 

Treatment of 2-benzoyl-l,2,3,6,7,l lh-hexahydro-4//-pyrazino[2,l-a]-isoquinolin-4-one with NaNH2, then with ethylene oxide yielded the 3-(2-hydroxyethyl) derivative (76GEP2441261). 4-Thioxo and 2-(cyclohexyl-thiocarbonyl)-4-thioxo derivatives were prepared from 1,2,3,6,7,116-hexa-hydro-4//-pyrazino[2,l-a]isoquinolin-4-one and its 2-cyclohexylcarbonyl derivative by treatment with P4Si0. 

Pyrazino[l,2-5]isoquinolin-5-ium 2-oxide perchlorate and its 3-methyl and 3-phenyl derivatives were obtained by cyclization of the appropriate 3-oximidomethyl-l-acylmethylisoquinolinium salt (or its oxime) through heating in an acidic medium (72JHC177). Swern oxidation of 2-acyl-3-hydroxymethyl-l,2,3,4-tetrahydroisoquinolines (298) proceeded smoothly to yield a diastereomeric mixture of l-hydroxy-l,3,4,6,ll,lla-hexahydro-2//-pyrazino[l, 2-5] isoquinolin-4-ones 136 (87TL4065). Heating (3-carboxy-... 

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