Synthesis and conformational analysis of stereoisomeric 1- and 2-methyl-2H,4H-1,6,7,11b-tetrahydro-1,3-oxazino[4,3-a]isoquinolines☆ (original) (raw)

Swittg fronl diastereotnerically pure I-(P_l?ydmxy~~~yl)-l'-t~le~}lyl-or 2'-methyl-4 7-dirnethaxy-1,2,3,4telmhydmisoquinolines (3a,b and Ssb), kotsubstituted, +nitrophenyl-and 4-a~I-or 2-methylS IO-dimethe2&4H-1,6,7, Ilb-tetrahydro-1,3_arazino[4,3-a]isoquinoline diastereomers (a and b) 6-9, 12 and 13 were prepand. The relative conjigurafions and the predominant conjonnalions were determined by 1H and 13C NMR spectroscopy, use also being made of DR, DEPT, DNOE and 2D-HSC measurements. INTRODUCIION 5a-SOCIZ Me0-Me0 hydrol. 5b hydrol. 5a Scheme 2 Methyl-2H,4H-tetrahydro-1,3-oxazino[4,3-a]isoquinolines 4939 Treatment of the aminoalcohols 3a,b and Sa,b with formaldehyde gave the pairs of oxazinoisoquinolines 6a,b-7a,b; with p-nitrobenzaldehyde, 8a,b-9a,b were obtained. In the cases of the 4-@-nitrophenyl) derivatives 8a,b and 9a,b, formation of the pairs of C-4 epimers is possible. The NMR spectra described below indicated that the reaction gives only the diastereomer in which H-llb and H-4 are in the cis position (Scheme 3). The 4-0~0 derivatives 12n,b and 13a,b were synthesized in two different ways; either the urethanes lOa,b and lla,b, prepared from the aminoalcohols with ethyl chloroformate, were reacted with sodium methoxide, or the aminoalcohols were treated with phosgene.