207615-49-4

Upstream product

• 213686-55-6 (-)-benzyl N-<(αR)-2-<<(4R,5R)-4,5-bis(2-methoxypropan-2-yl)-1,3-dioxolan-2-yl>methyl>benzhydryl>carbamat 
• 3297-72-1 1-phenylisoquinoline 
• 501-53-1 benzyl chloroformate 
• 172794-66-0 (4S,5S)-2-(2-Bromo-benzyl)-4,5-bis-methoxymethyl-[1,3]dioxolane 
• 112396-13-1 2-(2-bromophenyl)acetaldehyde dimethyl acetal 
• 1613-90-7 4-methoxy-N-[(E)-phenylmethylidene]aniline 
• 51608-60-7 phenyl N-tosyl imine 
• 213595-50-7 (-)-N-<(αR)-2-<<(4R,5R)-4,5-bis(2-methoxypropan-2-yl)-1,3-dioxolan-2-yl>methyl>benzhydryl>-4-methylbenzenesulfonamide 
• 172794-67-1 (4R,5R)-2-(2-Bromo-benzyl)-4,5-bis-(1-methoxy-1-methyl-ethyl)-[1,3]dioxolane 

Relevant academic research and scientific papers

Asymmetric hydrogenation of quinolines and isoquinolines activated by chloroformates

(Chemical Equation Presented) Active ingredient: Optically active tetrahydroquinolines and tetrahydroisoquinolines can be obtained by the asymmetric hydrogenation of quinolines and isoquinolines with chloroformates as the activating reagent (e.g., ClCO2Bn, see scheme). The method has been applied to the asymmetric synthesis of several naturally occurring alkaloids. Bn = benzyl.

Diastereoselective addition of chiral (2-lithiophenyl)acetaldehyde acetals to various imines as key step in the asymmetric synthesis of 1- aryltetrahydroisoquinolines, part 4

A novel asymmetric synthesis of 1-aryl-1,2,3,4-tetrahydroisoquinolines has been developed. The key step in this synthesis is the diastereoselective addition of homochiral (2-lithiophenyl)acetaldehyde acetals to the sulfonylimine 25 and to the arylimines 28 and 31. The best diastereoselectivity is obtained by addition of the bis(2-methoxypropan-2- yl)-substituted 1,3-dioxolane 6e to benzylidene-p-anisidine (31) with an HPLC-determined diastereomeric ratio 32c/33c = 92.1:7.9. The N-tosyl and the N-(4-methoxyphenyl) groups of the addition products 26d, 27d, 32c, and 33c are cleaved with sodium in liquid ammonia and ammonium cerium(IV) nitrate, respectively, to yield the primary amines 35 and 36. The acid-catalysed cyclization of the sulfonamides 26d and 27d and the carbamates 37 and 38, prepared from 35 and 36, leads to the enantiomerically pure dihydroisoquinolines 40 and 41, respectively. During the cyclization of the sulfonamides 26d, 27d and the carbamates 37, 38 the chiral auxiliary - the diol 39 - is cleaved unchanged and can be recovered in good yields.

Preparation of Chiral 2-(2-Bromobenzyl)-1,3-dioxolanes and Their Addition to Acylimines

A series of enantiomerically pure 2-(2-bromobenzyl)-1,3-dioxolanes 10 has been prepared by transacetalization of the dimethyl acetal 8 or the enol ether 7 with enantiomerically pure C2 symmetric 1,2-diols. We investigated the ability of the chiral 1,3-dioxolane moiety to control the diastereoselectivity during the addition of the aryllithium intermediates 18 to the acylimines 17. Those reactive aryllithium species were generated by bromine/lithium exchange at the bromo acetals 10. In this series the best diastereoselectivity was obtained by addition of the aryllithium intermediate 18b to the acylimine 17a to yield the diastereomeric addition products 19c/ 20c in a ratio of 72:28. After separation, the main diastereomer 19c was cyclized to afford the dihydroisoquinoline (R)-21, which was then hydrogenated to give the NMDA antagonistic 1-phenyl-1,2,3,4-tetrahydroisoquinoline (R)-2. The chiral auxiliary, the diol 9b, cleaved during the cylization of 19c, could be recovered in 89% yield.