Diastereoselective Pomeranz–Fritsch–Bobbitt synthesis of (S)-(−)-salsolidine using (R)-N-tert-butanesulfinylimine as a substrate

Asymmetric Synthesis of Isoquinoline Alkaloids: 2004–2015

“…In another approach to the total synthesis of Et-743 (1) Zhu et al 40 Grajewska and Rozwadowska performed diastereoselective total synthesis of both enantiomeric (S)-salsolidine (559) 172 and (R)-salsolidine (ent-559) 173 using chiral N-tert-butanesulfinylimines 674 and 675, as substrates, respectively, and Pomeranz− Fritsch−Bobbitt cyclization for the construction of tetrahydroisoquinoline ring system (Scheme 90). To prepare chiral αbenzylamines (S,R)-676 and (R,R)-676, two parallel reaction pathways were performed.…”

“…Herr and co-workers, 64 using commercially available methyl esters of (S)-and (R)-3,4-dimethoxyphenylalanine (171 and ent-171) and 4-chloro-1,1-dimethoxybutane (172) as substrates, synthesized the natural (R)-crispine A (177), a pyrroloisoquinoline alkaloid, and its (S)-enantiomer (ent-177) using the Pictet− Spengler methodology. Scheme 17 shows the three-step synthesis of the natural and unnatural alkaloids.…”

Synthesis and Applications of tert-Butanesulfinamide

“…The synthesis of ( R )-(+)-salsolidine ( 264 ) via the diastereoselective reduction of N - tert -butanesulfinyl ketimine 261 was accomplished by Rozwadowsak and Grajewska (Scheme ) . This route complemented their previous approach to ( S )-(−)-salsolidine ( 164 ), which was achieved via the nucleophilic addition of a Grignard reagent to the appropriate N - tert -butanesulfinyl aldimine (see section ) . A number of reaction conditions for the reduction of 261 were examined, with DIBALH yielding 262 in 87% yield and with a 98:2 diastereomeric ratio.…”

“…Kosciolowicz and Rozwadowska reported the stereoselective addition of MeMgBr to aldimine 162 in THF to provide N-tert-butanesulfinyl amine 163 in 89% yield with 97:3 dr, which upon crystallization was increased to 99:1 dr (Scheme 45). 105 Other reaction conditions were investigated, including the use of MeLi and the use of alternative solvents; however, inferior results were obtained. Subsequent transformations provided the isoquinoline alkaloid (S)-salsolidine (164) with 98% ee in 24% overall yield from the precursor aldehyde (over five steps).…”

tert-Butanesulfinimines: structure, synthesis and synthetic applications

“…Since these pioneering works, the 1,2-addition of Grignard reagents to tBS-imines has been applied to the synthesis of highly functionalized dipeptide isosters, 44 (-)-aphanorphine, 45 2-substituted pyrrolidines, 46 a key intermediate for antihistamic (S)-cetirizine, 47 and the total synthesis of (S)-(À)salsolidine. 48 Organolithiums have been involved in similar reactions for the synthesis of a-branched and a,a-dibranched propargylamines using lithium acetylide, 49,50 (2-indolyl)methanamine derivatives, 51 (6R,7S)-7-amino-7,8-dihydroa-bisabolene through CeCl 3 -mediated addition of methylithium, 36 and a-amino acids through the 1,2-addition of 5-methylfuryllithium followed by ruthenium(III)-catalyzed oxidation. 52 The reaction of Bu 3 SnLi with tBS-aldimines has also been reported to give a-amino organostannanes with high yields and stereoselectivities.…”