Sulfenyliminium ions

In 2007, Hiemstra et al. established a catalytic asymmetric Pictet-Spengler reaction that proceeds via (V-sulfenyliminium ions (Scheme 15) [27], Treatment of iV-sulfenylated tryptamines 42 with aldehydes 40 and BINOL phosphate (R)-3f (5 mol%, R = 3,5-(CF3)2-CgH3) afforded tetrahydro-P-carbohnes. After completion of the cyclization the sulfenyl group was cleaved by the use of HCl. This one-pot... 

Scheme 15 Pictet-Spengler reaction via iV-sulfenyliminium ions...

Based on the previous findings by Koomen [21], the Hiemstra group subsequently reported the Pictet-Spengler reaction of N-tritylsulfenyl tryptamines and various aliphatic and aromatic aldehydes by 11 (Scheme 5.11) [22]. Notably, the authors found that stabilization of the N-sulfenyliminium ion by the sulfenyl substituent facilitated preferential cyclization over enamine formation. 

More recently, Jacobsen s group [67] developed a similar approach under dual catalysis combining a chiral thiourea and a weak Brpnsted acid for the enantioselective synthesis of A-unsubstituted carboline derivatives. Alternatively, Hiemstra and co-workers [68] considered the use of A-sulfenyliminium ions as intermediates in the asymmetric Pictet-Spengler reaction in the presence of chiral phosphoric acids. Due to the easy acid-mediated removal of the sulfenyl group, this methodology is also powerful for accessing A-unsubstituted products. 

Wanner et al. developed an efficient Pictet-Spengler reaction of secondary amines and aldehydes via the formation of active sulfenyliminium ions in situ from N-sulphenyltryptamine 16, catalyzed by chiral Brpnsted acids 5d (Scheme 2.6b) [9a], The enantioselectivity may be delivered from asymmetric counterion-directed catalysis [9a], Based on a similar strategy, they achieved the total synthesis of (+)-yohimbine via a phosphoric acid-catalyzed Pictet-Spengler reaction, which employed an A -(5-oxy-2,4-pentadienyl)tryptamine derivative and methyl 5-oxo-2(phenylseleno)pentanoate as starting materials [9b],... 

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