Pictet-Spengler-type reactions

In one route, tidopidine (1) was assembled via Sn2 displacement of 2-chlorobenzyl chloride (9) with 4,5,6,7-tetrahydro-thieno[3,2-c]pyridine (8). " The nucleophile 8 was synthesized by heating 2-thiophen-2-yl-ethylamine (6) with 1,3-dioxolane in the presence of concentrated hydrochloric acid. 1,3-Dioxolone gave better yields than with formaldehyde, paraformaldehyde and 1,3,5-ttioxane. The interesting transformation 6 —> 8 first involved the formation of the corresponding Mannich base 7, which then underwent a Pictet-Spengler type reaction to afford the ring-closure product 8. It was of interest to note that a possible intramolecular aminomethylation did not take place. 

Dihydro-1,3-benzoxazines (196) are formed by the reaction of phenols with a mixture of formaldehyde and primary aromatic amines in the molar ratio 2 1. Presumably the phenol first reacts with the appropriate iminium species to form an intermediate amine (195), which is then cyclized in a Pictet-Spengler type reaction (Scheme 81) (44JA1875). If 2-hydroxybenzylamines are employed then methylene derivatives are obtained, and if the formaldehyde is replaced by a-dicarbonyl compounds dehydro dimers (197) are produced (Scheme 82) <70BCJ226>. 

F-L (Fig. 2). The Friedel-Crafts reaction (limited in the 1-benzazepine series), Dieckmann, acyloin, and aldol condensations, Bischler-Napieralski, Vilsmeyer, and Pictet-Spengler-type reactions, and phenolic oxidative... 

A variety of spiro-tetrahydroisoquinoline-piperidines have been synthesized by established routes. The compounds and methods include (30) by a Pictet-Spengler-type reaction, (31) by cyclization of an N-3,4-dimethoxybenzylglycine nitrile derivative, and (32) via Schmidt rearrangement of a 3-spiro-indan-l-one derivative. ... 

Greater success has been achieved with chiral Bronsted acid or chiral hydrogen bond donor-catalyzed Pictet-Spengler-type reactions involving the... 

Carboline stmcture was constructed by one-pot reaction, which involves the three-component indole formation and nucleophilic cycUzation by the addition of t-BuOK or MsOH. This is the first example of multi-component synthesis of carbolines, except for those using the Pictet-Spengler type reaction. Utilizing the three-component indole formation, indole-fused 1,4-diazepines were also synthesized through deprotection/iV-arylation at nitrogen atom of indole by one-pot addition of MeONa after the formation of indole. These reactions form four bonds in a single reaction vessel, which involves two C-C bonds/two C—N bonds or one C-C bond/three C-N bonds. 

Pictet-Spengler-type reaction of pyrrole-derived amine 1096 and enamines 1097 was used recently for the preparation of pyrrolo[l,2-a]pyrazine derivatives 1098 - a [5+1] approach to the construction of pyrazine ring (Scheme 233) [669],... 

The first enantioselective synthesis of 5,6-dihydroindolo[l,2-a]quinox-alines (200) has been achieved by using a newly developed Hg-BINOL-lype imidodiphosphoric acid catalyst (201) in the Pictet-Spengler-type reactions of indolyl anilines (198) with ketones (199) to afford the products in high yields (up to 97%) and excellent enantioselectivities (up to 98% ee) (Scheme 53). ... 

Scheme 35.22 Chiral phosphoric acids in a cascade Pictet-Spengler-type reaction.

R2=AllQrl, Ph R3=H, COzMe, P(0)(0Me)2, SOzPh Scheme 35.22 Chiral phosphoric acids in a cascade Pictet-Spengler-type reaction. 

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