Asinger condensation

Finally, in the most complex multicomponent reaction involving isocyanides, the 7-CC proposed by Ugi in 1993 [93], a moderate diastereoselectivity, leading to a 2 1 mixture of epimeric thiazolidines 109 was observed. The reaction is a combination between an Asinger condensation, involving an a-mercaptoaldehyde (generated from the a-bromoaldehyde and SH ) and an Ugi-type 4-CC with a monoalkyl car-boxylate as acid component (Scheme 1.38). Although the relative configuration of the major stereoisomer was not demonstrated, it is probably trans, in line with the results of Ugi condensation with chiral thiazolines, reported above in Scheme 1.19. 

We were surprised to find that despite the general lability of penam derivatives, the products (154) could be purified by sublimation in vacuo. Using a similar scheme, Sjoberg synthesized the amide of a stereoisomer of penicillin G, but in very low overall yield, because formation of the required 3-thiazoline derivative by the Asinger condensation did not proceed satisfactorily. 

The condensation reaction between a 1,3-oxazine 134 and 3-hydroxy-2,2-dimethylpropionaldehyde generates an intermediate product 135 which undergoes intramolecular cyclization via the Asinger reaction to give compound 136 (Scheme 16) <1995ZSK976>. 

Asinger-type condensations allow the synthesis of a wide range of 5-, 6- and 7-membered heterocyclic compounds, such as 2,5-dihydro-l,3-oxazolines718 and 5,6-dihydro-2//-l,3-oxazines719. In the latter, a /J-hydroxyaldehyde is treated with a ketone (or aldehyde) and ammonia, giving up to 50% yields of the useful heterocyclic product (equation 203). 

The enantiomerically pure 3-thiazoline 50, obtained via Asinger reaction using a galactose-derived chiral auxiliary, was successfully submitted to an Ugi condensation affording the trans adduct 51 with good stereoselectivity, as reported in Scheme 1.19 [56],... 

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