Ketene-iminiums, cycloaddition

The stereochemistry with respect to the ketene iminium salt in cases of monosubstituted or unsymmetrically disubstituted derivatives in cycloadditions to alkenes show differences from the ketene counterpart. In contrast to ketene cycloadditions of monosubstituted ketenes with alkenes where the substituent in the bicyclic derivative ends up in the endo position, the cycloaddition of two monosubstituted ketene iminium salts with cyclopentene and cyclohexenc gives the e.wp-substituted derivatives 4.6... 

The regiochemistry of ketene iminium salt cycloadditions can also differ from ketene cycloadditions. Whereas reaction of styrene with a series of ketene iminium salts gave 3-phenyI-cyclobutanones7 (60-70% yield) similar to the regiochemistry of ketene cycloadditions, reaction with a series of acrylates and a,/J-unsaturated ketones gave cyclobutanones 5 with regiochemistry opposite to what would be expected from electrostatic considerations of ketene cycloadditions.s... 

Unlike ketcnc cycloadditions, very few mechanistic studies have been carried out with ketene iminium salt cycloadditions. Differences in regiochemistry in the latter examples suggest that these reactions are not concerted and that a carbcne-type addition to the alkene leading to an intermediate such as 6 is responsible for these reactions.8... 

The ketene iminium salt cycloaddition route has been used to prepare a key intermediate 7 for the synthesis of grandisol.10... 

Although the ketene iminium salt route has advantages over the ketene route, limitations of this method include the nonstereospecificity of these cycloadditions in some instances because of the nonconcerted nature of these reactions. Of greater concern is the fact that the major product from alkenes which can form a tertiary carbocation is often the Friedel-Crafts product. This method is therefore largely limited to mono- and 1,2-disubstituted alkenes. 

The intramolecular 2 + 2-cycloaddition reaction of ketenes and ketene-iminiums with alkenes yielded cyclobutanones that could be converted to the tricyclic lactone core of (+)-GR-24, a synthetic analogue of stigolactone plant hormones ... 

The [2 -I- 2] cycloaddition of ketenes and imines is an important route to the P-lactam ring (azetidinone), which is a crucial structural feature of the penicillin class of antibiotics. A number of theoretical treatments of this reaction indicate that in solution phase this is a two-step reaction, with the second step being rate determining. The stepwise nature of the reaction is accommodated by the relative stability of both charged moieties, an iminium cation and an enolate anion. 

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