Ketene equivalents

The reactions of ketenes or ketene equivalents with imines, discussed above, all involve the imine acting as nucleophile. Azetidin-2-ones can also be produced by nucleophilic attack of enolate anions derived from the acetic acid derivative on the electrophilic carbon of the imine followed by cyclization. The reaction of Reformatsky reagents, for example... 

A key transformation in Corey s prostaglandin synthesis is a Diels-Alder reaction between a 5-(alkoxymethyl)-l,3-cyclopenta-diene and a ketene equivalent such as 2-chloroacrylonitrile (16). As we have already witnessed in Scheme 3, it is possible to bring about a smooth [4+2] cycloaddition reaction between 5-substituted cyclopentadiene 15 and 2-chloroacrylonitrile (16) to give racemic 14 as a mixture of epimeric chloronitriles. Under these conditions, the diastereomeric chloronitriles are both produced in racemic form because one enantiotopic face of dienophile 16 will participate in a Diels-Alder reaction with the same facility as the other enantiotopic face. In subsequent work, Corey s group demonstrated that racemic hydroxy acid 11, derived in three steps from racemic 14 (see Scheme 3), could be resolved in a classical fashion with (+)-ephe-... 

Diels-Alder reactions of 1-(phenylseleno)-2-(p-toluensulphonyl)ethyne a novel die-nophile and ketene equivalent [138]... 

Nitroalkenes are good dienophiles and the variety of transformations available for nitro groups makes them versatile intermediates.65 Nitro groups can be converted to carbonyl groups by reductive hydrolysis, so nitroethylene can be used as a ketene equivalent.66... 

Notice that the a-acetoxyacrylonitrile is in fact a "ketene equivalent" [30] in the Diels-Alder condensation with furan, since ketene itself undergoes [2 + 21-cycloadditions rather than [4 + 2] cycloadditions. 

A) Synthesis of A ring system Retrosynthetic analysis of cyclohexanone 2a leads to diene 5 and 2-chloroacrylonitrile 6 as a ketene equivalent (Scheme 13.6.2) as the starting materials. 

Another example of the use of the [5-1-2] cycloaddition as a strategy-level reaction is provided in the total synthesis of (-i-)-aphanamol I (138) [41], isolated in 1984 as a minor toxic principle of Aphanamhcis grandifolia. This target presents an array of synthetic challenges that are addressed quite effectively using the allenyl [5-1-2] cycloaddition. In this case, the allenyl unit ultimately functions as a ketene equivalent in the... 

J. L. Reymond and P. Vogel, Application of new optically pure ketene equivalents derived from tartaric acids to the total, asymmetric syntheses of (+)-6-deoxycastanospermine and (+)-6-deoxy-6-fluorocastanospermine,/. Chem. Soc., Chem. Commun. (1990) 1070-1072. 

Ketene acetals and thioacetals can be used as ketene equivalents in cyclobutanone synthesis in situations where ketene to alkene cycloadditions are inefficient such as in the case of electron-deficient alkenes.14 Although thermal cycloadditions of ketene acetals and thioacetals with electron-deficient alkenes have been observed (see Section 1,3.2.1.), such cycloadditions proceed more efficiently and under milder conditions with metal catalysts. Efficient cycloadditions between ketene dimethyl acetal and alkenes substituted by a single electron-withdrawing group have been reported.15... 

Ketene thioacetals can also be used as ketene equivalents in the preparation of cyclobutanones and cyclobutanes. Boron trifluoride catalyzes the [2 + 2] cycloaddition of 2-[(l-pyrro-lidinyl)mcthylene]-1,3-dithiane (39) with dimethyl maleate (40).17 Although the cycloadduct is obtained in good yield, stereochemical integrity is not maintained and the thermodynamically most stable isomer predominates. 

---