Ketenes, vinyl cycloaddition synthesis

Among the most commonly applied chiral moiety for nitrones (2) is the N-a-methylbenzyl substituent (Scheme 12.6) (18-25). The nitrones 8 with this substituent are available from 1 -phenethylamine, and the substituent has the advantage that it can be removed from the resulting isoxazolidine products 9 by hydrogeno-lysis. This type of 1,3-dipole has been applied in numerous 1,3-dipolar cycloadditions with alkenes such as styrenes (21,23), allyl alcohol (24), vinyl acetate (20), crotonates (22,25), and in a recent report with ketene acetals (26) for the synthesis of natural products. Reviewing these reactions shows that the a-methylbenzyl group... 

The principal method of synthesis of the 1-oxides is the cycloaddition of A-sulfinylsulfonamides, for example, 417, to vinyl ethers." " " " N-phenyl-dimethylketimine" " (correction of an earlier " "" proposed structure), and A-sulfinylamines, for example, 418," ° to ketenes" " " " or alkenes." The adducts obtained from ketene itself are unstable above — 78°750,754,755a Pfeatment... 

The Bose research group has developed a large variety of [2+2] cycloaddition reactions of ketenes with imines to form yS-lactams [16, 112, 113]. In 1991, Bose et al. described the synthesis of a-vinyl yS-lactams by [2-p2] cydoaddition of a,p-unsaturated acyl chlorides with a SchifF base in chlorobenzene. Reaction times were reduced from several hours with conventional methods to 5 min under the action of microwaves [112], and yields of the desired adducts were improved from very low to approximately 70% when compared with classical methods. 

Vinyl ketene (392) is generated by the carbonylation of the allyl phosphate 390 in the presence of a base as shown by 391. A useful application of the ketene formation is the synthesis of -lactam skeleton by [2 -I- 2] cycloaddition of the ketene with imines. Thus, reaction of the imine 393, derived from vicinal dicarbonyl compounds, with the ketene 392 afforded cw-lactam 394 [152], On the other hand, the transAacism 397 was obtained by the carbonylation of the allyl phosphates 395 in the presence of the imine 396 derived from aldehyde [153]. 

Shenone et al. have reported numerous examples of [4 + 2] cycloadditions of dichloroketene with N,N-disubstituted vinyl ketones 99 to afford 5-lactones or 2-pyrone 100 derivatives (Scheme 33) (1979JHC93, 1978JHC181). The synthetic usefulness of this less frequently observed, 1,4-addition reaction of a ketene has been well estabHshed for the synthesis... 

For references see Williams, R. V. Lin, X. New ketene equivalents for the Diels-Alder reaction. Vinyl sulfoxide cycloaddition. /. Chem. Soc., Chem. Commun. 1989, 1872-1873. Ruden, R. Bonjouklian, R. Cycloaddition of vinyl triphenyl-phosphonium bromide. New synthesis of cyclic phosphonium salts. Tetmhedron Lett. 1974, 15, 2095-2098. Ranganathan, S. Ranganathan, D. Mehrotra, A. K. Nitroethylene as a versatile ketene equivalent. Novel one-step preparation of prostaglandin intermediates by reduction and abnormal Nef reaction. J. Am. Chem. Soc. 1974, 96, 5261-5262. Kozikowski, A. P. Floyd, W. S. Kuniak, M. P. 1,3-Diethoxycarbonylallene an active dienophile and ethoxycar-bonylketene equivalent in the synthesis of antibiotic C-nucleosides. J. Chem. Soc., Chem. Commun. 1977, 582-583. 

As [2 + 2]cycloaddition, carbo[2 + 2] cycloaddition of a, P-unsaturated carbonyls with vinyl ethers and P-lactone synthesis through [2 + 2]cycloaddition of ketenes with aldehydes were examined. As shown in Scheme 6.99, since under nonpho-tochemical conditions the concerted mechanism for both reactions are disallowed by Woodward-Hoffmann rules, ground-state catalytic reactions must proceed through a stepwise mechanism. 

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