Formaldehyde Lewis acid catalyzed alkene addition

Fluorine-containing aldehydes, ketones and acid fluorides undergo photoinitiated cycloaddition reactions with fluorinated alkenes to give oxetanes.90 91 The addition of hexafluoroacetone (11) to fluoroalkenes can also be performed in the presence of the Lewis acid, aluminum chloride fluoride.92-1 22-1 23 Unlike the photochemical cycloaddition of hexafluoroacetone with trifluoroethene, the Lewis acid catalyzed addition is regioselective.92 Fluorooxetanes (c. g., 14) have also been synthesized by the addition of formaldehyde to fluoroalkenes in hydrogen fluoride.94 Examples of the formation of fluorooxetanes by [2 + 2]-cycloaddition reactions arc-given in Table 8. 

In a clever piece of work, Snider et al. have used a quasi intramolecular carbonyl Diels-Alder cycloaddition to produce a key intermediate for syntheses of pseudomonic acid A (175) (Scheme 20). Thus a Lewis acid catalyzed ene reaction of alkene (170) and formaldehyde afforded (171), which com-plexed with additional formaldehyde to give (172). Intramolecular [4 + 2] cycloaddition of (172) gave adduct (173) which produced dihydropyran (174) upon hydrolysis. 

The side products obtained in Lewis acid catalyzed ene reactions of formaldehyde with mono-and 1,2-disubstituted alkenes are consistent with the mechanistic scheme shown in Figure 2. When only 1 equivalent of Me2AlQ is used chloro alcohols are formed as by products. When excess Lewis acid is used chloroalcohols are fonned as transient intermediates which are converted to ene adducts and other products. The chloroalcohols formed from 1,2-disubstituted alkenes result from the stereospecifically cis addition of the hydroxymethyl and chloride groups to the double bond. This result was unexpected since all previous Prins additions have been shown to proceed predominantly by trans addition. 4 Cis addition of chloride and hydroxymethyl groups would be expected from intermediates such as 4 or 5 and 6. 

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