Hydroxymethylation Barbier-type reaction

A very convenient hydroxymethylation process has been developed based on the Smiz-mediated Barbier-type reaction. Treatment of aldehydes or ketones with benzyl chloromethyl ether in the presence of SmIz provides the alkoxymethylated products in good to excellent yields. Subsequent reductive cleavage of the benzyl ether provides hydroxymethylated products. Even ketones with a high propensity for enolization can be alkylated by this process in reasonable yields. The method was utilized by White and Somers as a key step in the synthesis of ( )-deoxystemodinone (equation 27). ° This particular ketone substrate resisted attack by many other nucleophilic reagents (such as methyllithium) owing to competitive enolate formation. 

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