ok, time for _Organic Syntheses_ roulette. with the new rule, choosing a pseudorandom four-digit number and then searching orgsyn.org for it!
and the number is 2564 - heh well at least we know it's divisible by 4
ooh, what a curious one this time
http://orgsyn.org/demo.aspx?prep=v92p0320
direct *asymmetric* alpha-hydroxymethylation of aliphatic aldehydes. here, isovaleraldehyde (or, if you like, 2-methyl-n-butyraldehyde) is converted to the formaldehyde acetal of the (R)-hydroxymethylated aldehyde
the reaction is carried out with formalin (the standard 37% solution of formaldehyde in methanol that is the usual reagent form of formaldehyde) in the presence of toluene, a pH 7 buffer, and a chiral phosphine catalyst, (S)-1,1-diphenylprolinol trimethylsilyl ether, a catalyst undoubtedly synthesized from naturally occurring amino acid proline
presumably, plain mild hydrolysis of the resulting acetal of the hydroxymethylated aldehyde would yield the aldehyde itself, but (cont'd)
(cont'd) here, an oxidative hydrolysis is carried out with sodium chlorite (a popular mild aqueous oxidant for a number of organic reactions) buffered with monobasic sodium phosphate in t-butyl alcohol. that gives the alpha-hydromethylated isovaleric acid, rather than the aldehyde.
neat! working with formaldehyde is kind of a bummer and I wonder if there's any way to jigger the synthesis to use sym-trioxane instead.