[Babcock_Hall]

I would like to perform a Michaelis-Becker reaction with di-tert-butylphosphite, sodium hydride as the base, and 1,4-diiodobutane as the electrophile.  I would like to alkylate a derivative of isonicotinamide with the intermediate compound and deprotect.  I have seen a similar series of reactions with diethylphosphite, HP(O)(OEt)₂ and 1,5-diiodopentane in the literature:  Kim et al., J. Medicinal Chemistry, 33, 1207, 1990.  http://www.ncbi.nlm.nih.gov/pubmed/1648622

The _tert-butyl groups are quite labile to acid, but the conditions in the first step are obviously basic.  The advantage is that removal of the tert-butyl groups in the final step would be easier than the removal of the ethyl groups.  Does anyone see a problem with this approach?  Would a scheme help?

[discodermolide]

I see no reasons for this reaction not to work.
Good luck

[Babcock_Hall]

We tried this reaction first with diethylphosphite, and it worked OK, with slightly lower yield than was reported.  We tried the reaction with di-tert-butylphosphite, and most of the P-31 signal (sample dissolved in CDCl₃) was either HP(OtBu)₂ or DP(OtBu)₂.  There was a small signal around 24 ppm.  The NMR sample showed some evolution of gas for a couple of minutes, at least.

My working hypothesis is that the attack of the phosphite anion was slower with tert-butyl ester groups than with ethyl ester groups.  I imagine that we still had some of the phosphite anion which could remove the deuterium from the solvent, or perhaps get quenched by water or Si-OH groups from the NMR tube.  By the time we took the NMR, we had already removed THF (the solvent).  We thought that we would increase the reaction temperature and monitor by P-31 NMR time points.  Any thoughts or suggestions?

[Babcock_Hall]

We increased the temperature, and that seemed to cause the reaction to go to completion.  In both of the reactions (with ethyl and with tert-butyl protecting groups), there was some evidence to suggest that attack at both -CH₂-I groups had occurred to a small extent.  We were able to run a silica column to clean up the product.