Science of Synthesis

Whitehead, A.; Sieck, S. R.; Mukherjee, S.; Hanson, P. R., Science of Synthesis, (2005) 21, 907.

The unique reactivity of acylphosphonates, owing to their particular physical properties, is evident in the renewed interest in this class of compounds as reagents and synthetic intermediates. Some key features include the s-trans relationship between P=O and C=O, which is the lowest energy conformer, the lower pKa values α to the carbonyl, and the instability of the C—P bond toward hydrolytic and acidic conditions. This high reactivity requires careful handling procedures to avoid product decomposition via hydrolysis and rearrangement pathways. The interesting reactivity pattern of acylphosphonates is largely dependent on the phosphorus substituents. The commonest methods for assembling acylphosphonates include the Arbuzov reaction of an acyl chloride with a trialkyl phosphite and the oxidation of α-hydroxy phosphonates. α-Hydroxy phosphonates can be readily generated from the Pudovik reaction of an aldehyde with a trialkyl phosphite. Examples of oxidations of α-hydroxy phosphonates, however, are much less prevalent in the literature than Arbuzov reactions and also lack broad applicability.