The difference in reactivity of (−)-mono and dimenthyl vs. diethyl alkylphosphonates in the α-lithiation reaction: Carbanionic synthesis of unknown (−)-dimenthyl 1-iodoalkylphosphonates and their first use in the radical iodine atom transfer addition (I-A

Unknown (−)-dimenthyl and ethyl (−)-menthyl 1-iodoethylphosphonates were synthesized via 1-lithio derivatives in 85–87% yields. Starting (−)-dimenthyl alkylphosphonates (R = Me, Et, i-Pr) were obtained in the Michaelis–Becker reaction (75–81% yields) and/or in the methylation reaction of the corresponding 1-lithio-alkylphosphonates (78–92% yields). An interesting concentration and time correlations, never observed for diethyl alkylphosphonates, were found for the metalation of bulky (−)-menthyl alkylphosphonates with n-BuLi and general reaction conditions for the carbanion generation were elaborated. The first example of the I-ATRA reaction of (−)-dimenthyl 1-iodoethylphosphonate with 1-hexene (AIBN) gave four diastereomers (1.6:1:1:0.4), separated into two pairs. The I-ATRC reaction was not effective due to a steric hindrance around the reactive center. The X-ray analysis of (−)-dimenthyl methylphosphonate confirmed a considerable steric hindrance in higher (−)-dimenthyl alkylphosphonate esters in comparison to their diethyl analogs.

(−)-Mono and dimenthyl alkylphosphonates as well as (−)-dimenthyl phosphites revealed much lower reactivity in metalation and radical reactions (I-ATRA and I-ATRC) than their diethyl analogs due to a steric hindrance around reactive centers. New protocols for metalation reactions of these classes of compounds have been elaborated.Figure optionsDownload as PowerPoint slide