(Dialkoxymethyl)lithiums: Generation, Stability, and Synthetic Transformations

Article abstract of DOI:10.1021/ja00186a036

(Dialkoxymethyl)lithium reagents, (RO)2CHLi, can be generated simply and efficiently and employed as synthetically useful one-carbon nucleophiles.Reductive lithiation of phenylthio-substituted precursors, (RO)2CHSPh, at -95 deg C or transmetalation of tri-n-butylstannyl compounds, (RO)2CHSn(n-Bu)3, at -110 to -111 deg C afforded the acyclic species (MeO)2CHLi (4) and (EtO)2CHLi (5).The cyclic reagents, 2-lithio-1,3-dioxolane (6) and 2-lithio-1,3-dioxane (7), were similarly prepared at -78 deg C by reductive lithiation or transmetalation.Reactions of(dialkoxymethyl)lithiums with electrophiles, including aldehydes, ketones, 2-cyclohexen-1-one (1,2- or 1,4-addition as desired), dimethyl sulfate, primary alkyl bromides, epoxides, oxetane, and n-Bu3SnCl, afforded structurally diverse, functionalized acetals.In these experiments, which emphasized transformations of lithiodioxane 7, yields of products generally exceeded 90percent.The thermal stability of each reagent was investigated at several temperatures.The acyclic compounds 4 and 5 decompose rapidly even at -95 deg C, whereas lithiodioxolane 6 and dioxane derivative 7 are relatively stable at -78 and -45 deg C, respectively.These striking differences in solution lifetimes can be rationalized in terms of alternative decomposition pathways and steric and stereoelectronic factors.The primary products of thermal decomposition of 7 can be ascribed to formation of a reactive carbene or carbenoid via α-elimination.Equilibration experiments established that (dialkoxymethyl)lithium 7 is more stable thermodynamically than the α-monoalkoxy species <(benzyloxy)methyl>lithium, in accord with previous ab initio calculations.