S_N2 Reaction of Diarylmethyl Anions at Secondary Alkyl and Cycloalkyl Carbons

Abstract

The substitution reactions of diphenyl sec‐alkyl phosphates with Ar₂CH anions were swift and proceeded with inversion. In contrast, the diphenyl substituted‐cyclohexyl phosphates proceeded with inversion, but showed different reactivity depending on the relative stereochemistry of the substituent and the (PhO)₂PO₂ leaving group. The difference in reactivity was rationalized by computational calculation of the transition energies.

Abstract

The substitution reaction of the diethyl allylic and propargylic phosphates with Ar₂CH anions was applied to sec‐alkyl phosphates to compare reactivity and stereoselectivity. However, the substitution took place on the ethyl carbon of the diethyl phosphate group. We then found that the diphenyl phosphate leaving group ((PhO)₂PO₂) was suited for the substitution at the sec‐alkyl carbon. Enantioenriched diphenyl sec‐alkyl phosphates with different substituents (Me, Et, iPr) on the vicinal position underwent the substitution reaction with almost complete inversion (>99% enantiospecificity). The substitution reactions of cyclohexyl phosphates possessing cis or trans substituents (Me and/or tBu) at the C4, C3, and C2 positions of the cyclohexane ring were also studied to observe the difference in reactivity among the cis and trans isomers. A transition‐state model with the phosphate leaving group ((PhO)₂PO₂) in the axial position was proposed to explain the difference. This model was supported by computational calculation of the virtual substitution reaction of the structurally simpler “dimethyl” cyclohexyl phosphates (leaving group = (MeO)₂PO₂) with MeLi. Furthermore, the calculation unexpectedly indicated higher propensity of (PhO)₂PO₂ as a leaving reactivity than alkyl phosphate groups such as (MeO)₂PO₂ and (iPrO)₂PO₂.