C ( sp 3 ) – P bond formation with non-activated alkyl halides and tosylates †

Organic phosphorus compounds are a group of molecules important to a broad range of elds including synthetic chemistry, biology, materials chemistry, catalytic chemistry, coordination chemistry, agriculture, and pharmaceutical chemistry, for which reason they have drawn considerable attention. In recent years, reactions catalyzed by transition metals (Pd, Ni, Cu) have been developed to construct C(sp)–P and C(sp)– P bonds. Nonetheless, longstanding methods of C(sp)–P synthesis include (1) substitution reactions of carbon electrophiles with alkali metal phosphides or carbon nucleophiles (organolithiums or Grignard reagents) with P–Cl derivatives, which are hindered by air-unstable substrates and low functional group tolerance; (2) the Michaelis–Arbusov reaction and the base-promoted H-phosphinate alkylation, the former of which is limited to the generation of products of primary P-alkyl phosphine oxides and the latter of which is not only limited by the poor compatibility of functional groups due to the employment of strong basic condition (such as BuLi, NaH, Na, LDA, and KHMDS,) but also not easily applied to the production of secondary alkyl halides. In this context, developing a new method for C(sp)–P synthesis, especially for the secondary C(sp)–P compounds, remains a serious challenge, particularly because of the problem of b-hydride elimination. The current work reports a new method of performing the coupling reaction using non-activated primary and secondary alkyl electrophiles with P–H compounds. In this method, LiOMe served as a mild base and TMEDA served as the additive to inhibit b-hydride elimination, and no transition metal catalyst was used. The reaction can be applied to both pentavalent P(O)–H compounds (secondary phosphine oxide, and H-