We report a Pd-catalyzed intermolecular hydrophosphinylation of 1,3-dienes to afford chiral allylic phosphine oxides. Commodity dienes and air stable phosphine oxides couple to generate organophosphorus building blocks with high enantio- and regiocontrol. This method constitutes the first asymmetric hydrophosphinylation of dienes.

In this article, we expand upon the catalytic hydrothiolation of 1,3-dienes to afford either allylic or homoallylic sulfides with high regiocontrol. Mechanistic studies support a pathway where regioselectivity is dictated by the choice of counter-ion associated with the Rh-center. Noncoordinating counter-ions, such as SbF 6 − , allow for η 4-diene coordination to Rh-complexes and result in allylic sulfides. In contrast, coordinating counter-ions, such as Cl − , favor neutral Rhcomplexes where the diene binds η 2 to afford homoallylic sulfides. We propose mechanisms that rationalize a fractional dependence on thiol for the 1,2-Markovnikov hydrothiolation while accounting for an inverse dependence on thiol in the 3,4-anti-Markovnikov pathway. Through the hydrothiolation of an essential oil (β-farnesene), we achieve the first enantioselective synthesis of (−)-agelasidine A.

A diastereomeric mixture of secondary phosphine oxide is stereospecifically converted to chlorophosphine salt by treatment with oxalyl chloride, which stereoselectively affords P-inverted or retained tertiary phosphines, depending on the substitution with aliphatic or aromatic Grignard reagents, respectively, in high to 99% yield and 99:1 dr. The repulsion of π-electron on aryl to lone electron pair on phosphorus is proposed for the P-retained substitution.