Catalyst-controlled regioselectivity in the synthesis of branched conjugated dienes via aerobic oxidative Heck reactions

Abstract

Pd-catalyzed aerobic oxidative coupling of vinylboronic acids and electronically unbiased alkyl olefins provides regioselective access to 1,3-disubstituted conjugated dienes. Catalyst-controlled regioselectivity is achieved by using 2,9-dimethylphenanthroline as a ligand. The observed regioselectivity is opposite to that observed from a traditional (nonoxidative) Heck reaction between a vinyl bromide and an alkene. DFT computational studies reveal that steric effects of the 2,9-dimethylphenanthroline ligand promote C-C bond formation at the internal position of the alkene.

Figure 1

Energies for the two regioisomeric alkene insertion pathways involving the Si and Re face of the alkene. The chemical structures of the Re-face insertion pathway and the +1 charges on all structures are omitted for clarity. See Supp. Info. for additional details.

Scheme 1

Regioisomeric Conjugated Dienes Potentially Accessible via Heck-Type Cross-Coupling Reactions.

Scheme 2

Steric Effects that Favor Formation of Branched Diene Products.

Chart 1

Ligand Effects on the Oxidative Heck Coupling of Styrenylboronic Acid and Octene^{a a} Reaction conditions: vinyl boronic acid (1.5 equiv), alkene (0.2 mmol), NMP (0.5 mL). Reactions were monitored on GC using 4-methylanisole as the internal standard. ^b GC yield. ^c Determined by GC and ¹H NMR. ^d Pd(TFA)₂ (20 mol%) and ligand (40 mol%) were used. ^e LiTFA (0.2 equiv) was added.