Jason Williams

A novel and efficient palladium-catalyzed hydroaminocarbonylation of alkenes with aminals has been developed under mild reaction conditions, and allows the synthesis of a wide range of N-alkyl linear amides in good yields with high regioselectivity. On the basis of this method, a cooperative catalytic system operating by the synergistic combination of palladium, paraformaldehyde, and acid was established for promoting the hydroaminocarbonylation of alkenes with both aromatic and aliphatic amines, which do not react well under conventional palladium-catalyzed hydroaminocarbonylation.

Back to basics: The basicity of aliphatic amines precludes their use in the palladium-catalyzed hydroaminocarbonylation. This issue was overcome by using aminals as surrogates of aliphatic amines. A cooperative catalytic system was discovered to operate by the synergistic combination of palladium, paraformaldehyde, and acid for promotion of the hydroaminocarbonylation of alkenes with both aromatic and aliphatic amines.

Asymmetric C(sp)C(sp²) bond formation to give enantiomerically enriched 1,3-butadienyl-2-carbinols occurred through a homoallenylboration reaction between a 2,3-dienylboronic ester and aldehydes under the catalysis of a chiral phosphoric acid (CPA). A diverse range of enantiomerically enriched butadiene-substituted secondary alcohols with aryl, heterocyclic, and aliphatic substituents were synthesized in very high yield with high enantioselectivity. Preliminary density functional theory (DFT) calculations suggest that the reaction proceeds via a cyclic six-membered chairlike transition state with essential hydrogen-bond activation in the allene reagent. The catalytic reaction was amenable to the gram-scale synthesis of a chiral alkyl butadienyl adduct, which was converted into an interesting optically pure compound bearing a benzo-fused spirocyclic cyclopentenone framework.

That important first step: The ability of chiral phosphoric acids to interact simultaneously with a 2,3-dienylboronic ester and an aldehyde through hydrogen bonding enabled enantiospecific C(sp)C(sp²) bond formation to give versatile synthetic intermediates. A chiral alkyl butadienyl adduct formed in this way on a gram scale was transformed into an optically pure benzo-fused spirocyclic cyclopentenone derivative (see scheme).

In recent years, considerable effort has focused on the development of novel carbonylative transformations using CO surrogates. Consequently, toxic CO gas can be replaced by more convenient inorganic or organic carbonyl compounds. Herein, the first regioselective methoxycarbonylation of alkenes with paraformaldehyde and methanol as CO substitutes is reported. This new procedure is applicable to a series of alkenes in the presence of a palladium catalyst under relatively mild conditions and is highly atom efficient.

CO-llaboration: An efficient synthetic carbonylation without the utilization of hazardous CO gas is described. For the first time, highly regioselective methoxycarbonylation using paraformaldehyde and methanol as carbonyl sources proceeds in the presence of a suitable palladium catalyst. This provides a green and atom-efficient process for the synthesis of methyl esters in high yield and regioselectivity.

We present a direct cross-coupling reaction between arylaluminum compounds (ArAlMe₂⋅LiCl) and organic halides RX (R=aryl, alkenyl, alkynyl; X=I, Br, and Cl) without any external catalyst. The reaction takes place smoothly, simply upon heating, thereby enabling the efficient and chemo-/stereoselective formation of biaryl, alkene, and alkyne coupling products with broad functional group compatibility.

All in Al: Simply heating an arylaluminum (ArAlMe₂⋅LiCl) and an organic halide RX (R=aryl, alkenyl, alkynyl; X=I, Br, Cl) without any external catalyst results in a smooth and direct cross-coupling reaction taking place. This approach enables the efficient, chemo-/stereoselective formation of coupling products with broad functional group compatibility.