Recent Developments in Palladium-Catalyzed Asymmetric Intermolecular Heck Reaction

Abstract

Some important progress has been made in palladium-catalyzed asymmetric intermolecular Heck reaction in re- cent years. The breakthrough was achieved in the use of acyclic olefins, the aryl halide and benzylic electrophiles in asym- metric intermolecular Heck reaction with some newly developed chiral ligands by Jung, Sigman and Zhou groups. Asymmet- ric intermolecular oxidative Heck-type reaction of acyclic α,β-unsaturated carbonyls and boronic acids was realized by Jung group in high enantioselectivity in the presence of chiral NHC-amidate-alkoxide Pd(II) complexes as catalyst. The Heck re- action of acyclic hydroxyl alkenes and allyl alcohol aryldiazonium salts was achieved by Sigman group with a catalyst de- rived from Pd2dba3 and chiral pyridine oxazoline by using a redox-relay strategy, affording β-, γ-, and δ-aryl carbonyl prod- ucts in excellent enantioselectivity. Sigman group also reports a catalytic and enantioselective intermolecular Heck-type reac- tion of trisubstituted-alkenyl alcohols with aryl boronic acids, providing direct access to diverse molecular building blocks containing an enantiomerically enriched quaternary carbon center. The first examples of asymmetric Mizoroki-Heck reaction using benzyl electrophiles was reported by Zhou group with their newly developed phosphoramidite as the optimal chiral ligand. With this strategy, a key intermediate in asymmetric synthesis of (+)-anisomycin was quickly afforded when p-methoxybenzyl trifluoroacetate was adopted as starting material. Zhou group also realized the first Heck reaction of aryl bromides and chlorides with various cyclic olefins in high enantioselectivities with (R)-Xyl-SDP(O) as the ligand. The use of alcoholic solvents and alkylammonium salts were essential to creating cationic aryl-Pd species for enantioselective olefin insertion. Zhou group has also realized desymmetrization of substituted cyclic olefins successfully via asymmetric Heck reac- tion and found that the use of bisphosphine mono oxide as ligand was important. The Heck reaction of substituted cyclopen- tenes gives almost exclusively trans isomers and establishes two stereocenters in high ee. Under the effect of some newly developed chiral ligands, fused carbo- and heterocycles are synthesized in high ee via asymmetric domino cyclizations. The method is applied to a short synthesis of chiral diamine en route to (-)-martinellic acid. Keywords palladium-catalysis; asymmetric catalysis; Heck reaction; intermolecular reaction