The asymmetric alkoxycarbonylation of vinylarenes catalysed by palladium complexes bearing chiral phosphine ligands has attracted much attention over the last decades. The products of both mono- and bis(alkoxycarbonylation) reactions are important intermediates in the syntheses of pharmaceuticals such as 2-arylpropionic acids, the most important class of non-steroidal anti-inflammatory drugs. In this article, a general overview of the topics will be presented and the recent advances in this field will be particularly detailed. Besides the term alkoxycarbonylation, hydroesterification and hydroalkoxycarbonylation are also used in the literature to describe this reaction. Furthermore, more specific terms such as methoxycarbonylation can be found. In this report, the term alkoxycarbonylation will be used as the general term, and specific terms will be used to unambiguously define which reaction is meant.

Pd-catalysed asymmetric mono- and bis-alkoxycarbonylation of vinylarenes

A class of novel diphosphine ligands bearing pyridine substituents was designed and synthesized for the first time The resulting palladium complexes of L1 allow for chemo- and regioselective dialkoxycarbonylation of various aromatic and aliphatic alkynes affording a wide range of 1,4-dicarboxylic acid diesters in high yields and selectivities Kinetic studies suggest the generation of 1,4-dicarboxylic acid diesters via cascade hydroesterification of the corresponding alkynes Based on these investigations, the chemo- and regioselectivities of alkyne carbonylations can be controlled as shown by switching the ligand from L1 to L3 or L9 to give α,β-unsaturated esters

Selective Palladium-Catalyzed Carbonylation of Alkynes: An Atom-Economic Synthesis of 1,4-Dicarboxylic Acid Diesters.

The preparation of new palladium complexes that are composed of a series of chiral dipyridylphosphines [( R )-P-Phos ( 1 ), ( R )-tol-P-Phos ( 2 ) and ( R )-Xyl-P-Phos) ( 3 )] have been described. The structure of the complex [{( R )- 1 }Pd(H 2 O) 2 ](OTf) 2 was unambiguously determined by single-crystal X-ray diffractometry. These complexes were found to be effective in the asymmetric bis-methoxycarbonylation of styrene, reaching up to 84% e.e. and 79% chemoselectivity for dimethyl-2-phenylsuccinate (DMPS) under the optimal conditions. In addition, the complexes exhibited almost identical enantioselectivity on DMPS.

Enantioselective bis-alkoxycarbonylation of styrene catalyzed by novel chiral dipyridylphosphine cationic palladium(II) complexes

Cationic palladium(II) complexes of the type [Pd(L^L′)(S2)]X2 (where L^L′ is a chelate ligand with C2 symmetry, S is a solvent molecule, and X is an anion with low coordination properties) are able to catalyse the enantioselective bis-alkoxycarbonylation of 1-olefins to substituted succinates. Using atropisomeric fully aromatic ligands high enantio- and chemoselectivity have been obtained when styrene is the substrate. For aliphatic olefins, such as propene and 4-methyl-1-pentene, the chemoselectivity is lower than for styrene owing to multiple olefin insertion. In these cases enantioselectivity is usually modest, probably due to two competing regiochemical pathways for the insertion of the olefin into the palladium carbomethoxy-intermediate. In the case of 3-phenyl-1-propene, dicarbonylation products after isomerization processes are also formed.

Palladium-catalysed enantioselective bis-alkoxycarbonylation of 1-olefins. Synthesis of optically active 2-substituted-butanedioates

Large scale preparation of chiral building blocks for the P3 site of renin inhibitors.

An efficient synthesis of methyl N-[2-(R)-(1-napthylmethyl)-3-(morpholinocarbonyl)propionyl]-(S)-histidinate, the key synthetic intermediate of renin inhibitors

Fuyuhiko Matsuda

Papers

An efficient synthesis of methyl N-[2-(R)-(1-napthylmethyl)-3-(morpholinocarbonyl)propionyl]-(S)-histidinate, the key synthetic intermediate of renin inhibitors