Hydroformylation, enantioselective

Conceptually at least, these compounds can be obtained via initial enantioselective hydroformylation of the appropriate vinyl aromatic to branched chiral aldehyde and subsequent oxidation. 

The most common oxidatiou states and corresponding electronic configurations of rhodium are +1 which is usually square planar although some five coordinate complexes are known, and +3 (t7 ) which is usually octahedral. Dimeric rhodium carboxylates are +2 (t/) complexes. Compounds iu oxidatiou states —1 to +6 (t5 ) exist. Significant iudustrial appHcatious iuclude rhodium-catalyzed carbouylatiou of methanol to acetic acid and acetic anhydride, and hydroformylation of propene to -butyraldehyde. Enantioselective catalytic reduction has also been demonstrated. 

Rhodium complexes of (R,i )-1-benzyl-3,4-dithioether-pyrrolidines were also prepared by these authors, who further investigated them as ligands of rhodium complexes in the hydroformylation of styrene but, in all experiments, the enantioselectivity was lower than 3% ee, whereas the chemoselectivity was of 97% (Scheme 10.5). ... 

In 2000, better results were obtained by Bonnet et al. by using readily available chiral thioureas as new ligands in the asymmetric rhodium-catalysed hydroformylation of styrene. In general, the conversion of styrene and enantioselectivities were modest, but when the reaction was carried out in heptane as the solvent, an enantioselectivity of 41% ee was obtained (Scheme 10.6). 

Abstract Recent advances in synthetic aspects of the rhodium-catalyzed hydroformylation of alkenes are reviewed. Emphasis is given to practical improvements, efficient new catalysts for regioselective and enantioselective hydroformylation, and to applications of the reaction in organic synthesis. Furthermore, new developments in directed hydroformylation are covered as well as new approaches toward efficient hydroformylation catalysts employing the concept of self-assembly. 

Many chiral diphosphine ligands have been evaluated with regard to inducing enantioselectivity in the course of the hydroformylation reaction [25,26]. However, a real breakthrough occurred in 1993 with the discovery of the BI-NAPHOS ligand by Takaya and Nozaki [65]. This was the first efficient and rather general catalyst for the enantioselective hydroformylation of several classes of alkenes, such as aryl alkenes, 1-heteroatom-functionalized alkenes, and substituted 1,3-dienes, and is still a benchmark in this area [66,67]. But still a major problem in this field is the simultaneous control of enantio-... 

Second generation BINAPHOS-type ligands have been developed recently. Placing 3-methoxy substituents on the aryl phosphine unit furnishes a catalyst which allows for an enantioselective hydroformylation of vinylfurans (Scheme 19) [68]. 

The discovery of the bisphospholane scaffold as a new privileged structure for asymmetric induction in alkene hydroformylation has triggered research for new and improved bisphospholane-type ligands. In this context (k,k)-Ph-bpc has been identified as an excellent ligand for asymmetric hydroformylation, which gives state-of-the-art regio- and enantioselectivities... 

The major problem remains control of regioselectivity in favor of the branched regioisomer. While aryl alkenes as well as heteroatom-substituted alkenes favor the chiral branched isomer, for aliphatic alkenes such an intrinsic element of regiocontrol is not available. As a matter of fact branched-selective and asymmetric hydroformylation of aliphatic alkenes stands as an unsolved problem. In this respect regio- and enantioselective hydroformy-... 

Alkylated diphosphines (R,R)-(92) and (93) were used as chiral ligands in the Pt-catalyzed hydroformylations of some alkeneic substrates. These ligands bring about a loss of catalytic activity with respect to the corresponding diphenylphosphine homolog, particularly in the case of the platinum systems. The regioselectivity favors the straight-chain (or less branched) isomer in the case of terminal alkenes with the exception of styrene the enantioselectivity is very low in all cases.320... 

Systematic variation in chirality at both the chelate backbone and the terminal groups revealed a remarkable effect on the enantioselectivity of the catalysts. Ligand (109) generates chiral cooperativity between the backbone and the terminal moieties in Pt-catalyzed hydroformylation. The highest ee (65%) for 2-phenylpropanal was found for the ligand R-bis(S)-(110) in combination with Pt. The chemoselectivities with all ligands described in association with Pt were rather low. The comparative... 

Homochiral pyridyl, bipyridyl, and phosphino derivatives of 2,2-dimethyl-1,3-dioxolane (113)-(115) were prepared from T-(+)-tartrate. These compounds were assessed in metal-catalyzed asymmetric hydroformylation of styrene enantioselectivity was generally low.342... 

Chiral diphosphites based on (2R,3R)-butane-2,3-diol, (2R,4R)-pentane-2,4-diol, (25, 5S)-hexane-2,5-diol, (lS -diphenylpropane-hS-diol, and tV-benzyltartarimide as chiral bridges have been used in the Rh-catalyzed asymmetric hydroformylation of styrene. Enantioselectivities up to 76%, at 50% conversion, have been obtained with stable hydridorhodium diphosphite catalysts. The solution structures of [RhH(L)(CO)2] complexes have been studied NMR and IR spectroscopic data revealed fluxional behavior. Depending on the structure of the bridge, the diphosphite adopts equatorial-equatorial or equatorial-axial coordination to the rhodium. The structure and the stability of the catalysts play a role in the asymmetric induction.218... 

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