Declan G. Gilheany

Recent progress towards the understanding of metal–salen catalysed asymmetric alkene epoxidation

The history of the development of useful catalyst systems for the asymmetric epoxidation of alkenes is described. An overview is presented of the present state of understanding of the mechanism of the most successful catalysts to date, metal–salen complexes. Recent results from the chromium–salen series are presented and their implications for the mechanism are discussed.

Chromium catalysed asymmetric alkene epoxidation. greater selectivity for an E-alkene versus its Z-isomer

Abstract E -β-methylstyrene can be asymmetrically epoxidised stoichiometrically with up to 83% ee and catalytically with up to 77% ee by chiral chromium complexes in the presence of phosphine oxides, DMSO or DMF. In all cases the analogous reaction with Z -β-methylstyrene gives lower ee.

Unsymmetrical salen ligands: Synthesis and use in chromium mediated asymmetric epoxidation

Abstract Chiral non-racemic salen ligands with two different salicylidene moieties can be synthesised via trapping of the intermediate mono-salicylidene using (+)- O,O′ -dibenzoyl-D-tartaric acid. The chromium complexes of these ligands can be used in asymmetric epoxidation of alkenes. The presence of triphenylphosphine oxide substantially raises the selectivity (ee) of the epoxidation.

Unequivocal Experimental Evidence for a Unified Lithium Salt-Free Wittig Reaction Mechanism for All Phosphonium Ylide Types: Reactions with β-Heteroatom-Substituted Aldehydes Are Consistently Selective for cis-Oxaphosphetane-Derived Products

The true course of the lithium salt-free Wittig reaction has long been a contentious issue in organic chemistry. Herein we report an experimental effect that is common to the Wittig reactions of all of the three major phosphonium ylide classes (non-stabilized, semi-stabilized, and stabilized): there is consistently increased selectivity for cis-oxaphosphetane and its derived products (Z-alkene and erythro-β-hydroxyphosphonium salt) in reactions involving aldehydes bearing heteroatom substituents in the β-position. The effect operates with both benzaldehydes and aliphatic aldehydes and is shown not to operate in the absence of the heteroatom substituent on the aldehyde. The discovery of an effect that is common to reactions of all ylide types strongly argues for the operation of a common mechanism in all Li salt-free Wittig reactions. In addition, the results are shown to be most easily explained by the [2+2] cycloaddition mechanism proposed by Vedejs and co-workers as supplemented by Aggarwal, Harvey, and co-workers, thus providing strong confirmatory evidence in support of that mechanism. Notably, a cooperative effect of ortho-substituents in the case of semi-stabilized ylides is confirmed and is accommodated by the cycloaddition mechanism. The effect is also shown to operate in reactions of triphenylphosphine-derived ylides and has previously been observed for reactions under aqueous conditions, thus for the first time providing evidence that kinetic control is in operation in both of these cases.

Improved Resolution Methods for (R,R)- and (S,S)-Cyclohexane-1,2-diamine and (R)- and (S)-BINOL

Abstract Starting from inexpensive l -(+)-tartaric acid, it was possible to resolve and obtain pure both enantiomers of trans -cyclohexane-1,2-diamine 1 and thence both enantiomers of BINOL 2 , two of the most powerful, chiral inducing backbones in asymmetric catalysis. The modified method is very economic, not only due to an almost doubling of the overall yields of enantiomerically pure compounds (86% 1 , 83% 2 ) but also due to the easy recovery of resolving agent 1 [66% ( R , R )- 1 , 79% ( S , S )- 1 ] in the BINOL resolution. An improvement in the yield of the preparation of racemic BINOL is also recorded.

Chromium salen catalysed asymmetric alkene epoxidation. Influence of substituents at the 3,3′-positions on the salen rings

Any substituent at the 3,3′-positions is sufficient to give greater than 80% ee in the epoxidation of E-β-methylstyrene with chromium-salen complexes.

Chromium–Salen‐Mediated Alkene Epoxidation: A Theoretical and Experimental Study Indicates the Importance of Spin‐Surface Crossing and the Presence of a Discrete Intermediate

The mechanism of alkene epoxidation by chromium(v) oxo salen complexes has been studied by DFT and experimental methods. The reaction is compared to the closely related Mn-catalyzed process in an attempt to understand the dramatic difference in selectivity between the two systems. Overall, the studies show that the reactions have many similarities, but also a few critical differences. In agreement with experiment, the chromium system requires a change from low- to high-spin in the catalytic cycle, whereas the manganese system can proceed either with spin inversion or entirely on the high-spin surface. The low-spin addition of metal oxo species to an alkene leads to an intermediate which forms epoxide either with a barrier on the low-spin surface or without a barrier after spin inversion. Supporting evidence for this intermediate was obtained by using vinylcyclopropane traps. The chromium(v) oxo complexes can adopt a stepped shape or form a more concave surface, analogous to previous results on manganese salen complexes.

The synthesis and use in asymmetric epoxidation of metal salen complexes derived from enantiopure trans-cyclopentane- and cyclobutane-1,2-diamine

A complete synthesis of enantiopure trans-cyclopentane-1,2-diamine and trans-cyclobutane-1,2-diamine is described. These diamines have been used as components of novel chiral salen ligands whose chromium and manganese complexes were then evaluated as oxygen transfer agents in the asymmetric epoxidation of alkenes.

Co-operative ortho-effects on the Wittig reaction. Interpretation of stereoselectivity in the reaction of ortho -halo-substituted benzaldehydes and benzylidenetriphenylphosphoranes

Abstract The E/Z ratios of the stilbenes 1 formed in the Wittig reaction of ortho -halo substituted benzyltriphenylphosphonium salts 2 and benzaldehydes 3 were determined. It was found that there is a co-operative effect of one ortho -halo group on each of the two reacting partners which increases Z -selectivity, but two such groups on the same reactant gives high E -selectivity. The effects are strong enough to be preparatively significant in certain cases and can be interpreted within the modern framework of the Wittig mechanism established by Vedejs and co-workers.

Ligand-based improvement of enantioselectivity in the catalytic asymmetric dihydroxylation of dialkyl substituted olefins

A high level of asymmetric induction was achieved in the asymmetric dihydroxylation of dialkyl substituted olefins using 9-O-aryldihydroquinidines as ligands.