Pd Catalysed Carbonylations

More details of our work in these areas can be seen by following the 'ref' links or the link to recent publications.

We are studying the synthesis of d-lactams 1 using our Palladium catalysed carbonylative cyclisation. ^ref The precursors can be synthesised in enantiomerically pure form from amino acid starting materials (chiral pool). The stereochemistry remains intact during the key palladium catalysed step and we have proved that the carbonylation is stereospecific.^ref We have investigated the diastereoselective alkylation of enolates derived from 1 and found that this is highly dependent on the nature of the nitrogen substituent.^ref We have used this methodology for the total synthesis of polyhydroxylated piperidines deoxymannojirimycin and mannolactam,^ref and are extending it to the synthesis of other natural products such as nojirimycin, indolizidine alkaloids such as pumiliotoxin 235B and ergot alkoloids such as agroclavine.

We have recently begun exploring the synthesis of the corresponding d-lactones by a related palladium-mediated carbonylation.^ref Carbonylation of alkynyl dioxolanones (1) or epoxides (2) occurs under mild conditions to give the allenes (3). These are then extended to form sugar-related lactones. This work is aimed at the stereoselective synthesis of natural and unnatural sugar derivatives.

We are also studying the enantioselective construction of carbon-carbon and carbon-nitrogen bonds using a chiral catalysts. We have designed ^{ref, ref} the chiral tartrate-derived bis-oxazoline ligands (3) shown below. These ligands were effective in the enantioselective cyclopropanation of styrene; giving e.e.s up to 80%.

We are currently interested in extending these ligands to the asymmetric aziridination of alkenes. Iodine (III) - nitrogen ylids ^ref (4) are used to form transition metal nitrenoid species (5) (M is usually Cu). These electrophilic nitrenoids are able to transfer the nitrogen to double bonds, enol equivalents, and alkyl boranes to form C-N bonds. We are studying the diastereoselective reactions of chiral alkenes (chiral R) with achiral metal catalysts (MLn), and also the use of chiral ligands (L*, such as 3)on the metal in order to make these processes enantioselective. Ring opening reactions and rearrangements of the aziridine products (6) are also being studied. ^ref

In collaboration with Simon Doherty's group, we have discovered a zirconium-mediated synthesis of a new class of C4-bridged diphosphine, NUPHOS,^ref that bears a close structural similarity to BINAP, the classical axially chiral diphosphine used in numerous platinum group catalysed reactions. We are currently exploiting this new discovery to develop and optimize catalysts for achiral and chiral transformations including Grignard cross-coupling, Suzuki coupling,^ref and transfer hydrogenation.^ref

We are involved in the development of other chiral and achiral diphosphines (e.g. ligands 1a-d) for applications in hydroformylation, CO-ethylene copolymerisation^{ref, ref} and fundamental transformations such as asymmetric hydrogenation, cross couplings, and aminations. We are also studying the synthesis and applications of bidentate PN ligands such as iminophosphines 2 ^ref and phosphole oxazoline derivatives 3.

We are also currently involved in the preparation of novel polymer supported diphosphines. These aspects of my research are supported by a strong collaboration with Dr Simon Doherty.

Under Construction