Robert A. Stockman

Synthesis of natural-product-like scaffolds in unprecedented efficiency via a 12-fold branching pathway

Tying the knot! The marriage of two-directional synthesis and tandem reactions allows access to twelve skeletally diverse scaffolds in just fifteen reactions. Two-directional synthesis yields a symmetrical linear “rope-like” keto-dienoate which is then subjected to twelve separate tandem reactions to “tie the rope in knots” thus creating twelve diverse natural product-like scaffolds containing useful functionality for further elaboration.

Combining two-directional synthesis and tandem reactions: an efficient strategy for the total syntheses of (+/-)-hippodamine and (+/-)-epi-hippodamine.

Two-directional total stereoselective syntheses of (+/-)-hippodamine and (+/-)-epi-hippodamine, utilising a tandem deprotection/intramolecular double Michael addition sequence as the key step, are presented.

Two-directional synthesis. Part 1: A short formal synthesis of (±)-histrionicotoxin and (±)-histrionicotoxin 235A

Abstract The formal synthesis of (±)-histrionicotoxin and (±)-histrionicotoxin 235A using a two-directional strategy has been accomplished. The key feature of the synthesis is a tandem oxime formation/Michael addition/nitrone cycloaddition sequence, which form the azaspiro[5.5]undecane skeleton in two operations from an acyclic symmetrical precursor.

Combining two-directional synthesis and tandem reactions, part 11: second generation syntheses of (±)-hippodamine and (±)-epi-hippodamine

Background Hippodamine is a volatile defence alkaloid isolated from ladybird beetles which holds potential as an agrochemical agent and was the subject of a synthesis by our group in 2005. Results Two enhancements to our previous syntheses of (±)-hippodamine and (±)-epi-hippodamine are presented which are able to shorten the syntheses by up to two steps. Conclusion Key advances include a two-directional homologation by cross metathesis and a new tandem reductive amination/double intramolecular Michael addition which generates 6 new bonds, 2 stereogenic centres and two rings, giving a single diastereomer in 74% yield.

Asymmetric synthesis of trisubstituted aziridines via aza-Darzens reaction of chiral sulfinimines.

The aza-Darzens reaction of substituted 2-bromoesters with chiral tert-butane- and mesitylsulfinimines provides a rapid access to a range of highly substituted aziridines in good yields and excellent levels of stereoselectivity. The synthetic potential of this protocol is further enhanced by the successful removal of the sulfinyl motif, yielding simple access to chiral N-H aziridines in just three steps from commercial aldehyde precursors.

Cycloaddition of chiral tert-butanesulfinimines with trimethylenemethane.

The cycloaddition of chiral tert-butanesulfinimines with trimethylenemethane is found to give facile access to methylene-pyrrolidines with good yields and diastereoselectivities. The full scope of the cycloaddition is explored, and a range of transformations of the formed methylenepyrrolidines to give a range of functionalized chiral pyrrolidines is presented.

A two-directional approach to the anatoxin alkaloids: second synthesis of homoanatoxin and efficient synthesis of anatoxin-a

Total syntheses of the potent neurotoxins, environmental hazards, and biochemical probes anatoxin-a and homoanatoxin have been achieved from a common intermediate using a combined two-directional synthesis-tandem reaction strategy which includes key advances in oxidative desymmetrisation, tandem Michael-intramolecular Mannich cyclisations and a new method for deprotection of N-tosyl anatoxin-a.

Combining two-directional synthesis and tandem reactions. Part 21: Exploitation of a dimeric macrocycle for chain terminus differentiation and synthesis of an sp3-rich library

The application of a tandem condensation/cyclisation/[3+2]-cycloaddition/elimination reaction gives an sp(3)-rich tricyclic pyrazoline scaffold with two ethyl esters in a single step from a simple linear starting material. The successive hydrolysis and cyclisation (with Boc anhydride) of these 3-dimensional architectures, generates unprecedented 16-membered macrocyclic bisanhydrides (characterised by XRD). Selective amidations could then be achieved by ring opening with a primary amine followed by HATU-promoted amide coupling to yield an sp(3)-rich natural product-like library.

On the utility of S-mesitylsulfinimines for the stereoselective synthesis of chiral amines and aziridines

The synthetic utility of S-mesitylsulfinimines for the synthesis of chiral amines and aziridines was examined through their reactions with Grignard reagents, with the ylides derived from trimethylsulfonium iodide and S-allyl-tetrahydrothiophenium bromide and through an aza-Darzens manifold, affording convenient access to a diverse range of highly substituted chiral amines and aziridines in high yields and excellent stereoselectivities.

A facile and green route to terpene derived acrylate and methacrylate monomers and simple free radical polymerisation to yield new renewable polymers and coatings

We present new acrylic monomers derived directly from abundant naturally available terpenes via a facile, green and catalytic approach. These monomers can be polymerised to create new polymers with a wide range of mechanical properties that positions them ideally for application across the commodity and specialty plastics landscape; from packaging, cosmetic and medical, through to composites and coatings. We demonstrate their utility through formation of novel renewable polymer coatings.