Studies on a catalytic version of the Matteson asymmetric homologation reaction.

Studies of a catalytic asymmetric version of the Matteson reaction between dichloromethylboronates and organolithium reagents have been undertaken. From several different chiral catalytic systems studied, only one based on a mannitol derivative has given substantial asymmetric induction close to that previously achieved with a bis(oxazoline) derivative and ytterbium triflate. More detailed study of the latter reaction revealed that fresh ytterbium triflate actually reduced the level of asymmetric induction, while "aged" ytterbium triflate, or a fresh sample that had been treated with water, brought about improved induction. The implications of these findings are discussed.

3-Chloro-1-lithiopropene, a functional organolithium reagent, and its reactions with alkylboronates to give 3-alkylprop-1-en-3-ols.

The reagent 3-chloro-1-lithiopropene (4) can be generated by treating 1-bromo-3-chloropropene with t-BuLi. It is unstable but if generated at low temperature in the presence of alkylboronic esters, such as 3, is trapped in situ to give rearrangement products 2, which on oxidation give 3-alkylprop-1-en-3-ols in good yields. The reaction works for primary, secondary, benzylic, and even tertiary alkylboronic esters, providing allylic alcohols bearing almost any alkyl group available using organoborane chemistry and incorporating all features of such groups.

Factors affecting migration of tertiary alkyl groups in reactions of alkylboronic esters with bromomethyllithium.

The reactions of bromomethyllithium with tert-alkylboronic esters could be of great potential for the formation of quaternary carbon centers but often give poor yields/conversions. Calculations and experimental evidence show that tert-alkyl groups migrate less effectively than other types of alkyl group in such reactions and that O-migration competes. Furthermore, slow/incomplete capture of the bromomethyl reagent by the boronic ester is a problem in more hindered systems, and an additional competing reaction, possibly Li-Br exchange on the bromomethylborate species, also leads to lower yields of migrated products. Based on this, experimental protocols have been devised in which the competing reactions are largely suppressed, leading to higher conversions to migrated product for several substrates.

(E)-2-(1,1-Di-cyclo-hexyl-3-phenyl-all-yl)-5,5-dimethyl-1,3,2-dioxaborinane.

The crystal structure of the title compound, C26H39BO2, which contains no strong hydrogen bond donors, displays only long C-H⋯O contacts between inversion-related pairs of mol-ecules. The structure contains layers rich in oxygen and boron parallel to the ac plane. The dioxaborinane ring adopts an envelope conformation with the C atom attached to the two methyl groups as the flap .

Diastereoselective alkylation reactions of 1-methylcyclohexa-2,5-diene-1-carboxylic acid.

The deprotonation and alkylation of 1-methylcyclohexa-2,5-diene-1-carboxylic acid has been investigated under a range of conditions. In all cases, the formation of compounds 14 was found to be completely stereoselective, although compound 14c was formed as an impurity when alkyl iodides were used as electrophiles, and doubly-alkylated compounds 17 were formed in some cases when alkyl bromides were used.

Reaction of heterocyclic enamines with nitrile oxide and nitrilimine precursors.

Alkylidenepyrrolidines 1, 21, 24 and 26 undergo reactions with nitrile oxides and nitrilimines or their precursors to give a range of novel heterocyclic compounds. With alkylidenepyrrolidine ester 1, nitrolic acids give products in which the liberated nitrous acid reacts with the alkylidenepyrrolidine, followed by two cycloadditions to give adducts 3. In contrast, hydroximoyl chlorides give isoxazoles 10, presumably by cycloaddition/elimination. With hydrazonyl chlorides, simple acylation of the alkylidenepyrrolidine occurs to give compounds 17. With sulfonyl alkylidenepyrrolidines 24 and 26, cycloaddition onto the imine tautomer is the preferred pathway, with a stereoselective reaction taking place in the latter case.

Studies towards the total synthesis of lycoposerramine A. Synthesis of a model for the tetracyclic core.

Lycoposerramine A (1) is a pentacyclic alkaloid isolated in 2001 by Takayama and co-workers. A concise synthesis of a model compound 8 for the tetracyclic core of this natural product is described. Key steps include the desymmetrising free-radical cyclisation of compound 7 to give compound 18 and spirocyclisation of compound 26 to give compound 8. Earlier approaches using a novel high-yielding stereoselective anionic cyclisation of a cyclohexa-1,4-diene are also reported.

Synthesis and stereochemical determination of batzelladine C methyl ester.

Batzelladine C (3) is a tricyclic guanidine alkaloid of unknown stereochemistry at one centre as well as unknown absolute stereochemistry. The two possible diastereoisomers of the methyl ester corresponding to this compound have been synthesised, permitting the relative and absolute stereochemistry of this compound to be assigned.

Directed epoxidation of cyclohexa-1,4-dienes-stereoselective formation of up to six contiguous stereogenic centres.

Epoxidation/cyclisation of cyclohexa-1,4-dienes containing pendant hydroxyl groups provides stereocontrolled access to highly-functionalised reduced benzol[b]furan derivatives.

Concise synthesis of the tricyclic core of lycoposerramine S.

The tricyclic core of lycoposerramine S has been synthesised in 10 steps from a symmetrical cyclohexadiene precursor by way of a desymmetrising free-radical cyclisation and iodocyclisation.

Chiral N-heterocyclic carbene ligands based on a biisoquinoline template.

New chiral imidazolinium salts with tunable steric features, based on a biisoquinoline template, have been developed and structurally characterised using single crystal X-ray crystallography. The trans PdI(2)(NHC)(2) complex was prepared by reaction of the parent H(4) imidazolinium salt with Pd(OAc)(2) in the presence of NaI, and the solid state structure determined by X-ray crystallography. The rigid, chiral, biisoquinoline geometry of the H(4) imidazolinium salt was found to be maintained upon ligand complexation. The sterically unencumbered parent biisoquinoline ligand has been found to give high conversion with modest enantioselectivity in the copper-catalysed asymmetric addition of diethylzinc to cyclohexenone.

Studies towards the total synthesis of batzelladine A.

Application of a diastereoselective three-component coupling to the bicyclic core of the batzelladine alkaloids is described. The synthesis features the elaboration of glutamic acid by use of Eschenmoser sulfide contraction. An earlier approach is also included, which shows some limitations of dithiane chemistry when applied to the particular compounds required for this target.

Synthesis and reactions of partially reduced biisoquinolines.

An improved synthesis of the 1,1',2,2',3,3',4,4'-octahydro-1.1'-biisoquinoline ring system is described. The reactivity of this system has been investigated, including the unusually high basicity of the parent compound and its N.N'-dimethyl derivative. The resolution of the parent compound has been achieved for the first time, along with the development of a straightforward method for assaying its enantiomeric purity.