David Lathbury

Palladium(II)-mediated routes to functionalised heterocycles

Abstract A series of allenic amines/amides 3 have been prepared and shown to undergo a palladium(II)-catalysed cyclisation, in the presence of carbon monoxide and methanol, to give α-(heterocyclic) acrylates 4 .

A new approach to cyclic nitrones: Application to the synthesis of α,α′-disubstituted piperidines and pyrrolidines

Abstract A new synthesis of nitrones is described. This involves the Ag(I)-catalysed cyclisation of allenic oximes, the resulting nitrones being trapped by various 1,3-dipolarophiles.

Electrophile-mediated cyclisations involving the allene π-system. Stereoselectivity and synthetic utility of PdII-catalysed heteroatom cyclisation reactions. X-Ray molecular structure of methyl 2-[trans-3-phenyl-N-(p-tolylsulfonyl)pyrrolidin-2-yl]acrylate

PdII-Mediated cyclisation and methoxycarbonylation of the phenyl-substituted allenic sulfonamides 4,5 and 6 gave the corresponding N-sulfonyl 2,3-, 2,4- and 2,5-disubstituted pyrrolidines 9, 10 and 11, respectively. With the exception of compound 4, cyclisations were not highly selective and similar trends were observed with the α-amino allenic esters 7 and 8. Some improvement, both in yield and diastereoselectivity, was apparent when cyclisations were carried out in the presence of an excess of Et3N. The isolation of acyclic by-products 14 and 15 from α-amino allenic ester 7 suggests that chloropalladiation may play a key role in the mechanism of this cyclisation sequence and similar byproducts were obtained from cyclisation of the unsubstituted allenic sulfonamides 16 and 20 leading to 6- and 7-membered rings, respectively. Other synthetic aspects of this palladium-based chemistry, including efforts directed towards coupling of the cyclisation step with a Heck-type olefination, are also described.

Asymmetric synthesis via allenes: synthesis of (R)-(–)-coniine

The silver(I)-catalysed cyclisation of an amine to a chiral allenic unit is described; the efficiency of this process has been evaluated by a synthesis of (R)-(–)-coniine.

Heterocyclic ketones as pre-formed building blocks. Synthesis of (−)-slaframine

Summary A synthesis of lactam 2 , which constitutes a formal total synthesis of (−)-slaframine 1 , is described with key steps being (a) intramolecular aldol reaction of ketoaldehyde 4 to establish the indolizidine framework and (b) diastereoselective reduction of enone 5 using the Corey oxazaborolidine 7 .

Stereoselectivity in the synthesis of 2,5-disubstituted pyrrolidines

Under homogeneous conditions, the silver(I)-catalysed cyclisation of the allenic amine derivatices (3a–c), thogh not (3d), is stereoselective giving cis-2,5-disubstituted pyrrolidines in high yield; cyclisation on (3a), using a heterogeneous silver(I)-catalyst, is nonstereoselective.

Preparation of 2-aryl and 2-heteroaryl substituted penems by palladium mediated cross coupling

A novel procedure for the synthesis of 2-aryl and 2-heteroaryl substituted penems via a palladium mediated cross coupling of a penem stannane with aryl and heteroaryl halides is described.

Oxazaborolidine-mediated reduction of prochiral 2-alkylidene cycloalkanones

Abstract Asymmetric reduction of enones 1a-g using either a stoichiometric or catalytic amount of oxazaborolidine 3 proceeds to give the synthetically useful allylic cycloalkanols 2a-g in 83–96% e.e.

Synthetic and stereochemical studies directed towards anatoxin-a

The synthesis and stereocontrolled AgI-catalysed cyclisation of a series of allenic amino esters 8a–e is described. For compounds 8a–d the cis-2,5-disubstituted pyrrolidine 9 is formed exclusively but the primary amine 8e undergoes cyclisation nonselectively to give a mixture of cis- and trans-pyrrolidines 9e and 10e. The synthetic potential of this allene-based methodology has been illustrated by the conversion of compound 8avia9a into (±)-anatoxin-a 1 and the methoxy phosphine oxides 18 and 19 have been studied as ketone homologating agents within this context. The enzymatic resolution of (±)-8a using chymotrypsin is also described.

Synthesis of an α-(aminooxy)arylacetic ester by the reaction of an α-diazo ester with n-hydroxyphthalimide

The α-diazo esters (6) and (7) react, in the absence of any catalyst, with a variety of HONR2 and HONCR2 compounds to give the 0-alkylated adducts (8) to (16). In particular, reaction of (7) with N-hydroxyphthalimide in refluxing benzene followed by deprotection gives the title compound (1)