Roger F. Newton

The Cleavage of t-Butyldimethylsilyl Ethers with Boron Trifluoride Etherate

Abstract The t-butyldimethylsilyl protecting group for alcohols was introduced by Corey in 19722. Since then it has proved a popular choice in many syntheses.

Suzuki cross-coupling reactions using reverse-phase glass beads in aqueous media

Reverse-phase glass beads have been employed in Suzuki reactions to provide, in aqueous media, a route to diverse polar substrates in good yield and with low levels of palladium leaching.

Preparation of optically active 6′-fluorocarbocyclic nucleosides utilising an enantiospecific enzyme-catalysed Baeyer–Villiger type oxidation

Kinetic resolution of the racemic ketone (±)-(1) was achieved using Acinetobacter NCIB 9871: the optically active norbornanone was converted into the carbocyclic nucleosides (5) and (7).

Enantioselective opening of spiro epoxides derived from cis bicyclo[3.3.0]octan-3,7-dione using chiral lithium amide bases

The monoketal derived from cis-bicyclo[3.3.0]octane-3,7-dione was converted to epoxides 3. The meso exo epoxide was cleaved via enantioselective deprotonation using chiral lithium amide bases to provide the synthetically useful alcohol 7 with up to 76%ee. The enantiomeric excess of the alcohol was determined by 1H NMR chiral shift techniques.

Synthesis of imidazo-fused bridgehead-nitrogen 2′-deoxyribo-C-nucleosides: coupling-elimination reactions of 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonic acid

A short synthesis of imidazo-fused bridgehead-nitrogen 2′-deoxyribo-C-nucleosides has been developed. This is based on a coupling–elimination reaction of 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonic acid with a series of aminoalkyl-substituted heterocycles and alcohols. The intermediate α,β-unsaturated carboxamides and esters thus formed are converted into novel imidazo[1,5-a]pyridine, imidazo[1,5-b]pyridazine, and imidazo[5,1-f][1,2,4]triazine 2′-deoxyribo-C-nucleosides, including analogues of 2′-deoxyguanosine and 2′-deoxyadenosine. Assignment of the anomeric configuration of the nucleosides is made on the basis of proton n.O.e. experiments.

A new synthesis of (±)-carbocyclic 2′-deoxyuridines

Abstract (±)-Carbocyclic 2′-deoxyuridine (1a) and its (E-5-(2-bromovinyl) derivative (1b) have been synthesized in 8 steps from (1α,3α,5α)-6-oxabicyclo[3.1.0]hexan-3-ol (2).

Synthesis and use of 7-substituted norbornadienes for the preparation of prostaglandins and prostanoids

Syntheses of 7-substituted norbornadienes from 7-t-butoxy- and 7-halogeno-norbornadienes are described. Rearrangement of the products in the presence of peracetic acid gives bicyclic aldehydes (2) in equilibrium with enol ethers (3) which are hydrolysed to hydroxycyclopentenylacetaldehydes (4), and converted into key intermediates for the synthesis of prostaglandins and their analogues. Syntheses of prostaglandin J analogues with n-hexyl and phenyl groups replacing the ω-side-chain are described.

Synthesis of imidazo-fused bridgehead-nitrogen C-nucleosides via dehydrative coupling reactions of 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonic acid

A short, efficient synthesis of novel imidazo-fused bridgehead-nitrogen C-nucleosides has been developed. Dehydrative coupling of 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonic acid (14) with a series of aminoalkyl-substituted heterocycles (6)–(8) gives the amides (15)–(17). The latter are subsequently converted into novel imidazo[1,5-a]pyridine, imidazo[1,5-a]pyrazine, imidazo[1,5-b]pyridazine, and imidazo[5,1-f]-1,2,4-triazine C-nucleosides (20) and (21). The synthesis of a novel adenosine isostere, 8-amino-3-β-D-ribofuranosylimidazo[1,5-a]pyrazine (32), is described.

Factors governing the ratio of isomeric oxabicyclo[3.2.1]octanones formed on Baeyer–Villiger oxidation of some 5-endo,7-anti-disubstituted bicyclo[2.2.1]heptan-2-ones

It was found that the outcome of Baeyer–Villiger oxidation of 5-endo,7-anti-disubstituted bicyclo[2.2.1]heptan-2-ones was influenced by at least three factors: (i) the electronegativity of the substituent at C-7; (ii) the hydrogen-bonding capability of the substituent at C-5; and (iii) the peracid employed. The optimum substituents and reaction conditions for oxidation of a bicycloheptanone to the corresponding 2-oxabicyclo[3.2.1]octan-3-one were delineated and used in the synthesis of a prostaglandin intermediate.

Cyclization of γδ-unsaturated sulphenic acids to give thietan 1-oxide derivatives. Crystal structure of rel-(1R,2S,3R,4R)-3-hexyl-2-hydroxymethyl-4-methylthietan 1-oxide

erythro- and threo-2-t-Butylthio-3-vinylnonan-1-ol have been prepared by Claisen rearrangement of the silylketen acetals derived from (E)-non-2-enyl t-butylthioacetate followed by reduction with lithium aluminium hydride. The sulphur function influenced the stereoselectivity of formation of the silylketen acetals which, in turn, determined the ratio of diastereoisomeric products obtained in the rearrangement. Thermolysis of erythro-2-t-butylsulphinyl-3-vinylnonan-l-ol at 140 °C for 5 min gave erythro-1-(hydroxymethyl)-2-vinyloctanesulphenic acid which cyclized spontaneously to a mixture of rel-(1R,2R,3S,4R)- and rel-(1R,2S,3R,4R)-3-hexyl-2-(hydroxymethyl)-4-methylthietan 1-oxide. threo-2-Butylsulphinyl-3-vinylnonan-1-ol under the same conditions gave a mixture of rel-(1R,2R,3R,4R)- and rel-(1R,2S,3S,4R)-3-hexyl-2-(hydroxymethyl)-4-methylthietan 1-oxide. Allocations of configuration to these thietan 1-oxide derivatives based on transition-state considerations have been substantiated by a determination of the crystal structure of the rel-(1R,2S,3R,4R)-isomer and by n.m.r. spectroscopy, which also led to tentative assignments of conformation.