David Holland

A chemical method of labelling oligodeoxyribonucleotides with biotin: A single step procedure using a solid phase methodology

Abstract Protected D(+)-biotin methylesters 3 were reduced to the corresponding alcohols 4 and phosphitylated with chloromethoxymorpholinophosphine. The resulting phosphoramidites 5 were used on a commercial DNA synthesiser to biotinylate synthetic DNA.

Catalytic asymmetric synthesis of cyclopropane carboxylates: ligand—reagent interactions in diazoacetate reactions catalysed by copper (II) species bearing sugar—Schiff base ligands

Abstract The concept that ligand—reagent interactions might be useful in asymmetric catalysis has been used in designing copper (II) catalysts bearing Schiff base ligands derived from naturally occurring sugars. In reactions of ethyl diazoacetate with certain halogeno olefins, these catalysts have afforded precursors of photostable pyrethroids rich in the insecticidally important 1R cyclopropane isomers. In one case the cyclopropane carboxylate product contained 58% of the insecticidally most desirable cis-1R isomer. Less than 15% of this isomer is present in an equilibrium mixture of the carboxylates. The most stereoselective catalysts give the cyclopropane carboxylates in low yields, about 10%, based on ethyldiazoacetate used.

Stereoselective epoxidation of divinylmethanol: A synthetic approach to the pentitols

Abstract Peroxy-acid epoxidation of divinylmethanol ( 9 ), followed by acetylation afforded the acetylated monoepoxides 1 and 2 having the erythro (53%) and threo (47%) configurations. Peroxy-acid epoxidation of 1 and 2 yielded the acetylated diepoxides 3 ( erythro-erythro , 36%) and 4 ( erythro-threo , 64%) (from 1 ), and 4 ( erythro-threo , 47%) and 5 ( threo-threo , 53%) (from 2 ). Relative configurational assignments were made to 1–5 on the basis of ( a ) 1 H-n.m.r. chemical-shift and coupling-constant data, ( b ) the observation that 1 gave only 3 and 4 , and that 2 gave only 4 and 5 on epoxidation, and ( c ) the fact that 3–5 separately undergo epoxide-ring opening preferentially at their primary carbon atoms with acetate ion in acetic anhydride, to afford the penta-acetates of ribitol, dl -arabinitol, and xylitol, respectively, as major products. Epoxide-ring formation favours the erythro configuration when either peroxy acids or tert -butyl hydroperoxide with catalytically active Ti 4+ , V 5+ , or Mo 6+ complexes are employed as epoxidation reagents. However, the diastereoselectivities characterising the epoxidations and the regioselectivities governing the epoxide-ring openings are not sufficiently high to constitute an attractive synthesis of either ribitol, dl -arabinitol, or xylitol from divinylmethanol.

A stereoselective synthesis of xylitol

Abstract Rel-(2S, 3R, 4R)- (6) and rel-(2R,3R,4R)- (7) 1,2,5-triacetoxy-3,4-epoxypentanes have been obtained in seven steps starting from cyclopentadiene. Both diastereoisomers afford xylitol pentaacetate (8) selectively upon epoxide cleavage with acetate ion. In the case of (6), rel-(1s,3R,4r,5S)-3,-bisacetoxymethyl-1-methyl-2,6,7-trioxabicyclo- [2.2.1]heptane (11) has been isolated and characterised as an intermediate in the reaction.

Regioselective and stereoselective methods for the synthesis of the pentitols

Several different approaches to the stereoselective synthesis of xylitol (1), as well as the other two pentitols, ribitol (2) and DL-arabinitol DL-(3), from the (Z)- and (E)-1-hydroxpentadienes (4) and (5) and the (Z)- and (E)-4,5-epoxypent-2-enals (6) and (7) are described. They rely upon either (a) epoxidations of allylic CC double bonds followed by stereospecific (anti) and sometimes regioselective epoxide cleavages, or (b)syn-hydroxylations of allylic CC double bonds. Employing approach (a), the (Z)-isomers (4) and (6) do not afford any ribitol (2) among the products and the (E)-isomers do not afford any xylitol (1). The consequences are reversed when approach (b) is adopted. The most convenient synthesis of xylitol (1) starts from the (Z)-isomer (6) of 4,5-epoxypent-2-enal. The formyl group in (6) is reduced, provided acidic work-up conditions are employed, to yield (Z)-(4RS)-4,5-epoxy-1-hydroxypent-2-ene (9), which is characterised as its acetate (10). Opening of the epoxide ring in (10) with acetate ion gives the triacetate (11), which is deacetylated to afford a key intermediate, (Z)-(4RS)-1,4,5-trihydroxypent-2-ene (12). Epoxidation of (12) with peracids (e.g. p-nitroperbenzoic acid) yields (t-butyl hydroperoxide with catalytically active Ti4+, V5+, and Mo6+ complexes fails) two epoxides (13) and (14), arbitrarily named isomers A (13) and B (14) subsequently shown to have the relative stereochemistries (2S,3R,4R) and (2R,3R,4R), respectively. Epoxide ring opening with acetate ion in acetic anhydride of the more abundant isomer B (14), obtained with 70% diastereoselectivity, yields xylitol penta-acetate (16) as the major product (>80% diastereoselectivity) along with small and trace amounts of the other two pentitol penta-acetates. Epoxide ring opening of isomer A with acetate ion in acetic anhydride is not a straightforward reaction for the most part and has been found to involve the intermediacy of an isolatable bicyclic orthoester (23)en route to some of the xylitol penta-acetate (16) formed as the principal stable product during this reaction. These variations of approach (a) constitute stereoselective syntheses of xylitol (1), which are claimed to be acceptable on a laboratory scale. They provide a slightly better route than an alternative one involving the transformations (4)→(33)→(34)→(39)→(16)→(1), starting from (Z)-1-hydroxypenta-2,4-diene (4), principally because this particular precursor is less readily accessible than (Z)-4,5-epoxypent-2-enal (6). By contrast, the (E)-isomer (5) of 1-hydroxypenta-2,5-diene is obtainable in high yield from the reduction of vinyl acrylic acid and the analogous transformations [(5)→(26)→(27)→(28)→DL-(5)→DL-(3)] provide a highly stereoselective (91%) synthetic route to DL-arabinitiol DL-(3). Osmium-catalysed syn-hydroxylation of (E)-(4RS)-triacetoxypent-2-ene (22), prepared from (E)-4,5-epoxypent-2-enal (7) in two steps [(7)→(20)→(22)], provides yet another approach to DL-arabinitol DL-(3), but the stereoselectivity (76%) of this oxidation is not as good as that observed for the epoxidation of rel-(3R,4R)-3,4,5-triacetoxypent-1-ene (27) in the above transformation. The synthesis of ribitol (2) by osmium-catalysed syn-hydroxylation of the (Z)-isomer (11) of (22) was achieved with a modest stereoselectivity of 66% for the oxidation step.

Oxidative coupling of isobutene with vinylidene chloride by palladium (II) Salts

Abstract Reaction of isobutene and vinylidene chloride with palladium acetate at 60° yields 1,1-dichloro-4-methylpentadienes as well as 2,5-dimethylhexadienes. The reaction is highly dependent on the presence of nitrite, which is essential for the cross-coupling and which suppresses dehydrodimerisation of isobutene.

Formation of 1,1-dihalogeno-4-methylpenta-1,4-dienes by reactionof isobutene with trihalogenoethylenes

Isobutene reacts with trihalogenoethylenes in the gas phase at ca. 500° to give 1,1-dihalogeno-4-methylpenta-1,4-dienes which are precursors of photostable pyrethroid insecticides. The reaction appears suited to large scale continuous operation. The results are interpreted in terms of a free-radical chain mechanism.

The resistance of cyclo-octa-1,5-diene to liquid-phase metal-centered autoxidation

Abstract Cyclo-octa-1,5-diene is resistant to autoxidation at a Rhodium (I) centre under conditions where cyclo-octene is rapidly oxidised. This observation is consistent with the known chelating ability of the diene and with the concept that metal-centred autoxi- dation requires coordination of dioxygen within a square-planar intermediate. The autoxidation is compared with other metal- centred reactions in which cyclo-octa-1,5-diene reacts more readily than do monoenes.

Liquid-phase metal-centred autoxidation of cyclo-octene promoted by rhodium species

The rhodium(I)-promoted autoxidation of cyclo-octene, in benzene at 74 °C, gives non-catalytic yields of cyclo-oct-1-en-3-one and cyclo-octanone by a route independent of radical chains and a Wacker cycle. With added styrene, or in NN-dimethylacetamide, the oxidation is catalytic (6 mol of products per mol Rh). The oxidation is interpreted in terms of a rate-limiting metal-centred insertion of oxygen into an allylic carbon–hydrogen bond and subsequent reactions of the resulting cyclo-oct-1-en-3-ol.

Liquid-phase metal-centred autoxidation of styrene catalysed by rhodium species

During the autoxidation of styrene, catalysed by [{RhCl(C2H4)2}2] at 110 °C in the presence of radical inhibitor, acetophenone and benzaldehyde arise by a path avoiding both radical chains and a Wacker cycle. Only about half of the oxygen and styrene consumed appear as measured products, and the nature of the side-reactions is unknown. The various activities of several rhodium(I) complexes suggest that co-ordination of both the styrene and oxygen to the metal is essential for reaction, and the co-ordination of each of these ligands to rhodium has been observed under conditions approaching those of reaction. The initial rate of acetophenone formation accords with the expression: Rate =C[styrene][catalyst][O2]//1 +C′[O2] A sequential mechanism is proposed in which an initially formed catalyst-styrene adduct reacts with oxygen. In oxygen-saturated solution, the activation energy is 70 kJ mol–1. The catalyst undergoes rapid oxidative deactivation, but is not regenerated by treatment with hydrogen. Styrenes having methyl or phenyl substituents at the olefinic positions are resistant to oxidation.