G. Richard Stephenson

Transition metal mediated asymmetric synthesis, part 151 directing group competition in organoiron intermediates in the synthesis of (±)-O-methyljoubertiamine☆

Abstract Directing groups work first in concert and then in competition to control the introduction of aryl and 2-dimethylaminoethyl groups by a sequence of two nucleophile additions to cationic tricarbonyl(η 5 -cyclohexadienyl)iron(1+) intermediates in a synthesis of O -methyljoubertiamine that employs an iterative approach. This synthesis provides an example of the successful use of directing group competition to effect the reversal of undesired directing effects in target oriented applications of electrophilic π-complexes.

Transition metal mediated asymmetric synthesis: X. Homochiral π-complexes with planar chirality: synthetic equivalents of chiral cyclohexadiene dications

Abstract Homochiral 6-methoxy-substituted dienyltricarbonyliron complexes have been obtained from 1-methylcyclohexa-1,3-diene-5,6-diol (available via microbial oxidation of toluene) by complexation and removal of an allylic substituent with acids or with triphenylcarbenium tetrafluoroborate. A variety of optically active tricarbonyliron complexes have been produced from these compounds. The optical purity of the product and the stereochemistry of the complexation reaction have been determined. The high efficiency of chirality transfer during complexation of 5,6-dimethoxy-substituted dienes makes this method suitable as a general route to resolved organoiron complexes.

Asymmetric synthesis of optically active tricarbonyliron complexes of 1,3-dienes

Abstract Asymmetric coordination of prochiral 1,3-dienes to form optically active (diene)Fe(CO)3 complexes has been achieved by direct transfer of the Fe(CO)3 group from chiral enone complexes.

Preparative-scale kinetic resolutions catalysed by microbial lipases immobilised in AOT-stabilised microemulsion-based organogels: cryoenzymology as a tool for improving enantioselectivity.

Gelatin-containing microemulsion based organogels have been used as an immobilisation matrix for lipases from a number of different sources. Kinetic resolutions of octan-3-ol, 1-octen-3-ol and 1-octyn-3-ol by esterification with decanoic acid have been performed using Chromobacterium viscosum (CV) lipase. CV lipase is highly enantioselective in favour of the (R)-(-) isomer of octan-3-ol, but the enantioselectivity is both reversed and decreased by the introduction of unsaturation at the 1-position. Marked improvements in enantioselectivity were achieved by carrying out the reaction at -15 degrees C, the enantiomeric excess of the ester product increasing from 47% (E = 3) to 73% (E = 8) in the case of 1-octen-3-ol, and from 17% (E = 1.4) to 38% (E = 2.5) in the case of 1-octyn-3-ol. The enantiomeric excess was approximately 85% (E approximately 15) for octan-3-ol, and there was no marked improvement in enantioselectivity even at -15 degrees C. Apparent activation energies for the esterification using decanoic acid of octan-3-ol, 1-octen-3-ol and 1-octyn-3-ol by CV lipase were 32 kJ mol-1, 31 kJ mol-1 and 41 kJ mol-1, respectively. This compares to an activation energy of 21 kJ mol-1 for the esterification of octan-1-ol with decanoic acid using CV lipase under the same conditions. Lipases from Pseudomonas (Fluka), Pseudomonas (Genzyme) and lipoprotein lipase ex Microbial (Genzyme) also selectively esterified the (R)-(-) isomer of racemic octan-3-ol, the two Pseudomonas preparations yielding product with an enantiomeric excess of 90%. Candida cylindracea lipase did not exhibit activity in gelatin-containing MBGs. Large-scale syntheses were performed in a 1 dm3 batch reactor in which 200 cm3 of pelleted MBG (containing 350 mg of CV lipase) was used repeatedly for the kinetic resolution of octan-3-ol.

Macrocyclic lactone synthesis by lipases in water-in-oil microemulsions

Five microbial lipases from Chromobacterium viscosum, Candida cylindracea, Pseudomonas (source Fluka), Pseudomonas (source Genzyme) and lipoprotein lipase ex Microbial (Genzyme) have been screened for lactonisation activity towards 16-hydroxyhexadecanoic acid (HHA) in a variety of different w/o microemulsion systems. With the exception of Candida cylindracea (CC), all the lipases exhibited lactonisation activity although they were inherently more active in microemulsion systems based on the anionic surfactant sodium bis(2-ethylhexyl)sulphosuccinate (AOT) than in those based on the cationic surfactant cetyltrimethylammonium bromide (CTAB). Lactone yields are typically 50-60% and are markedly better than those reported previously using microemulsions in combination with chemical catalysts. Lipase stability is superior in the CTAB microemulsion systems, while lipase stability in the low water content AOT microemulsion systems was still good with the exception of CC lipase, which is rapidly inactivated. Buffering the water pools of AOT microemulsions using diglycine buffer at pH 8.0 improved biocatalyst stability. The lactonisation activity of lipases in CTAB w/o microemulsion systems compares favourably with that obtained using the same preparations as a solid suspension in the corresponding water-saturated organic solvent. In addition, the unusual solubility properties of microemulsions allowed the use of considerably higher concentrations of substrate in the microemulsion systems as compared to water-saturated organic solvents such as n-heptane. Lactone yields obtained at equivalent concentrations in the corresponding organic solvents containing conventional condensation catalysts were consistently measured at approx. 10%.

Switching regiocontrol in 1-aryl-substituted cyclohexadienyliron complexes in a formal total synthesis of lycoramine

Abstract 1-(o-Alkoxyaryl)cyclohexadienyl tricarbonyliron complexes reverse the regiochemistry of nucleophilic addition compared to that observed for o-(alkoxymethyl)aryl substituted complexes, allowing access to key intermediates in a formal total synthesis of lycoramine.

Optically active tricarbonyl(cyclohexadienyl)iron(1+) salts: Synthetic equivalents to spatially directed organic cations

Abstract Optically active tricarbonyl (cyclohexdienyl)iron(1+) salts I, II and III are examples of olefin complexes with moleoular asymmetry due to coordination uith a transition metal. Their reactions serve to direct the eventual specific formation of a new chiral centre of known absolute configuration. The absolute configuration of the 2-methoxy-5-methyl salt I is defined its application to the asymmetric synthesis of λ-disubstituted cyclohexenones is described.

Regioselectivity of nucleophilic additions to tricarbonyl[η5-2-methyl-2,4-cyclohexadien-1-yl]iron(1+)PF6-: temperature dependence of hydride reductions

Abstract Reduction of [(η5-CH3C6H6)Fe(CO)3]+PF6− by NaBH4, LiBH4, LiEt3BH and KBu53BH becomes less regioselective at lower temperatures. Regioselectivity of reduction by 9-BBN, however, improves as the temperature is lowered. Factors affecting nucleophilic addition are discussed in terms of likely transition states for the competing processes.

FTIR study of π-stacking effects in (η6-arene)tricarbonylchromium complexes: application as a molecular sensor for aromatic analytes

Abstract FTIR spectra of (η6-benzene)tricarbonylchromium (1) in cyclohexane solutions containing aromatic substrates have been measured. From a study of the ν(CO) modes, it is shown that at least two distinct species are present, free 1, and an adduct in which 1 and a molecule (or molecules) of the substrate are associated via a π-stacking interaction between the exo-face of the η6-benzene ligand and the substrate. Changes in the ν(CO) region of the spectrum can be correlated with substrate concentration. The incorporation of (η6-arene)tricarbonylchromium moieties as spectroscopic reporting groups into molecular receptors for aromatic analytes is discussed, and a simple illustrative example is described.

Transition metal mediated organic synthesis, part 11: 2-aryl substituents: new directing groups in cyclohexadienyl π-complexes

Abstract The regioselective formation and alkylation of tricarbonyl(η5-2-arylcyclohexadienyl)iron(1+) salts provides a new, controlled route to intermediates for the preparation of 5-substituted 2-arylcyclohexadienes. The best regiocontrol was obtained when an electron donating group was placed on the arene substituent.