Andrew J. Carnell

Enantioselective Rhodium‐Catalyzed Addition of Potassium Alkenyltrifluoroborates to Cyclic Imines

Chiral α-branched allylic amines are important building blocks for organic synthesis, and several catalytic asymmetric methods have been developed for their synthesis. For example, enantioselective metal-catalyzed amination of allylic electrophiles 1 , 2 , 3 ] and rearrangement of allylic imidates have proven to be highly effective. An alternative approach to chiral allylic amines that can be advantageous from the viewpoint of convergency is the catalytic enantioselective union of an alkenyl nucleophile with an imine. In view of the widespread success of enantioselective Rh(I)-catalyzed additions of arylboron reagents to imines as a means to access chiral α-aryl branched amines, development of the corresponding reactions of alkenylboron reagents to prepare chiral α-branched allylic amines should be an attractive goal. Surprisingly however, only very limited precedent exists for this transformation. Brak and Ellman have developed highly diastereoselective Rh(I)-catalyzed additions of alkenylboron reagents to N-tertbutanesulfinyl aldimines (Scheme 1A). The only existing enantioselective variant is that of Shintani, Hayashi, and coworkers who, as part of a study involving additions of potassium aryltrifluoroborates to N-sulfonyl ketimines, also described one example using an alkenyltrifluoroborate (Scheme 1B). Also of relevance is a single example of an enantioselective Rh(I)-catalyzed addition of an alkenylsilane to an N-sulfonyl aldimine. 18 ] Therefore, a general enantioselective Rh(I)-catalyzed addition of alkenylboron reagents to imines remains undeveloped. Herein, we demonstrate that cyclic imines are highly effective substrates for enantioselective Rh(I)-catalyzed additions of potassium alkenyltrifluoroborates, providing products in excellent enantioselectivities and generally good yields. The cyclic structure of these imines, where the C=N bond is constrained in the Z-geometry, appears to be N

Enzyme cascade reactions: synthesis of furandicarboxylic acid (FDCA) and carboxylic acids using oxidases in tandem

A one-pot tandem enzyme reaction using galactose oxidase M3–5 and aldehyde oxidase PaoABC was used to convert hydroxymethylfurfural (HMF) to the pure bioplastics precursor FDCA in 74% isolated yield. A range of alcohols was also converted to carboxylic acids in high yield under mild conditions.

Stereoinversions Using Microbial Redox-Reactions

This paper aims to provide a summary of the recent literature on the use of redox enzymes to carry out stereoinversion reactions on chiral secondary alcohols. Emphasis has been placed on biotransformations which result in the deracemization of a racemic substrate to give high value synthetic intermediates in a theoretical 100% yield. Most of the biocatalysts which are competent to carry out such transformations are whole cell systems, which contain the necessary cofactor recycling machinery to facilitate this otherwise entropically disfavoured process. The first section deals with deracemization of compounds such as mandelic acid and pantoyl lactone using two microorganisms which display enantiocomplementary stereospecificity. The deracemization of chiral alcohols such as beta-hydroxyesters, aryl ethanols and terminal 1,2-diols with single microorganisms will then be discussed and the influence of growth and reaction conditions on the selectivity observed will be emphasised. Then the ability of several microorganisms to deracemize by double stereoinversion substrates with two stereocentres such as cyclohexan-1,2-diol, cis and trans indan-1,2-diol and pentan-2,4-diol will be presented and some mechanistic rationale proposed. Lastly enzymes known as epimerases which are important in sugar and deoxysugar biosynthesis will be discussed with reference to some recent work on the mechanism of UDP-glucose epimerase.

Catalytic bio-chemo and bio-bio tandem oxidation reactions for amide and carboxylic acid synthesis

A catalytic toolbox for three different water-based one-pot cascades to convert aryl alcohols to amides and acids and cyclic amines to lactams, involving combination of oxidative enzymes (monoamine oxidase, xanthine dehydrogenase, galactose oxidase and laccase) and chemical oxidants (TBHP or CuI(cat)/H2O2) at mild temperatures, is presented. Mutually compatible conditions were found to afford products in good to excellent yields.

N,N-Dialkylalloxans—a new class of catalyst for dioxirane epoxidations

N,N-Dimethyl- and N,N-dibenzylalloxans 1a and 1b have been prepared and used as novel dioxirane catalysts for the epoxidation of a range of di- and tri-substituted alkenes in good to excellent yield. The dibenzylalloxan 1b can be recovered in high yield with no evidence of catalyst decomposition.

Preparation of optically active cyclohexanediols and (+)-α- hydroxycycloheptanone by an enzyme catalysed stereoinversion/oxidation process

(±)-trans and cis Cyclohexane-1,2-diols have been shown to undergo a double stereoinversion process to give trans (S,S)-cyclohexane-1,2-diols on incubation with the fungus C. cassiicola.

Biotransformations by fungi

SummaryThe regio-and stereoselective characteristics of biotransformations involving oxidative ring expansion of bicyclo[3.2.0]hept-2-en-6-one have been characterised in various dematiaceous fungi of the generaCurvularia andDrechslera.

The synthesis of buprenorphine intermediates by regioselective microbial N- and O-demethylation reactions using Cunninghamella echinulata NRRL 1384

A biotransformation procedure, using the filamentous fungus Cunninghamella echinulata NRRL 1384, for the high yielding regioselective demethylation of a thebaine derivative to give intermediates for the synthesis of buprenorphine is reported. The thebaine derived substrate can be converted to a mixture of N-demethylated and N,O-demethylated products. Manipulation of the growth conditions of the organism and time of substrate addition resulted in a optimised conversion to the N-demethylated compound of 94%. The underlying enzymatic basis for this process is investigated and a pathway for the formation of these two products is proposed.

Enzyme-catalysed Baeyer-Villiger oxidations of some substituted bicyclo[3.2.0]heptanones

The ketones 1 and 4 are oxidized to γ-lactones 2 and 5 with low enantioselectivity by both Acinetobacter sp. NCIB 9871 and Pseudomonas sp. NCIB 9872; in contrast the ketones 7 and 10 are biotransformed to products 8/9 and 11 respectively of very high optical purity.

Desymmetrisation of prochiral ketones by catalytic enantioselective hydrolysis of their enol esters using enzymes

Abstract Desymmetrisation of 4-cyano-4-phenylcyclohexanone 1 has been achieved by enzyme-catalysed enantioselective alcoholysis with n-butanol of the derived racemic enol acetate 2 in tetrahydrofuran. The absolute configuration of the enol acetate (−)-(S)- 2 (100% e.e.) obtained was determined by X-ray analysis of the camphanyl derivative 7 .