Keith Mills

Synthesis of α- alkoxysilanes: Birch reduction of 2-trialkylsilylfurans

Abstract The Birch reduction of (2 -trialkysilyl)furan-3-carboxylic acids has been applied to the synthesis of methyl (2-trialkylsilyl)tetrahydrofuran-3-carboxylates. It is believed that the silicon moiety in such substrates controls the sense of asymmetric induction observed in Michael reaction of the derived enolates with methyl cinnamate. Mild oxidative removal of the silicon moiety generates an oxonium cation which undergoes nucleophilic capture to afford a functionalised furanopyran.

α-Alkoxystannyl ethers in organic synthesis: Synthesis of functionalised γ-butyrolactones

Abstract Ozonolysis of a variety of (tetraydrofuran-2-yl)tri-n-butylstannanes affords the corresponding γ-butyrolactones in good to excellent yields. This reaction is tolerant to a range of other functional groups and provides access to substituted γ-butyrolactones not available from aldol reactions of the parent lactone.

Chapter 6.2 (2006) Six-membered ring systems: diazines and benzo derivatives (2006)

Publisher Summary This chapter discusses the synthetic and reactivity aspects of the three diazine systems and their benzo-derivatives and mentions some other interesting and significant applications. The chemistry of diazines remains an area of intense interest, both academic and industrial, with applications in many areas, from biomedical to materials science and electronics. They are versatile, having very varied reactivity, giving many opportunities for manipulation of substituents. Nucleophilic substitutions, electrophilic substitution in oxy and amino derivatives, organometallic, and transition metal-catalyzed coupling reactions are all subjects of substantial research effort. There are obvious similarities in the reactivity of the three diazine systems but also many interesting and practically important, often subtle, differences. All three systems are amenable to sequential substitutions, giving opportunities for use as scaffolds and also, particularly for pyrimidines, rapid muticomponent, often one pot, ring constructions are possible. Both these features give great potential for combinatorial chemistry and library construction.

A stereoselective synthesis via a 5-exo-trig cyclisation of trans-2-oxohexahydro-2H-furo[3,2-b]pyrroles (pyrrolidine-trans-lactones)—potent, novel elastase inhibitors

trans-2-Oxohexahydro-2H-furo[3,2-b]pyrroles (such as 2) are conformationally strained 5,5-fused ring systems and are potent human neutrophil elastase (HNE) inhibitors. A stereoselective synthesis is described based on intramolecular 5-exo-trig cyclisations of aldehyde acrylates 4 and 5 mediated by samarium(II) iodide to give predominantly trans-products 9 and 15. The n-propyl group in 15 is also generated with stereoselectivity for the desired β-isomer.

Fischer indole synthesis of 3-acyl- and 3-alkoxy-carbonylindoles

N-Benzyl-N-phenylhydrazine derivatives of 1,3-diketones and 1,3-ketoesters undergo normal Fischer cyclisations to indoles, but no method could be found for the subsequent removal of the N-protecting group. No method could be found for the indolisation of N-aroyl-N-phenylhydrazine derivatives of dimedone with retention of the N-protecting group, though heating in tetralin did effect the electrocyclic step of the Fischer sequence and the formation of a carbon–carbon bond.