Ronald N. Warrener

A new building block technique based on cycloaddition chemistry for the regiospecific linking of alicyclic sub-units as a route to large, custom-functionalised structures

A new building BLOCK approach to synthesis has been developed where functionalised norbornenes (BLOCK A) are coupled with functionalised cyclobutene epoxides (BLOCK B) to produce A + B structures of defined geometry; use of a dual (spacer) BLOCK allows the formation of large structures where crown ether, ligand and redox centres are incorporated in similar or mixed pairings.

Crystal structure of (13S*, 13aR*)-2,3-dimethoxy-13-hydroxy-13a-methyl-8-oxo-5,6,13,13a-tetrahydro-8H- dibenzo[a, g]quinolizine, C20H21NO4

C20H21NO4, monoclinic, P121/c1 (No. 14), a = 7.521(2) A, b = 23.257(2) A, c = 9.784(2) A, = 95.57(2)°, V = 1703.3 A 3 , Z =4 ,Rgt(F) = 0.060, wRref(F 2 ) = 0.183, T = 293 K. Source of material To a cooled solution (195 K) of diisopropylamine (0.7 ml, 5 mmol) in dry tetrahydrofuran (THF, 90 ml) under dry nitrogen was added n-butyllithium (5 mmol) dropwise using a syringe. A solution of phthalide (0.670 g, 5 mmol) in dry THF (20 ml) was then added dropwise, using a syringe, to generate the bright yellow phthalide anion. After stirring for 5 min a solution of 6,7dimethoxy-3,4-dihydroisoquinoline (1.03 g, 5 mmol) in dry THF (20 ml) was added dropwise, from a syringe, and the resulting mixture maintained at 195 K with stirring for a further 30 min. The solution was allowed to slowly warm to 293 K, diluted with hydrochloric acid (2 M, 120 ml) and extracted with chloroform (4 × 40 ml). The combined extracts were washed with brine, dried over MgSO4, filtered and evaporated to dryness. The resultant gum was purified by column chromatography on silica gel using a gradient of hexane in ethyl acetate. The product was isolated in 71% yield and recrystallised from ethyl acetate as colourless rods, mp 490 K – 491 K. Experimental details The H atoms were placed in their geometrically calculated positions and included in the final refinement in the riding model approximation.

Asymmetric synthesis of protoberberine alkaloids via a tandem nucleophilic addition and intramolecular cyclisation of a chiral o-toluamide anion with 3,4-dihydroisoquinoline

The reaction of o-toluamide anions, derived from the (S)-(–)- and (R)-(+)-1-phenylethylamine, with 6,7-dimethoxy-3,4-dihydroisoquinoline gives (13aS)-(–)- and (13aR)-(+)-8-oxoprotoberberine, respectively, with enantiomeric excesses >96%.