Takeo Iwakuma

A novel asymmetric reduction of imines with chiral sodium triacyloxyborohydrides

Abstract There has been described a novel and convenient synthesis of optically active alkaloids by the asymmetric reduction of cyclic imines using the chiral sodium triacyloxyborohydrides, easily prepared from the reaction of NaBH 4 and N-acyl L-prolines.

Asymmetric reduction of cyclic imines with chiral sodium acyloxyborohydrides

Asymmetric reduction of prochiral cyclic imines with chiral sodium acyloxyborohydrides (5a–i), which are easily prepared by the reaction of NaBH4 with various N-acyl α-amino-acids, has been investigated. Of these new reducing agents, triacyloxyborohydrides (5c–f), derived from NaBH4(1 equiv.) and (S)-N-acylproline (3 equiv.), were found to reduce 3,4-dihydropapaverine (2) in tetrahydrofuran to (S)-norlaudanosine (3) hydrochloride in 60% optical yield. The N-benzyloxycarbonyl derivative (5c) could be isolated as a powder and characterized. The effect of solvents on this asymmetric reduction has been examined by the use of the isolated reagent (5c); halogenated alkane solvents such as CH2Cl2 or CHCl2CH3 gave a better optical yield of compound (3)(70% e.e.). The reagent (5c) also reduced other cyclic imines (6a–c) and (8) to the corresponding alkaloids (7a–c) and (9) in excellent optical yields (70–86% e.e.), providing an effective route to the asymmetric synthesis of these alkaloids. A possible reaction path for this reduction is also presented.

‘One-pot’ conversion of mannich bases via quaternary ammonium salts into the corresponding methyl compounds with sodium cyanoborohydride in hexamethylphosphoramide

Sodium cyanoborohydride in hexamethylphosphoramide reduces quaternary ammonium salts of Mannich bases to give the corresponding methyl compounds in good yields.

Hydrogenation of cyclobutanes in strained cage compounds. Synthesis of ditwistane and bisnorditwistane (ditwistbrendane)

The central bond of the bicyclo[2.2.0]hexane system of the dimeric cage compound synthesized photochemically from N-chloroacetyltyramine was hydrogenated with 10% Pd–C to give the dihydro-compound. Similarly 7,10-dihydroxy-1,4,7,10-tetramethylpentacyclo[6.4.0.02,5.03,12.04,9]dodecane-6,11-dione gave 6,12-dihydroxy-2,6,9,12-tetramethyltetracyclo[6.2.2.02,7.04,9]dodecane-5,11-dione, and its spectral data revealed the correct structure, which was confirmed by the X-ray analysis. This hydrogenation was extended to the synthesis of [8]-ditwistane and bisnorditwistane (ditwistbrendane). Thus, pentacyclo[6.4.0.0.2,503,12.04,9]dodecane-6,11-dione synthesized from salicyl alcohol was hydrogenated to give ditwistanedione. Dithioketalization and desulphurization gave ditwistane. All the rings of this compound are six-membered and in the distorted twist-boat conformation. Similarly, hydrogenation of pentacyclo[5.3.0.02,5.03,10.04,8]decane and its 6-one gave bisnorditwistane.

Synthetic studies on pyrroloquinolines. Part III. Improved synthesis of 7-chloro-2,3-dihydro-4-methoxy-1H-pyrrolo[2,3-b]quinoline and its conversion into 3a,10b-diazacyclopenta[jk]phenanthrene derivatives

3-(2-Aminoethyl)-7-chloro-4-methoxy-2-quinolone (7) was prepared by methylation of 7-chloro-4-hydroxy-3-(2-pnthalimidoethyl)-2-quinolone and removal of the phthaloyl group. Cyclization of the 3-(2-acetamidoethyl) derivative (9) gave, after hydrolysis, the pyrrolo[2,3-b]quinoline (12). An addition reaction with ethyl acrylate followed by reduction with aluminium hydride led to the pyrroloquinolin-1-ylpropanol (14), which was cyclized to the diazacyclopenta[jk]phenanthrene (16)via the quaternary salt (15). Hydrolysis of compound (16) gave the 6-ketone (17), whose structure was confirmed by its n.m.r. spectrum.

Synthesis of ditwistane and bisnorditwistane: novel ring systems

Catalytic hydrogenation of the central bond in the bicyclo[2,2,0]hexane system is applied to the synthesis of ditwistane and bisnorditwistane.