The stereochemistry of intermediates in the total synthesis of d1-aspidospermine

Exploiting multiple nucleophilic sites on pyrrole for the assembly of polyheterocyclic frameworks: application to a formal total synthesis of (±)-aspidospermidine

“…22) possessing the equivalent trans ring junction and that under conditions of thermodynamic control production of the latter system will be favoured. Unfortunately, whilst compound 22 has been described previously 16 there are no spectral data available in the literature for comparison with our own. Nevertheless, our data (see Experimental) are fully consistent with the assigned structure.…”

“…Thus, exposure of an ethanol-acetic acid solution of compound 16 to dihydrogen in the presence of rhodium on alumina afforded the ketoenamine 21 (80% at 50% conversion) which could be reduced to the fully saturated ketone 22 (65%) on treatment with lithium aluminium hydride. The illustrated stereochemistry for amino ketone 22 follows from mechanistic considerations and by analogy with the production of the same and a closely related compound as described by Ban 16 and Saxton, 17 respectively. Thus, the reduction of compound 21 is probably best interpreted (Fig.…”

“…C 13 H 19 NO requires M ϩؒ , 205.1467); ν max (neat) 2934, 1562, 1515 cm Ϫ1 ; δ H 0.87 (3H, t, J 7.5), 1.12 (1H, td, J 13.5 and 3.3), 1.46-2.00 (7H, complex m), 2.25 (1H, ddd, J 17.4, 5.4 and 2.1), 2.43 (1H, ddd, J 17.4, 13.5 and 4.8), 2.60 (1H, m), 2.78 (2H, m), 3.17 (1H, q, J 10.5), 3.28 (1H, dd, J 11.4 and 5.4), 3.58 (1H, ddd, J 11.4, 10.5 and 4.0); δ C 7.8, 18.6, 23.9, 25.2, 28.5, 32.4, 33.2, 35.0, 46.9, 54.0, 107. 4, 175.8, 190.0; m/z 205 (M ϩ , 45%), 177 (90), 162 (100), 148 (17), 135 (16).…”

“…The combined organic extracts were dried (sodium sulfate), filtered and concentrated under reduced pressure to give a light-yellow oil. Subjection of this material to flash chromatography (silica gel, 180 : 19 : 1 v/v/v CHCl 3 -MeOH-NH 3 elution) afforded, after concentration of the appropriate fractions, ketone 22 16 (12 mg, 65%) as a clear, colourless oil [Found: (M Ϫ H ؒ ) ϩ , 206.1547, C 13 H 21 NO requires (M Ϫ H ؒ ) ϩ , 206.1545]; ν max (KBr, neat) 2933, 1717 cm Ϫ1 ; δ H 0.73 (1H, m), 0.89 (3H, t, J 7.5), 1.12 (1H, tdd, J 13.2, 5.1 and 1.5), 1.44-1.84 (7H, complex m), 1.89-2.04 (4H, complex m), 2.21-2.42 (2H, complex m), 2.73 (1H, m), 3.13 (2H, m); δ C 7.8, 17.6, 19.8, 21.9, 32.9, 34.7, 35.7, 39.0, 48.6, 53.6, 54.2, 76.8, 209.4; m/z 207 (M ϩ , 30%), 206 (100), 177 (10).…”

Total synthesis of (+-)-6,7-didehydroaspidospermine

“…The terminal carbon of the required chain was introduced by treatment of a glyme solution of the lithium acetylide of ketal acetylene 14 with excess monomeric formaldehyde to provide ketal propargyl alcohol 15 in 97% yield. Partial catalytic hydrogenation (PtC>2, ethyl acetate containing triethylamine) afforded a 99% yield of ketal allylic alcohol 16 as an approximately 3:1 mixture of cis to trans isomers.11 Separation of these isomers was postponed to a later stage in the synthesis.…”