Quinolizidines catalytic hydrogenation

The C/C double bonds in the quinolizine system can be reduced by catalytic hydrogenation. One example, involving the transformation of an indolo[2,3- ]quinolizidine substrate 76 into compound 77, can be found in... 

This strategy was further developed so as to prepare the quinolizidine polyol 155 (315), by separating the racemic furoisoxazoline acetals (21,82,293,294) derived from the imidazolidine derivatives, which in turn, were obtained from (15, 25)-diphenylethylenediamine (316) (see Scheme 6.78). Aminal hydrolysis led to aldehyde 153, and this was followed by aldehyde reduction and catalytic hydrogenation (221,313) to give (-l-)-deoxynojirimycin (natural). Its enantiomer was... 

Demethoxyabresoline (67) was obtained as a noncrystalline solid. Spectroscopic investigation revealed the presence of a phenolic OH, a 1-phenyl-quinolizidine system, and a trans-cinnamyl group. The stereochemistry at C-l, C-3, and C-5 was the same as in abresoline. The molecular formula C25H29N05 was established by mass spectrometry. The presence of fragment ions at m/e 259 (M —164) and 258 was characteristic of p-hydroxy-cinnamyl esters of the phenylquinolizidol (63a). The assigned structure 68 was confirmed by basic hydrolysis to 63a and p-hydroxycinnamic acid as well as by catalytic hydrogenation to a known dihydro derivative (52). 

No systematic study of catalytic hydrogenation of quinolizinium salts is available. In most cases reduction has been by palladium or platinum with hydrogen at atmospheric pressure to yield the decahydro derivative (the quinolizidine). The first example is provided by Boekelheide and Gall,125 who produced quinolizidine (104). Benzo[b]quinolizinium salts are cata-lytically reduced first in the central ring to give 6,11-dihydro derivatives (105).126 Benzo[c]quinolizinium salts (cf. 4) can be reduced in two stages.120... 

Catalytic hydrogenation of both double bonds yielded the quinolizidine-1,4-dione ( )-2234, the ketone of which was converted into a vinyl triflate before Stille coupling with aUyltributylstannane afforded the conjugated diene ( )-2235. Hydrogenation then produced a 5 2 mixture of racemic di-astereomers 2236 and 2237, which were separated by HPLC. Finally, addition of allylmagnesium chloride to the separated lactams followed by reduction of the adducts with sodium cyanoborohydride gave ( )-quinolizidine 2071 (rac-1728) and ( )-l-ept-quinoHzidine 2071 (rac-2238) as the sole isomers from 2236 and 2237, respectively. 

Yttrium-catalyzed diene cyclization/hydrosilylation was applied to the synthesis of aliphatic nitrogen heterocycles such as the indolizidine alkaloid ( )-epilupinine. l-Allyl-2-vinylpiperidine 30 was synthesized in four steps in 59% overall yield from commercially available ( )-2-piperidinemethanol (Scheme 10). Treatment of 30 with phenylsilane and a catalytic amount of Gp 2YGH3(THF) gave silylated quinolizidine derivative 31 in 84% yield, resulting from selective hydrometallation of the A-allyl G=G bond in preference to the exocyclic vinylic G=G bond. Oxidation of the crude reaction mixture with tert-huVf hydrogen peroxide and potassium hydride gave (i)-epilupinine in 51-62% yield from 30 (Scheme 10). 

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