Hydroformylation indolizidine alkaloid

Hydroformylation can be highly tolerant of functional groups. An azide, normally highly reactive towards transition metals, can survive. This property has been exploited in a synthesis of the pyridine alkaloids anaba-sine 4.158 and nicotine 4.159 from the same hydroformylation reaction (Scheme 4.58). Another approach to both of these alkaloids can be found in Chapter 8, Schemes 8.76 and 8.77. Double hydroformylation of the azido diene 4.160 gave the bis-aldehyde 4.161 (Scheme 4.59). Tandem azide reduction and double reductive amination then gave the indolizidine alkaloid, lupinine 4.162. ... 

In contrast to the previous examples, the preferred formation of linear aldehydes was the main target in some syntheses to construct a cyclic derivative with an appropriate ring size in the next step or for simply elongating a carbon chain. The linear aldehydes are the proper intermediates for the synthesis of indolizidine alkaloids [11], the tricyclic marine alkaloid lepadiformine [12], ACE inhibitors such as MDL 27210 and its analogues [13,14], and bryostatin, a remarkably potent anticancer agent [15]. Rhodium complexes of bisphosphite ligands provide one of the best known classes of linear-selective hydroformylation catalysts for simple ot-olefins. Except for the lepadiformine intermediate, where hydroformylation was carried out in the presence of the Rh(acac)(CO)2/P(OPh)3 catalyst system, in other... 

The combination of rhodium dicarbonyl acetylacetonate complex (Rh(acac)(CO)2) and a diphosphite ligand, (2,2 -bis[(biphenyl-2,2 -dioxy)phosphinoxy]-3,3 -di-/i t/-butyl-5,5 -dimethoxy-l,T-biphenyl (BIPHEPHOS), is an excellent catalyst system for the linear-selective hydroformylation of a wide range of alkenes. This catalyst system has been successfully applied to the cyclohydrocarbonylation reactions of alkenamides and alkenylamines, which are employed as key steps for the syntheses of piperidine,indolizidine, and pyrrolizidine alkaloids. ... 

Cuny GD, Buchwald SL. Regioselective olefin hydroformylation as a route to indolizidine and pyrrolizidine alkaloids. Synlett 1995 519-522. 

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