Enantioselective Synthesis of (7R,8R,8aR)- and (7S,8S,8aS)-7-Hydroxy-8-indolizidinemethanol by 1,3-Dipolar Cycloaddition of 1-PyrrolineN-Oxide to Chiral Pentenoates

Abstract

The 1,3-dipolar cycloadditions of pyrroline N-oxide (1) with (1R,2S)-trans-2-phenylcyclohexyl-and with (1R,2S,5R)-8phenylmenthyl-pent-2-enoates (9 and 10) proceed with op- [a]

Stereodivergent Approach to Enantiopure Hydroxyindolizidines Through 1,3-Dipolar Cycloaddition of 3-Hydroxypyrroline N-Oxide Derivatives

“…), and PPh 3 (polystyrene-supported PPh 3 was used with 14) (3 equiv. ) in CH 2 Cl 2 (14) or in THF (15) was cooled at 0°C, and DEAD (3 equiv.) was added dropwise.…”

“…As expected, [14] the sole cycloadduct 29, deriving from an anti(OtBu)-endo(CO 2 CH 3 ) approach of the two reagents (TS B, Scheme 8), was formed. (2S,3R,3aS,4S)-Pyrrolo [1,2-b]isoxazolidine 29 was sequentially mesylated and hydrogenated on Pd/C to give the indolizidine 30 in 83% overall yield.…”

Indolizidine and quinolizidine alkaloids

“…101 In model studies aimed at the synthesis of sparteine analogues, lithiation of N-(tertbutyloxy)carbonyl (N-Boc) bispidine derivatives 241 (R = H) followed by treatment with electrophiles yielded products 241 (R = Me, allyl, Bn, SiMe 3 ) in moderate to fair yield. 104 103 In one specific case (R = but-4-en-1-yl), the product was converted in several steps into the tricyclic product 244, a model for rings BCD of sparteine.…”

“…Finally, the synthesis of both enantiomers of the tashiromine analogue 245 by dipolar cycloaddition of 1-pyrroline N-oxide to chiral esters of trans-4-methylsulfonyloxypent-2-enoic acid has been reported. 104…”

Stoichiometric asymmetric processes

“…286 Asymmetric nitrone cycloadditions have also been used in the synthesis of indolizidines using chiral nitrone 287 and olefin acceptors. 288 Denmark and co-workers described alternative routes to similar targets by making use of elegant tandem asymmetric [4 ϩ 2]/[3 ϩ 2] cyclisations giving products with good to excellent levels of diastereoselectivity that were used in the synthesis of (ϩ)-casuarine, (Ϫ)-7-epiaustraline and (Ϫ)-1epicastanospermine. 289, 290 Azomethine ylides have previously been used extensively in the facile preparation of polycyclic ring systems and novel amino acids.…”