Enantioselective Total Syntheses of (−)‐Rhazinilam, (−)‐Leucomidine B, and (+)‐Leuconodine F

Abstract

A divergent total synthesis of three structurally distinct natural products from imine 9 was accomplished through an approach featuring: 1) a Pd-catalyzed decarboxylative cross-coupling, and 2) heteroannulation of 9 with bromoacetaldehyde and oxalyl chloride to give tetrahydroindolizine 6 and dioxopyrrole 7, respectively. The former was converted into (-)-rhazinilam, while the latter was converted into (-)-leucomidine B and (+)-leuconodine F. A substrate-directed highly diastereoselective reduction of a sterically unbiased double bond by using a homogeneous palladium catalyst was developed. A self-induced diastereomeric anisochronism (SIDA) phenomenon was observed for leucomidine B.

Enantioselective Total Syntheses of (−)‐Rhazinilam, (−)‐Leucomidine B, and (+)‐Leuconodine F

“…[22] It is worth noting that hydrogenation of 21 in the presence of Pd/C or Pd(OH) 2 /C afforded a1 :1 diastereomeric mixture of tetracycle 23.W e also synthesized the (AE)-leucomidine B( 2)b yf ollowing the same synthetic route and obtained an X-ray crystal structure of (AE)-2 that confirmed the relative stereochemistry between C20 and C21. Ah eterodimer was formed in the crystal packing of (AE)-2 ( Figure 2), [23] which nicely explains the concentration dependence of the [a] D value of our enantiomerically enriched (À)-2 in apolar solvent [89 % ee,[ a] D = À21 (c 1.0, CHCl 3 )[a] D = À29 (c 0.3, CHCl 3 ); lit. 2 [a] D = À18 (c 0.3, CHCl 3 )].…”

Direct amidation of esters with nitroarenes

“…6b). Importantly, our method allowed a single-step synthesis of a natural product, (-)-rhazinilam ( 6f ), from methyl ( R )-3-(8-ethyl-1-(2-nitrophenyl)-5,6,7,8-tetrahydroindolizin-8-yl)propanoate26 (Fig. 6c).…”

“…6c). Previous amidation from the same intermediate relied on the reaction of carboxylic acid with aniline, which required two extra steps for hydrogenation of nitroarene and hydrolysis of ester26.…”

Stereoselective Synthesis of Quaternary Pyrrolidine-2,3-diones and β-Amino Acids

“…Synthetic transformations of 1,5-dihydro-2 H -pyrrol-2-ones 14 have previously provided entry to other complex structures such as α -keto γ -lactams, 15a natural products, 15b and related biologically active small molecules. 16 Interestingly, rearrangement reactions of 1,5-dihydro-2 H -pyrrol-2-ones remain largely underexplored yet would provide a significant increase in molecular complexity and access to quaternary substituted heterocycles.…”