One-Pot Synthesis of Multisubstituted Butyrolactonimidates: Total Synthesis of (−)-Nephrosteranic Acid

Abstract

Multisubstituted chiral butyrolactonimidates have been synthesized via a one-pot, three-step cascade reaction in which (R)-N-tert-butanesulfinyl imidates and α,β-unsaturated diesters undergo highly stereoselective Michael addition, anion-oxidative hydroxylation, and cyclization. The synthesized butyrolactonimidates are versatile intermediates for preparation of substituted butyrolactones and furans. The usefulness of this cascade reaction is demonstrated through the concise total synthesis of natural product (−)-nephrosteranic acid.

Total Syntheses of (−)‐Isoschizogamine and (−)‐2‐Hydroxyisoschizogamine

“…The retrosynthetic analysis of (À)-isoschizogamine (1)a nd (À)-2-hydroxyschizogamine (15)i ss hown in Scheme1.W e envisioned that the amide bond in isoschizogamine (1) Based on the retrosynthetic analysis, we began the total synthesis by preparing the intermediate 20 with C, D, and Er ings (Scheme 2). Our group and Liu'sg roup [13,14] have reported that chiral N-tert-butanesulfinyl imidate-induced [15] Michael addition to a,b-unsaturatede ster usually provides adducts with excellent yields and diastereoselectivities. The addition reaction of imidate (R)-24 with diester 25 afforded two separabled iastereomers 26 a and 26 b in a5 :1 ratio in 90 %c ombined yield.…”

Evolution of Strategies in Paraconic Acids Synthesis

“…Qin and co-workers [75] in 2015 developed a one-pot cascade stereoselective Michael addition, anion-oxidative hydroxylation, and cyclization strategy in the total synthesis of (À )-nephrosteranic acid (Scheme 43). The known reaction of 217 with 218 led to 219, [76] which on cascade reaction with known 220 [77] furnished the butyrolactonimidate 221.…”

Total Synthesis of Lignan Lactone (–)-Hinokinin

“…We recently developed a one-pot, three-step cascade reaction from enantiomerically pure ( R )- N - tert -butanesulfinyl imidates 7 and α , β -unsaturated diesters 8 [ 48 ] to generate butyrolactonimidates 11 (Scheme 1 ). This reaction proceeded through highly stereoselective Michael addition ( 7 – 9 ), followed by anion-oxidative hydroxylation ( 9 – 10 ) and oxygen anion cyclization ( 10 – 11 ).…”

“…The synthesized butyrolactonimidates 11 are versatile intermediates for preparing substituted butyrolactones and furans. We also used this approach to achieve the concise total synthesis of natural product (–)-nephrosteranic acid [ 48 ]. In this paper, we report the total synthesis of lignan lactone (–)-hinokinin 1 as shown in Schemes 2 and 3 .…”