A Total Synthesis of Paeoveitol

Abstract

A four-step total synthesis of paeoveitol (1), a recently disclosed norditerpene natural product from Paeonia vetchii, is reported. This highly concise synthetic route was guided by biosynthetic considerations and enabled by an unusual intermolecular ortho-quinone methide [4 + 2]-cycloaddition reaction, which proceeded with excellent regio- and diastereoselectivity. Density functional theory (DFT) calculations point to a crucial intermolecular hydrogen bond and π-π stacking interaction that govern selectivity in this process.

Divergent Synthesis of Disulfanes and Benzenesulfonothioates Bearing 2‐Aminofurans From N‐Tosylhydrazone‐Bearing Thiocarbamates

“…[6c,d] Given the difficulty in accessing the starting materials in the above three strategies,w ew ondered whether an ew strategy could be developed by using readily accessible starting materials in ao ne-step protocol. [12] In the past decades,t he N-tosylhydrazone moiety has become ar eadily available and widely employed precursor to access carbenes, [13] therefore,t he inexpensive and commercially available salicylaldehyde caught our eye because of its structural versatility:1 )iti sacommon precursor for benzofuran framework, [14] 2) the phenolic hydroxy group can link the thiocarbamate moiety through esterification, 3) the aldehyde group can serve as ap recursor to the N-tosylhydrazone moiety,w hich can generate ad iazo compound through ag entle Bamford-Stevens reaction. [9] Tr ansition-metal carbene complexes have emerged as very active intermediates for the construction of new CÀCo rC Àheteroatom bonds.…”

“…[10,11] To activate the thiocarbamate and incorporate the ideal S, O, and Nsources into the final products,weenvisioned introduction of either a" carbene" or carbenoid and thiocarbamate into one molecule.T he thiocarbamate could attack ac arbene to form at hree-membered episulfide intermediate (B;S cheme 2b)w hich might rearrange to the disulfane-bearing 2aminofuran framework by ring-opening. [12] In the past decades,t he N-tosylhydrazone moiety has become ar eadily available and widely employed precursor to access carbenes, [13] therefore,t he inexpensive and commercially available salicylaldehyde caught our eye because of its structural versatility:1 )iti sacommon precursor for benzofuran framework, [14] 2) the phenolic hydroxy group can link the thiocarbamate moiety through esterification, 3) the aldehyde group can serve as ap recursor to the N-tosylhydrazone moiety,w hich can generate ad iazo compound through ag entle Bamford-Stevens reaction. [15] Based on our strategy,w e synthesized the N-tosylhydrazonebearing thiocarbamate 1a as the starting material and it was easily obtained in 80 %y ield (gram scale), without column separation, [16] from commercially available salicylaldehyde and dimethylcarbamoyl chloride (Scheme 2b).…”

Recent Applications of the Diels–Alder Reaction in the Synthesis of Natural Products (2017–2020)

“…Paeoveitol, can be isolated as a mixture of enantiomers from the root of Paeonia veitchii 11 possessing immunomodulation and anti-inflammatory properties. 13 For the total synthesis of both enantiomers of paeoveitol, Li et al envisioned the construction of the annulated 6/5/6/6-skeleton through a hetero-Diels-Alder reaction. This strategy generates two ring systems and three stereocenters in one single step.…”

Pivotal Reactions in the Creation of the Polycyclic Skeleton of Cryptotrione

“…The first total synthesis of the unique norditerpene natural product paeoveitol (257) was achieved by Zhao with a high level of efficiency and scalability. 79 As demonstrated in Scheme 60, the desired 257 was obtained via the key intermolecular [4+2] cycloaddition reaction in 66% yield as a single diastereomer. Density functional theory (DFT) calculations point to a crucial intermolecular hydrogen bond and π-π stacking interaction that govern selectivity in this process.…”