Stereoselective Substrate‐Controlled Asymmetric Syntheses of both 2,5‐cis‐ and 2,5‐trans‐Tetrahydrofuranoid Oxylipids: Stereodivergent Intramolecular Amide Enolate Alkylation

Abstract

The concise, highly stereoselective, substrate-controlled asymmetric total syntheses of both 2,5-cis- and 2,5-trans-tetrahydrofuranoid nematocidal oxylipids from the Australian brown algae Notheia anomala have been accomplished in a stereodivergent fashion. The highly stereoselective intramolecular amide enolate alkylation strategy provides access to both stereoisomers of the 3-hydroxy-2,5-disubstituted tetrahydrofuran core of these marine natural products through chelate and nonchelate control, which is driven by the C3-hydroxy protecting group. This approach offers an optional and highly stereoelective access to any of the eight possible stereoisomers of the 2,5-disubstituted-3-oxygenated tetrahydrofuran skeleton, an important structural feature which is present in many biologically active natural products.

Construction of 6,10-syn- and -anti-2,5-Dioxabicyclo[2.2.1]heptane Skeletons via Oxonium Ion Formation/Fragmentation: Prediction of Structure of (E)-Ocellenyne by NMR Calculation

“…Our preparation of the rearrangement substrates 9a and 9b began with the application of our direct ketone synthesis protocol to known oxocene amide 10 using 3-benzyloxypropylmagnesium bromide. Subsequent l -Selectride reduction − of the resultant ketone 11 gave Felkin–Anh selectivity to provide the requisite (6 R )-oxocene alcohol 9b in 74% overall yield (Scheme ).…”

“…Our preparation of the rearrangement substrates 9a and 9b began with the application of our direct ketone synthesis protocol to known oxocene amide 10 using 3-benzyloxypropylmagnesium bromide. Subsequent l -Selectride reduction − of the resultant ketone 11 gave Felkin–Anh selectivity to provide the requisite (6 R )-oxocene alcohol 9b in 74% overall yield (Scheme ). A straightforward Mitsunobu inversion–saponification sequence on 9b furnished the corresponding (6 S )-oxocene alcohol 9a in 78% overall yield for the two steps, setting the stage for the pivotal organoselenium-mediated oxonium ion formation/SiO 2 -promoted fragmentation …”

Stereoselective Protection-Free Asymmetric Total Synthesis of (+)-Chamuvarinin, a Potent Anticancer and Antitrypanosomal Agent: Substrate-Controlled Construction of the Adjacently Linked Oxatricyclic Core by Internal Alkylation

“…Homoallylic alcohol 12 was then uneventfully transformed into the desired IAEA substrate 15 in 76% overall yield by a three-step sequence analogous to that employed for synthesis of tosylate 10 , (1) Williamson ether coupling with N , N -dimethyl α-chloroacetamide, (2) ozonolysis and subsequent reductive workup with NaBH 4 , and (3) tosylation, thus setting the stage for the pivotal IAEA reaction. When tosylate 15 was subjected to IAEA with KHMDS as the base, the 2,5- cis -disubstituted THF 5 was generated in an excellent yield with >99:1 stereoselectivity, probably via an “ H-eclipsed ” conformation C with the bulky R group in a pseudoequatorial position. , The observed NOE interactions between the protons on C20 and C23 are supportive of the structural assignment of 5 .…”

Advances in Total Synthesis of Some 2,3,5‐Trisubstituted Tetrahydrofuran Natural Products

“…In 2016, Kim and co-workers [83] demonstrated an interesting stereoselective synthesis of oxylipids by "protecting-groupdependent" intramolecular amide enolate alkylation strategy (Scheme 31). The synthesis began with known threo-epoxy alcohol 202 [84] synthesized form readily available (E)-oct-2-en-1ol by chlorination, Sharpless asymmetric dihydroxylation [37] and epoxidation (3 steps).…”