The Shortest (Four‐Step) Total Synthesis of the Eight‐Membered Cyclic Ether (rac)‐ and (–)‐cis‐Lauthisan

Abstract

Access to the eight‐membered cyclic ether (rac)‐ and (–)‐cis‐lauthisan was achieved in two complementary ways in only four steps for the longest linear sequence by starting from commercially available materials. The sequence features a cis‐stereoselective reductive cyclization as the key step.

Eight-Membered Rings With One Oxygen Atom

“…Starting from (R)-13-hydroxypentadecan-7-one (R)-227, reductive cyclization provided a mixture of (−)-cis-lauthisan 95 and diastereomeric diols 228 (Scheme 35). 177,178 Olefin-ester cyclization reaction of ester 229, in a multistep strategy, gave a mixture of the eight-membered ring 230 in 40% yields and the ether 231 in 56% yield (Scheme 36). This synthetic approach was used in the synthesis of the FGHI-ring system of YTX 26 and adriatoxin 30.…”

Stereoselective Synthesis of Medium-Sized Cyclic Ethers: Application of C-Glycosylation Chemistry to Seven- to Nine-Membered Lactone-Derived Thioacetals and Their Sulfone Counterparts

“…The construction of medium-sized cyclic ethers poses a formidable challenge to synthetic chemists because their closure inherently accompanies unfavorable entropic penalty and transannular interactions . The vast majority of synthetic methods for medium-sized oxacycles can be categorized into the following three types: (i) intramolecular C–O bond formation of linear alcohols; (ii) intramolecular C–C bond formation of linear ethers; and (iii) functionalization of medium-sized lactones (Scheme ). , It is known that direct construction of medium-sized oxacycles via an intramolecular C–O bond formation, i.e., etherification, is difficult in many cases because of the low nucleophilic character of alcohols. Accordingly, considerable attention has been paid to the development of synthetic methods based on an intramolecular C–C bond formation of linear ethers.…”

Michael Addition of Soft Carbon Nucleophiles to Alkylidene Isoxazol-5-ones: A Divergent Entry to β-Branched Carbonyl Compounds

“…In this regard, the assembly of 3-substituted pent-4-yn-1-oyl motifs can be seen as an emblematic case study of a β-branched carbonyl compound. Often, this is a fragment found in prominent candidate molecules tested as pharmaceuticals and in building blocks employed toward natural products (Scheme ). Classically, the synthesis of such fragments involves the conjugate addition of metal acetylides to α,β-unsaturated carbonyl compounds.…”