One‐Flask Tethered Ring Closing Metathesis–Electrocyclic Ring Opening for the Highly Stereoselective Synthesis of Conjugated Z/E‐Dienes

Abstract

A one‐flask reaction sequence comprising ring closing metathesis (RCM) of butenoates derived from allylic alcohols and a base‐mediated ring opening gives 2Z,4E‐configured dienoic acids in high yields and stereoselectivities. Application of the method to the synthesis of the natural product fusanolide A suggests that the originally published structure was erroneously assigned and should be revised.

Formal Ring‐Opening/Cross‐Coupling Reactions of 2‐Pyrones: Iron‐Catalyzed Entry into Stereodefined Dienyl Carboxylates

“…This step resembles the base-mediated ring-opening of unsaturated lactones, which has ample precedent in the literature. [34] Although this pathway is suggestive, the actual mechanism of the newly discovered formal ring-opening/cross-coupling reaction must be more involved. In any case, an ordinary electrocyclic opening of an enolate of type B hardly explains why the incoming methyl group replaces the lactone entity of the 2pyrone ring with strict retention of configuration of the enolic double bond.…”

Stereoselective Synthesis of Dienyl-Carboxylate Building Blocks: Formal Synthesis of Inthomycin C

“…7 An elegant example of such a tactic is the development by Burke of an assembly of so-called MIDA-boronate building blocks, that allow the deployment of iterative cross-couplings en route to polyenic natural products. 8 Nevertheless, the syntheses of the basic mono-olefinic fragments are typically multi-step and mandate the introduction of a halide and organometallic residue in each fragment.…”

Stereospecific Formation of E- and Z-Disubstituted Double Bonds by Dehydratase Domains from Modules 1 and 2 of the Fostriecin Polyketide Synthase

“…(Scheme 2). 11,12 In like manner, (2 Z,4 E)-2,4-hexadienoic acid ( 19 ), prepared as previously described by ring-closing metathesis–base-induced ring opening, 13 and (2 E ,4 E )-2,4-hexadienoic acid ( 20 ) were each converted via their -SCoA esters to the corresponding (2 Z ,4 E )-2,4-hexadienoyl-FosACP2 ( 21 ) and (2 E ,4 E )-2,4-hexadienoyl-FosACP2 ( 22 ).…”

“…13 The cis -olefin geometry was verified by 1 H NMR and chiral GC-MS by which the (2Z,4E)-2,4-hexadienoic acid ( 18 ) was readily separated from commercially available (2E,4E)- 17 either as the carboxylic acids or derived methyl esters 17-Me and 18-Me . The carboxylic acid forms were analyzed with an Agilent ChiraSil-Dex capillary GC column, (0.32 mm ID × 25 m length × 0.25 μm film) using a temperature program (GC Method A) with a 1 min hold at 50 °C, followed by a 7.5 °C/min increment to 200 °C.…”