A Straightforward and Mild Synthesis of Functionalized 3‐Alkynoates

Abstract

Diazoacetates in coupling reactions: CuI serves as an effective catalyst for coupling terminal alkynes with diazo compounds to generate 3‐alkynoates (see scheme). This method is efficient (1:1 ratio of reactants), mild (room temperature), and simple (no additional ligand), and a range of functional groups are tolerated (e.g., CC double bonds, heteroatoms, and hydroxy groups).

Coupling of N‐Tosylhydrazones with Terminal Alkynes Catalyzed by Copper(I): Synthesis of Trisubstituted Allenes

“…[12] Notably, cyclopropenation of the alkyne, which may be expected for such catalytic system, [13] was not observed. Instead, allene was detected as a minor by-product (up to 8 % yield).…”

“…It is worth mentioning that in the copper(I)-catalyzed coupling of terminal alkynes with diazoesters or diazoamides previously reported by Suµrez and Fu,alkynoates, which correspond to 5, are the main products. [12] Although the reaction mechanism has not been mentioned in Fus paper, we conjecture that a similar migratory insertion of a copper-carbene intermediate may also be involved, followed by the protonation at the carbon atom attached to the copper center. [14] In conclusion, we have developed a novel synthesis of substituted allenes from terminal alkynes and tosylhydrazones through the copper(I)-catalyzed alkynyl migratory insertion.…”

Total Synthesis of (−)-Lasonolide A

“…Our first tier of experiments would focus on incorporating this side chain via Horner-Wadsworth-Emmons olefination. Alternatively, if complications arose from the proposed HWE reaction, we also developed a convenient new strategy to form 2,4-dienoates that evolved from the reaction of terminal alkynes with ethyl diazoacetate 29 followed by subsequent phosphine-catalyzed isomerization. 30 A series of model studies, as illustrated in the conversion of alkyne 43 to dienoate 46 via intermediate 45 , validated this latter approach (see Scheme 7).…”

Total syntheses of echinopines A and B, sesquiterpenes with a unique tetracyclic [3-5-5-7] skeleton

“…28 The requisite alkynoate 66 was smoothly prepared on multigram scale by means of a CuI catalyzed CeH insertion method reported by Fu from terminal alkyne 70. 29 Then, a dilute solution of chromium complex 67 and alkyne 66 was irradiated using a 450-W medium-pressure mercury vapor lamp to afford the bicyclic intermediate (AE)-71 in 71% yield. Numerous conditions were tested for the optimization of the key radical cyclization involving an inactivated cyclic diene.…”