A Method for the Late‐Stage Formation of Ketones, Acyloins, and Aldols from Alkenylstannanes: Application to the Total Synthesis of Paecilonic Acid A

Abstract

Treatment of alkenylstannanes with Cu(OAc) /Et N affords the corresponding enol esters or ketones under conditions that proved compatible with many common functionalities; these include groups that would neither survive under the standard Tamao-Fleming conditions for the oxidation of Csp2 -SiR bonds nor under the conditions commonly used to oxidize C-B bonds. Chiral centers adjacent to the unveiled carbonyls are not racemized and competing protodestannation is marginal, even if the substrate carries unprotected -OH groups as internal proton sources. Therefore, the procedure is well suited for the preparation of acyloin and aldol derivatives. These enabling virtues are illustrated by a concise approach to the bicyclic lipid paecilonic acid A.

Scalable De Novo Synthesis of Aldgarose and Total Synthesis of Aldgamycin N

“…[27,28] Once again, the faithful delivery of the Bu 3 Sn-residue to the C-atom of the triple bond proximal to the directing propargylic -OH group is noteworthy,asisthe unorthodox trans-selective course of the addition process itself that violates conventional logic. [29] At this stage,the use of Cu(tfa) 2 instead of Cu(OAc) 2 for the subsequent Chan-Lam-type coupling,which has already been alluded to in the accompanying paper, [1,30] proved instrumental:a lthough Cu-(OAc) 2 transformed the alkenylstannane into the targeted ketone,i ts use inevitably leads to acylation of the adjacent hydroxy group; [30] the resulting tertiary acetate,h owever,i s unstable under the reaction conditions and succumbed to elimination as can be judged from the isolation of small amounts of the exocyclice none 27 from one of the resulting mixtures.T his fatal path is prevented with Cu(tfa) 2 as the reagent, which furnished the desired unprotected acyloin 28 in 61 %yield [31] in readiness for attachment of the yet missing mycinopyranose and completion of the total synthesis.…”

Total Synthesis of Mycinolide IV and Path‐Scouting for Aldgamycin N

“…With the macrocyclic frame closed, we faced the challenge of transforming the propargylic entity of 20 into the acyloin motif characteristic of aldgamycin N ( 1 ) by regioselective hydration of the triple bond at the more hindered site. This goal was reached by resorting to a method previously developed in our laboratory, [52] which was slightly modified and further improved for this particular application. Specifically, 20 was subjected to a ruthenium catalyzed trans ‐hydrostannation, because this reaction faithfully delivers the ‐SnBu 3 moiety to the position proximal to the ‐OH substituent [53, 54] .…”

“…As expected, this directing effect was also operative in the present case in that alkenylstannane 21 was formed in good yield as a single regio‐ and stereoisomer. This compound was then subjected to a Chan‐Lam‐type coupling: rather than using Cu(OAc) 2 in DMSO/Et 3 N as previously described, [52] we resorted to Cu(tfa) 2 in DMSO in the presence of catalytic amounts of DMAP. Under these conditions, the reaction proceeded under milder conditions and delivered the unprotected acyloin 22 right away instead of the corresponding acetate derivative that is generated when Cu(OAc) 2 is used as the reagent [52] …”

Advances in the Asymmetric Total Synthesis of Natural Products Using Chiral Secondary Amine Catalyzed Reactions of α,β-Unsaturated Aldehydes

“…In 2017, the Fürstner group [94] reported the first enantioselective total synthesis of bicyclic fatty acid (+)-paecilonic acid A (Scheme 34), which had been isolated from Paecilomyces varioti in 2016 by the Jung group [95] and possessed a unique 6,8-dioxabicyclo [3.2.1]octane core structure. The group employed an organocatalytic trans -dihydroxylation reaction [96] to construct two contiguous chiral centers.…”