Palladium‐Catalyzed Completely Linear‐Selective Negishi Cross‐Coupling of Allylzinc Halides with Aryl and Vinyl Electrophiles

Abstract

Completely linear: a general and practical palladium-catalyzed linear-selective Negishi coupling of 3,3-disubstituted allylzinc reagents with aryl, heteroaryl and vinyl electrophiles at ambient temperature is described. This method provides an effective means to access a wide range of prenylated arenes or skipped dienes in a completely linear-selective fashion, as demonstrated by a concise synthesis of the anti-HIV natural product siamenol. Finally, DFT calculations shed light on the origin of the excellent regioselectivity observed with the current catalyst system.

Programmable meroterpene synthesis

“…Yet palladium-catalyzed cross-coupling methods, especially direct prenylation, have historically proven challenging on similar bicyclo[3.3.1] nonane-containing PPAP scaffolds and we assumed deactivated vinyl chloride 58 would be no different 15 . Although recent advances in ligand-controlled, linear-selective prenylation methodology boded well for such endeavors [68][69][70] , the sensitivity of vinylogous ester 58 to hydrolysis and base-induced decomposition proved problematic. After significant experimentation, we successfully applied Buchwald's Pd/CPhos-system 71 to the Suzuki coupling of 58 and prenylBpin, affording garsubellin A (8) directly in 57% yield.…”

Iron‐Catalyzed Arene Prenylation

“…Additionally, the incorporation of an isoprene unit into bioactive molecules increases lipophilicity, which is shown to increase potency in many cases The importance of accessing these structures has driven the development of many methods to incorporate prenyl groups into substituted arenes . Catalytic installation of the isoprene unit represents the most utilized method for arene prenylation, where the catalysts include precious metals and Lewis acids . Additionally, the isoprene unit is often derived from prenyl surrogates such as prenyl halides[6a] and organometallic reagents ,.…”

“…Catalytic installation of the isoprene unit represents the most utilized method for arene prenylation, where the catalysts include precious metals and Lewis acids . Additionally, the isoprene unit is often derived from prenyl surrogates such as prenyl halides[6a] and organometallic reagents ,. [6b] The most efficient and atom‐economic route to prenylated arenes and 2,2‐dimethylchromans is the direct implementation of isoprene.…”

Regioselective Arylboration of 1,3‐Butadiene

“…An allylic transmetallation is likely to occur via transition state 16 to generate allylÀ Pd complex 17. [21] Due to the steric bulk of QPhos, it is likely that rapid reductive elimination of 17 occurs prior to isomerization via πallyl intermediates that might lead to the minor isomer (e. g., 4). [19] In comparison to our previously reported arylboration of isoprene, use of QPhos-ligated Pd results in selective 1,4arylboration.…”