Synthesis of Symmetrical and Nonsymmetrical Polyenes by Iterative and Bidirectional Palladium‐Catalyzed Cross‐Coupling Reactions

Abstract

Bifunctional unsaturated reagents designed to undergo palladium‐catalyzed cross‐coupling reactions with complementary polyenyl connective fragments are highly useful for the undoubtedly challenging synthesis of polyenes. The current toolkit of building blocks for the bidirectional formation of Csp2−Csp2 single bonds of polyenes includes homo‐bisfunctionalized reagents with equal or unequal reactivity (due to steric and/or electronic factors), and hetero‐bisfunctionalized counterparts containing either two different nucleophiles, two electrophiles or one of these functionalities and a latent nucleophile that can be unmasked when desired. The combination of these bifunctional linchpin reagents using tactics that modulate the reactivity of each terminus in order to achieve the required connection have streamlined the synthesis of polyenes of great complexity using (iterative) cross‐coupling methods for Csp2−Csp2 bond formation. Reaction conditions for the Pd‐catalyzed cross‐coupling reactions are mild and functional‐group‐tolerant, and therefore these protocols allow to construct the polyene structures using shorter unsaturated reactants with the desired geometries, since in general the products preserve the stereochemical information of the connected cross‐coupling partners.

State-of-the-art methodological investigation of carotenoid activity and metabolism – from organic synthesis via metabolism to biological activity – exemplified by a novel retinoid signalling pathway

“…This is particularly true when used as tandem processes to more efficiently generate molecular complexity, thus highlighting the advantages of the Hiyama–Denmark cross-coupling reaction for stepwise polyene construction of highly unstable cis -carotenoids in general. 26,33…”

Total Synthesis of Pentamycin by a Conformationally Biased Double Stille Ring Closure with a Trienyl-bis-stannane

“…The group of Nicolaou (1995) had previously used a vinyl-bisstannane during the total synthesis of rapamycin, 19 and further application of this shorter reagent, as well as other bismetallic reagents in other synthetic projects have been reported. 20,21 However, in contrast to this C2 unit, our strategy with linear triene unit 4 is considerably more demanding, as it dramatically increases the synthetic challenge and conformational complexity of this transformation, also as it sets a notoriously labile pentaene fragment. Likewise, the conformational bias required for this ambitious macrocylization is notable, in comparison to a stepwise intermolecular usage of 4.…”