Sequential Processes in Palladium‐Catalyzed Silicon‐Based Cross‐Coupling

Abstract

Although developed somewhat later, silicon-based cross-coupling has become a viable alternative to the more conventional Suzuki-Miyaura, Stille-Kosugi-Migita, and Negishi cross-coupling reactions because of its broad substrate scope, high stability of silicon-containing reagents, and low toxicity of waste streams. An empowering and yet underappreciated feature unique to silicon-based cross-coupling is the wide range of sequential processes available. In these processes, simple precursors are first converted to complex silicon-containing cross-coupling substrates, and the subsequent silicon-based cross-coupling reaction affords an even more highly functionalized product in a stereoselective fashion. In so doing, structurally simple and inexpensive starting materials are quickly transformed into value-added and densely substituted products. Therefore, sequential processes are often useful in constructing the carbon backbones of natural products. In this review, studies of sequential processes involving silicon-based cross-coupling are discussed. Additionally, the total syntheses that utilize these sequential processes are also presented.

Cross‐Coupling Reactions of Organosilicon Compounds in the Stereocontrolled Synthesis of Retinoids

“…By contrast, synthesis of the retinoid skeleton by a sequential one‐pot process combining the platinum‐catalysed hydrosilylation of an alkyne with the palladium‐catalysed Hiyama coupling was successful (Scheme ) 53. Following Denmark’s protocol,54 enyne 10 was hydrosilylated with inexpensive, non‐toxic tetramethyldisiloxane under [Pt(DVDS)( t Bu 3 P)] catalysis, and the resulting vinyldisiloxane coupled in situ to iodide 6 under fluoride‐promoted Pd catalysis, giving trans ‐ O ‐tetrahydropyranyl retinyl ether 18 in a valuable 74 % overall yield.…”

“…[52] By contrast, synthesis of the retinoid skeleton by a sequential one-pot process combining the platinum-catalysed hydrosilylation of an alkyne with the palladium-catalysed Hiyama coupling was successful (Scheme 2). [53] Following Denmarks protocol, [54] Finally, synthesis of the natural retinoids 1 and 2 was completed by deprotection of retinyl ethers 18 and 22 (TMSCl, H 2 O, MeOH, 5 min), which afforded trans-retinol (1) and 11-cis-retinol (23) in 74 and 83 % yield, respectively, followed by mild oxidation of 23 with BaMnO 4 (90 %; Table 4).…”

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

“…Sequential palladium‐catalyzed cross‐coupling reactions of symmetrical and non‐symmetrical 1,4‐bissilyl‐1,3‐butadienes with electrophiles [11, 14b, 21b,c, 31] have been extensively developed by Denmark et al [11, 13b, 26] . The bifunctional bissilane linchpin reagents could be combined with two electrophiles under complementary activation conditions (Brønsted base by formation of the silanolate or fluoride ions by generation of the fluorosiliconate) [11, 13b, 26, 32] in order to synthesize nonsymmetrical polyenes [33]…”

“…This iterative cross‐coupling tactic has been achieved using the temporary phantom or “safety catch” silanes that bear a fluoride cleavable carbon‐based residue, [11, 13b, 26] and the boron‐masking strategy with formation of a sp 3 ‐hybridized and neutral alkenylboron species ( N ‐methyliminodiacetic acid boronate or MIDA‐boronate), [1] which secures its lack of reactivity under certain reaction conditions. Recent advances in methodologies [1] and development of automated platforms [27] have provided novel routes to polyene natural products based on the use of these bisfunctionalized conjunctive building blocks, having one of them being designed to remain temporarily protected as MIDA boronate.…”

Why You Really Should Consider Using Palladium-Catalyzed Cross-Coupling of Silanols and Silanolates

“…The 3-substituted-2-indolylsilanols in Scheme are prepared by a variant of the Larock indole synthesis that employs alkynylsilyl ethers and places the silanol group in the 2-position for coupling (eq ). , 2-Iodo- N -alkyl anilines are used as precursors with both isopropyl and tert -butylsilyl ethers. These silyl ethers are sufficiently robust to withstand the Larock heteroannulation conditions and can be deprotected with very mild acid hydrolysis.…”