Cross-Coupling of Ketone Enolates with Grignard and Zinc Reagents with First-Row Transition Metal Catalysts

Abstract

The stereoselective transformation of ketones to substituted olefins has become of great importance in organic synthesis. This Review helps to define the scope and limitations of the first-row transition metal-catalyzed cross-couplings between various enolates and aryl, heteroaryl, alkenyl, alkynyl, and alkyl Grignard and zinc reagents.

Palladium‐Catalyzed Regiodivergent Synthesis of 1,3‐Dienyl and Allyl Esters from Propargyl Esters

“…In conclusion, we have developed an unprecedented catalyst‐controlled regiodivergent strategy for the transformation of challenging internal aliphatic PADs into structurally diverse 1,3‐dienyl and allyl esters with high regio‐ and stereoselectivity. This protocol allows for highly stereoselective access to a diverse range of valuable 1,3‐dienyl and alkenyl esters with latent functionalities for further synthetic elaboration [34] . The regioselectivity pattern can easily be manipulated by an appropriate selection of either ligand structure or metal catalyst source.…”

“…This protocol allows for highly stereoselective access to a diverse range of valuable 1,3-dienyl and alkenyl esters with latent functionalities for further synthetic elaboration. [34] The regioselectivity pattern can easily be manipulated by an appropriate selection of either ligand structure or metal catalyst source. In this regard, depending on the choice of phosphine ligand backbone, two general approaches have been well established using the common palladium: 1) oxidative addition-reductive elimination pathway and 2) electrophilic palladium catalysis (π-Lewis acid activation) pathway.…”

“…Different propargyl esters (3,32) were suitable for this transformation that also could be performed on a preparative scale in high yield (3). This reaction showed broad substrates scope such as electron-donating (39, 43), electron-withdrawing (33)(34)(35)37), and sterically demanding substituents (36, 40, 48); but also, numerous useful functional groups (33-35, 37, 38, 40-43), as well as the challenging heteroaryl compounds (43-48), were ideally accomplished for the transformation in good to excellent yield. Noteworthy is the substrates bearing a phenyl group at the alkyne terminus were also eligible for the highly stereoselective formation of allyl esters in a practical yield (3,(49)(50)(51)(52)(53).…”

Stereoconvergent and -divergent Synthesis of Tetrasubstituted Alkenes by Nickel-Catalyzed Cross-Couplings

“…The diastereoconvergent reaction is highlighted in this report due to its synthetic utility, as it obviates the need for stereoselective starting material preparation, which is particularly challenging for the corresponding ( Z )-configured enol tosylates . An optimization study was designed − using kraken , a computational database of descriptors for >1500 phosphorus ligands, to identify a diverse set of phosphines to evaluate, which enabled the identification of reaction conditions for a Ni-catalyzed Suzuki–Miyaura cross-coupling. − The optimized conditions were then applied to the synthesis of a variety of tetrasubstituted alkene scaffolds in typically high diastereomeric ratios of up to ∼90:10 E / Z and Z / E . Notably, the unique mechanistic features of this catalytic transformation contrast with the thermodynamic control of previously developed convergent cross-couplings for the synthesis of di- and trisubstituted alkenes, which typically proceed via metal hydride catalyzed isomerizations. − Our mechanistic hypothesis is supported by a combination of DFT calculations and experimental insights to shed insight into the elusive isomerization step that has previously been observed in several cross-coupling reactions of alkenyl electrophiles. ,, …”

“…59−61 Our mechanistic hypothesis is supported by a combination of DFT calculations and experimental insights to shed insight into the elusive isomerization step that has previously been observed in several cross-coupling reactions of alkenyl electrophiles. 49,56,62 ■ RESULTS AND DISCUSSION Optimization Studies. At the outset of the investigation, preliminary experimental data indicated that monophosphine ligands effectively promoted a nickel(0) cross-coupling of enol tosylate 1a and pinacol boronate 2a to access representative tetrasubstituted alkene diastereomers 3aa (Figure 3A, see Supporting Information for details).…”