Palladium-Catalyzed Branch- and Z-Selective Allylic C-H Amination with Aromatic Amines.

Allylamines are important building blocks in the synthesis of bioactive compounds. The direct coupling of allylic C-H bonds and commonly available amines is a major synthetic challenge. An allylic C-H amination of 1,4-dienes has been accomplished by palladium catalysis. With aromatic amines, branch-selective allylic aminations are favored to generate thermodynamically unstable Z-allylamines. In addition, more basic aliphatic cyclic amines can also engage in the reaction, but linear dienyl allylic amines are the major products.

Cobalt-Catalyzed Intermolecular Hydrofunctionalization of Alkenes: Evidence for a Bimetallic Pathway.

A functional group tolerant cobalt-catalyzed method for the intermolecular hydrofunctionalization of alkenes with oxygen- and nitrogen-based nucleophiles is reported. This protocol features a strategic use of hypervalent iodine(III) reagents that enables a mechanistic shift from conventional cobalt-hydride catalysis. Key evidence was found supporting a unique bimetallic-mediated rate-limiting step involving two distinct cobalt(III) species, from which a new carbon-heteroatom bond is formed.

Asymmetric α-Allylation of Aldehydes with Alkynes by Integrating Chiral Hydridopalladium and Enamine Catalysis.

A palladium-catalyzed asymmetric α-allylation of aldehydes with alkynes has been established by integrating the catalysis of enamine and chiral hydridopalladium complex that is reversibly formed from the oxidative addition of Pd(0) to chiral phosphoric acid. The ternary catalyst system, consisting of an achiral palladium complex, a primary amine, and a chiral phosphoric acid allows the reaction to tolerate a wide scope of α,α-disubstituted aldehydes and alkynes, affording the corresponding allylation products in high yields and with excellent levels of enantioselectivity.

Palladium(II)-Catalyzed Deacylative Allylic C-H Alkylation.

The first deacylative allylic C-H alkylation has been established by employing the palladium-catalyzed allylic C-H activation and decarboxylative nucleophile generation. A wide scope of nucleophiles are tolerated and densely functionalized alkylation products turn out to be furnished in moderate to good yield. More importantly, this strategy provides an alternative method for the allylic C-H alkylation with less stabilized carbon nucleophiles, and can be further expanded to the synthesis of unconjugated enynes.

Enantioselective Functionalization of Inactive sp(3) C-H Bonds Remote to Functional Group by Metal/Organo Cooperative Catalysis.

A metal/organo cooperative catalysis to enable the enantioselective functionalization of inactive C-H bonds γ to the formyl group in aliphatic aldehydes has been established. Instead of using enals as substrates in traditional organocatalytic cyclization reactions, the aliphatic aldehydes directly participated in [4 + 2] cyclization with quinone derivatives exploiting molecular oxygen as oxidants to afford optically active cyclic molecules with excellent levels of enantioselectivity. This method features a combination of pot, step, and atom economy.

Asymmetric organocatalysis combined with metal catalysis: concept, proof of concept, and beyond.

Asymmetric catalysis has been considered to be the most intriguing means for building collections of functionalized optically active compounds. In particular, metal and organocatalysis have been well established to allow many fundamentally different reactions. Metal catalysis has enabled the participation of a much broader scope of chemical bonds in organic transformations than are allowed by organocatalysis, while organocatalysis permits a broader scope of functional groups to undergo a diverse range of enantioselective transformations, individually, simultaneously, or sequentially. Theoretically, the combination of organocatalysts and metal complexes could probably render new transformations through the simultaneous or sequential activation and reorganization of multiple chemical bonds if the superior features of both the catalysts are adopted. In 2001, both our research group and Takemoto's group separately described an asymmetric allylation of glycine imino esters with allyl acetate catalyzed by palladium complexes and chiral ammonium salts. In these cases, the oxidative addition of palladium complexes to allyl acetate formed the π-allylic fragments, while the chiral ammonium salts were actually responsible for controlling the stereoselectivity. These reactions in fact marked the beginning of asymmetric organo/metal combined catalysis. Since then, asymmetric organocatalysis combined with metal catalysis, including cooperative catalysis, relay catalysis, and sequential catalysis, has been a versatile concept for the creation of unknown organic transformations. Sequential catalysis describes a one-pot reaction involving two or more incompatible catalytic cycles. Alternatively, cooperative and relay catalyses require high compatibility of principally distinct catalysts and will be the focus of this Account. The catalysts in cooperative catalytic reactions must be able to simultaneously and individually activate both substrates to drive a bond-forming reaction, while relay catalysis is basically defined as a cascade process in which two or more sequential bond-forming transformations are independently catalyzed by distinct catalysts. In the past decade, we have discovered a variety of binary catalytic systems consisting of metals, including Rh(II), Pd(0), Au(I), and Mg(II), and chiral organocatalysts, including chiral phosphoric acids and quinine-based bifunctional molecules, for cooperative catalysis and relay catalysis, allowing the accomplishment of many unprecedented asymmetric transformations. In this Account, these achievements will be summarized, particularly focusing on the description of the concept and proof of the concept, to demonstrate the robustness of combined organo/metal catalysis in the creation of efficient enantioselective transformations. In addition, elegant studies from other laboratories using chiral phosphoric acid/Au(I) for the establishment of asymmetric cascade reactions involving the carbon-carbon triple bond functionality and typical combined organo/metal catalytic systems, very recently disclosed, will also be highlighted.

Palladium(II)/Lewis acid synergistically catalyzed allylic C-H olefination.

The first allylic C-H olefination with α-diazo esters synergistically catalyzed by a palladium(II) complex and (salen)CrCl has been established to directly generate conjugated polyene derivatives in moderate to high yields and with excellent stereoselectivities.

An organocatalytic asymmetric allylic alkylation allows enantioselective total synthesis of hydroxymetasequirin-A and metasequirin-B tetramethyl ether diacetates.

The first highly stereoselective organocatalytic intermolecular allylic alkylation of allylic alcohols with 1,3-dicarbonyls has been developed to allow the first enantioselective total synthesis of hydroxymetasequirin-A and metasequirin-B tetramethyl ether diacetates.

Enantioselective relay catalytic cascade intramolecular hydrosiloxylation and Mukaiyama aldol reaction.

Cascading chemistry! The first practical relay catalytic cascade intramolecular hydrosiloxylation of arylacetylene and asymmetric Mukaiyama aldol reaction has been established to give synthetically useful products in high yields and with excellent ee (see scheme).