Dialkylbiaryl phosphines are a valuable class of ligand for Pd-catalyzed amination reactions and have been applied in a range of contexts. This perspective attempts to aid the reader in the selection of the best choice of reaction conditions and ligand of this class for the most commonly encountered and practically important substrate combinations.

Dialkylbiaryl phosphines in Pd-catalyzed amination: a user's guide

Trifluoromethyltrimethylsilane: nucleophilic trifluoromethylation and beyond.

Recent Advances in Transition-Metal-Catalyzed Functionalization of Unstrained Carbon–Carbon Bonds

Secondary, but second to none: The use of secondary alkyl halides in transition-metal-catalyzed cross-coupling reactions (see scheme) has advanced significantly over the last five years. Selected examples of these transformations are examined, including mechanistic and stereochemical aspects.

Enormous effort has gone into the development of metal-catalyzed cross-coupling reactions with alkyl halides as electrophilic coupling partners. Whereas a wide array of primary alkyl halides can now be used effectively in cross-coupling reactions, the synthetic potential of secondary alkyl halides is just beginning to be revealed. This Minireview summarizes selected examples of the use of secondary alkyl halides as electrophiles in cross-coupling reactions. Emphasis is placed on the transition metals employed, the mechanistic pathways involved, and implications in terms of the stereochemical outcome of reactions.

Secondary alkyl halides in transition-metal-catalyzed cross-coupling reactions.

BACKGROUND The development of useful new methods for the construction of carbon-carbon bonds has had an impact on the many scientific disciplines (including materials science, biology, and chemistry) that use organic compounds. Tremendous progress has been made in the past several decades in the creation of bonds between sp 2 -hybridized carbons (e.g., aryl-aryl bonds), particularly through the use of transition metal catalysis. In contrast, until recently, advances in the development of general methods that form bonds between sp 3 -hybridized carbons (alkyl-alkyl bonds) had been rather limited. A variety of approaches, such as classical S N 2 reactions and transition metal catalysis, typically led to side reactions rather than the desired carbon-carbon bond formation. With transition metal catalysis, the unwanted but often facile β-hydride elimination of alkylmetal complexes presented a key impediment to efficient cross-coupling of alkyl electrophiles. In the case of many alkyl-alkyl bonds, there is an additional challenge beyond construction of the carbon-carbon bond itself: controlling the stereochemistry at one or both carbons of the new bond. It is important to control the stereochemistry of organic molecules because of its influence on properties such as biological activity. Each of these two challenges is difficult to solve individually; addressing them simultaneously is even more demanding. Until recently, the methods for achieving alkyl-alkyl bond formation were comparatively limited in scope, typically involving the use of unhindered (e.g., primary) electrophiles and unhindered, highly reactive nucleophiles (e.g., Grignard reagents, which have relatively poor functional group compatibility). With respect to enantioconvergent reactions, there were virtually no examples. ADVANCES In recent years, it has been established that, through the action of an appropriate transition metal catalyst, it is possible to achieve a broad range of alkyl-alkyl bond-forming processes; nickel-based catalysts have proved to be especially effective. With respect to the electrophilic coupling partner, a wide range of secondary alkyl halides are now suitable. This has enabled the development of enantioconvergent reactions of readily available racemic secondary electrophiles. In view of the abundance of tertiary stereocenters in organic molecules, this is a noteworthy advance in synthesis. With respect to the nucleophilic partner, alkylboron and alkylzinc reagents (Suzuki- and Negishi-type reactions, respectively) can now be used in a wide variety of alkyl-alkyl couplings, which greatly increases the utility of such processes, as these nucleophiles are more readily available and have much improved functional group compatibility relative to Grignard reagents. These new methods for alkyl-alkyl bond formation have been applied to the synthesis of natural products and other bioactive compounds. OUTLOOK A number of major challenges remain. For example, with regard to the electrophilic coupling partner, there is a need to develop general methods that are effective for tertiary alkyl halides, including enantioconvergent processes. With regard to the nucleophilic partner, there is a need to discover more versatile catalysts that can use a wide range of hindered (e.g., secondary and tertiary) alkylmetal reagents, as well as to achieve a broad spectrum of enantioconvergent couplings of racemic nucleophiles. These advances can enable the doubly stereoconvergent coupling of a racemic electrophile with a racemic nucleophile. The synthesis of alkyl-alkyl bonds is arguably the most important bond construction in organic synthesis. The ability to achieve this bond formation at will, as well as to control the product stereochemistry, would transform organic synthesis and empower the many scientists who use organic molecules. Recent work has provided evidence that transition metal catalysis can address this exciting challenge.

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Transition metal-catalyzed alkyl-alkyl bond formation: Another dimension in cross-coupling chemistry.

Allyl-, Allenyl-, and Propargyl-Transfer Reactions through Cleavage of CC Bonds Catalyzed by an N-Heterocyclic Carbene/Copper Complex: Synthesis of Multisubstituted Pyrroles†

Silver-catalyzed intramolecular chloroamination of allenes: easy access to functionalized 3-pyrroline and pyrrole derivatives.

Highly diastereo- and enantioselective Mukaiyama aldol reaction catalyzed by a new chiral Bronsted acid, N-(perfluorooctanesulfonyl)thiophosphoramide, is described. The perfluorooctyl substituent o...

Chiral Brønsted Acid as a True Catalyst: Asymmetric Mukaiyama Aldol and Hosomi-Sakurai Allylation Reactions.

http://ccc.chem.pitt.edu/wipf/Current%20Literature/Jennie_1.pdf

Masahiro Sai

Papers

Allyl-, Allenyl-, and Propargyl-Transfer Reactions through Cleavage of CC Bonds Catalyzed by an N-Heterocyclic Carbene/Copper Complex: Synthesis of Multisubstituted Pyrroles†

Silver-catalyzed intramolecular chloroamination of allenes: easy access to functionalized 3-pyrroline and pyrrole derivatives.

Chiral Brønsted Acid as a True Catalyst: Asymmetric Mukaiyama Aldol and Hosomi-Sakurai Allylation Reactions.

Copper-Catalyzed Reaction of Alkyl Halides with Cyclopentadienylmagnesium Reagent

A heterogeneous Ru/CeO2 catalyst effective for transfer-allylation from homoallyl alcohols to aldehydes.