https://www.chem.ccu.edu.tw/~joyce/referance/ericyang/Coord.%20Chem.%20Rev/Coord.%20Chem.%20Rev.%202004,%20248,%202337-2364.pdf

Copper in cross-coupling reactions: The post-Ullmann chemistry

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.

Cross-coupling reactions have become indispensable tools for creating carbon–carbon (or heteroatom) bonds in organic synthesis. Like in other important transition metal catalyzed reactions, such as metathesis, addition, and polymerization, unsaturated compounds are usually employed as substrates for cross-coupling reactions. However during the past decade, a great deal of effort has been devoted to the use of alkyl halides as saturated compounds in cross-coupling reactions, which has resulted in significant progress in this undeveloped area by introducing new effective ligands. Many useful catalytic systems are now available for synthetic transformations based on Csp3–Csp3, Csp3–Csp2 and Csp3–Csp bond formation as complementary methods to conventional Csp2–Csp2, Csp2–Csp and Csp–Csp coupling. This tutorial review summarizes recent advances in cross-coupling reactions of alkyl halides and pseudohalides catalyzed by a palladium complex.

Pd-catalyzed cross-coupling reactions of alkyl halides

Easy access: An unprecedented copper-catalyzed cross-coupling reaction of the title compounds with diboron reagents is described (see scheme; Ts = 4-toluenesulfonyl). This reaction can be used to prepare both primary and secondary alkylboronic esters having diverse structures and functional groups. The resulting products would be difficult to access by other means.

Alkylboronic Esters from Copper-Catalyzed Borylation of Primary and Secondary Alkyl Halides and Pseudohalides

Transition metal-catalyzed cross-coupling reactions of organic halides and pseudo-halides containing a C−X bond (X = I, Br, Cl, OTf, OTs, etc.) with organometallic reagents are among the most important transformations for carbon−carbon bond formation between a variety of sp, sp2, and sp3-hybridized carbon atoms. In particular, researchers have widely employed Ni- and Pd-catalyzed cross-coupling to synthesize complex organic structures from readily available components. The catalytic cycle of this process comprises oxidative addition, transmetalation, and reductive elimination steps. In these reactions, various organometallic reagents could bear a variety of R groups (alkyl, vinyl, aryl, or allyl), but the coupling partner has been primarily limited to sp and sp2 carbon compounds: alkynes, alkenes, and arenes. With alkyl coupling partners, these reactions typically run into two problems within the catalytic cycle. First, oxidative addition of alkyl halides to a metal catalyst is generally less efficient th...

Cross-Coupling Reaction of Alkyl Halides with Grignard Reagents Catalyzed by Ni, Pd, or Cu Complexes with π-Carbon Ligand(s)

A mixture of equal amounts of CuBr−SMe2, LiBr, and LiSPh in THF at 0 °C furnished a new soluble copper catalyst that was highly efficient at coupling primary, secondary, tertiary, aryl, vinyl, and allylic Grignard reagents to primary tosylates and primary Grignard reagents to secondary tosylates and mesylates, all with the use of only 1 equiv of Grignard reagent. The new catalyst was shown to be much more reactive than copper catalysts CuBr and Li2CuCl4 and more efficient in the transference of secondary and tertiary alkyl groups than lower order cuprates (Gilman reagents) and demonstrated more reactivity than the lower order cuprates with its ability to couple primary Grignard reagents to secondary sulfonates. The Grignard reagent/catalyst system was compatible with an ester functionalized tosylate, thus proving to be more chemoselective than a Grignard reagent without the catalyst. The catalyst exhibited good reactivity below room temperature, and with the addition of 6% v/v of HMPA to the catalyst solu...

Scope and Utility of a New Soluble Copper Catalyst [CuBr−LiSPh−LiBr−THF]: A Comparison with Other Copper Catalysts in Their Ability to Couple One Equivalent of a Grignard Reagent with an Alkyl Sulfonate

A general strategy for the preparation of the family of exo-[n.m.n.m]metacyclophanes (n,m ≥ 3) in 6-steps (starting from 2-bromoanisole) that utilizes a [2 + 2] approach to furnish the exo-metacyclophane ring in good to moderate yield is described. The soluble copper catalyst [CuBr−LiSPh−LiBr−THF] is used to efficiently couple Grignard and alkyl or ether tosylate reagents in several of the synthetic steps, including the ring construction in the final step. The exo-[n.m.n.m]metacyclophane ring is conformationally mobile on the NMR time scale, and X-ray crystallography reveals that exo-[3.3.3.3]metacyclophane 2a assumes a cone conformation, and that exo-[6.6.6.6]metacyclophane 6a assumes a chair conformation. Molecular mechanics calculations show that both conformations for each exo-metacyclophane are very similar in energy. Regiocontrol over the alkylation and acylation of the phenolic oxygens of 2b is problematic, although the preparation of the tetraacetylated 18 and alkylation of 2b with CH2BrCl to furn...

Synthesis, modification, and characterization of a family of homologues of exo-calix

Synthesis and characterization of [3.3.3.3]metacyclophane

Synthesis of 6,16,22,32-tetrahydroxy[3.3.3.3]metacyclophane with the aid of a new copper catalyst

Metacyclophane 2 has been prepared in 4 steps starting from 2-bromoanisole with the aid of a new copper catalyst. The catalyst was prepared by mixing CuBr-SMe 2 with LiSPh and LiBr in THF.

Jeffrey D. Miller

Papers

Scope and Utility of a New Soluble Copper Catalyst [CuBr−LiSPh−LiBr−THF]: A Comparison with Other Copper Catalysts in Their Ability to Couple One Equivalent of a Grignard Reagent with an Alkyl Sulfonate

Synthesis, modification, and characterization of a family of homologues of exo-calix

Synthesis and characterization of [3.3.3.3]metacyclophane

Synthesis of 6,16,22,32-tetrahydroxy[3.3.3.3]metacyclophane with the aid of a new copper catalyst

Synthesis of 6,16,22,32-Tetrahydroxy(3.3.3.3)metacyclophane with the Aid of a New Copper Catalyst.