Nickel-Catalyzed Enantioselective Reductive Cross-Coupling Reactions.

Question

1. What are the contributions mentioned in the paper "Nickel-catalyzed enantioselective reductive cross-coupling reactions" ?

2. What is the role of reductive crosscouplings in the synthesis of small molecules?

3. What is the reason for the enantioconvergent coupling of NHP este?

4. What is the enantioselective mechanism of olefins?

Accepted Answer

Nickel-catalyzed reductive cross-coupling reactions have emerged as powerful methods to join two electrophiles this paper.

Accepted Answer

In particular, Ni-catalyzed reductive cross-couplings have enabled the development of mild reaction conditions that give the desired products in good yields with high levels of enantioselectivity.

Accepted Answer

In the NHP ester couplings, a significant amount of (E)1-(2-chlorovinyl)-4-methoxybenzene was observed when using a chloride-containing precatalyst or TMSCl as an additive, presumably due to a Nicatalyzed halide exchange process.

Accepted Answer

Chiral BiOX ligands were found to be uniquely effective in this three-component reaction; while previously developed L4 promoted formation of the 1,2- fluoroalkylarylated products in high yields, extending the alkyl chains of the ligand (L12) did not result in enhanced enantioselectivity.

Accepted Answer

When employing two electrophilic coupling partners, a large excess of the less-reactive electrophile can be one way to outcompete the homocoupling process.

Accepted Answer

Ortho-substituted and ortho,ortho-disubstituted benzylic electrophiles exhibit low reactivity, as do those featuring sterically bulky α-substituents.40

Accepted Answer

In the case of diarylalkane formation, the development of a new bioxazoline (BiOX) ligand bearing secondary alkyl substituents with long alkyl chains (L4) was required to obtain good yield and enantioselectivity (Scheme 7a).53

Accepted Answer

An advantage of using olefin coupling partners is the ability to access all-carbon quaternary centers, which has yet to be realized in enantioconvergent RCCs.

Accepted Answer

In addition, for the Ni-catalyzed asymmetric reductive alkenylation of N-hydroxyphthalimide (NHP) esters,46,47 the best results were obtained with the organic reductant tetrakis(dimethylamino)ethylene (TDAE);8,48 Mn0 and Zn0 as the terminal reductants provided significantly lower yield (Scheme 5).

Accepted Answer

The coupling of NHP esters was advantageous for improving the scope of electron-rich benzylic systems, where the corresponding benzylic chlorides were unstable.

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Catalysis1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 593 Investigations of Ni-catalyzed reductive crosscouplings have been conducted by several groups and can be organized into two limiting possibilities that are referred to as 1) the sequential reduction mechanism and 2) the radical chain mechanism (Figure 1).29,30

Accepted Answer

Extensive methods development and mechanistic investigations by Fu and coworkers on the enantioconvergent cross-coupling of sec-alkyl electrophiles have demonstrated the feasibility of generating an alkyl radical through halide abstraction by a Ni(I) complex and engaging this species in enantioselective catalysis.

Accepted Answer

Seminal reports by Semmelhack,15 Kende,16 and Kumada17 demonstrated the ability of nickel to mediate the reductive homocoupling of C(sp2) halide electrophiles to form biaryl products (Scheme 1).18 However, extension of this reactivity from homocoupling to the cross-coupling of distinct partners remained elusive for several decades, due to the challenges associated with achieving crossselectivity.

Nickel-Catalyzed Enantioselective Reductive Cross-Coupling Reactions.

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Most frequently asked questions

1. What are the contributions mentioned in the paper "Nickel-catalyzed enantioselective reductive cross-coupling reactions" ?

2. What is the role of reductive crosscouplings in the synthesis of small molecules?

3. What is the reason for the enantioconvergent coupling of NHP este?

4. What is the enantioselective mechanism of olefins?

5. What is the way to achieve cross-coupling?

6. What are the limitations of ortho-substituted benzylic electrophile?

7. What is the role of a ligand in the enantioconvergent?

8. What is the advantage of using olefin coupling partners?

9. What is the way to achieve asymmetric couplings of NHP esters?

10. What is the way to improve the scope of electron-rich benzylic systems?

11. What is the simplest way to explain the enantioconvergent crosscoupling?

12. What is the simplest way to generate an alkyl radical?

13. What is the role of nickel in the reductive homocoupling of C(sp?

Citations

Synthesis of gem ‐Difluoroalkenes via Ni‐Catalyzed Three‐Component Defluorinative Reductive Cross‐Coupling of Organohalides, Alkenes and Trifluoromethyl Alkenes

C2-ketonylation of carbohydrates via excited-state palladium-catalyzed 1,2-spin-center shift

Nickel-Catalyzed Ipso/Ortho Difunctionalization of Aryl Bromides with Alkynes and Alkyl Bromides via a Vinyl-to-Aryl 1,4-Hydride Shift.

Synthesis of P‐Stereogenic Phosphine Oxides via Nickel‐Catalyzed Asymmetric Cross‐Coupling of Secondary Phosphine Oxides with Alkenyl and Aryl Bromides

Enantioselective Reductive (Hetero)Arylation of Cyclic N-Sulfonyl Imines by Cobalt Catalysis.

References

Advances in transition metal (Pd, Ni, Fe)-catalyzed cross-coupling reactions using alkyl-organometallics as reaction partners.

Recent advances in homogeneous nickel catalysis

Tools and techniques for solvent selection: green solvent selection guides

Recent Advances in Homogeneous Nickel Catalysis

Methods and Mechanisms for Cross-Electrophile Coupling of Csp2 Halides with Alkyl Electrophiles

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