Amide activation for cyclopropane ortho-lithiation

Eaton, Philip E.; Daniels, Rhys G.; Casucci, D.; Cunkle, Glen T.; Engel, Peter

doi:10.1021/jo00386a040

Cited by 36 publications

(12 citation statements)

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“…The well‐documented amide‐directed lithiation reactions of cyclopropanes18 prompted us to determine if this newly developed catalytic system could functionalize the secondary cyclopropyl CH bond in the presence of a methyl group. Cyclopropane substrate 16 a was subjected to the same conditions as described.…”

Section: Methodsmentioning

confidence: 99%

Palladium‐Catalyzed Asymmetric Iodination of Unactivated CH Bonds under Mild Conditions

2005

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The catalytic activation of C(sp 3 )ÀH and C(sp 2 )ÀH bonds in readily available, inexpensive starting materials would provide a valuable array of new transformations for organic chemistry research and the fine chemical industry.[1] Activation of C(sp 2 )ÀH bonds in benzene and ortho-substituted arenes has been successfully exploited in the development of catalytic CÀC bond-forming reactions by coupling to olefins. [2,3] The selective activation of C(sp 3 )ÀH bonds under mild conditions could be an attractive strategy for the development of catalytic reactions with wide applicability. Despite extensive efforts that have focused mainly on carbene and nitrene insertions, metathesis, Shilov chemistry, and biomimetic approaches, the catalytic and asymmetric functionalization of C(sp 3 )ÀH bonds remains a significant challenge.[4]We report herein an auxiliary approach for the chemoselective and asymmetric room-temperature iodination of

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Section: Methodsmentioning

confidence: 99%

Palladium‐Catalyzed Asymmetric Iodination of Unactivated CH Bonds under Mild Conditions

2005

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“…Pendant amides and carbamates effectively direct lithiation of arenes 32 and alkanes, 1 including cyclopropanes. 33,34 The enhanced acidity of the deprotonated hydrogen in these cases is attributed variously to dipole-stabilization 1,35 and the complexinduced proximity effect. 36 For the sake of computational economy, deprotonation of trans-␤-formylcyclopropylnitrile 5c was examined (Fig.…”

Section: Chiral Lithiated Cyclopropylnitrilesmentioning

confidence: 99%

Configurational stability of chiral lithiated cyclopropylnitriles: A density functional study

Carlier

2003

Chirality

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Chiral, configurationally stable lithiated nitriles would be valuable intermediates for asymmetric carbon-carbon bond-forming reactions. To gain insight into the design of such species, Walborsky's attempted enantioselective deprotonation/trapping reactions of a chiral cyclopropylnitrile were studied computationally up to the MP2(fc)/6-31+G* and B3LYP/6-31+G* levels. Investigation of cyclopropylnitrile/LiNH(2) deprotonation transition structures demonstrated a significant (20-23 kcal/mol) kinetic preference for N-lithiation, and a facile (4-6 kcal/mol barrier) "conducted tour" racemization pathway for the N-lithiated nitrile product. Addition of a model directing group (formyl) to the beta-carbon of the cyclopropyl ring is predicted to significantly favor C-lithiation over N-lithiation, both kinetically and thermodynamically. Thus, chiral beta-Lewis base substituted cyclopropylnitriles may serve as precursors to chiral, configurationally stable organolithium reagents.

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“…47 Recourse to sugar-derived ferrocene esters possessing chiral directing groups, either combined to chiral lithium amides as above or with LiTMP-Zn(TMP) 2 (1:1), proved to be more promising. 48 Eaton and co-workers showed in the eighties that LiTMP can be used in the presence of mercury chloride to more efficiently perform amide-directed cubane 49 and cyclopropane 50 deprotonation. The idea was to make use of the small amount of organolithium in equilibrium with the starting material, and to use mercury salts as the situ trap to shift the lithiation equilibrium toward the aryllithium.…”

Section: Zinc-based In Situ Trapsmentioning

confidence: 99%

In Situ ‘Trans-Metal Trapping’: An Efficient Way to Extend the Scope of Aromatic Deprotometalation

et al. 2018

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Deprotometalation is an efficient method to functionalize regioselectively aromatic compounds including heterocycles. This short review shows how it is possible to intercept aryllithiums (and other polar arylmetals) as soon as they are formed by in situ ‘trans-metal trapping’. The approach avoids long contact between aryllithiums and sensitive substrates. In addition, it allows less activated substrates to be deprotonated by non-nucleophilic lithium amides. While using chlorosilanes and borates still arouses the interest of chemists, more recently, methods based on zinc, aluminum and gallium have appeared, enabling this chemistry to grow dramatically.1 Introduction2 Silicon-Based In Situ Traps3 Boron-Based In Situ Traps4 Zinc-Based In Situ Traps5 Aluminum- and Gallium-Based In Situ Traps6 Other In Situ Traps7 Continuous-Flow In Situ ‘Trans-Metal Trapping’8 Conclusion

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Amide activation for cyclopropane ortho-lithiation

Cited by 36 publications

References 0 publications

Palladium‐Catalyzed Asymmetric Iodination of Unactivated CH Bonds under Mild Conditions

Palladium‐Catalyzed Asymmetric Iodination of Unactivated CH Bonds under Mild Conditions

Configurational stability of chiral lithiated cyclopropylnitriles: A density functional study

In Situ ‘Trans-Metal Trapping’: An Efficient Way to Extend the Scope of Aromatic Deprotometalation

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