Recent advances in benzylic and heterobenzylic lithiation

Wong, J. Y.; Barker, Graeme

doi:10.1016/j.tet.2020.131704

Cited by 9 publications

(5 citation statements)

References 100 publications

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“…These results indicate that the Boc group rotates slowly in comparison with lithiation at −78 °C. For lithiation to occur, the carbonyl oxygen atom that coordinates to n ‐BuLi needs to be located on the side of the benzylic proton [14,15] . To quantify the ratio of rotamers and the rate of rotation of the Boc group, we carried out variable temperature (VT) NMR spectroscopic studies (Scheme 3, Figure 2).…”

Section: Resultsmentioning

confidence: 99%

“…For lithiation to occur, the carbonyl oxygen atom that coordinates to n ‐BuLi needs to be located on the side of the benzylic proton. [ 14 , 15 ] To quantify the ratio of rotamers and the rate of rotation of the Boc group, we carried out variable temperature (VT) NMR spectroscopic studies (Scheme 3 , Figure 2 ). The 1 H NMR spectrum showed that the ratio of rotamers was about 6 : 1.…”

Section: Resultsmentioning

confidence: 99%

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Asymmetric Synthesis of 2‐Arylindolines and 2,2‐Disubstituted Indolines by Kinetic Resolution

Choi

El‐Tunsi

Wang

et al. 2021

Chemistry A European J

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Kinetic resolution of 2‐arylindolines (2,3‐dihydroindoles) was achieved by treatment of their N‐tert‐butoxycarbonyl (Boc) derivatives with n‐butyllithium and sparteine in toluene at −78 °C followed by electrophilic quench. The unreacted starting materials together with the 2,2‐disubstituted products could be isolated with high enantiomer ratios. Variable temperature NMR spectroscopy showed that the rate of Boc rotation was fast (ΔG≠≈57 kJ/mol at 195 K). This was corroborated by DFT studies and by in situ ReactIR spectroscopy. The enantioenriched N‐Boc‐2‐arylindolines were converted to 2,2‐disubstituted products without significant loss in enantiopurity. Hence, either enantiomer of the 2,2‐disubstituted products could be obtained with high selectivity from the same enantiomer of the chiral ligand sparteine (one from the kinetic resolution and the other from subsequent lithiation‐trapping of the recovered starting material). Secondary amine products were prepared by removing the Boc group with acid to provide a way to access highly enantioenriched 2‐aryl and 2,2‐disubstituted indolines.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Asymmetric Synthesis of 2‐Arylindolines and 2,2‐Disubstituted Indolines by Kinetic Resolution

Choi

El‐Tunsi

Wang

et al. 2021

Chemistry A European J

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“…Another area of interest involves the extension of the metalation chemistry of ArOAms to alkenyl and alkyl O-carbamates, e.g., (hetero)benzylic compounds. 514,515 Since this has not yet been reported, it is implicit that these systems are too unreactive.…”

Section: Broadening the Scope Of Metalation Chemistry To Include Alke...mentioning

confidence: 99%

“…Another area of interest involves the extension of the metalation chemistry of ArOAms to alkenyl and alkyl O -carbamates, e.g., (hetero)benzylic compounds. , Since this has not yet been reported, it is implicit that these systems are too unreactive. Nevertheless, the ready access to linear, cyclic, and annulated (e.g., adamantyl) aliphatic O -carbamates − beckons a foray into this potentially rich field.…”

Section: Conclusion and Implications For Future Researchmentioning

confidence: 99%

The Versatile and Strategic O-Carbamate Directed Metalation Group in the Synthesis of Aromatic Molecules: An Update

Jansen-van Vuuren,

Liu,

Miah

et al. 2024

Chem. Rev.

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“…[17][18][19][20][21][22][23][24] The method involving lithiation followed by electrophilic substitution is an attractive procedure to synthesize the C-1-substituted THIQs as it ensures regioselectivity. 25 This can be achieved either by prior BF 3…”

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confidence: 99%

Evaluation of Phenyldiazenyl as a Protective/Activating Group in Lithiation–Substitution Reactions of Tetrahydroisoquinolines

Singh,

Kaur,

Kaur

et al. 2023

Synlett

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Phenyldiazenyl moiety has been utilized both as a protective and activating group to synthesize C-1-substituted tetrahydroisoquinolines via lithiation–substitution strategy. This reaction sequence involves generation of α-amino carbanions, derived from N-phenyldiazenyl tetrahydroisoquinolines, followed by coupling with various electrophiles, e.g., aldehyde, ketones, alkyl halide, oxiranes, isocyanates, and with in situ generated arynes. Deprotection of the protecting group was carried out under acidic conditions to afford the desired α-substituted products in moderate to good yields. So, triazene as a protecting/directing group and its compatibility with strong bases provide a good synthetic utility for the synthesis of a variety of α-substituted secondary amines via lithiation substitution reaction.

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Recent advances in benzylic and heterobenzylic lithiation

Cited by 9 publications

References 100 publications

Asymmetric Synthesis of 2‐Arylindolines and 2,2‐Disubstituted Indolines by Kinetic Resolution

Asymmetric Synthesis of 2‐Arylindolines and 2,2‐Disubstituted Indolines by Kinetic Resolution

The Versatile and Strategic O-Carbamate Directed Metalation Group in the Synthesis of Aromatic Molecules: An Update

Evaluation of Phenyldiazenyl as a Protective/Activating Group in Lithiation–Substitution Reactions of Tetrahydroisoquinolines

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