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. 2018 Feb 8;9(11):2873-2878.
doi: 10.1039/c8sc00181b. eCollection 2018 Mar 21.

Intramolecular hydride transfer onto arynes: redox-neutral and transition metal-free C(sp3)-H functionalization of amines

Fahima I M Idiris  1 , Cécile E Majesté  1 , Gregory B Craven  1 , Christopher R Jones  1
Affiliations

Intramolecular hydride transfer onto arynes: redox-neutral and transition metal-free C(sp3)-H functionalization of amines

Fahima I M Idiris et al. Chem Sci. .

Abstract

Transition metal-free intramolecular hydride transfer onto arynes is reported for the first time. This unique transformation is utilized in redox-neutral intermolecular α-functionalization reactions of different tertiary amines, generating C(sp3)-C(sp3/sp2/sp) bonds in a single synthetic operation. Deuterium labeling studies support initial cleavage of the α-C-H bond via intramolecular 1,5-hydride transfer onto the aryne, which leads to activation of a range of integrated pronucleophiles and ultimately affords a new approach to cross-dehydrogenative coupling reactions which utilize aryne intermediates.

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Figures

Scheme 1
Scheme 1. C(sp3)–H bond activation via intramolecular hydride transfer.
Scheme 2
Scheme 2. Intramolecular hydride transfer onto aryne with THIQ derivatives. Reaction conditions: amine 1 (1.0 equiv.), KF (2.0 equiv.), 18-crown-6 (2.0 equiv.), DME : CH3CN (3 : 1 by volume, 0.01 M), 90 °C, 12 h. Yields of isolated products throughout. aRatio determined by 1H NMR spectroscopy.
Scheme 3
Scheme 3. Hydride transfer from linear and cyclic amine derivatives. Reaction conditions are as shown in Scheme 2. Yields of isolated products throughout. aRatio determined by 1H NMR spectroscopy.
Scheme 4
Scheme 4. Alternative pronucleophiles. Reaction conditions are as shown in Scheme 2. Yields of isolated products throughout. aRatio determined by 1H NMR spectroscopy. bDME : Nu-H (9 : 1 by volume, 0.01 M).
Scheme 5
Scheme 5. Mechanistic experiments. Reaction conditions are as shown in Scheme 2. aProducts 2a and 2a-d2 isolated as an inseparable mixture of isotopologues (5 : 3.5, as determined by 1H NMR spectroscopy) in a combined 70% yield.
Scheme 6
Scheme 6. Proposed mechanism.
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