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. 2019 Feb 18;10(13):3733-3737.
doi: 10.1039/c8sc05225e. eCollection 2019 Apr 7.

Dithiane-directed Rh(iii)-catalyzed amidation of unactivated C(sp3)-H bonds

Heyao Shi  1 , Darren J Dixon  1
Affiliations

Dithiane-directed Rh(iii)-catalyzed amidation of unactivated C(sp3)-H bonds

Heyao Shi et al. Chem Sci. .

Abstract

An oxidant-free Rh(iii)-catalyzed direct amidation of alkyl dithianes via C(sp3)-H bond activation utilizing diverse and robust dioxazolone reagents is reported. The reaction hinges on use of a Cp*Rh(iii) complex in combination with an essential amino-carboxylate additive to generate usefully protected 1,3-aminoaldehyde derivatives. The scalability of the reaction was demonstrated as was a series of downstream product functionalizations, including dithiane deprotection, anion alkylation and reductive desulfurization, highlighting the general applicability of this transformation in the synthesis of novel scaffolds and building blocks.

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Figures

Scheme 1
Scheme 1. (a) You's seminal report on Rh(iii)-catalyzed functionalization of unactivated C(sp3)–H bonds. (b) Miura's oxidative C(sp2)–H ortho alkenylation of benzylic dithianes. (c) This work.
Scheme 2
Scheme 2. Evaluation of amino acid additives. aReaction conditions: 1a (0.05 mmol), 2a (0.1 mmol), [Cp*Rh(MeCN)3][(SbF6)2] (10 mol%), Fmoc-Pro-ONa (40 mol%), solvent (0.5 mL), temperature, 36 h. bYield calculated by 1H NMR with methyl para-nitrobenzoate as internal standard.
Scheme 3
Scheme 3. C(sp3)–H amidation of a range of dithianes 1 with diverse dioxazolones 2.
Scheme 4
Scheme 4. (a) 56-fold scale-up reaction. (b) Oxidative deprotection of dithiane. (c) Corey–Seebach alkylation with allyl bromide. (d) Reductive desulfurization.
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