康 · 学术 | Reaction of the Day No. 1729

Thiourea-Catalyzed, Hypervalent Iodine-Assisted Deoxygenative or Desulfurative Amidation of Alcohols

Erjuan Xu, Taotao Qiao, Shaojun Li, Chuhong Xie, Shan Long, and Wen-Xin Lv*

State Key Laboratory of Green Pesticide, Center for R&D of Fine Chemicals of Guizhou University, Guizhou University, Guiyang 550025, China;

—Org. Lett. 2026, 28, 10139?10144

Recommended by Xuemei Yao_MC3

KEY WORDS: Ritter Reaction, deoxygenativeamidation, desulfurativeamidation (反应类型), alcohols, thiols, nitriles (原料),  amides (产物), Csp3-N (成键类型) thiourea,PIFA (其他)

ABSTRACT: Hydroxyl groups are ubiquitous in natural products and pharmaceuticals. The dehydroxyamidation of alcohols via the Ritter reaction offers a valuable route to amide compounds but faces limited substrate scope due to its reliance on acid-catalyzed carbocation formation. Herein, we report a cooperative thiourea/(bis(trifluoroacetoxy)iodo)benzene catalytic system for the deoxygenative amidation of diverse alcohols under mild conditions. This method exhibits broad substrate compatibility and excellent functional group tolerance, enabling the challenging dehydroxylation of secondary OH groups in saccharides while preserving the acid-sensitive anomeric C(1)–O bond. The utility of this strategy is demonstrated by the direct, one-step synthesis of a rare ribosamine derivative bearing a chiral methyl group at the C5″ position from commercially available rhamnose, achieving excellent stereo- and chemoselectivity.

Background: New strategy for deoxyamidation of alcohols

Scope for alcohols and thiols (selected examples)

Proposed Mechanism

Summary and Comments

Wenxin Lv and colleagues reported a novel method for the deoxygenative or desulfurative amidation of alcohols and thiols has been established through a thiourea/PIFA cooperative catalytic system. This approach operates under mild conditions, displays broad substrate scope and good functional group tolerance, thereby significantly expanding the applicability of Ritter reaction. A key breakthrough is the efficient dehydroxylation of secondary OH groups in saccharides, exemplified by the one step conversion of commercially available rhamnose into a rare ribosamine derivative with high stereoselectivity and chemoselectivity. This step-economic transformation avoids both the removal of acid-sensitive ketal protecting groups and the cleavage of the anomeric C(1)?O bond, which underscores its potential for the late-stage modification of complex carbohydrates. Therefore, this method not only enriches the synthetic toolbox for alcohol and thiol editing but also opens new avenues to diverse complex amines such as glycosylamines, thus facilitating the development of novel drug candidates. Nevertheless, the current method still shows limited efficiency in the transformation of less reactive secondary alcohols. Future efforts will focus on achieving their efficient conversion to address this limitation.