Synlett 2021; 32(05): 521-524
DOI: 10.1055/s-0040-1707161
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The Power of Transition Metals: An Unending Well-Spring of New Reactivity
© Georg Thieme Verlag Stuttgart · New York

Zinc-Catalyzed Transacetalization of N,O-Acetals into N,N-Acetals with Benzotriazoles, Indazoles, and Azides

Sang Ik Shin
,
Nguyen H. Nguyen
,
Jangbin Im
,
Department of Chemistry, Center for New Directions in Organic Synthesis (CNOS) and Research Institute for Natural Sciences, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea   Email: [email protected]
› Author Affiliations
This work was supported by the National Research Foundation of Korea (Grant Numbers NRF-2012M3A7B4049653, NRF-2014–011165, and NRF-2017R1A2B4010888).
Further Information

Publication History

Received: 02 May 2020

Accepted after revision: 31 May 2020

Publication Date:
23 June 2020 (online)


This paper is dedicated to Professor Barry M. Trost to celebrate his career on the occasion of 20 years of Science of Synthesis.

Abstract

N,O-Acetals obtained from β-oxidation of ynamides underwent transacetalization with benzotriazoles, leading to N,N-acetals. The Zn(OTf)2 efficiently catalyzed the process, and the reaction is further accelerated in hexafluoroisopropanol, providing a single N1-regiosiomer. The transacetalization conditions developed could be extended to other N-donors, such as 1H-indazole and TMSN3 to afford the corresponding N,N-acetals.

Supporting Information

 
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  • 12 Synthesis of 3 – Typical Procedure for 3a In a 4 mL vial, the N,O-acetal 1a (38.2 mg, 0.1 mmol), benzotriazole (2, 35.7 mg, 0.3 mmol), and Zn(OTf)2 (3.6 mg, 0.01 mmol) were dissolved in hexafluoroisopropanol (HFIP, 1 mL). The reaction mixture was then heated to 60 °C for 9 h, when the reaction was judged to be complete (TLC). The mixture was concentrated to dryness, and the residue was purified by SiO2 flash chromatography (EtOAc/n-hexane/CH2Cl2 = 1:15:5) to afford 3a (30 mg, 87%) as a white solid; mp 108–110 ℃. 1H NMR (400 MHz, CDCl3): δ = 8.11 (d, J = 9.2 Hz, 1 H), 7.92 (s, 1 H), 7.83 (d, J = 8.4 Hz, 1 H), 7.79 (d, J = 7.3 Hz, 2 H), 7.63 (t, J = 15.4 Hz, 1 H), 7.55 (t, J = 14.9 Hz, 1 H), 7,48 (t, J = 15.4 Hz, 1 H), 7.38 (t, J = 13.9 Hz, 2 H), 3.10 (s, 3 H), 2.94 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 189.0, 145.8, 134.5, 133.5, 132.4, 129.1, 128.5, 125.0, 120.5, 109.7, 71.4, 38.9, 31.3. HRMS (EI): m/z [M]+ calcd for C16H16N4O3S+: 344.0938; found: 344.0941.