Aerobic Metal-Free Dioxygenation of Alkenes with tert-Butyl Nitrite and

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Aerobic Metal-Free Dioxygenation of Alkenes with tert-Butyl Nitrite and N‑Hydroxylamines Raghunath Bag, Dinabandhu Sar, and Tharmalingam Punniyamurthy* Department of Chemistry, Institute of Technology Guwahati, Guwahati 781039, India S Supporting Information *

ABSTRACT: Metal-free dioxygenation of alkenes with tertbutyl nitrite and N-hydroxylamines (N-hydroxyphthalimide, N-hydroxybenzotriazole, and N-hydroxysuccinimide) is described to produce β-aminoxy nitrate esters using air as the oxidant. These organic nitrates can be readily converted into 1,2-diols and 1,2-diketone with broad substrate scope and functional group diversity.

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INTRODUCTION Recent advances in dioxygenation of alkenes have led to the development of effective methods for the construction of regioselective C−O bond formation.1−3 From an industrial standpoint, the use of air or molecular oxygen as an oxidant is attractive for this synthetic goal as it is readily available and environmentally benign.2 Transition-metal-catalysts have been considerably explored for this purpose.3 In contrast, metal-free protocols are rare, which are valuable from an economical and environmental viewpoint.4 Alexanian and co-workers reported dilauroyl peroxide-catalyzed dioxygenation of alkenes with hydroxamic acids and molecular oxygen to afford β-oxyamine alcohol at moderate temperature (Scheme 1a).4b More recently, Adimurthy and co-workers demonstrated phenyliodonium diacetate-mediated dioxygenation of alkenes with hydroxylamines and molecular oxygen to give β-keto alkoxyamines at

room temperature (Scheme 1b).4e These strategies provide an efficient synthetic tool for a selective radical 1,2-dioxygenation of alkenes. Herein, we report a simple, general, and efficient dioxygenation of alkenes with tert-butyl nitrite (tBuONO) and N-hydroxylamines using air to afford β-aminoxy nitrate esters at room temperature via tandem C−O and O−N bond formations, which are important functional scaffolds of natural products5 and biologically active compounds6 (Scheme 1c and Figure 1).7 The selectivity, broad substrate scope, and

Scheme 1. Metal-Free Aerobic Dioxygenation of Alkenes

Figure 1. Examples of important nitrate-ester drugs: (a) GTN, (b) ISDN, and (c) ISMN.

functional group diversity are the important practical features. The nitrate esters can be further converted into 1,2-diols and 1,2-diketone that are versatile building blocks in organic synthesis.

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RESULTS AND DISCUSSION Initially, the optimization of the reaction was performed using 4-methylstyrene 1a with N-hydroxyphthalimide (NHPI) 2a as a model substrate in the presence of tert-butyl nitrite (tBuONO) under ambient conditions (Table 1). Gratifyingly, the dioxygenation efficiently occurred to furnish nitrate ester 3a in 63% yield along with peroxide 4a (5%), alcohol 4a′ (6%), and ketone 4a″ (7%) as byproducts at 24 h in 1,2Received: August 1, 2017 Accepted: September 19, 2017 Published: September 29, 2017 © 2017 American Chemical Society

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DOI: 10.1021/acsomega.7b01111 ACS Omega 2017, 2, 6278−6290

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Table 1. Optimization of the Reaction Conditionsa

yield (%)b entry

1a (equiv)

solvent

1 2 3 4 5 6 7 8 9 10 11 12 13 14

2 2 2 2 2 2 2 2 3 1.5 2 2 2 2

(CH2Cl)2 CH2Cl2 chlorobenzene toluene CH3CN THF DMSO DMF chlorobenzene chlorobenzene chlorobenzene chlorobenzene chlorobenzene chlorobenzene

3a 63 59 69 53 42 55

61 47 60c 58d 62e tracef

4a

4a′

4a″