Electricity Driven 1,3‐Oxohydroxylation of Donor‐Acceptor Cyclopropanes: a Mild and Straightforward Access to β‐Hydroxy Ketones

Abstract

An unprecedented external oxidant-free electrochemical protocol for 1, 3-oxohydroxylation of donor-acceptor cyclopropane is disclosed. The strategy encompasses the activation of the labile π-electron cloud of the aryl ring to cleave the strained C sp 3 À C sp 3 bond of cyclopropane to afford the β-hydroxy ketones via insertion of molecular oxygen. More significantly, based on the detailed mechanistic investigations and cyclic voltammetry experiments, a plausible mechanism is proposed.The magnificent journey of the most strained carbocycle named cyclopropane began long back in the 1970s. [1] The fundamentals laid by the frontiers have enabled the scientific community to exploit them for the construction of several complex molecular architectures cleverly. Bearing the ring strain of 115 KJ mol À 1 with an inefficient orbital overlap induces a significant amount of π-character in the bent CÀ C bonds of Cylclopropanes. [2] Further, the introduction of the donor and acceptor groups at the vicinal position of these CÀ C bonds induces a push-pull effect which polarizes the cycloalkane. [3] The previous decade has encountered a huge renaissance in the area of donor-acceptor cyclopropanes (DACs). [4] However, most of these documented protocols rely on the concept of Lewis [5] or Bronsted acid [6] catalysis, which cleaves the CÀ C bond in a heterolytic fashion and renders a zwitterionic species. [4] These 1,3-dipole species have been utilized for several cycloadditions, [7] rearrangements, [8] and ring-opening reactions. [9] Among them, 1,3-bifunctionalization of these DACs are still rare and relatively underexplored. However, there are several reports which demonstrate that these 1,3-dipoles can be seized with amines, [10a] azides, [10b] phenols, [10c] thiols [10d] etc. wherein, the ensuing anion traps the proton. In 2011, Sparr and Gilmour manifested the enantioselective 1,3-dichlorination of cyclopropane carbaldehyde in an organocatalytic fashion. [11] Later, in 2014, Werz and coworkers disclosed the ring-opening 1,3-dichlorination in the presence of iodobenzene dichloride (Scheme 1a). [12a] Followed by this, in 2017, the same group documented the reactivity of DACs with chalcogenyl chloride and bromides (Scheme 1b). [12b-c] In continuation to the endeav-[a

Aza-Oxyallyl Cation Driven 3-Amido Oxetane Rearrangement to 2-Oxazolines: Access to Oxazoline Amide Ethers

“…3, 130.8, 128.8, 127.1, 77.7, 45.2, 20.0 192.1025, found 192.1026. 4-Methoxy-N-(oxetan-3-yl)benzamide (1c). Title compound was prepared by following the same procedure for the synthesis of 1a (1.69 g, 82% yield, Colorless liquid): 1 H NMR (400 MHz, CDCl 3 ) δ 7.74 (d,J = 8.8 Hz,2H),6.92 (d,J = 8.8 Hz,2H),6.60 (s,1H), δ 5.32−5.13 (m, 1H), 5.00 (t, J = 7.1 Hz, 2H), 4.59 (t, J = 6.5 Hz, 2H), 3.84 (s, 3H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 166. 6, 162.5, 128.9, 125.9, 113.9, 78.7, 55.5, 45.3; HRMS (ESI, Q-TOF) m/z [M + H]+ calculated for C 11 H 14 NO 3 208.0974, found 208.0974.…”

“…N-(Oxetan-3-yl)-4-((trifluoromethyl)thio)benzamide (1d). Title compound was prepared by following the same procedure for the synthesis of 1a (1.99 g, 72% yield, white solid, mp = 119−121 °C): 1 H NMR (400 MHz, CDCl 3 ) δ 7.81 (d,J = 8.3 Hz,2H),7.72 (d,J = 8.3 Hz,2H),6.81 (s,1H), 5.28−5.17 (m, 1H), 5.01 (t, J = 7.1 Hz, 2H), 4.63− 4.57 (m, 2H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 166. 0, 136.1, 135.8, 128.0, 78.4, 45.5; 19 4-Fluoro-N-(oxetan-3-yl)benzamide (1e).…”

“…Yield: 74%. Nature: Colorless liquid: 1 H NMR (400 MHz, CDCl 3 ) δ 10.58 (s, 1H), 7.95−7.89 (m, 2H), 7.30 (s, 5H), 7.05 (t, J = 8.7 Hz, 2H), 4.85 (d,J = 2.3 Hz,2H),4.46 (dd,J = 10.0,8.0 Hz,1H),4.38 (dt,J = 11.4,4.9 Hz, 1H), 4.03 (t, J = 8.2 Hz, 1H), 3.61 (dd,J = 9.4,3.4 Hz,1H),3.32 (dd,J = 9.3,6.5 Hz,1H), 1.44 (s, 3H), 1.37 (s, 3H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 172. 4,164.8,164.3 (d,J = 105.4 Hz),135.4,130.8 (d,J = 8.8 Hz),130.4,129.4,128.9,128.6,128.4,123.3,115.7 (d,J = 22.0 Hz),79.3,77.7,69.4,66.3,66.3,25.4,23.9;19 N-(Benzyloxy)-2-((2-(4-chlorophenyl)-4,5-dihydrooxazol-4-yl)methoxy)-2-methylpropanamide (3af).…”

“…Yield: 78%. Nature: Colorless liquid: 1 H NMR (400 MHz, CDCl 3 ) δ 10.25 (s,1H),2H),5H),6.96 (tt,J = 8.6,2.4 Hz,1H),4.87 (d,J = 2.2 Hz,2H),4.48 (dd,J = 10.1,7.9 Hz,1H),1H), 4.07 (t, J = 8.3 Hz, 1H), 3.60 (dd, J = 9.4, 3.5 Hz, 1H), 3.35 (dd, J = 9.4, 6.2 Hz, 1H), 1.43 (s, 3H), 1.37 (s, 3H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 172.4, 164.0 (d,J = 12.3 Hz),163.8,161.6 (d,J = 12.4 Hz),135.2,130.1 (t,J = 10.0 Hz),129.6,128.7,128.4,116.2,111.7,111.6,111.5,111.4,107.3 (t,J = 25.3 Hz),79.3,77.8,69.75,66.4,65.9,25.1,24. N-(Benzyloxy)-2-((2-(3,4-dichlorophenyl)-4,5-dihydrooxazol-4yl)methoxy)-2-methylpropanamide (3ao). Reaction time: 3 h. 1o (0.10 g, 0.4 mmol), 2a (0.16 g, 0.6 mmol), 3ao (0.13 g, 0.2 mmol).…”

Lewis acid triggered N-alkylation of sulfoximines through nucleophilic ring-opening of donor–acceptor cyclopropanes: synthesis of γ-sulfoximino malonic diesters

“…On the other hand, cyclopropane dicarboxylates 8 are simple and commercially available starting materials extensively used to synthesize natural products. The unique D–A characteristics of cyclopropane have made it a valuable component in a wide range of ring-opening, 9 cycloaddition, 10 and rearrangement reactions. 11 As a result, D–A cyclopropane has been studied for several decades and its applications in natural product synthesis, and heterocyclic and medicinal chemistry have been explored.…”