Chemo‐ and Regioselective Anionic Fries Rearrangement Promoted by Lithium Amides under Aerobic Conditions in Sustainable Reaction Media

Abstract

A straightforward and efficient protocol to promote the metalation/anionic Fries rearrangements of O‐aryl carbamates, using for the first time a lithium amide as metalating agent under aerobic/ambient‐friendly reaction conditions, is reported. This approach enables the sustainable preparation of salicylamide derivatives with high levels of chemoselectivity within ultrafast reaction times, working at room temperature in the presence of air/moisture, and using environmentally responsible cyclopentyl methyl ether as a solvent. Furthermore, the regioselective manipulation of O‐2‐tolyl carbamates has been accomplished using interchangeably alkyllithiums or lithium amides, with an unexpected beneficial contribution from the employment of biorenewable protic eutectic mixtures as non‐innocent reaction media.

One-Pot, Telescoped Alkenylation of Amides via Stable Tetrahedral Intermediates as Lithium Enolate Precursors

“…The formal alkenylation of amides using organometallic reagents could however be realized resorting to canonical multistep approaches proceeding via isolated ketone intermediates. 17 In the course of our studies on the reactivity of s-block polar organometallic reagents under bench-type aerobic conditions, 18 we reported a general chemoselective route to ketones from amides using non-activated N-acylpyrrolidines as privileged acylating agents of organolithiums. 19 The notorious overaddition reaction was effectively suppressed, owing to the stabilizing effect of the reaction medium [cyclopentyl methyl ether (CPME)] on the dimeric tetrahedral intermediates.…”

Microreactor-based micro/nanomaterials: fabrication, advances, and outlook

“…Their designed CMR is fabricated by thermal bonding of six layers of polyimide film, and its internal volume is 25 nL provided by a rectangular serpentine channel (width 200 mm, height 125 mm, and length 1 mm). With sub-millisecond fast mixing, unwanted anionic Fries rearrangement 207,208 can be bypassed to obtain the desired product before it occurs.…”

Visible‐Light‐Induced Multicomponent Reaction of Aromatic Aldehydes, Amines and Sodium Difluoromethanesulfinate: Synthesis of CF2H‐Substituted Secondary Amines

“…In addition, the product 4 ga could undergo a smooth reaction with ethylmethyl-carbamic chloride 5 to give rivastigmine scaffold containing product 6 in 65% yield (Scheme 2b). [19] To gain further insight into the reaction mechanism, several control experiments were performed (Scheme 3). Under the standard reaction conditions, the reaction was completely suppressed by the addition of the free radical trapping reagent TEMPO (2, 2, 6, 6-tetramethylpiperidinooxy) (Scheme 3a).…”

“…As shown in Scheme 2a, under the optimized reaction conditions, antibiotic sulfadimethoxine 2 r provided the desired product 4 ar in 55% yield. In addition, the product 4 ga could undergo a smooth reaction with ethylmethyl‐carbamic chloride 5 to give rivastigmine scaffold containing product 6 in 65% yield (Scheme 2b) [19] …”