Amine-mediated synthesis of amides from 1,3-dicarbonyl compounds through a domino diazo transfer/aminolysis process

Stereoselective Bioreduction of α-diazo-β-keto Esters

“…Azido diazo ester 2a was prepared according to the one-pot procedure from commercially available ethyl 4-chloroacetoacetate (1b), as described elsewhere [37]. The product 2a was obtained as a yellowish oil (86% yield; see Table 1) and its spectral data are in agreement with those reported in the literature [37,53]…”

“…The synthesis of α-diazo-β-keto esters 2b-i was performed following a similar protocol to the one described in the literature [37]. t-BuNH 2 (5.0 mmol, 525 µL) was added dropwise to a solution of the corresponding β-ketoester 1b-i (5.0 mmol) and 4-acetamidobenzenesulfonyl azide (5.0 mmol, 1.20 g) in dry THF (10 mL) under inert atmosphere at 25 • C. The mixture was stirred at room temperature and monitored by TLC analysis (4:1 hexane/EtOAc).…”

“…">Chemical Synthesis of α-Diazo-β-keto Esters 2a-i and Racemic α-Diazo-β-hydroxy Esters 3a-iThe investigation commenced with the racemic synthesis of representative α-diazo-β-hydroxy esters 3a-i through the chemical reduction of selected α-diazo-β-keto esters 2a-i with different substitution patterns (Scheme 1) in order to develop adequate analytical methods for the measurement of conversion and enantiomeric excess of the optically active alcohols obtained from bioreduction experiments (see below). Firstly, the amine-catalyzed diazo transfer reaction developed by Sá and cols [37] was the method of choice to prepare diazo compounds 2 due to its high efficiency and broad substrate scope. Therefore, the preparation of the starting α-diazo-β-keto esters 2b-i was readily achieved in 81-96% yield (3-5 mmol scale) through the diazo transfer protocol from 4-acetamidobenzenesulfonyl azide (p-ABSA) and the corresponding β-keto esters 1b-i (right side of Scheme 1 and Table 1), which are commercially available or can be easily prepared from simple reagents (see the Experimental section).…”

Continued Exploration of Trifunctional Alkyl 4-Chloro-2-diazo-3-oxobutanoates: Streamlined Entry into [1,2,3]Triazolo[5,1-c][1,4]benzoxazines and [1,2,3]Triazolo[5,1-c][1,4]benzoxazepines

“…the formation of bicyclic 6,7-dihydro-4H- [1,2,3]triazolo [5,1-c] [1,4]thiazines 2. 5 These reactions proceeded in good to excellent (67-96%) yields and no fragmentation of -oxo--diazocetate moiety (known to be triggered by nucleophilic primary amines 6 ) was observed. Encouraged by this initial success, we were keen to extend this methodology to other bis-nucleophilic partners such as phenols bearing an amino functionality (in a protected form to ensure the selectivity of the initital SN2 event 7 ) attached to the o-position of the phenyl ring either directly or via a 1-2 carbon linker.…”

“…NMR (400 MHz, CDCl3) δ 7.46 (br. s, 1H, OH), 7.14 (ddd, J = 7.66, 7.60, 1.51 Hz, 1H, 4-Ar), 7.08 (dd, J = 7.5, 1.7 Hz, 1H, 6-Ar), 6.89 (dd, J = 7.95, 1.10 Hz, 1H, 3-Ar),6.84 (ddd, J = 7.43, 7.39, 1.08 Hz, 1H, 5-Ar), 4.98 (br. s, 1H, NH), 3.35 (q, J = 6.7 Hz, 2H, ArCH2CH2), 2.86 (t, J = 7.1 Hz, 2H, ArCH2CH2), 1.48 (s, 9H, C(CH3)3).…”