A Lewis Acid-Catalyzed Diastereoselective Synthesis of Functionalized 2-Diazo-1,5-dicarbonyl Compounds

Abstract

A diverse array of 2-diazo-1,5-dicarbonyl compounds were formed by the Lewis acid-catalyzed reaction of enoxysilanes with β-hydroxy-α-diazo carbonyls. This reaction proceeds via the Zn­(OTf)2-catalyzed dehydroxylation of the β-hydroxy-α-diazo carbonyl to form a vinyl diazonium ion intermediate that is intercepted by the enoxysilane nucleophile to give diazo-containing scaffolds with increased molecular complexity. The reaction appears to be general, and a variety of functional groups, including common protecting groups, are well tolerated. The 2-diazo-1,5-dicarbonyl products are formed in yields of up to 99% with diastereoselectivity up to >20:1.

Acid-Catalyzed Decomposition of O-Silylated α-Diazo-β-hydroxy Esters: Access to Mixed Monosilyl Acetals

“…Concerning the formation of acetal 16 , a second mechanism seems likely to be involved, initiated by the protonation of the TBS-ether oxygen (Scheme , pathway 2). Accordingly, elimination of TBS–OH would generate stabilized carbocation d , prone to undergo alcohol addition, in a similar way than the trapping of vinyldiazonium intermediates by various nucleophiles recently reported by Brewer’s team . The resulting β-alkoxy-α-diazoester could be easily protonated by TfOH on the diazotated carbon as in pathway 1 and undergo 1,2-Ar migration triggered by dediazotation .…”

Lewis Acid-Catalyzed [3 + 2]-Cyclization of Iodonium Ylides with Azadienes: Access to Spiro[benzofuran-2,2′-furan]-3-ones

“…On the basis of the results obtained and literatures, a plausible reaction pathway was proposed (Scheme ). First, HFIP as the solvent could significantly enhance the acidity of Lewis acid, thereby promoting the enol isomerization of iodonium ylides, and obtaining the Zn complex A , which was detected by high-resolution mass spectra (HRMS).…”

Lewis Acid Mediated Conjugate Addition of Isocyanides to β-Hydroxy-α-diazo Carbonyls: Synthesis of β-Carboxamido-α-diazo Carbonyl Compounds

“…Scope of the Reaction with Respect to the β-Hydroxy-α-diazo Carbonyls 2 a,b a Reaction conditions: 1a (0.2 mmol), 2b−p (0.2 mmol), La(OTf) 3 (0.4 mmol), Yb(OTf) 3 (0.02 mol), THF (1.0 mL), at 0 °C for 30 min, and then further at 25 °C for 8−12 h. b Isolated yield. Based on the experimental results and related reports, 5,6,12 4). The requirement of 2.0 equiv of Lewis acid suggests that the isonitrile and/ or product also bind the Lewis acid and prevent productive reaction.…”

“…In particular, the β-hydroxy-α-diazo carbonyls have received particular attention and have been intensively applied in the synthesis of important molecules by ring fragmentation, C–H insertion, and intramolecular cyclization reactions employing a vinyl cation as the key intermediate in the presence of Lewis acids. Recently, the β-hydroxy-α-diazo carbonyls can also serve as the precursor of vinyl diazonium ions accompanying the retention of the diazo group to take part in the conjugate addition reaction. , In 2020, Brewer and co-workers reported the Sc­(OTf) 3 -promoted conjugate addition reactions of indole or enoxysilanes with β-hydroxy-α-diazo carbonyls as a vinyl diazonium ion precursor for the first time (Scheme , (1)) . More recently, this addition reaction of enoxysilanes with β-hydroxy-α-diazo carbonyls has been made in the presence of a catalytic amount of Zn­(OTf) 2 .…”

“…Recently, the β-hydroxy-α-diazo carbonyls can also serve as the precursor of vinyl diazonium ions accompanying the retention of the diazo group to take part in the conjugate addition reaction. , In 2020, Brewer and co-workers reported the Sc­(OTf) 3 -promoted conjugate addition reactions of indole or enoxysilanes with β-hydroxy-α-diazo carbonyls as a vinyl diazonium ion precursor for the first time (Scheme , (1)) . More recently, this addition reaction of enoxysilanes with β-hydroxy-α-diazo carbonyls has been made in the presence of a catalytic amount of Zn­(OTf) 2 . Obviously, it is very necessary to carry out the conjugate addition reaction of new nucleophiles to β-hydroxy-α-diazo carbonyls as a vinyl diazonium ion precursor.…”