Base-free two-step synthesis of 1,3-diketones and β-ketoesters from α-diazocarbonyl compounds, trialkylboranes, and aromatic aldehydes

Abstract

We describe a convergent, base-free two-step synthesis of 1,3-diketones and β-ketoesters from α-diazocarbonyl compounds, trialkylboranes, and aromatic aldehydes in a three-component process. The synthetic potential of this protocol was underscored by the synthesis of several symmetrical 1,3,5-triaryl-4-alkyl and 1,3,4,5-tetraryl substituted pyrazoles in a three-step sequence.

Metal‐Free Tandem Rearrangement/Lactonization: Access to 3,3‐Disubstituted Benzofuran‐2‐(3H)‐ones

“…Examination of the in situ 1 H and 19 F NMR spectra suggests the formation of two main intermediates: the boron enolate I , which rearranges to the phenol derivative II (Scheme ). Mechanistically, the first step is the 1,2‐aryl shift from the borane to the substrate 2 , with loss of dinitrogen and formation of I as reported previously for similar reactions . Boron enolate I is not stable at room temperature and is fully converted into II within 1 h. Finally, II forms lactone 4 a and the diarylboronic ether 5 as a side product within 24 hours.…”

“…Initially, these boranes were investigated in 1,2‐aryl transfer reactions in which an aryl group is transferred from BAr 3 to an α‐diazocarbonyl compound 2 a – f to yield 3 a – o in excellent conversions (>90 %) when reacted in a 1:1 ratio (Scheme ). Importantly, the reaction was found to be sensitive to steric hindrance between the boron reagent and the diazo substrate, and typically only one aryl group is transferred ,. However, when employing the less sterically demanding ethyl 2‐diazopropanoate ( 2 a ), the efficiency of the reaction was greatly improved.…”

“…[12] In particular, we and the groups of Davies and Hashimoto have reported rhodium-catalyzed decomposition of a-diazocarbonyl compounds to yield chiral dihydrobenzofuranes, [13] novel chiral indolines, [14] and precious lactone intermediates through flow synthesis. [18] Herein we present an ovel, metal-free route to 3,3disubstituted lactones from the reaction between a-diazocarbonyl compounds and triarylboranes.I nitially,alibrary of boranes [BAr F 3 ;A r F = 4-FC 6 H 4 (1b), 2,6-F 2 C 6 H 3 (1c), C 6 F 5 (1d), and 3,4,5-F 3 C 6 H 2 (1e)] was prepared with varying Lewis acidities as determined by the Gutmann-Beckett method, and compared to the Lewis acidity of commercially available BPh 3 (1a). But this approach to a-functionalized carbonyl compounds has found only afew applications in organic chemistry,o ften limited by steric hindrance between the organoborane and the diazo substrate.…”

Metallfreie Tandem‐Umlagerung/Lactonisierung: Zugang zu 3,3‐disubstituierten Benzofuran‐2‐(3H)‐onen

“…[12] Sowohl wir als auch die Gruppen von Davies und Hashimoto haben über die Rhodium-katalysierteR eaktion von a-Diazocarbonylverbindungenu nter Bildung chiraler Dihydrobenzofurane berichtet, [13] neue chirale Indoline [14] und wertvolle Lacton-Zwischenprodukte kçnnen durch Flußsynthesen erhalten werden. [18] Hier stellen wir einen neuen, metallfreien Wegz u3 ,3-disubstituierten Lactonen durch Reaktion von a-Diazocarbonylverbindungen und Tr iarylboranen vor.Z unächst wurde eine Bibliothek von Boranen [BAr F 3 ;A r F = 4-FC 6 H 4 (1b), 2,6-F 2 C 6 H 3 (1c), C 6 F 5 (1d)u nd 3,4,5-F 3 C 6 H 2 (1e)] mit verschiedenen Lewis-Aciditäten hergestellt, die durch das Gutmann-Beckett-Verfahren bestimmt und mit der Lewis-Aciditätvon kommerziell verfügbarem BPh 3 (1a)verglichen wurden. Diese Syntheserouten zu afunktionalisierten Carbonylverbindungen haben jedoch in der organischen Chemie nur wenige Anwendungen gefunden, die häufig durch die sterische Hinderung zwischen dem Organoboran und dem Diazosubstrat limitiert sind.…”

Borane promoted aryl transfer reaction for the synthesis of α-aryl functionalised β-hydroxy and β-keto esters

“…5 Already, as early as in the 1970s, Hooz et al conducted the first studies by trapping boron enolates generated from diazo precursors with aldehydes, 6 ketones, 9 dimethylethylenammonium iodide, 7 N -bromo- or N -chlorosuccinimide 8 and nitriles (Scheme 1B–E). 9 Later, Miranda et al 10 prepared 1,3-diketones and β-keto esters from reacting α-diazocarbonyl compounds with BR 3 (R = ethyl, n -propyl, phenyl) and aldehydes followed by oxidation (Scheme 1E). 13 To explore further the utility of this approach, we developed the scope for the use of electrophilic aryl boranes as arylation reagents with diazo compounds.…”