Understanding the Mechanism of the Divergent Reactivity of Non-Heteroatom-Stabilized Chromium Carbene Complexes with Furfural Imines: Formation of Benzofurans and Azetines

Abstract

The mechanisms of the reaction between non-heteroatom-stabilized alkynyl chromium carbene complexes prepared in situ and furfural imines to yield benzofurans and/or azetines have been explored by means of density functional theory method calculations. The reaction proceeds through a complex cascade of steps triggered by a nucleophilic addition of the imine nitrogen atom. The formation of two benzofuran regioisomers has been explained in terms of competitive nucleophilic attacks to different positions of the carbene complex. Each of these regioisomers can be obtained as the major product depending on the starting materials. The overall sequence could be controlled to yield benzofurans or azetines by adjusting the substituents present in the initial carbene complex. This mechanistic information allowed for the preparation of new benzofurans and azetinylcarbenes in good yields.

Fischer Carbene Complexes: A Glance at Two Decades of Research on Higher‐Order Cycloaddition Reactions

“…Since the first reports by Öfele [156] and Casey, [157] non‐heteroatom‐stabilized carbene complexes (NHSCCs) have been identified by some authors as a new group of compounds, similar to FCCs but with different characteristics and reactivity [160–162] . In contrast, NHSCCs have been labeled by other researchers as a particular type of FCC without a heteroatomic stabilizer.…”

“…Finally, the imine‐enamine tautomerization completes the synthesis of compound 213 (Scheme 38). [160,164] …”

1- and 2-Azetines via Visible Light-Mediated [2+2]-Cycloadditions of Alkynes and Oximes

“…Synthesis of 2-azetines is similarly limited, relying on eliminations [27][28][29][30][31][32][33] (7), and metal mediated cycloadditions via ring expansion of diazoaziridines (8). Arguably, [2+2]-cycloadditions between alkenes and nitriles 34,35 or alkynes and imines [36][37][38] represent the most efficient strategies to access 1-and 2-azetines, however they suffer from a limited scope and the competing formation of azadiene byproducts 39 (12 and 16, Fig. 1C).…”

“…Sterically demanding internal alkynes (30,(35)(36) were amenable to the reaction conditions, albeit resulting in decreased yields. Moreover, aryl alkynes incorporating electron-donating groups in the para position resulted in up to 34% yield (39,40) while an electron-withdrawing substituent proved superior (38) and resulted in 55% yield. Importantly, an alkyne lacking an aryl activating group but incorporating two ester groups allowed formation of the product in an excellent yield of 88% (37) demonstrating that aryl alkynes are not required if the resulting intermediates can be sensitized through TTEnT.…”

Unexpected [4 + 2] Cycloaddition through Chromium Non-Heteroatom-Stabilized Alkynyl Carbene Complexes: Regioselective Access to Substituted 6-Azaindoles

“…However, to the best of our knowledge, no examples have been reported to date of participation of group VI carbene complexes through formal [4 + 2] cycloadditions involving the C carbene and C α positions. Additionally, after poor applications for decades, non-heteroatom-stabilized carbene complexes, first reported by Casey in 1973, have been a particular object of attention, since a new methodology for their synthesis has been established in our group. , Following this methodology, in addition to open-chain compounds, [2 + 1], [2 + 2], [3 + 3], and [4 + 3] carbo- and heterocycloadditions have also been achieved (Figure ). However, no examples of formal [4 + 2] cycloadditions have been reported to date.…”