Matthias Brewer

We report a metal-free synthesis of N-alkyl-4-vinyl oxazolidinones. In the presence of sodium hydride, 4-chloro-1-hydroxy-2-butene reacts efficiently with N-alkyl carbamoylimidazoles to give carbamate intermediates, which undergo a subsequent S_N2′ ring closure, providing the N-alkyl-4-vinyl oxazolidinones in high yield on a gram scale. Received: 05 March 2026 Accepted after revision: 10 April 2026 Article published online: 28 April 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

The addition of enoxysilanes to vinyl diazonium ions occurs with varying levels of diastereoselectivity. To understand the origins of the stereoselectivity, we studied these transformations using density functional theory (DFT) calculations. The selectivity stems from a stabilizing cation-π interaction that orients the nucleophile and the diazonium ion.

The Lewis acid mediated allylation of β-hydroxy-α-diazo carbonyls gives β-allyl-α-diazo carbonyl products. The diazo functional group is retained over the course of the reaction giving functional group rich products.

The conjugate addition of alcohols to vinyl diazonium ions formed via Zn(OTf)2-catalysis gives alpha-diazo-beta- alkoxy carbonyls. The diazo group is retained in this reaction, and this process is an efficient way to couple a reactive partner to the diazo fragment. As an example, we disclose that addition of allyl alcohols provides tetrahydro-3H-furo[3,4-c]pyrazoles via an addition/cycloaddition sequence. This two-step sequence provides good yields and good diastereoselectivity of these sterically hindered pyrazoline scaffolds with up to three quaternary centers and four stereogenic centers. These products can be elaborated to cyclopropane-fused tetrahydrofurans upon liberation of nitrogen. The reaction conditions are mild, operationally simple, and avoid the use of expensive transition metal catalysts.

Structurally complex diazo‐containing scaffolds are formed by conjugate addition to vinyl diazonium salts. The electrophile, a little studied α‐diazonium‐α,β‐unsaturated carbonyl compound, is formed at low temperature under mild conditions by treating β‐hydroxy‐α‐diazo carbonyls with Sc(OTf)₃. Conjugate addition occurs selectively at the 3‐position of indole to give α‐diazo‐β‐indole carbonyls, and enoxy silanes react to give 2‐diazo‐1,4‐dicarbonyl products. These reactions result in the formation of tertiary and quaternary centers, and give products that would be otherwise difficult to form. Importantly, the diazo functional group is retained within the molecule for future manipulation. Treating an α‐diazo ester indole addition product with Rh₂(OAc)₄ caused a rearrangement to occur to give a 2‐(1H‐indol‐3‐yl)‐2‐enoate. In the case of diazo ketone compounds, this shift occurred spontaneously on prolonged exposure to the Lewis acidic reaction conditions.

Structurally complex diazo‐containing scaffolds are formed by conjugate addition to vinyl diazonium salts. The electrophile, a little studied α‐diazonium‐α,β‐unsaturated carbonyl compound, is formed at low temperature under mild conditions by treating β‐hydroxy‐α‐diazo carbonyls with Sc(OTf)₃. Conjugate addition occurs selectively at the 3‐position of indole to give α‐diazo‐β‐indole carbonyls, and enoxy silanes react to give 2‐diazo‐1,4‐dicarbonyl products. These reactions result in the formation of tertiary and quaternary centers, and give products that would be otherwise difficult to form. Importantly, the diazo functional group is retained within the molecule for future manipulation. Treating an α‐diazo ester indole addition product with Rh₂(OAc)₄ caused a rearrangement to occur to give a 2‐(1H‐indol‐3‐yl)‐2‐enoate. In the case of diazo ketone compounds, this shift occurred spontaneously on prolonged exposure to the Lewis acidic reaction conditions.

Substituted α-alkylidene cyclopentenones are formed in up to 93% yield by the intramolecular capture of vinyl cations with pendent alkenes. An increased level of substitution at the β-position of the β-hydroxy-α-diazoketone starting material changed the course of the reaction to instead give a lactone product. A reaction path that involves bond reorganization via an acylium ion intermediate is proposed to explain these results. Substrate scope studies showed that more stable vinyl cations gave higher α-alkylidene cyclopentenone yields. This study provides a mild and efficient method to form α-alkylidene cyclopentenones that complements C–H insertion and Nazarov cyclization strategies.

The Lewis acid-promoted generation of destabilized vinyl cations from β-hydroxy diazo ketones leads to an energetically favorable 1,2-shift across the alkene followed by an irreversible C–H insertion to give cyclopentenone products. This reaction sequence overcomes typical challenges of counter-ion trapping and rearrangement reversibility of vinyl cations and has been used to study the migratory aptitudes of nonequivalent substituents in an uncommon C(sp²) to C(sp) vinyl cation rearrangement. The migratory aptitude trends were consistent with those observed in other cationic rearrangements; the substituent that can best stabilize a cation more readily migrates. However, density functional theory calculations show that the situation is more complex. Selectivity in the formation of one conformational isomer of the vinyl cation and facial selective migration across the alkene due to an electrostatic interaction between the vinyl cation and the adjacent carbonyl oxygen work in concert to determine which group migrates. This study provides valuable insight into predicting migration preferences when applying this methodology to the synthesis of structurally complex cyclopentenones that are differentially substituted at the α and β positions.

Vinyl cations derived from diazo ketones participate in transition-metal-free C–H insertion reactions, but the corresponding amide and ester analog exhibit divergent reactivity profiles. Whereas cations formed from diazo ketones undergo a rearrangement and C–H insertion sequence, those from diazo amides do so less efficiently and tend to be competitively trapped before the insertion step occurs. Diazo esters undergo several rearrangement steps and fail to insert. DFT calculations reveal that this disparity stems from two factors: differing levels of electrostatic stabilization of the initially formed vinyl cation by the adjacent carbonyl oxygen and predistortion of the ketone and amide systems toward C–H insertion. The computational data is in strong agreement with experimental results, and this study explains how structural and electronic factors determine the outcome of reactions of diazo carbonyl-derived vinyl cations.