A Conjugate Addition Approach to Diazo‐Containing Scaffolds with β Quaternary Centers

Abstract

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.

β‐Diazocarbonyl Compounds: Synthesis and their Rh(II)‐Catalyzed 1,3 C−H Insertions

“…It is worth highlighting that compound 3 s exemplifies the ability of this method to reach diazo compounds α‐substituted with all‐carbon quaternary stereogenic centers. Such structural motifs are hardly accessible by classical or modern diazo synthesis [17] …”

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

“…Very recently, we reported that indoles added to vinyl diazonium ions in high yield to give tertiary and all-carbon quaternary centers while retaining the diazo functional group within the molecule (Scheme 1). 30 A complementary and concomitant study by Doyle and coworkers demonstrated a similar reactivity stemming from vinyl diazo compounds in the presence of Tf 2 NH. 31 We also provided a limited set of examples showing that enoxysilanes were competent nucleophiles in these reactions.…”

Brønsted Acid Catalyzed Oxocarbenium-Olefin Metathesis/Rearrangements of 1H-Isochromene Acetals with Vinyl Diazo Compounds

“…We recently reported that bis­(trifluoromethanesulfonyl)­imide (HNTf 2 ) serves as a uniquely efficient Brønsted acid that selectively protonates the vinylogous position of vinyl diazo compounds forming reactive vinyl diazonium ions . Brewer has developed the Lewis acid mediated dehydroxylation of β-hydroxy-α-diazo carbonyl compounds that also forms vinyl diazonium ion intermediates, and they are also accessed from N -nitrosoamides and, possibly, vinyl triazines . For reactions with diazo compounds, the vinyl diazonium ion is formed either by elimination of a leaving group α to a diazo functional group , or by proton addition to a vinyl diazo compound .…”

“…Brewer has developed the Lewis acid mediated dehydroxylation of β-hydroxy-α-diazo carbonyl compounds that also forms vinyl diazonium ion intermediates, and they are also accessed from N -nitrosoamides and, possibly, vinyl triazines . For reactions with diazo compounds, the vinyl diazonium ion is formed either by elimination of a leaving group α to a diazo functional group , or by proton addition to a vinyl diazo compound . In each process, synthetically viable electrophilic reactions of the vinyl diazonium ion or the vinyl cation formed by dinitrogen extrusion have been reported.…”