α‐Aryliodonio Diazo Compounds: S_N Reactions at the α‐C Atom as a Novel Reaction Type for Diazo Compounds

Abstract

α‐Onio‐substituted diazo compounds 2 are formed by reaction of nucleophiles Nu with α‐aryliodonio diazo compounds such as 1. These are the first SN reactions at the α‐C atom of diazo compounds that proceed with retention of the diazo function. Nu = pyridine, SMe2, AsPh3, SbPh3, NEt3.

Reactions between Diazo Compounds and Hypervalent Iodine(III) Reagents

“…As described above, Weiss and Bonge‐Hansen had shown that α‐aryliodonio diazo compounds could release iodobenzene and react with thioethers to produce the corresponding sulfonium diazo products in high yields . In the following years, related research was sluggish until Gaunt and co‐workers focused their attention on the S‐Me group in the side chain of methionine and made a substantial advance in bioconjugation chemistry by using linear λ 3 ‐iodonio diazo reagents 54 (Scheme ) .…”

“…The first successful combination of diazo compounds and hypervalent iodine(III) reagents in one molecular skeleton was implemented by Weiss and co‐workers in 1994 (Scheme ) . Either aryl iodonium salts 48 or PIDA ( 30 ) can be used to smoothly transform diazoacetates 47 into the corresponding α‐aryliodonio diazo compounds ( 49 and 50 ) at room temperature in good yields.…”

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

“…Recently, our group reported the synthesis of a new class of cyclic and pseudocyclic hypervalent iodine reagents substituted with diazomethyl groups and exploited them in photocatalytic arene C−H bond diazomethylations via diazomethyl radicals; [8] and in the catalytic cleavage of C−C double bonds with Rh‐carbynoids [9, 10] . In 1994, the group of Weiss reported the synthesis of the parent linear hypervalent iodine derivate and demonstrated its ability to react with nucleophiles such as sulfides, phosphines or amines [11] . More recently, the groups of Bonge‐Hansen [12] and Gaunt [13] demonstrated applications of the linear hypervalent iodine reagents in nucleophilic halogenations and in a methionine bioconjugation of peptides and proteins, respectively [14] …”

A protein functionalization platform based on selective reactions at methionine residues

“…Tailoring the substituents and counteranion on the I(III) atom should allow tuning of the reactivity of the polarizable I(III) nodal center to dovetail with the electron lone pair of the thioether and, also, the stability of the resulting sulfonium conjugate through modulation of the electronic features of the groups directly attached to the cationic sulfur motif. We had noted that a structurally remarkable iodonium salt ( 1 in Figure 1, R=Et and X=OTf) reacts rapidly with dimethylsulfide (the simplest possible mimic of the thioether motif in methionine) to form a sulfonium adduct21,22. Successful reaction of this iodonium salt with methionine would not only represent a distinct method for bioconjugation, but also deliver a high-energy conjugate equipped with reactive ‘on protein’ groups that could serve as a basis for designing new transformations towards diversely-functionalized protein constructs (Figure 1b).…”