Rediscovering Sulfinylamines as Reagents for Organic Synthesis

Abstract

Sulfinylamines (RÀ N=S=O), monoaza analogues of sulfur dioxide, have been known for well over a century, and their reactivity as sulfur electrophiles and in Diels-Alder reactions is well-established. However, they have only rarely been used in organic synthesis in recent decades despite the increasing prominence of compounds containing N=S=O functionality, such as sulfoximines and sulfonimidamides. This Minireview aims to bring wider visibility to the unique chemistry enabled by this class of compounds. We focus on advances from the last 10 years, including the first examples of their use in the one-pot syntheses of sulfoximines and sulfonimidamides. Also covered are the reactions of sulfinylamines with carbon-centred radicals, their use for formation of heterocycles through cycloadditions, and catalytic enantioselective allylic oxidation of alkenes via a hetero-ene reaction. These examples highlight the different reactivity modes of sulfinylamines and their underappreciated potential for forming molecules which contain high-or low-valent sulfur, or even no sulfur at all.

Sulfinimidate Esters as an Electrophilic Sulfinimidoyl Motif Source: Synthesis of N-Protected Sulfilimines from Grignard Reagents

“…Otherwise, sulfilimines are accessible from sulfoxides using Burgess-type reagents, and from sulfinylamines as recently reported by Willis . Due to the growing interest in accessing biologically relevant sulfur-based structural motifs, , several advances in the reactivity of sulfur functionalities have been reported during the past decade. , As an example, Stockman disclosed the electrophilic character of sulfonimidates in reactions with organometallic reagents (Scheme , a) . In detail, the reaction of Grignard reagents with sulfonimidates resulted in the stereospecific preparation of sulfoximines via the formation of a new S–C bond, by a formal substitution of the alkoxy group linked to the sulfur­(VI) atom .…”

Cycloadditions of Donor–Acceptor Cyclopropanes and ‐butanes using S=N‐Containing Reagents: Access to Cyclic Sulfinamides, Sulfonamides, and Sulfinamidines

“…[8] Sulfur has been ap opular choice of heteroatom for the reactions of D-A cyclopropanes, [9] not only because of its reactivity,but also its prevalence in important pharmaceutical compounds and natural products. [10] Sulfinylamines have recently been utilized heavily by Willis and co-workers [11] as stable starting materials for the synthesis of both sulfur(IV) in S-imino isothiazolidines.These isothiazolidine products are potentially of great interest as bioactive compounds,w ith isothiazolidine dioxides and isothiazolidinones already known to be useful as antirheumatic and anticancer agents. [15] While syntheses for sultams are relatively common, [16] very few are known for S-oxo isothiazolidines,a nd the requirement for radical initiators such as AIBN,o rl engthy starting material synthesis makes them al ess attractive route.…”

“…Sulfur has been a popular choice of heteroatom for the reactions of D–A cyclopropanes, [9] not only because of its reactivity, but also its prevalence in important pharmaceutical compounds and natural products. [10] Sulfinylamines have recently been utilized heavily by Willis and co‐workers [11] as stable starting materials for the synthesis of both sulfur(IV) and sulfur(VI) containing compounds including sulfil‐ imines, [12] sulfonamides, [13] and sulfonimidamides. [14] Inspired by this, we decided to explore the use of the S=N double bond of sulfinylamines as a 2π component in the ( n +2)‐cycloaddition reactions of D–A cyclopropanes and D–A cyclobutanes.…”

Cycloadditions of Donor–Acceptor Cyclopropanes and ‐butanes using S=N‐Containing Reagents: Access to Cyclic Sulfinamides, Sulfonamides, and Sulfinamidines

“…[8] Sulfur has been ap opular choice of heteroatom for the reactions of D-A cyclopropanes, [9] not only because of its reactivity,but also its prevalence in important pharmaceutical compounds and natural products. [10] Sulfinylamines have recently been utilized heavily by Willis and co-workers [11] as stable starting materials for the synthesis of both sulfur(IV) and sulfur(VI) containing compounds including sulfilimines, [12] sulfonamides, [13] and sulfonimidamides. [14] Inspired by this,wedecided to explore the use of the S=Ndouble bond of sulfinylamines as a2 p component in the (n + 2)-cycloaddition reactions of D-A cyclopropanes and D-A cyclobutanes.Ease of synthesis makes sulfinylamines an attractive choice of starting material, particularly because of the possibility of having al eaving group at the nitrogen atom, thus allowing formal insertion of HNSO 2 upon cleavage and potentially of great interest as bioactive compounds,w ith isothiazolidine dioxides and isothiazolidinones already known to be useful as antirheumatic and anticancer agents.…”