α‐Imino Gold Carbene Intermediates from Readily Accessible Sulfilimines: Intermolecular Access to Structural Diversity

Abstract

Catalytic approaches to pharmaceutically important bioactive skeletons through gold carbene intermediates have experienced a dramatic development in the last decade. Although various carbene precursors continue to play an important role in heterocyclic syntheses, these reagents are associated with some drawbacks in terms of functional group tolerance, synthetic methods and safety limitations. A new generation of nitrene transfer reagents was established in 2019: the sulfilimines. These are safe, inexpensive and readily available. They can conveniently be stored and handled, and thus represent ideal reagents for the fast and modular modification of scaffolds and the preparation of libraries by intermolecular reactions of two components. Both the practical methods for synthesizing sulfilimines and the versatility of these ylidic species in gold‐catalyzed preparation of structural diversity, for both heterocycles and carbocycles, will be outlined in this Concept article.

Divergent Gold Catalysis: Unlocking Molecular Diversity through Catalyst Control

“…Gold catalysts, among all other transition metal catalysts, have secured an important position in the field of carbene chemistry. Because of their unique structural features, gold carbenes offer a distinct reactivity and selectivity profile compared to any other transition metal carbenes. − As a result, the past decade has witnessed an exponential growth in the reports of the transformation of gold carbenes. − ,− In 2012, Davies and co-workers reported an enantioselective cyclopropenation reaction of aryl alkyl alkynes and donor/acceptor diazoesters by using the binuclear chiral gold­(I) complex ( S )-xylylBINAP­(AuCl) 2 activated by AgSbF 6 . Interstingly, when alkyne 33b was used in the reaction along with methyl phenyldiazoacetate 33a , an unanticipated bicyclic product 33c was obtained instead of the expected cyclopropenation product (Scheme ).…”

Gold-Catalyzed Synthesis of Small Rings

“…They employed N -arylsulfilimines 459 for the formation of α-imino gold carbenes 461 through intermolecular attack on gold-activated ynamides followed by N–S cleavage ( Scheme 103 ). 613 The intermediates could be trapped in a number of ways, 599 including by a tethered alkene to deliver 3-azabicyclo[3.1.0]hexan-2-imines 460 in good to excellent yields. In order for the reaction to proceed efficiently, more Lewis acidic gold(III) rather than gold(I) catalysts were beneficial, a temperature of 80 °C was required, and the sulfilimines had to carry a strong electron-withdrawing group on the arene.…”

“…In the same way as α-oxo gold carbenes can be accessed from gold-activated alkynes by oxygen transfer using N -oxides and sulfoxides (see section ), α-imino gold carbenes 439 can be obtained employing nitrogen-based nucleophiles 437 that bear a leaving group on the N atom (Scheme ). − These reagents are also termed nucleophilic nitrenoids, because they perform a net nitrene transfer to the alkyne. Their anti addition to a gold­(I) or gold­(III) activated alkyne delivers vinyl gold species 438 .…”

“…In order for the reaction to proceed efficiently, more Lewis acidic gold­(III) rather than gold­(I) catalysts were beneficial, a temperature of 80 °C was required, and the sulfilimines had to carry a strong electron-withdrawing group on the arene. Sulfilimines are the nitrogen counterpart of sulfonium ylides, previously used by Maulide and co-workers in gold-catalyzed cyclopropanations (see section ). − …”

Anthranils: versatile building blocks in the construction of C–N bonds and N-heterocycles

“…46 6. Gold-catalysed annulation of anthranils with alkynes Gold carbene complexes 47 have been recognized as versatile and powerful intermediates in gold catalysed organic synthesis. In this field, α-imino gold carbene complexes 48 have emerged as useful intermediates towards the synthesis of N-heterocycles.…”