Design and synthesis of stable α-diazo-β-oxo sulfoxides

Abstract

Diazo transfer adjacent to a sulfoxide moiety to provide stable, isolable α-diazo-β-oxo sulfoxides has been achieved. Use of monocyclic and bicyclic sulfoxide precursors is critical in enabling isolation of stable derivatives, through introduction of conformational constraint, while acyclic α-diazo-β-oxo sulfoxides are too labile to isolate and characterize.

Delivering Enhanced Efficiency in the Synthesis of α-Diazosulfoxides by Exploiting the Process Control Enabled in Flow

“…The sulfoxide substrates 1a-d (Scheme 2) were selected as precursors for this study because they provide a good insight in Diazo transfer to β-oxosulfoxides under batch conditions is typically conducted overnight to effect reaction completion, providing only moderate yields but with complete consumption of the sulfoxide precursor [27]. The batch procedure consists of 1 eq.…”

“…While careful design of the cyclic substrates led to successful isolation of α-diazosulfoxides [26,27], the efficiency of their synthesis was significantly limited by partial decomposition of the labile α-diazosulfoxides within the basic reaction conditions, leading to recovered yields of typically 30% or less. Based on our recent success in effecting diazo transfer to standard precursors in flow systems [18], the potential to control more closely the synthesis and isolation of α-diazosulfoxides by diazo transfer in a continuous-flow system was investigated with the objective of improving product recovery.…”

“…Based on this work, the instability of simple acyclic α-diazosulfoxides is believed to be due to the overlap of the sulfinyl lone pair with the anti-bonding orbital of the diazo moiety [26]. Constraining the orientation of the sulfoxide and the diazo moiety in cyclic systems provides sufficient stability to isolate and characterize these novel compounds [27].…”

“…However, in contrast, diazo transfer to generate α-diazosulfoxides has proven elusive due to the inherent instability of the α-diazosulfoxide moiety [24]. Careful substrate design by our group led to isolation, for the first time, of stable α-diazosulfoxides, in both racemic and enantiopure form [25]; conformational constraint in lactones and lactams was essential to enable isolation of stable compounds possessing the diazosulfoxide moiety [26,27]. Based on this work, the instability of simple acyclic α-diazosulfoxides is believed to be due to the overlap of the sulfinyl lone pair with the anti-bonding orbital of the diazo moiety [26].…”

p-Toluenesulfonyl Azide

“…(D) Collins et al 9 reported the application of TsN 3 as a reagent in the synthesis of α-diazo-β-oxo-sulfoxides by a diazo-transfer reaction. In this work, the authors utilized sulfoxides containing monocyclic, bicyclic, or acyclic lactones and lactams.…”