Metal-free cross-coupling reaction of aldehydes with disulfides by using DTBP as an oxidant under solvent-free conditions

Abstract

A DTBP-promoted C–H thiolation of aldehydes with disulfides under metal-free and solvent-free conditions is described. The system shows good functional group tolerance to afford thioesters in moderate to excellent yields.

Organocatalytic Transformation of Aldehydes to Thioesters with Visible Light

“…[8] Metalf ree acyl radical engaged thioester formation processb ye mploying widely availablea ldehydes as radical coupling progenitors [9] hasl ong been investigateds ince the seminalw ork by Takagi. However,stoichiometric radical initiators, [11] or oxidants [12] are essen-tial for effective radical generation (Scheme 1a). However,stoichiometric radical initiators, [11] or oxidants [12] are essen-tial for effective radical generation (Scheme 1a).…”

“…[15] Nonetheless, they mediated HATg enerally carried out under UV light. [4,11,12] Our exploratory studies began with am odel reaction of aldehyde 1a (0.2 mmol) with commonlyu sed sulfenyl donors (0.24 mmol) including thiol, disulfide and thiosulfonate S-ester 2a in the presence of ak etone catalyst( 0.01 mmol) in MeCN (2.0 mL) irradiated with blue LEDs under N 2 atmosphere (Table 1). [16] Studies have shown that bond dissociation enthalpy (BDE) considerations are less important than CÀHb ond polarity in HAT.…”

“…[10] These transformations are generally carriedo ut with ac atalyst. However,stoichiometric radical initiators, [11] or oxidants [12] are essen-tial for effective radical generation (Scheme 1a). Such al arge amount of reagents particularly peroxides and the accumulation of in situ produced highly concentrated radicals often inducem ore side reactions and displays lowf unctional tolerance, which is crucially important in the elaborationo fs tructurallyc omplex, medicinally relevant frameworks.…”

“…Notably,t he process displayed broad substrate scope and wide functional group tolerance, and enabled late-stage modification of complex structures, which are difficult to achieve with the existing protocols. [4,11,12] Our exploratory studies began with am odel reaction of aldehyde 1a (0.2 mmol) with commonlyu sed sulfenyl donors (0.24 mmol) including thiol, disulfide and thiosulfonate S-ester 2a in the presence of ak etone catalyst( 0.01 mmol) in MeCN (2.0 mL) irradiated with blue LEDs under N 2 atmosphere (Table 1). Thiol and disulfide did not produce desired product 3a with phenylglyoxylic acid (I), whereas 10 %o f3a was obtained with thiosulfonate 2a (entry 1).…”

Microwave‐assisted Synthesis of Thioesters from Aldehydes and Thiols in Water

“…Recently, our research group reported the copper‐ and iron‐catalyzed coupling of aldehydes with thiols in water by using tert ‐Butyl hydroperoxide (TBHP) as an oxidant . Very recently, we have also reported a metal‐ and solvent‐free direct C–H thiolation of aldehydes promoted by Di‐ tert ‐Butyl peroxide (DTBP) . This system showed good functional group compatibility with electron‐donating and electron‐withdrawing groups and also with halo groups, as they are all tolerated by the reaction conditions employed.…”