Dibenzoylperoxide‐Mediated Oxidative α‐Thio/Seleno‐Cyanation of β‐Ketoesters and Oxindoles

Abstract

We herein report a protocol for the α‐thio‐ and α‐seleno‐cyanation of different cyclic β‐ketoesters and oxindoles by using NaSCN or KSeCN as easily accessible inorganic nucleophilic S(e)CN sources under oxidative conditions. Key to success for both transformations is the use of dibenzoylperoxide as an oxidant allowing for the coupling of two inherently nucleophilic species under operationally simple conditions in high yields and with broad functional group tolerance.

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

“…We started our investigations by optimizing the α-azidation of the tert -butyl-containing β-ketoester 1a ( Table 1 gives an overview of the most significant results obtained hereby). First experiments testing different oxidants in combination with Bu 4 NI (30 mol %) in 1,2-dichloroethane (DCE), a solvent that we found to be well-suited for oxidative α-heterofunctionalizations before [ 39 ], showed that DBPO clearly outperforms all the other oxidants tested under these conditions ( Table 1 , entries 1–5). While H 2 O 2 gave 2a in low yield only ( Table 1 , entry 1), the use of mCPBA ( Table 1 , entry 3) and t -BuOOH ( Table 1 , entry 4) mainly resulted in the formation of the α-OH-ketoester 4 .…”

“…These oxidative approaches, which usually proceed via the in situ formation of catalytically-competent ammonium hypoiodite species, can normally be carried out under operationally simple conditions, thus allowing for the use of easily accessible starting materials. Our group has a longstanding research interest in α-heterofunctionalization reactions under oxidative conditions [ 37 – 39 ] and we [ 30 ], as well as others [ 28 – 29 31 ], have recently also explored the use of simple quaternary ammonium iodides for oxidative α-azidations of carbonyl compounds ( Scheme 1A ). Hereby different strategies using different quaternary ammonium iodide derivatives and different azide sources were investigated and especially Uyanik’s and Ishihara’s recent approach using NaN 3 in combination with the carefully designed achiral catalyst C1 represents a remarkable advancement in this field ( Scheme 1B [ 31 ]).…”

“…Furthermore, it turned out that addition of PBN (phenyl N - t ert-butylnitrone) has a beneficial effect on the reaction and that carefully buffered conditions are best-suited. We have recently established the use of dibenzoyl peroxide (DBPO) as a very powerful oxidant for oxidative heterofunctionalization reactions using simple nucleophilic inorganic salts as heteroatom transfer reagents [ 39 , 41 ]. This was successfully demonstrated for the non-catalyzed α-S(e)CN-functionalization of different pronucleophiles [ 39 ] as well as the benzylic azidation of alkylphenol derivatives with NaN 3 using TBAI as a catalyst [ 41 ].…”

“…We have recently established the use of dibenzoyl peroxide (DBPO) as a very powerful oxidant for oxidative heterofunctionalization reactions using simple nucleophilic inorganic salts as heteroatom transfer reagents [ 39 , 41 ]. This was successfully demonstrated for the non-catalyzed α-S(e)CN-functionalization of different pronucleophiles [ 39 ] as well as the benzylic azidation of alkylphenol derivatives with NaN 3 using TBAI as a catalyst [ 41 ]. Considering the fact that TBAI clearly represents one of the most easily available quaternary ammonium iodides and keeping in mind our successfully demonstrated matching combination of this catalyst with NaN 3 and DBPO for our benzylic azidations [ 41 ], we were thus wondering if the use of these simple bulk chemicals also allows for the oxidative α-azidation of different carbonyl-based pronucleophiles.…”