Palladium‐Catalyzed Enantioselective Thiocarbonylation of Styrenes

Abstract

A highly enantioselective thiocarbonylation of styrenes with CO and thiols has been achieved by Pd catalysis, providing highly enantioenriched thioesters in good to excellent yields. Key to the successful execution of this reaction is the use of a chiral sulfoxide‐(P‐dialkyl)‐phosphine (SOP) ligands. This thiocarbonylation proceeds smoothly under mild reaction conditions (1 atm CO and 0 °C) and displays broad substrate scope. Also demonstrated is that this transformation can be conducted using surrogates of CO, greatly increasing the safety aspects of running the reaction. The generality and utility of the method is manifested by its application to the synthetic transformations of thioester products and the direct acylation of cysteine‐containing dipeptides. A primary mechanism was investigated and a plausible catalytic cycle was proposed.

Sulfinyl‐Mediated Stereoselective Functionalization of Acyclic Conjugated Dienes

“…In summary,anew general method for the synthesis of 1,4diols and 1,4-aminoalcohols from conjugateds ulfinyl dienes has been reported.T his is the result of ac ascade reaction encompassing ac onjugate addition followed by diastereoselective protonation to an allylic sulfoxidea nd a [ 2,3]-sigmatropic rearrangement. The processh as been studied in depth and the advantages and limitations for an umerousc ollection of compounds covering aw ide structural scope have been defined.…”

“…The chemo-and stereocontrolled functionalization of acyclic molecules still remains am ajor challengei ns ynthetic organic chemistry.C onjugated dienes have attracted the attention of different groups and this has led to av ariety of usefuls trategies within this field. [1] Readily available enantiopure sulfoxides are also suitable precursors for acyclic stereocontrol, [2] and the [2,3]-sigmatropic rearrangemento fa llylic sulfoxides stands out as ap romising strategyt oc ontribute in solving this problem. [3] This rearrangement,d iscoveredi ndependently by Mislow,B raverman and Evans, [4] allows for the transformation of allylic sulfoxides into rearranged sulfenates that, in the presence of at hiophile, lead irreversibly to allylic alcohols (Scheme 1a).…”

“…In connection with our interest in the development of stereocontrolled methodologies using enantiopure sulfinyl auxiliaries, [5] and our interesti na cyclic stereocontrol,w ec onsidered that functionalized sulfinyl dienes A could undergo ac onjugate addition of an appropriate nucleophile, [6] to generate intermediate B (Scheme 1b). Subsequent protonation, either to alkenyl sulfoxides B' with ensuing isomerization, or to allylic sulfoxides C,c ontrolled by the preexisting contiguous chiral center,w ould eventually trigger the highly selective [ 2,3]-sigmatropic rearrangementt op roduce unsaturated 1,4-diol or 1,4-aminoalcohold erivatives D,a fter sulfenate cleavage by excess nucleophile acting as thiophile. [7] The 1,4-aminoalcohol and 1,4-diol are motifs foundi na wide range of natural and bioactive products, such as, halicholactone, amphidinolide Ha nd megluminea ntimoniate, at reatment for leishmaniasis( Figure 1).…”

“…[8] However,t he development of new methods to access theses ubstructures has attracted much less attention than the related1 , 2-, 1,3-, or 1,5-compounds. Scheme1. [2,3]-Sigmatropic rearrangement of allylic sulfoxides and proposed cascadep rocesses for the synthesiso f1,4-diol and 1,4-aminoalcohol derivatives. Existing approaches to prepare unsaturated 1,4-diols rely on nucleophilic additions, [9] reductions or metathesis, [10] of adequately functionalizedp recursors and suitable transformations carried out on oxiranes, [11] dienes and alkenes.…”

“…[13] A recent report exemplifies the synthesis of unsaturated 1,4diols, 1,4-aminoalcohols and 1,4-diamines from a-thioaldehydes. [14] We presenth erein af ull account of the results of our study on the stereoselective functionalization of acyclic sulfinyl 1,3dienes to produce highly enantioenriched 1,4-diols and 1,4aminoalcohols, via [2,3]-sigmatropic rearrangement of an in situ generated allylic sulfoxide (Scheme1). [15] This transformation renders an et chemo-and stereoselective 1,2-difunctionalization of the terminal double bond in as ulfinyl 1,3-diene, along with removal of the chiral auxiliary.…”