Solid-Phase Synthesis of Unfunctionalized Arenes Via the Traceless Cleavage of Sulfonate Linkers

Abstract

The hydrogenolysis of polymer-bound arenesulfonates by 2-propylmagnesium chloride was performed through reductive cleavage of the C−S bond in the presence of a nickel catalyst. The reaction underwent in the highest efficiency by adding 15 equiv of the nucleophile in two additions with dppfNiCl 2 in THF. Various unfunctionalized naphthalene, biphenyl, and stilbene derivatives were produced in good yields by the traceless sulfonate linker system at room temperature.

Traceless Solid-Phase Organic Synthesis

“…Pyridinone 157 was prepared in solution phase and reacted with resin 156 under Pd catalysts to form fused heterocycles 158. To increase the product diversity, 75 The reductive cleavage of the C−S bond was carried out by hydrogenolysis of arylsulfonates 165 with 2-propylmagnesium chloride in the presence of a nickel catalyst. This method was applied in the synthesis of biphenyl compounds (Suzuki coupling, section 6.2, Scheme 195) and trans-stilbenes (Horner−Wadsworth−Emmons reaction, section 6.2, Scheme 196).…”

“…Arylsulfonate resin 164 (Scheme 26), prepared from 1hydroxypropan-2-yl resin 162 by a reaction with aromatic sulfonyl chlorides, 75 underwent reductive cleavage/crosscoupling of the C−S bond (Scheme 195). 310 In addition to biphenyls 1065, terphenyls 1067 were synthesized by the reaction of p-bromobenzenesulfonate 164a with two different phenylboronic acids in the presence of Pd(PPh 3 ) 4 and aqueous Na 2 CO 3 in DME (resin 1066) prior to reductive cleavage.…”

“…In anchoring Scenario B , polymer-supported arylsulfonates 164 , prepared by the sulfonylation of 1-hydroxypropan-2-yl PS/DVB resin 162 with benzenesulfonyl chlorides 163 , served as traceless C–H linkers via cleavage of the C–S bond (Scheme ). The reductive cleavage of the C–S bond was carried out by hydrogenolysis of arylsulfonates 165 with 2-propylmagnesium chloride in the presence of a nickel catalyst. This method was applied in the synthesis of biphenyl compounds (Suzuki coupling, section , Scheme ) and trans -stilbenes (Horner–Wadsworth–Emmons reaction, section , Scheme ).…”

“…Scenario B is illustrated in the following two examples. A multifunctional cleavage strategy enabled the arylsulfonate linker to serve as a C–H linker (Scheme , section ) as well as allowed its displacement by Grignard reagents, namely phenylmagnesium bromides, to access biphenyls, terphenyls, or trans -stilbenes. , The regeneration of the resin was explored.…”

Cu(acac)2-Catalyzed Synthesis of Functionalized Bis(arylmethyl)zinc Reagents and Their Olefination Reaction with Aromatic Aldehydes

“…Next, we screened the reaction by varying the substituent on the aromatic ring of the bis(arylmethyl)zinc reagents 1. Bis(arylmethyl)zinc reagents bearing either electronwithdrawing substituents (chloro, bromo, or fluoro, en-tries [13][14][15][16][17][18][19] or electron-donating substituents (methoxy, benzyloxy, or phenyl groups, entries 20-23) on the phenyl ring all reacted efficiently with arylaldehydes 2 to give the corresponding stilbenes 3l-s in moderate to high yields, which shows that both types of substituents are well tolerated. Some fragile substituents such as cyano and ester groups were not retained in these reactions, although the corresponding functionalized bis(arylmethyl)zinc reagents themselves can be successfully obtained.…”