Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, UK.
Medicine Design, Pfizer Inc., Eastern Point Road, Groton, CT, 06340, USA.
Angew Chem Int Ed Engl. 2021 Oct 4;60(41):22461-22468. doi: 10.1002/anie.202109146. Epub 2021 Sep 8.
Heteroaromatic sulfinates are effective nucleophilic reagents in Pd -catalyzed cross-coupling reactions with aryl halides. However, metal sulfinate salts can be challenging to purify, solubilize in reaction media, and are not tolerant to multi-step transformations. Here we introduce base-activated, latent sulfinate reagents: β-nitrile and β-ester sulfones. We show that under the cross-coupling conditions, these species generate the sulfinate salt in situ, which then undergo efficient palladium-catalyzed desulfinative cross-coupling with (hetero)aryl bromides to deliver a broad range of biaryls. These latent sulfinate reagents have proven to be stable through multi-step substrate elaboration, and amenable to scale-up.
杂芳基磺酸盐是钯催化的芳基卤与芳基卤交叉偶联反应中的有效亲核试剂。然而，金属磺酸盐盐很难纯化，在反应介质中溶解度低，并且不能耐受多步转化。在这里，我们介绍了碱激活的、潜伏的磺酸盐试剂：β-腈和β-酯砜。我们表明，在交叉偶联条件下，这些物质原位生成磺酸盐盐，然后与（杂）芳基溴化物进行有效的钯催化脱磺基交叉偶联，以提供广泛的联芳基化合物。这些潜伏的磺酸盐试剂已经被证明在多步底物修饰过程中稳定，并且适合放大规模。
