Autotrophic theories for the origin of life propose that CO2 was the carbon source for primordial biosynthesis. Among the six known CO2 fixation pathways in nature, the acetyl CoA (or Wood-Ljungdahl) pathway is the most ancient, and relies on transition metals for catalysis. Modern microbes that use the acetyl CoA pathway typically fix CO2 with electrons from H2, which requires complex flavin-based electron bifurcation. This presents a paradox: How could primitive metabolic systems have fixed CO2 before the origin of proteins? Here we show that native transition metals (Fe0, Ni0, Co0) selectively reduce CO2 to acetate and pyruvate, the intermediates and end-products of the AcCoA pathway, in near mM levels in water over hours to days using 1-40 bar CO2 and at temperatures from 30-100 °C. Geochemical CO2 fixation from native metals could have supplied critical C2 and C3 metabolites before the emergence of enzymes.

Ideal organic syntheses involve the rapid construction of C-C bonds, with minimal use of functional group interconversions. The Suzuki-Miyaura cross-coupling (SMC) is a powerful way to form biaryl linkages, but the relatively similar reactivity of electrophilic partners makes iterative syntheses involving more than two sequential coupling events difficult to achieve without additional manipulations. Here we develop (hetero)aryl sulfones as electrophilic coupling partners for the SMC reaction, which display an intermediate reactivity between those of typical aryl (pseudo)halides and nitroarenes. The new complementary reactivity allows for rapid sequential crosscoupling of arenes bearing chloride, sulfone and nitro leaving groups, affording non-symmetric ter-and quateraryls in only 2 or 3 steps, respectively. The SMC reactivity of (hetero)aryl sulfones is demonstrated in 30 examples. Mechanistic experiments and DFT calculations are consistent with oxidative addition into the sulfone C-S bond as the turnover-limiting step. The further development of electrophilic cross-coupling partners with complementary reactivity may open new possibilities for divergent iterative synthesis starting from small pools of polyfunctionalized arenes.

Sulfonyl fluorides have emerged as powerful "click" electrophiles to access sulfonylated derivatives. Yet, they are relatively inert towards C À C bond forming transformations, notably under transition-metal catalysis. Here, we describe conditions under which aryl sulfonyl fluorides act as electrophiles for the Pd-catalyzed Suzuki-Miyaura cross-coupling. This desulfonative cross-coupling occurs selectively in the absence of base and, unusually, even in the presence of strong acids. Divergent one-step syntheses of two analogues of bioactive compounds showcase the expanded reactivity of sulfonyl fluorides to encompass both SÀNu and CÀC bond formation. Mechanistic experiments and DFT calculations suggest oxidative addition occurs at the CÀS bond followed by desulfonation to form a Pd-F intermediate that facilitates transmetalation.

Ideal organic syntheses involve the rapid construction of C-C bonds, with minimal use of functional group interconversions. The Suzuki-Miyaura cross-coupling (SMC) is a powerful way to form biaryl linkages, but the relatively similar reactivity of electrophilic partners makes iterative syntheses involving more than two sequential coupling events difficult to achieve without additional manipulations. Here we develop (hetero)aryl sulfones as electrophilic coupling partners for the SMC reaction, which display an intermediate reactivity between those of typical aryl (pseudo)halides and nitroarenes. The new complementary reactivity allows for rapid sequential crosscoupling of arenes bearing chloride, sulfone and nitro leaving groups, affording non-symmetric ter-and quateraryls in only 2 or 3 steps, respectively. The SMC reactivity of (hetero)aryl sulfones is demonstrated in 30 examples. Mechanistic experiments and DFT calculations are consistent with oxidative addition into the sulfone C-S bond as the turnover-limiting step. The further development of electrophilic cross-coupling partners with complementary reactivity may open new possibilities for divergent iterative synthesis starting from small pools of polyfunctionalized arenes.