The Atom Economy—A Search for Synthetic Efficiency

Abstract

Efficient synthetic methods required to assemble complex molecular arrays include reactions that are both selective (chemo-, regio-, diastereo-, and enantio-) and economical in atom count (maximum number of atoms of reactants appearing in the products). Methods that involve simply combining two or more building blocks with any other reactant needed only catalytically constitute the highest degree of atom economy. Transition metal-catalyzed methods that are both selective and economical for formation of cyclic structures, of great interest for biological purposes, represent an important starting point for this long-term goal. The limited availability of raw materials, combined with environmental concerns, require the highlighting of these goals.

Nickel-Catalyzed Synthesis of Acrylamides from α-Olefins and Isocyanates

“…Catalytic reactions that effect selective carbon-carbon bond formation facilitate this aim with economy of operations 1 and materials. 2 Methodology for the selective coupling of α-olefins and isocyanates to provide acrylamides has potential applications in the field of polymer science. Poly(N-alkylacrylamide)s and poly(N-alkylmethacrylamide)s have been extensively studied for their properties as temperature-sensitive aqueous microgels.…”

“…Control experiments run in the absence of either Ni(cod) 2 or IPr indicate that both species are necessary for catalysis.…”

Biocatalytic Parallel Interconnected Dynamic Asymmetric Disproportionation of α‐Substituted Aldehydes: Atom‐Efficient Access to Enantiopure (S)‐Profens and Profenols

“…An atom‐efficient26 convergent enzymatic route to ( S )‐ibuprofen based on HLADH‐mediated PIDAT of 1 g is currently being developed and will be reported elsewhere. Altogether, no clear pattern in line with the electronic effects of the substitution could be identified, despite anticipation that electron‐withdrawing groups would be beneficial by enhancing racemization and, possibly, hydration8 rates.…”

Lessons from the Synthetic Chemist Nature

“…rough estimate on the productivity in S. erythraea is possible. About 0.18-0.53% of the glucose fed ends up in erythromycin (2). 12 While this yield may not seem very impressive it is still signi-cantly larger than the yield in the only total synthesis (less than 0.02%).…”

“…Starting from propionyl-CoA 14 transformations (additional four steps have to be added, if one starts counting from acetyl-CoA, additional six steps if transacylation steps from AT to ACP on the PKS are included, and additional seven steps if the activation and loading of the starter and elongation units are included) occur in a linear fashion to yield 6-deoxyerythronolide B (1b). Aer this, ve additional biosynthetic tailoring steps fashion erythromycin A (2). 8 So far, the rst and only total synthesis of 2 was reported by Woodward and coworkers in 1981.…”