Reductive Coupling of Acrylates with Ketones and Ketimines by a Nickel‐Catalyzed Transfer‐Hydrogenative Strategy

Abstract

Nickel-catalyzed coupling of benzyl acrylates with activated ketones and imines provides g-butyrolactones and lactams,r espectively.T he benzyl alcohol byproduct released during the lactonization/lactamization event is relayed to the next cycle where it serves as the reductant for CÀCb ond formation. This strategy represents ac onceptually unique approach to transfer-hydrogenative C À Cbond formation, thus providing examples of reductive heterocyclizations where hydrogen embedded within an alcohol leaving group facilitates turnover.The identification of catalytic paradigms for the direct and atom-economical assembly of C À Cb onds is ak ey goal of organic chemistry.Within this context, transfer-hydrogenative C À Cb ond formation has emerged as ap owerful platform for reaction design. Forexample,hydrogen borrowing allows the direct a-alkylation of carbonyl compounds with alcohols by ac atalytic dehydrogenation/condensation/reduction sequence (Scheme 1a).[1] Therelated Guerbet reaction effects the dehydrative union of two alcohols,t hus providing an efficient method to upgrade bioethanol to butanol (Scheme 1b).[2] Krische and co-workers have pioneered transferhydrogenative alcohol CÀHfunctionalizations as exemplified by processes where alcohol dehydrogenation drives the reductive generation of nucleophilic metal allyls in advance of carbonyl addition (Scheme 1c).[3] Each of these reaction classes merges redox events with C À Cb ond formation, thus avoiding stepwise generation of reactive functionality and enhancing substantially atom economy.Assuch, new transferhydrogenative CÀCbond-forming strategies are likely to find wide utility in reaction design.Our studies in this area were initiated by considering synthetic entries to g-butyrolactones and lactams, [4][5][6][7] which are versatile intermediates as well as core motifs in an array of natural products.A na ppealing,y et unrealized approach to these compounds resides in metal-catalyzed reductive coupling of either ac arbonyl or imine with an acrylate to afford a g-amino or g-hydroxy ester,w hich upon cyclization would provide the target (Scheme 1d). This disconnection requires the identification of as trategy which enables reductive CÀC bond formation, but avoids nonproductive reduction of the starting materials.W er easoned that these criteria might be fulfilled by coupling the release of the reductant to the formation of either the lactone or lactam, thereby minimizing nonproductive background reduction events.Such aproposition appears practically challenging,h owever,asimple solution is availed by harnessing the native reducing power of the alcohol released upon cyclization to drive turnover. In this way,t he alcohol byproduct from one cycle is relayed to the next, where it then serves as the reductant for C À Cb ond formation. Herein, as proof-of-concept, we show that lactones and lactams can be generated by nickel-catalyzed union of activated ketones and ketimines,r espectively,w ith O-benzyl acrylates.T his approach provides unique examples of r...

Nucleophilic substitution reaction as an important tool in the synthetic protocol for selenium donor containing Schiff bases: applications of metal complexes in homogeneous catalysis

“…These processes are used as potent tools for the synthesis of several speciality chemicals including natural products, physiologically active molecules and medicines. 88–108…”

Stereoselective synthesis and applications of spirocyclic oxindoles

“…294 Yin has developed a Pd-catalysed cascade reaction involving dearomatisation of furans to form the THF core of the spirocycle. 295 Other metal-mediated approaches include the use of Cu-, 296 Ti-, 297 Ru-298 or Ni-catalysed 299 spirocyclisations. Trost has also applied his development of Pd-allyl complexes previously discussed in the spiropyrrolidine section to the synthesis of spiroTHFs.…”