Catalytic C−C Coupling via Transfer Hydrogenation:  Reverse Prenylation, Crotylation, and Allylation from the Alcohol or Aldehyde Oxidation Level

Abstract

We report byproduct-free carbonyl reverse prenylation, crotylation, and allylation from the alcohol oxidation state via alcohol−allene hydrogen autotransfer. Specifically, exposure of alcohols 1a−6a to 1,1-dimethylallene, methylallene, and allene in the presence of [Ir(cod)(BIPHEP)]BARF (5−7.5 mol %) delivers reverse prenylation products 1c−6c, crotylation products 1d−3d, and allylation product 1e. Similarly, under the conditions of transfer hydrogenation employing isopropanol as terminal reductant, aldehydes 1b−6b are converted to the very same adducts 1c−6c, 1d−3d, and 1e. Isotopic labeling studies corroborate a mechanism involving hydrogen donation from the reactant alcohol or sacrificial alcohol (i-PrOH). The ability to achieve carbonyl addition directly from the alcohol oxidation level circumvents the redox manipulations so often required to convert alcohols to aldehydes. Further, through hydrogen autotransfer, there resides the potential to develop myriad byproduct-free carbonyl additions wherein alcohols and π-unsaturated compounds are exploited as coupling partners.

Ruthenium-Catalyzed Transfer Hydrogenation for C–C Bond Formation: Hydrohydroxyalkylation and Hydroaminoalkylation via Reactant Redox Pairs

“…30 In 2008, the first ruthenium catalyzed reactions of this type were developed (Scheme 2). Specifically, it was found that exposure of alcohols to 1,3-dienes in the presence of catalysts derived from HClRu(CO) (PPh 3 ) 3 and various phosphine ligands resulting in hydrogen transfer to furnish aldehydeallylruthenium pairs that combine to form homoallylic alcohols as single regioisomers.…”

Hydrogenation for C  C Bond Formation

“…Remarkably, under transfer hydrogenation conditions employing 2-propanol as the terminal reductant, iridium-catalyzed reductive coupling of 1,1-dimethylallene to aldehydes occurs efficiently to deliver the products of reverse prenylation [86]. Even more surprising, under identical conditions but in the absence of 2-propanol, 1,1-dimethylallene engages in direct coupling to alcohols to furnish the very same set of reverse prenylated adducts [86].…”

“…Even more surprising, under identical conditions but in the absence of 2-propanol, 1,1-dimethylallene engages in direct coupling to alcohols to furnish the very same set of reverse prenylated adducts [86]. Whereas attempted allene-aldehyde reductive coupling to furnish products of allylation and crotylation suffers from over-reduction of the olefinic adduct under conditions that employ gaseous hydrogen as the terminal reductant, under the conditions of transfer hydrogenation and hydrogen autotransfer over-reduction is not observed (Scheme 8.17).…”

“…Insight into the catalytic mechanism is provided by the following experiments [86]. Coupling of dimethylallene to benzyl alcohol that is fully deuterated at the methylene position under hydrogen auto-transfer conditions provides an adduct that incorporates deuterium primarily at the internal vinylic position (85%).…”

Katalytische Carbonyladdition durch Transferhydrierung: weg von vorab gebildeten Organometallreagentien

“…[13,14] Hydrierende Carbonylallylierung mit Allenen als Allyldonoren (Schema 6,oben). [16] Es wurde gemutmaßt, dass eine direkte C-Allylierung von Alkoholen durch transferhydrierende C-C-Kupplungen erreicht werden könnte, indem ein alkoholischer Reaktant gleichermaßen als Wasserstoffdonor und Aldehydvorstufe fungiert. Tatsächlich wurde gefunden, dass Alkohole in Gegenwart eines kationischen Iridiumpräkatalysators und eines basischen Additivs direkt an 1,1-Dimethylallen kuppeln.…”