Diastereoselective Cyclization of 1,5‐Dienes with the C−H Bond of Pyridine Catalyzed by a Cationic Mono(phosphinoamide) Alkyl Scandium Complex

Abstract

The carbocyclization of non-conjugated dienes mediated by organometallicsi sa ni mportant reaction for the synthesis of a variety of carbocyclic derivatives, but the directa nnulation of dienes with an inert CÀHbond of asubstrate has remained unexplored to date. We herein report as eries of novel rare-earth dialkyl complexes bearing ap hosphinoamide anion and demonstrate that the combination of am ono(phosphinoamido)-ligated scandium dialkyl complex with B(C 6 F 5 ) 3 resultsi na ne xcellent catalyst for the cis-selective cyclization of 1,5-dienes with the ortho-C(sp 2 )ÀHb ond of pyridines to afford an ew family of pyridyl-functionalized 1,3-disubstituted cyclopentane derivatives containing monocyclic,bicyclic, spirocyclic, and heterocyclic skeletons in moderatet oexcellent yields with high diastereoselectivities (cis/trans up to 99:1).The cyclization of non-conjugated dienes prompted by organometallics has emergeda sap owerful methodt oc onvert simple, readilya ccessible substrates into more complex cyclic skeletons that exist widely in natural products and bioactive molecules. [1][2][3] In principle, the cyclization of dienesw ith the CÀHb onds of organic compounds is the most straightforward and atom-efficient route for the construction of C-substituted carbocyclic molecules. However,t he CÀH-activation-mediated annulation of dienes hasn ot been reported previously,d espite extensive studies on diene cyclizationc ombined with various transformationss uch as silylation, boration, hydrogenation, hydrogermylation, and carbometalation. [1b,c, 4-8] This is probably owing to the lack of as uitable catalyst that shows high activity not only for the CÀHa ctivation of an organic compound but also for the cyclization of ad iene.Some of us recently showed that cationic half-sandwich rare-earth alkyls served as efficient catalysts for the CÀHa ddition of heteroatom-containing aromatic compounds such as pyridines,a nisoles,a nd N,N-dimethylanilines to aw ider ange of C=Cb onds such as those in 1-alkenes, styrenes,a nd allenes; [9, 10] these catalysts were also found to be efficient for the cyclopolymerizationo f1 ,5-and 1,6-dienes. [11] We therefore envisioned that ac atalytic protocol based on the integration of theset wo processes might be feasible for the direct cyclization of dienes with the CÀHb onds of arenes mediated by an appropriate rare-earth complex. In these studies, we became interested in the analogous rare-earth complexes bearing noncyclopentadienyl (Cp) ligands such as phosphinoamides. [12,13] The h 2 -N-P coordinationm ode of ap hosphinoamide ligand could partly resemble the h 5 -bonding fashion of aC pl igand, but the catalytic potential of ac ationic phosphinoamido-ligated rare-earth alkyl species has remained unexplored to date. Herein, we reportt he first mono(phosphinoamido)-ligated rare-earth dialkyl complexesa nd their application in catalytic pyridine CÀHa ddition/diene cyclization reactions. We found that ac ationic alkyl scandium species bearing mono(phosphinoamide) ligands generated from ne...

3d Transition Metals for C–H Activation

“…Thereafter, the group of Hou succeeded in the carbocyclization of non-conjugated dienes 39 by means of scandium dialkyl complex 40 (Scheme ). Here, the catalytic system consisted of equimolar quantities of 40 and B­(C 6 F 5 ) 3 , which efficiently catalyzed the cis -cyclization of 1,5-dienes 39 with the ortho -C–H bond of pyridines 29 . The authors proposed a plausible catalytic cycle for the cis -selective cyclization, as shown in Scheme .…”

Mechanistic insights into rare-earth-catalysed C–H alkylation of sulfides: sulfide facilitating alkene insertion and beyond

“…Although the above proposed mechanism could schematically explain the products obtained experimentally, many details remained unclear, such as structural information on the active catalyst species, key intermediates and transition states, the energy profiles of the reaction processes, and rationale for the observation that C–H activation is the rate-determining step. Moreover, although the C–H functionalization of various heteroatom-containing substrates with alkenes catalysed by rare-earth complexes have been widely reported, 5–11 whether or how a heteroatom-containing substrate would influence the coordination or insertion of an alkene at the catalyst metal center remained elusive. In order to clarify these important issues, we performed density functional theory (DFT) studies on the Sc-catalysed C–H alkylation of sulfides with alkenes and dienes.…”

Substrate Facilitating Roles in Rare-Earth-Catalyzed C–H Alkenylation of Pyridines with Allenes: Mechanism and Origins of Regio- and Stereoselectivity

“…In principle, the direct C–H addition of pyridines to unsaturated π-bonds is the most atom-economical method to synthesize pyridine derivatives . In these contents, rare-earth complexes have been demonstrated to serve as excellent catalysts for the C–H addition of pyridines with alkenes and imines to synthesize alkylated or aminoalkylated pyridine derivatives. , Encouraged by the unique performance of rare-earth catalysts in C–H functionalization, Hou and co-workers reported the C–H alkenylation of pyridines with allenes catalyzed by a half-sandwich scandium catalyst for the first time, which featured high regio- and stereoselectivity (1,2- E -selective product, Scheme a) . Based on experimental and theoretical reports, , a plausible mechanism was outlined in Scheme b.…”

“…Therefore, it has received tremendous interest in organic synthesis . As an emerging field, cationic rare-earth (scandium, yttrium, and lanthanides) alkyl complexes have been found to be a powerful platform for the C–H addition of various heteroatom-containing substrates (such as pyridines, quinolines, aldimines, imidazoles, sulfides, anisoles, anilines, amines, and ferrocenes) to alkenes and alkynes in the past decade (Scheme ). Notably, these reactions often feature high regio-, stereo-, and chemo-selectivity, which are often superior or complementary to transition-metal catalysts due to their unique chemical reactivities .…”