Cobalt‐Catalyzed Enantio‐ and Diastereoselective Intramolecular Hydroacylation of Trisubstituted Alkenes

Abstract

Enantio‐ and diastereoselective synthesis of trans‐2,3‐disubstituted indanones is achieved by intramolecular hydroacylation of 2‐alkenylbenzaldehydes bearing trisubstituted alkenyl groups under cobalt‐chiral diphosphine catalysis. Notably, a high level of enantioselectivity is induced regardless of the stereochemistry (E/Z ratio) of the alkenyl group of the starting material. Deuterium‐labeling experiments shed light on the productive reaction pathways of the E‐ and Z‐isomers.

Enantioselektive C‐H‐Aktivierung mit natürlich vorkommenden 3d‐Übergangsmetallen

“…Aufi hren Vorarbeiten zur enantioselektiven intramolekularen Hydroacylierung von 2-Alkenylbenzaldehyden mit disubstituierten Alkenen aufbauend, [47] testete dieselbe Forschungsgruppe anspruchsvollere trisubstituierte Alkene für die Synthese hochsubstituierter chiraler cyclischer Ketone 57 (Schema 15). [50] Die hohe Enantioselektivitätlässt sich auf die Kombination aus CoBr 2 und (R,R)-BDPP (50)zurückführen. Erwähnenswert ist der nur sehr geringe Einfluss des E/Z-Verhältnisses der Reaktanten auf den Enantiomerenüberschuss der Produkte.…”

Enantioselective Cobalt(III)‐Catalyzed C−H Activation Enabled by Chiral Carboxylic Acid Cooperation

“…[4] In this context, highvalent pentamethylcyclopentadienyl cobalt(III) complexes [5] were identified as particularly powerful C À Ha ctivation catalysts. [14] In sharp contrast, enantioselective C À Ht ransformations by late 3d transition metals have largely been accomplished with superstoichiometric amounts of reactive Grignard reagents, [15,16] which leads to undesired byproducts, and, more importantly,l imits considerably the robustness in terms of functional group tolerance.B ased on our recent mechanistic findings on base-assisted internal electrophilic substitution (BIES)-C À Hm etalations, [17] we became intrigued to the development of unprecedented enantioselective cobalt(III)-catalyzed CÀHa ctivation, on which we wish to report herein ( Figure 1). [11] However,inthe scenario of enantioselective CÀHactivation, progress was thus far primarily limited to noble 4d and 5d transition metals,s uch as palladium, [12] rhodium, [13] and iridium.…”

“…[6][7][8][9][10] Thef ull control of selectivity is paramount to achieving synthetically meaningful CÀHf unctionalization. [14] In sharp contrast, enantioselective C À Ht ransformations by late 3d transition metals have largely been accomplished with superstoichiometric amounts of reactive Grignard reagents, [15,16] which leads to undesired byproducts, and, more importantly,l imits considerably the robustness in terms of functional group tolerance.B ased on our recent mechanistic findings on base-assisted internal electrophilic substitution (BIES)-C À Hm etalations, [17] we became intrigued to the development of unprecedented enantioselective cobalt(III)-catalyzed CÀHa ctivation, on which we wish to report herein ( Figure 1). [14] In sharp contrast, enantioselective C À Ht ransformations by late 3d transition metals have largely been accomplished with superstoichiometric amounts of reactive Grignard reagents, [15,16] which leads to undesired byproducts, and, more importantly,l imits considerably the robustness in terms of functional group tolerance.B ased on our recent mechanistic findings on base-assisted internal electrophilic substitution (BIES)-C À Hm etalations, [17] we became intrigued to the development of unprecedented enantioselective cobalt(III)-catalyzed CÀHa ctivation, on which we wish to report herein ( Figure 1).…”

“…[11] However,inthe scenario of enantioselective CÀHactivation, progress was thus far primarily limited to noble 4d and 5d transition metals,s uch as palladium, [12] rhodium, [13] and iridium. [14] In sharp contrast, enantioselective C À Ht ransformations by late 3d transition metals have largely been accomplished with superstoichiometric amounts of reactive Grignard reagents, [15,16] which leads to undesired byproducts, and, more importantly,l imits considerably the robustness in terms of functional group tolerance.B ased on our recent mechanistic findings on base-assisted internal electrophilic substitution (BIES)-C À Hm etalations, [17] we became intrigued to the development of unprecedented enantioselective cobalt(III)-catalyzed CÀHa ctivation, on which we wish to report herein ( Figure 1). Salient features of our findings include (a) first asymmetric Cp*Co III -catalyzed C À H activation, (b) robust functional group tolerance,(c) detailed mechanistic insights into cooperative catalysis by experiment and computation and (d) the de-novo design of ah ighly selective chiral carboxylic acid scaffold.…”

“…Decreasing the L2 loading led to al ower efficacya nd only as light improvement of the enantioselectivity (entry 7). Among acid additives, Amberlyst 15 was found instrumental for improving the performance with chiral acid L8 being optimal (entries [10][11][12][13][14][15][16]. Among acid additives, Amberlyst 15 was found instrumental for improving the performance with chiral acid L8 being optimal (entries [10][11][12][13][14][15][16].…”