Asymmetric Yttrium‐Catalyzed C(sp³)−H Addition of 2‐Methyl Azaarenes to Cyclopropenes

Abstract

An enantioselective C-H addition to a C=C bond represents the most atom-efficient route for the construction of chiral carbon-carbon skeletons, a central research topic in organic synthesis. We herein report the enantioselective yttrium-catalyzed C(sp )-H bond addition of 2-methyl azaarenes, such as 2-methyl pyridines, to various substituted cyclopropenes and norbornenes. This process efficiently afforded a new family of chiral pyridylmethyl-functionalized cyclopropane and norbornane derivatives in high yields and high enantioselectivities (up to 97 % ee).

C(sp3)‐H Functionalization of 2‐Methyl Azaarenes: Highly Facile Approach to Aza‐Heterocyclic Compounds

“…Similarly, alkylation reaction by the addition of 2‐methyl azaarenes to norbornene in presence of TIPS‐Y/[Ph 3 C][B(C 6 F 5 ) 4 in toluene at r.t for 24–96 h was reported . A total of 6 examples were made with yields ranging from 48–87 % (Scheme ).…”

“…Another alkylation was reported with Yttrium catalyzed addition of 2‐methyl azaarenes to chiral cyclopropenes in presence of TIPS‐Y/[Ph 3 C][B(C 6 F 5 ) 4 in toluene at –20to0 °C for 48 h to obtain the respective chiral compounds 28 (Scheme ) . The reaction of 2,4,6‐trimethyl pyridine with cyclopropene gave ortho cyclopropylation product 28b in high yield (94 %) with stereoselectivity (96 % ee , 8:1 d.r.).…”

“…A total of 6 examples were made with yields ranging from 48–87 % (Scheme ). Addition of various 2‐methyl pyridines to norbornenes, afforded the corresponding pyridyl methyl functionalized nor‐bornane derivatives with high enantioselectivity (90–97 % ee ) and in moderate to high yields. Pyridyl methyl functionalized nor‐bornane moieties are known to serve as core structures of useful chiral ligands …”

Enantioselective Synthesis of Alkyl Azaarenes

“…An enantioselective CÀ H addition to a C=C bond for the construction of chiral carbon-carbon skeletons was explored by Hou. [21] The Yttrium-catalyzed sp 3 CÀ H bond addition of 2methyl azaarenes 101 to variously substituted cyclopropenes 102 and norbornenes 104 afforded chiral pyridylmethylfunctionalized cyclopropane 103 and norbornane 105 derivatives in high yields and enantioselectivities up to 97%. The azaarenes are substituted pyridines or quinoline whilst all the cyclopropenes contain a quaternary carbon atom.…”

Cobalt‐Catalyzed Diastereo‐ and Enantioselective Hydroalkenylation of Cyclopropenes with Alkenylboronic Acids

“…[8] Introduction of an alkenyl group through C À Hf unctionalization of cyclopropanes in high efficiency and stereoselectivity with broad substrate scope remains scarce. [8b] In the field of catalytic enantioselective functionalization of cyclopropenes,R h-catalyzed hydrostannation, [9] hydroboration, [10] hydroformylation, [11] hydroacylation, [12] and Cucatalyzed hydroboration, [13] hydronitronylation, [14] carbocupration, [15] carbozincation, [16] carbomagnesiation, [17] hydroallylation, [18] and Fe- [19] and Pd-catalyzed carbozincation, [20] and lanthanide-catalyzed hydroamination, [21] hydroalkynylation, [22] addition of 2-methyl azaarenes, [23] and NHC-catalyzed hydroacylation [24] have been disclosed for enantioselective preparation of various functionalized cyclopropanes (Scheme 1b). However,i ntroduction of diversified alkenyl groups onto ac yclopropyl ring has been rarely reported despite all the strategies mentioned above.…”