Sodium Salts of Anionic Chiral Cobalt(III) Complexes as Catalysts of the Enantioselective Povarov Reaction

Abstract

The sodium salts of anionic chiral cobalt(III) complexes (CCC À Na + )h ave been found to be efficient catalysts of the asymmetric Povarov reaction of easily accessible dienophiles,s uch as 2,3-dihydrofuran, ethyl vinyl ether, and an N-protected 2,3-dihydropyrrole,w ith 2-azadienes. Ring-fused tetrahydroquinolines with up to three contiguous stereogenic centers were thus obtained in high yields,excellent diastereoselectivities (endo/exo up to > 20:1), and high enantioselectivities (up to 95:5 e.r.).The use of chiral anions as stereoinductors in the field of asymmetric catalysis has received increasing attention. [1] Whereas organic molecular anion catalysts have been widely employed, the potential of chiral metal complexes as counteranions in asymmetric catalysis has hardly been explored. Belokon et al. recently showed that salicylaldehyde-derived chiral Co III complexes can be employed to accelerate afew CÀCbond formation reactions by asymmetric counterion catalysis.[2b-d] However,t hese transformations proceeded with low to moderate enantioselectivities [2a-d] owing to the limitations of unsubstituted salicylaldehydes and the meridional stereoisomers of these complexes.[2e-f] We envisioned that easily prepared, structurally tunable,a nd stereochemically stable [2g] metal salts of anionic chiral Co III complexes (CCC À M + )that are derived from salicylaldehydes with bulky substituents and l-amino acids would be more applicable to asymmetric catalysis than anticipated by common sense (Scheme 1). We hypothesized that the achiral cation can activate as ubstrate while the chiral counteranion might be applied to control the stereoselectivity of the transformation. Thus,wedecided to test these catalysts in the challenging Povarov reaction [3] of simple 2-azadienes and dienophiles to generate structurally diverse 1,2,3,4-tetrahydroquinoline (THQ) derivatives with contiguous stereogenic centers,w hich are key structural motifs of numerous natural products and pharmacologically relevant molecules. [4] Thec atalytic enantioselective Povarov reaction has been intensively investigated [5][6][7] since the pioneering work by Ishitani and Kobayashi, who employed ac hiral ytterbium complex as the catalyst.[6a] In these cases,classical chiral Lewis acids [6] or chiral Brønsted acids [7] have generally been the catalysts of choice to promote asymmetric versions.Thus,the development of new chiral catalyst motifs that are principally distinct from traditional ones is still highly desirable.Herein, we show that the sodium salts of anionic chiral Co III complexes (CCC À Na + )a re able to act as promising chiral catalysts for the asymmetric Povarov reaction of aw ide variety of simple 2-azadienes and dienophiles,s uch as 2,3-dihydrofuran, ethyl vinyl ether, and an N-protected 2,3-dihydropyrrole,g iving rise to multiply substituted THQ derivatives in high yields and with excellent stereoselectivities (Scheme 1).Our initial investigation started with the reaction of N-phenyl benzaldimine (1a)with 2,3-dihydrofuran (2a)int...

Synthesis of the Hexahydropyrrolo-[3,2-c]-quinoline Core Structure and Strategies for Further Elaboration to Martinelline, Martinellic Acid, Incargranine B, and Seneciobipyrrolidine

“…The use of a 2-nitro phenyl aromatic imine 75 in the reaction favored formation of the endo-product 74b ( Table 2 , Entry 2). The endo-compound 74c was also obtained from the zinc triflate catalyzed Povarov reaction conducted by Wang and co-workers ( Table 2 , Entry 3) [ 59 ], as well as from the cobalt catalyzed reaction employing catalyst 76, presented by Gong and co-workers ( Table 2 , Entry 4) [ 60 ]. Other catalysts that have been explored for this reaction are the iodo catalyst 77 ( Table 2 , Entry 5) and helquat catalyst 78 ( Table 2 , Entry 6), both of which facilitated formation of approximately 1:1 mixtures of endo/exo isomers [ 61 , 62 ].…”

Switchable Stereoselectivity in Bromoaminocyclization of Olefins: Using Brønsted Acids of Anionic Chiral Cobalt(III) Complexes

“…[7] This feature is distinct from the traditional metal complexes wherein the positive charge on the metal is compensated by ligand coordination and thus would be able to make either the acid or salt form of anionic chiral metal complexes hold unique privilege in asymmetric catalysis.T herefore,t he creation of as tructurally diverse range of new chiral metal complexes and disinterment of their applications in asymmetric catalysis would be essentially important in synthetic organic chemistry.H erein, we describe the L-a nd Ddiastereomeric cobalt(III) complexes which act as "pseudoenantiomers" which render asymmetric reactions to give both enantiomers,a nd demonstrate the versatility of the chiral cobalt(III)-templated Brønsted acids as highly efficient catalysts for asymmetric bromoaminocyclization of olefins (Scheme 1). [7] This feature is distinct from the traditional metal complexes wherein the positive charge on the metal is compensated by ligand coordination and thus would be able to make either the acid or salt form of anionic chiral metal complexes hold unique privilege in asymmetric catalysis.T herefore,t he creation of as tructurally diverse range of new chiral metal complexes and disinterment of their applications in asymmetric catalysis would be essentially important in synthetic organic chemistry.H erein, we describe the L-a nd Ddiastereomeric cobalt(III) complexes which act as "pseudoenantiomers" which render asymmetric reactions to give both enantiomers,a nd demonstrate the versatility of the chiral cobalt(III)-templated Brønsted acids as highly efficient catalysts for asymmetric bromoaminocyclization of olefins (Scheme 1).…”

“…[5] In addition, in the cases concerning chiral metal complexes (Ru II ,C o III )w ith chiral ligands, [4,6] the nature of asymmetric induction has not been identified for the moment.We recently demonstrated that sodium salts of anionic chiral cobalt(III) complexes (Scheme 1, L-1c)were excellent catalysts for the asymmetric Povarov reaction of simple 2azadienes,a nd the weakly bonding nature of chiral ion-pair was believed to permit the alkali cation to work as aL ewis acid for the activation of imine functionality. [7] This feature is distinct from the traditional metal complexes wherein the positive charge on the metal is compensated by ligand coordination and thus would be able to make either the acid or salt form of anionic chiral metal complexes hold unique privilege in asymmetric catalysis.T herefore,t he creation of as tructurally diverse range of new chiral metal complexes and disinterment of their applications in asymmetric catalysis would be essentially important in synthetic organic chemistry.H erein, we describe the L-a nd Ddiastereomeric cobalt(III) complexes which act as "pseudoenantiomers" which render asymmetric reactions to give both enantiomers,a nd demonstrate the versatility of the chiral cobalt(III)-templated Brønsted acids as highly efficient catalysts for asymmetric bromoaminocyclization of olefins (Scheme 1).After the diastereoselective synthesis of sodium salts and Brønsted acids of anionic chiral cobalt(III) complexes was achieved, [8] we chose bromoaminocyclization of olefins as ab enchmark reaction, [9,10] which has received increasing interest as the corresponding products (e.g., pyrrolidines) are core structural elements in pharmaceuticals and organocatalysts, [11] and thereby are of high synthetic significance.T he reaction of the g-amino alkene 2a with N-bromosuccinimide (NBS) was initially examined in the presence of 5mol %o f the sodium salts of anionic chiral cobalt(III) complexes, L-(S,S)-1a-c (Table 1). As anticipated, the desired reaction proceeded smoothly to give the 2-substituted pyrrolidine 3a in good yields,b ut with low levels of enantioselectivity (entries 1-3).…”

“…We recently demonstrated that sodium salts of anionic chiral cobalt(III) complexes (Scheme 1, L-1c)were excellent catalysts for the asymmetric Povarov reaction of simple 2azadienes,a nd the weakly bonding nature of chiral ion-pair was believed to permit the alkali cation to work as aL ewis acid for the activation of imine functionality. [7] This feature is distinct from the traditional metal complexes wherein the positive charge on the metal is compensated by ligand coordination and thus would be able to make either the acid or salt form of anionic chiral metal complexes hold unique privilege in asymmetric catalysis.T herefore,t he creation of as tructurally diverse range of new chiral metal complexes and disinterment of their applications in asymmetric catalysis would be essentially important in synthetic organic chemistry.H erein, we describe the L-a nd Ddiastereomeric cobalt(III) complexes which act as "pseudoenantiomers" which render asymmetric reactions to give both enantiomers,a nd demonstrate the versatility of the chiral cobalt(III)-templated Brønsted acids as highly efficient catalysts for asymmetric bromoaminocyclization of olefins (Scheme 1).…”