Synthesis of axially chiral bipyridine N,N'-dioxides and enantioselective allylation of aldehydes

Abstract

N-oxides possessing the pyridine framework are strong Lewis bases that can activate the C-Si bond of allylhalosilanes to such an extent that they catalyze reactions with aldehydes. N-oxides embedded in chiral scaffolds are usually capable of highly selective chirality transfer to the derived products. Our goal was to develop a general synthetic method allowing the preparation of structurally varied N,N'-dioxides suitable for enantioselective organocatalysis. The underlying synthetic strategy was based on [2 + 2 + 2]-cyclotrimerization of suitably substituted diynes with nitriles catalyzed by Co-complexes to generate the desired bipyridines, their further oxidation and resolution of which furnished the corresponding chiral N,N'-dioxides. The prepared compounds were used in catalytic allylation of aromatic aldehydes to homoallyl alcohols with high enantioselectivity (up to 96 % ee). Enantioselectivity, enantiodiscrimination, and the reaction mechanism are controlled by the choice of solvent.

Emergence of Highly Enantioselective Catalytic Activity in a Helical Polymer Mediated by Deracemization of Racemic Pendants

“…Because of no catalytic activity of the monodentate pyridine N -oxide-bound monomer ( S )- 2a NO , the emergence of highly enantioselective catalytic activity observed for poly-( S )- 2a NO is most likely ascribed to the ( S )-2-arylpyridyl- N -oxide pendants that are favorably arranged in a one-handed helical array along the helical polymer backbone, so that the neighboring two chiral N -oxide residues can cooperatively coordinate to or interact with the silicon atom of allyltrichlorosilane in a bidentate chelating manner, − which enables the emergence of highly enantioselective catalytic activity of poly-( S )- 2a NO as observed for the highly enantioselective bidentate bis-pyridine N , N ′-dioxide organocatalysts. ,,, In contrast, poly-( R )- 2b NO showed no catalytic activity probably because the neighboring two chiral N -oxide residues cannot be arranged to each other in such a way to coordinate to the silicon atom in a chelating fashion like poly-( S )- 2a NO .…”

Rollover Cyclometalation Pathway in Rhodium Catalysis: Dramatic NHC Effects in the C–H Bond Functionalization

“…Our present study offers a straightforward access to 3,3′-disubstituted bipyridine, biquinoline and their derivatives with excellent regio- and seteroselectivity. As a synthetic application of the developed procedure, a preparative route was quickly established for the formation of optically active 3,3′-dialkyl-2,2′-biquinoline N , N ′-dioxides, derivatives of which display a high promise as an efficient chiral organocatalyst. , Hydroarylation of gaseous ethylene (5 atm) with 2,2′-biquinoline was readily performed to afford 3,3′-diethyl-2,2′-biquinoline ( 9 ) in quantitative yield using 1 mol % of a rhodium/IMes catalyst (Scheme a). Subsequent double N -oxidation of 9 proceeded easily with meta -chloroperbenzoic acid ( m -CPBA) to give racemic N , N ′-dioxide 10 .…”

“…For reference, no conversion of this allylation was observed in the absence of 10 . Considering the fact that the previous synthetic routes to the biquinoline N , N ′-dioxide and its derivatives suffer from lack of substrate scope even requiring multiple synthetic steps, our present approach offers notable advantages overcoming most known synthetic difficulties.…”

Asymmetric Synthesis of Diastereo‐ and Enantiopure Bioxahelicene 2,2′‐Bipyridines

“…As our endeavor has resulted in the development a general methodology for the synthesis of (hetero)helicenes, we have decided to explore its potential also in the synthesis of bioxahelicene 2,2′‐bipyridines. Interestingly, the usefulness of the [2+2+2] cycloisomerization reaction in the racemic or asymmetric synthesis of axially chiral 2,2′‐bipyridines and their derivatives using various π‐electron systems (alkynes, nitriles, isocyanates) was elegantly demonstrated by Bönnemann et al, Saá et al, Itoh et al, Tanaka et al, Kotora et al and Pla‐Quintana, Roglans et al However, the [2+2+2] cycloisomerization strategy has never been used in the synthesis of bihelicene 2,2′‐bipyridines as, to the best of our knowledge, no C 2 symmetric racemic/enantiopure azahelicenes directly connected in the 2,2′ positions with respect to the nitrogen atom have been described in the literature as yet.…”