Asymmetric Hydrogenation of Quinoxalines, Benzoxazines, and a Benzothiazine Catalyzed by Chiral Ruthenabicyclic Complexes

Abstract

The ruthenabicyclic complex RuCl[(R)‐daipena][(R)‐dm‐segphos] with potassium tert‐butoxide catalyzes the hydrogenation of 2‐alkylquinoxalines and a 3‐methyl‐2H‐1,4‐benzoxazine in toluene under 20–100 atm of hydrogen at 40 °C to afford S‐configured cyclic amino products in greater than 97% enantiomeric excess {DAIPENA=anion of DAIPEN at the 2‐position of an anisyl group, DAIPEN=1,1‐di(4‐anisyl)‐2‐isopropyl‐1,2‐ethylenediamine, DM‐SEGPHOS=(4,4′‐bi‐1,3‐benzodioxole)‐5,5′‐diylbis[di(3,5‐xylyl)phosphine]}. The high catalytic activity results in a turnover number as high as 9400. Hydrogenation of the benzoimine heterocycles with the RuCl[(R)‐daipena][(R)‐segphos]/potassium tert‐butoxide system yields the R‐configured products in high enantiomeric excess [SEGPHOS=(4,4′‐bi‐1,3‐benzodioxole)‐5,5′‐diylbis(diphenylphosphine)]. The mode of enantioselection is discussed based on transition state models involving six‐membered pericyclic structures.magnified image

Enantioselective reduction of sulfur-containing cyclic imines through biocatalysis

“…Afterwards we studied further reductions using other sulfur-containing heterocyclic imines such as 2H -1,4-benzothiazines ( 3 ) as substrates (Fig. 5 ), which have already been chemocatalytically reduced in an asymmetric fashion 16 , 17 , 38 . Therefore, the 2H -1,4-benzothiazines 3a – 3c were prepared.…”

Sequential Synthesis, Olfactory Properties, and Biological Activity of Quinoxaline Derivatives

“…88.1–89.5 °C); 8 [α] D 19 = −23.8 ( c 0.22, EtOH) (lit. [α] D 25 = −33.8 ( c 1.06, EtOH)); 17 1 H NMR (400 MHz, CDCl 3 ) δ 6.61–6.55 (m, 2H, Ar), 6.53–6.45 (m, 2H, Ar), 3.57 (brs, 1H, NH), 3.50 (t, J = 6.1 Hz, 1H), 3.30 (dd, J = 10.8, 2.2 Hz, 1H), 3.03 (t, J = 9.4 Hz, 1H), 1.18 (d, J = 6.1 Hz, 3H, Me); 13 C NMR (100 MHz, CDCl 3 ) δ 133.5, 133.1, 118.6 (2C), 114.4, 114.4, 48.2, 45.6, 19.8.…”

Advancement in Catalytic Asymmetric Hydrogenation of Ketones and Imines, and Development of Asymmetric Isomerization of Allylic Alcohols

“…Asymmetric hydrogenation of 2‐substituted quinoxalines as well as 3‐substituted 2 H ‐1,4‐benzoxadines and the benzothiazines was achieved by using chiral ruthenabicyclic complexes with bases as catalysts, producing the optically active bicyclic N ‐arylamines bearing a β‐heteroatom which are observed as core structures in various bioactive compounds 35. Some examples are shown in Scheme .…”