Enantioselective Conjugate Addition of 2-Acetyl Azaarenes to β,β-Disubstituted Nitroalkene for the Construction of All-Carbon Quaternary Stereocenters

Abstract

The first highly enantioselective conjugate addition of 2-acetyl azaarenes to α-substituted-β-nitroacrylates was successfully realized under mild conditions by a Ni(II)-bisoxazoline complex, providing the desired adducts bearing an all-carbon quaternary stereocenter in high yield with excellent enantioselectivity. The products obtained in this system could be readily converted into optically active β-amino esters, succinates, lactones, and lactams.

Acyl‐Imidazoles: A Privileged Ester Surrogate for Enantioselective Synthesis

“…The methodology could then be extended to the formation of quaternary centers (Scheme 15). [20,21] Wang and co-workers have described in 2017 the use of αsubstituted acyl-imidazoles 33 (if R 1 ¼ 6 H, Scheme 16). High anti diastereoselectivities, associated with excellent enantioselectiv-Scheme 12.…”

A convenient approach to difluoromethylated all-carbon quaternary centers via Ni(ii)-catalyzed enantioselective Michael addition

“…Based on our previous result, 9 the complex of Ni(acac) 2 -Ph-BOX L1 was selected as the optimal catalyst. The reaction in the presence of 10 mol% of Ni(acac) 2 and 11 mol% of L1 proceeded for 5 h in iso -propanol ( i -PrOH) at room temperature, and afforded the addition product 3aa in 97% yield with 74% ee ( Table 1 , entry 1), lowering the reaction temperature to 0 °C and −20 °C led to an obvious improvement of the enantioselectivity (79% and 91% ee , respectively, entries 2–3), albeit along with a longer reaction time.…”

“…However, in view of somewhat higher reactivity and lower enantioselectivity of difluoromethyl nitroalkenes in contrast to trifluoromethyl substrates under the same condition ( Table 1 , entries 1–3), it is believed that both electronic and steric effects of substituents on the nitroalkene have an impact on the efficiency and enantioselectivity of the reaction, but the steric effect could play a much more important role, which is basically in agreement with our previous report. 9 …”

“… 8 In our recent research work, we have demonstrated that the construction of all-carbon quaternary stereocenters bearing a CF 3 -group or –CO 2 R could be realized by a Ni-bis(oxazoline) catalyst. 9 Thus, we envision that whether the corresponding optical CF 2 H-containing compounds could be achieved by the same catalytic system. To the best of our knowledge, only two successful examples involving chiral all-carbon quaternary center bearing a difluoroalkyl group have been reported by Zhou and Jacobsen.…”

Enantioselective Synthesis of Alkyl Azaarenes

“…Later, Fu and Qin expanded the enantioselective conjugate addition of 2-acetyl azaarenes 40 to α-substituted β-nitroacrylates 48. [8] The reaction, catalyzed by Ni(II)-bisoxazoline complex, operates at room temperature leading to N-heterocyclic compounds 49 bearing an all-carbon quaternary stereocenter in high yields and up to 99% ee (Scheme 12, top). The authors presented a series of derivatization of the compounds 49 that can be easily converted in other useful scaffolds.…”