Asymmetric Synthesis of 3,4-Dihydroquinolin-2-ones via a Stereoselective Palladium-Catalyzed Decarboxylative [4 + 2]- Cycloaddition

Abstract

An efficient, palladium-catalyzed, decarboxylative [4 + 2]-cycloaddition of 4-vinyl benzoxazinanones with carboxylic acids has been developed with the employment of P-chiral monophosphorus ligand BI-DIME, affording a series of structurally diverse 3,4-dihydroquinolin-2-ones bearing two contiguous stereogenic centers in moderate to good yields with good to excellent stereoselectivities.

Asymmetric Synthesis of Spirooxindole β‐lactams via Isothiourea‐catalyzed Mannich/lactamization Reaction of Aryl Acetic Acids with Isatin‐derived Ketimines

“…In contrast to the electron‐donating groups, phenyl acetic acids with electron‐withdrawing groups (F, Cl, Br) provided cycloadducts 3 da – 3 fa in high yields (up to 97%) with excellent enantioselectivities (up to >99%) but lower diastereoselectivities (dr=70:30 to 83:17) (Table , entries 4–6). Due to the existence of α ‐H of the amide group, spirooxindole β ‐lactams with electron‐withdrawing groups on the phenyl group could more easily occur epimerization via keto‐enol tautomerization in the presence of base, providing decreased dr values (See the Table S1 of SI for details) . Additionally, indolyl, and thienyl acetic acids also worked efficiently in this reaction, producing the desired spirooxindole β ‐lactams 3 ha and 3 ja in high yields (98% respectively) with excellent eantioselectivities (>99% ee respectively) and good to high diastereoselectivities (dr up to 94:6) (Table , entries 8 and 10).…”

“…Due to the existence of a-H of the amide group, spirooxindole b-lactams with electron-withdrawing groups on the phenyl group could more easily occur epimerization via keto-enol tautomerization in the presence of base, providing decreased dr values (See the Table S1 of SI for details). [15] Additionally, indolyl, and thienyl acetic acids also worked efficiently in this reaction, producing the desired spirooxindole b-lactams 3 ha and 3 ja in high yields (98% respectively) with excellent eantioselectivities (> 99% ee respectively) and good to high diastereoselectivities (dr up to 94:6) ( Table 2, entries 8 and 10). However, 2-Naphthyl acetic acid provided 3 ia with poor diastereoselectivity (51:49 dr) in moderate yield (78%) (Table 2, entry 9).…”

Arylacetic Acids in Organic Synthesis

“…Similarly, treatment of arylacetic acids with pivaloyl chloride (PivCl) would lead to an electrophilic intermediate 44.1 , which then reacted with N, O, or Se‐nucleophiles (Eq. 44‐1).…”

“…44‐1). For example, the Deng group reported that 44.1 underwent a palladium‐catalyzed [4+2]‐cycloaddition with in situ generated 44.4 in the presence of a P‐chiral ligand, leading to stereoisomeric 3,4‐dihydroquinolin‐2‐ones 44.3 (84‐97% ee) (Eq. 44‐2) (Scheme ).…”

Formal [4+2] Cycloaddition of Vinyl Benzoxazinones with Oxazol‐5‐(4H)‐Ones for Diastereoselective Construction of 3,4‐Disubstituted Dihydro‐2(1H)‐Quinolinones

“…1-3). [1] Normally, under the catalysis of palladium/ ligand complexes, the N-Ts substituted vinyl benzoxazinones can readily perform decarboxylation, and deliver highly reactive zwitterionic Pd-π-allyl intermediates bearing a N-Ts group. [2] As for these in situ formed reactive intermediates, they can take part in the many efficient and useful chemical transformations.…”