Organocatalytic Enantioselective Synthesis of Trifluoromethyl‐Containing Tetralin Derivatives by Sequential (Hetero)Michael Reaction–Intramolecular Nitrone Cycloaddition

Abstract

Thee nantioselective synthesis of tetralin derivatives bearing at rifluoromethylateda ll-carbon quaternary stereocenter has been accomplished throughasynthetic sequence comprising an organocatalytic b-functionalization of ortho-1-trifluoromethylvinyl-(hetero)aromatic conjugated aldehydes followed by the intramolecular nitrone 1,3-cycloaddition reaction (INCR). Both nitromethane and N-Cbz-hydroxylamine were employed as nucleophiles in the initial organocatalytic conjugate addition step, which provided the chiral information required for the subsequent diastereoselective INCR. Although diastereoselectivity was moderate,g oody ields and enantioselectivities were,i ng eneral, obtained. Inter-estingly,a ni nversion of the selectivity in the intramolecular cycloaddition step waso bserved when either nitromethane or N-Cbz-hydroxylamine was employed. This outcome was studied by means of theoretical calculations, which were in agreement with the experimental results.I na ddition,t he ring opening of the isoxazolidine moietyf urnished the corresponding fluorinated diaminoa lcohols in av ery efficient manner.

Hydrogen Atom Transfer (HAT)-Triggered Iron-Catalyzed Intra- and Intermolecular Coupling of Alkenes with Hydrazones: Access to Complex Amines

“…N−N bond using Raney-Ni21 from N-Cbz hydrazine 12c allowed the isolation of the benzylic amine 13 in 79% yield; also from 12c, but using Pd/C in MeOH as the catalyst, an additional cleavage of the C-N bond took place to give 14 in 60% yield (Scheme 2).Retrosynthetically, the latter process involves the formation of a Csp 3 -Csp 3 bond by coupling of an alkene and a benzaldehyde. Finally, hydrazines 11c and 12g rendered primary amines 15 and 16, respectively, when using Raney-Ni in the hydrogenolysis reaction.Scheme 2.…”

Recent Advances in Catalytic Asymmetric Aza‐Michael Addition Triggered Cascade Reactions

“…Organocatalytic asymmetric sequential aza‐Michael/intramolecular nitrone cycloaddition (INCR) to synthesize trifluoromethyl containing tetralin derivatives was developed by the Pozo group in 2017 (Scheme 46). [54] Using ortho ‐1‐trifluoromethylvinyl (hetero)aromatic conjugated aldehydes 132 as the starting substrate, the desired products with moderate diastereoselectivities (2.4:1–>20:1 dr) and good enantioselectivities (54–99% ee) was obtained by asymmetric aza‐Michael/INCR reaction in moderate yields (14–70%). In addition, nitromethane was employed as the nucleophile in the initial organocatalytic conjugate addition step, the corresponding nitro compounds were obtained by nitro‐Michael addition/INCR reaction.…”

Fluoroalkyl N-sulfonyl hydrazones: An efficient reagent for the synthesis of fluoroalkylated compounds

“…Later, the Valdés group [26] discovered that the Pd-catalyzed crosscoupling of aryl bromides with N-tosyl hydrazones ( 16) derived from 1,1,1-trifluoroacetone yielded high yields of 3,3,3-trifluoromethylstyrenes (17). They are valuable synthetic intermediates used to synthesize a variety of fluoroalkylated benzo-fused bicyclic allylic amines [49], tetralins [50], tricyclic fused isoxazolidines [51], and polycyclic Scheme 2 Synthesis of fluoroalkylated pyrazolines from TFHz-Ts (color online).…”