Dearomative Michael addition involving enals and 2-nitrobenzofurans realized under NHC-catalysis

Abstract

In the manuscript the first enantioselective dearomative Michael addition between α,β-unsaturated aldehydes and 2-nitrobenzofurans realized under N-heterocyclic carbene activation has been described. The reaction proceeds via addition of homoenolate to...

N‐Heterocyclic Carbene‐Catalyzed Kinetic Resolution of 3‐Nitro‐1,2‐Dihydroquinolines: Asymmetric Synthesis of All C2‐, C3‐ and C4‐Functionalized Tetrahydroquinolines

“…Amongst all the bases screened, while the weak organic base PhCO 2 K was utilized, THQ product 4 a was obtained in 40 % yield and with good er 90 : 10, and the recovered ent-1 a was isolated in 44 % yield, and with extremely high enantioselectivity > 99 % (er > 99: < 1), with a selective factor of 49 (entry 11). Further, utilizing the base PhCO 2 K, other common solvents were also examined, no as such yields and enantioselectivities of 4 a and ent-1 a were improved (entries [13][14][15][16]. Finally, the KR reaction was also checked in the presence of lower catalyst loading (5 mol%), both the product 4 a and recovered ent-1 a were isolated in slightly lower yields after 24 h, albeit, a noticeable change in the enantioselectivities for both the 4 a and ent-1 a were observed in comparison using 10 mol% NHCcat.…”

“…Based on the experimental results and literature report on NHC-catalyzed homoenolate addition reaction to nitroolefins, [13][14][15][16][17] a plausible reaction mechanism for this KR protocol is presented in Scheme 7. The free carbene generated in situ from the NHC-cat.…”

“…Very recently, Albrecht et al described an NHCcatalyzed dearomative Michael addition reaction involving enal and 2-nitrobenzofuran to access chiral 2-nitro-2,3-dihydrobenzofuran heterocycles (Scheme 2B). [16] Recently, we reported a KR method of 2-aryl-3-nitrochromenes by means of NHC-catalyzed homoenolate reactions which afforded enantioenriched chromene and highly functionalized chroman cores (Scheme 2C). [17] To explore the new scope in NHC-catalyzed KR of nitroolefins embedded in heterocycle cores, we report herein a kinetic resolution of 2-substituted 3-nitro-1,2-dihydroquinolines, leading to access of highly enantioenriched densely functionalized tetrahydroquinolines with four contiguous stereocenters and 2substituted 3-nitro-1,2-dihydroquinolines in an highly efficient manner (Scheme 2D).…”

Multistep Cascade Catalytic Reactions Employing Bifunctional Framework Compounds

“…To further probe the Lewis basic nature of the catalyst, we attempted the Michael addition reaction . The Michael addition reaction is the addition of an enolate of a ketone or an aldehyde to an α,β-unsaturated carbonyl compound at the β-carbon. − To carry out this reaction, 1 mmol trans β-nitrostyrene and 1 mL of nitromethane in 5 mL of water were taken in an RB flask at 100 °C along with 1.6 mol % of the catalyst (compound I ). The reaction gave the product, 1-(1,3-dinitropropan-2-yl) benzene (E), with a yield of ∼96% after 1.5 h. Again, this study confirms the Lewis base nature of the catalyst.…”

Photoredox Catalyzed Thioformylation of Terminal Alkynes Using Nitromethane as a Formyl Source

“…Installing a formyl/carbonyl group onto the unsaturated systems is one of the most fundamental reactions that provides direct access to synthetically vital α,β-unsaturated aldehydes . These enals are highly versatile substrates in various catalytic reactions and have been widely used as Micheal acceptors, dienophiles in Diels–Alder reactions, and key intermediates in the synthesis of important natural products . Notably, a hydroformylation reaction employing syngas (CO/H 2 ) has been the mainstay approach to introducing carbonyl function across unsaturated substrates .…”