Catalyst- and Substituent-Controlled Switching of Chemoselectivity for the Enantioselective Synthesis of Fully Substituted Cyclobutane Derivatives via 2 + 2 Annulation of Vinylogous Ketone Enolates and Nitroalkene

Abstract

The first regioselective, diastereoselective, and enantioselective organocatalyzed Michael−Michael cascade of vinylogous ketone enolates and nitroalkenes for the construction of fully substituted cyclobutanes is achieved by the deployment of the appropriate chiral squaramide catalyst and the pertinent substituent on the substrate. The domino reaction provided cyclobutanes with four contiguous stereocenters, including a quaternary center in good yields with diastereomeric ratio of >20:1 and with enantioselectivities of mostly up to 98% enantiomeric excess (ee). The structures and the absolute configurations of the adducts were confirmed by single-crystal X-ray crystallographic analyses of the appropriate products.

Organocatalytic Remote Asymmetric Inverse‐Electron‐Demand Oxa‐Diels‐Alder Reaction of Allyl Ketones with Isatin‐Derived Unsaturated Keto Esters

“…13 C NMR spectra were measured at 100 MHz (Bruker Ascend 400 MHz spectrometer), chemical shifts were reported in ppm relative to TMS with the solvent resonance as internal standard (CDCl 3 at 77.00 ppm). 19 F NMR spectra were measured at 377 MHz (Bruker Ascend 400 MHz spectrometer). Proton coupling patterns are described as broad (br) singlet (s), doublet (d), triplet (t), quartet (q) and multiplet (m).…”

Unified Synthesis of Polycyclic Alkaloids by Complementary Carbonyl Activation**

“…In order to orchestrate the subsequent activations, we initially investigated the reaction using the amide 8a as the model substrate (for its preparation see the Supporting Information). We tested different conditions to achieve selective amide activation via reactive nitrilium ions, [3] including a variety of phosphorus (V) reagents frequently applied in the Bischler-Napieralski reaction [5] and the von Braun amide degradation (Table 1, entries 1-4). [6] We also screened strong electrophiles, such as Me 3 SiCl and (COCl) 2 , [7] and the Tf 2 O / 2-chloropyridine system [8] which have been used successfully in electrophilic amide activation recently (Table 1, entries 5-7).…”

“…Among them, a synthesis of (+)-and (-)-peganumine A (6) was achieved in a protecting-group-free sequence using a DSI catalyzed Pictet-Spengler reaction as the key step. Finally, we also applied this method to a synthesis of dimeric berberine alkaloid ilicifoline B (5).…”

Lewis acid-catalyzed asymmetric reactions of β,γ-unsaturated 2-acyl imidazoles

“…T he exploration of reaction diversity from β,γ-unsaturated carbonyl compounds is interesting and of great synthetic value. These compounds and their analogs bearing one potential enolization have been demonstrated as highly active nucleophiles in a number of catalytic asymmetric reactions for the synthesis of natural products and bioactive compounds [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] . Especially, γ-addition as dienolate pronucleophiles with either metal catalysis [17][18][19][20][21][22][23][24][25][26][27][28] or organocatalysis [29][30][31][32][33][34][35][36] has been widely documented during the past several years, and the maintained πconjugation of γ-addition process leading to thermodynamically stable conjugated products (Fig.…”