Enantioselective Addition of Dialkylzincs to Aldehydes Catalyzed by (−)‐MITH

Abstract

An effective catalytic system that imparts high enantioselectivity has been disclosed for the synthesis of optically active alcohols, which may undergo further chemical transformations. The enantioselective alkylation of aldehydes with dialkylzincs to afford the corresponding optically active alcohols with excellent enantioselectvities has been achieved in the presence of 0.1-0.5 mol % of the camphor-derived chiral ligand (-)-2-exo-morpholinoisobornane-10-thiol (MITH) (1) at room temperature or at 0 °C.

Modulation of Multifunctional N,O,P Ligands for Enantioselective Copper‐Catalyzed Conjugate Addition of Diethylzinc and Trapping of the Zinc Enolate

“…13 C NMR spectra were recorded at 100 MHz; chemical shifts are reported in ppm from TMS with the solvent resonance as the internal standard (CDCl 3 at d = 77.20 ppm). Reactions were monitored by thin-layer chromatography using silica gel.…”

“…1 H NMR spectra were recorded at 400 MHz; chemical shifts are reported in ppm relative to tetramethylsilane (TMS) with the solvent resonance employed as the internal standard (CDCl 3 at d = 7.26 ppm). 13 C NMR spectra were recorded at 100 MHz; chemical shifts are reported in ppm from TMS with the solvent resonance as the internal standard (CDCl 3 at d = 77.20 ppm). 31 P NMR spectra were recorded at 162 MHz; chemical shifts for phosphorous are reported in ppm referenced to the phosphorous resonance of phosphoric acid (d = 0 ppm).…”

“…Notably, to highlight the importance of the phosphine center and BINOL backbone, the Ar-BINMOL-derived phosphine ligand L6 was also prepared for the next asymmetric conjugate addition reaction of organozinc reagents to enone (Scheme 3). [13] Thus these observations inspired us with the confidence to study the catalytic activity of the new binaphthylmodified phosphine and its analogues (L1-L6) as well as the chiral primary-amine-based phosphine ligand (S)-1 in the model and enantioselective copper-catalyzed asymmetric conjugate addition of organozinc reagents to enones. The phosphine ligand has a large cavity and the phosphine atoms extend outward due to steric hindrance of two phenyl groups.…”

“…[15] In addition, the reaction of the organozinc reagent is an illustrative and model example of asymmetric multimetallic cat- alysis. [13] Thus these observations inspired us with the confidence to study the catalytic activity of the new binaphthylmodified phosphine and its analogues (L1-L6) as well as the chiral primary-amine-based phosphine ligand (S)-1 in the model and enantioselective copper-catalyzed asymmetric conjugate addition of organozinc reagents to enones.…”

Synthesis of a Camphor-Derived Auxiliary and the Application to the Asymmetric Darzens Reaction

“…13 Recently, the Darzens reaction using camphor derivatives as chiral auxiliaries has received general attention. 14,15 It has been discovered that amide stabilised sulfur ylides bearing a readily available chiral camphor-derived moiety react with aldehydes in the presence of base to give glycidic amides directly with complete diastereocontrol and almost complete control of enantioselectivity. 16 Bonner and Thornton established that a conformationally rigid camphor-derived N-propionyloxazolidinone effects asymmetric stereochemical control in syn-selectiv e aldol condensations of the derived lithium and titanium enolates with a variety of aldehydes, and a product was synthesised with high stereoselectivity.…”