Asymmetric Synthesis of All-Carbon Benzylic Quaternary Stereocenters via Cu-Catalyzed Conjugate Addition of Dialkylzinc Reagents to 5-(1-Arylalkylidene) Meldrum's Acids

Abstract

The asymmetric synthesis of all-carbon benzylic quaternary stereocenters has been successfully achieved through copper-catalyzed addition of dialkylzinc reagents to 5-(1-arylalkylidene) and 5-(dihydroindenylidene) Meldrum's acids in the presence of phosphoramidite ligand. The resulting benzyl-substituted Meldrum's acids and 1,1-disubstituted indanes were obtained in good yields and up to 99% ee. The significance of substituting the position para, meta, and ortho to the electrophilic benzylic center was highlighted. A benzyl Meldrum's acid product was further transformed to a 3,3-disubstituted 1-indanone and a beta,beta-disubstituted pentanoic acid.

Crystal structure of 2,2-dimethyl-5-(3,4,5-trimethoxybenzylidene)-1,3- dioxane-4,6-dione, C16H18O7

“…Meldrum's acid and its derivatives have widely used in organic synthesis owing to their interesting conformational features [1,2]. In the title compound, bond lengths and angles are in agreement with those of the similar structures [3].The dioxane ring is in a distorted envelope conformation with the C14 atom bonded to the two methyl groups forming the flap.…”

Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis

“…63 Fillion established that alkylidene Meldrum’s acid derivatives are excellent electrophiles in enantioselective conjugate additions of organozinc reagents. 64–67 Using a copper catalyst modified by phosphoramidite ligand VII , high yields and enantioselectivities are observed.…”

Phosphoramidite: privilegierte Liganden in der asymmetrischen Katalyse

“…[166] Diese Umsetzung wurde auch mit den Diarylalkyliden-substituierten Derivaten 50 der Meldrum-Säure durchgeführt und lieferte in Gegenwart des Phosphoramidit-Liganden L2a (siehe Abbildung 4) die Additionsprodukte 51 mit ausgezeichneten Ausbeuten und eeWerten bis 95 % (Schema 17). [167] . Die Reaktion ist ein interessanter Syntheseweg für chirale quartäre Kohlenstoffzentren [168][169][170][171][172][173][174] und wurde vor kurzem auf die asymmetrische Synthese der chiralen Succinimide 52 sowie der chiralen gButyrolactone 53 und 54 angewendet.…”