Brønsted Acid-Catalyzed Insertion of Aryldiazoacetates to sp² Carbon−CHO Bond:  Facile Construction of Chiral All-Carbon Quaternary Center

Abstract

General Information. Infrared (IR) spectra were recorded on a Shimadzu IRPrestige-21 spectrometer. 1 H NMR spectra were measured on a JEOL JNM-FX400 (400 MHz) spectrometer. Data were reported as follows: chemical shifts in ppm from tetramethylsilane as an internal standard, integration, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, dd = double-doublet, dt = double triplet, m = multiplet, br = broad, and app = apparent), coupling constants (Hz), and assignment. 13 C NMR spectra were measured on a JEOL JNM-FX400 (100 MHz) spectrometer with complete proton decoupling. Chemical shifts were reported in ppm from the residual solvent as an internal standard. High-resolution mass spectra (HRMS) were performed on Brucker microTOF. Optical rotations were measured on a JASCO DIP-1000 digital polarimeter. For thin layer chromatography (TLC) analysis throughout this work, Merck precoated TLC plates (silica gel 60 GF 254 , 0.25 mm) were used. The products were purified by flash column chromatography on silica gel 60 (Merck, 230-400 mesh).In experiments requiring dry solvent, dichloromethane and toluene ware purchased from Kanto Chemical Co. Inc. as "Dehydrated" and further purified by passing through neutral alumina under nitrogen atmosphere. Aldehydes were purchased or prepared according to the procedures 1 and used after distillation or column chromatography on silica gel. Aryldiazoacetates were synthesized according to the procedure 2 and purified by column chromatography on silica gel.

Construction of All-Carbon Quaternary Centers through Cu-Catalyzed Sequential Carbene Migratory Insertion and Nucleophilic Substitution/Michael Addition

“…The solution was evaporated in vacuo to remove the volatile compounds, and the residue was purified by column chromatography (silica gel, eluting with PE : EA = 30 : 1) to give the corresponding α-diazo ester 2a-j as a bright yellow oil (except 2f, which is an orange oil). 6,135.6,130.3,128.3,128.0,127.9,127.8,126.7,106.8,86.5,66.8,51.5,45.0,32.8,18.5,11.2,9.8;IR (film) 8,136.5,135.6,130.4,128.4,128.0,127.9,127.8,126.8,108.3,84.9,67.0,45.6,45.0,25.5,18.5,11.2;IR (film) …”

“…Notably, in addition to carbene migratory insertion, the strategy of electrophilic trapping of the metal-carbene induced zwitterionic intermediate established by Hu and others provides an alternative approach to quaternary center construction. 5,6 On the other hand, the efficient construction of quaternary carbon centers has remained a crucial issue in organic synthesis. 7 Since quaternary carbon centers are widely found in various natural products, pharmaceuticals and bioactive molecules, significant efforts have been devoted to the effective construction of quaternary centers in their total syntheses.…”

To Protonate or Alkylate? Stereoselective Brønsted Acid Catalysis of CC Bond Formation Using Diazoalkanes

“…Within a brief screen of acids, including BF 3 ·OEt 2 , MeAlCl 2 , and TiCl 4 , triflic acid provided the highest yield of isolated product and the greatest preference for aryl group migration when using an aryl aldehyde. [39] Extension to a chiral a-diazo ester derived from (À)-phenyl menthyl (27), and the use of toluene allowed the development of a diastereoselective homologation reaction that led to aldehydes of type 28 (Scheme 8). The authors propose a model for stereoselection in which the phenyl ring of the chiral auxiliary shields one face of the s-cis-diazoester carbon atom, thus leading to the diastereoselective formation of an intermediate diazonium (c.f.…”

Protonierung oder Alkylierung? Stereoselektive Brønsted‐Säure‐katalysierte C‐C‐Verknüpfungen mit Diazoalkanen

“…Laut der Literatur ist es nämlich nicht möglich, den Reaktionsweg effektiv zu steuern (Addition-Cyclisierung (oder alternativ Addition-Deprotonierung) gegenüber Addition-Verschiebung). Einer der größten Erfolge auf diesem Gebiet war die von Holmquist und Roskamp entdeckte Homologisierung von Aldehyden zu b-Ketoestern durch eine SnCl 4 -katalysierte Addition von Ethyldiazoacetat (Abbildung 2), [37] die wahrscheinlich als Addition-Hydridverschie- [39] Die Reaktionen des chiralen a-Diazoesters 27 mit einem (À)-Phenylmenthyl-Substituent in Toluol ermöglichten eine diastereoselektive Homologisierung zu Aldehyden wie 28 (Schema 8). Laut den Autoren schirmt der Phenylring der chiralen Hilfsgruppe eine Seite des Kohlenstoffatom im s-cisDiazoester ab und induziert somit die diastereoselektive Bildung einer Diazoniumion-Zwischenstufe (vgl.…”