Catalytic Homologation of Cycloalkanones with Substituted Diazomethanes. Mild and Efficient Single-Step Access to α-Tertiary and α-Quaternary Carbonyl Compounds

Abstract

Though volatile, toxic, and unstable, diazomethane is an indispensable one-carbon reagent with manifold uses in chemical synthesis. In this work, known protocols for hydrazone oxidation were adapted to permit facile access to a range of mono- and disubstituted aryl- or alkyldiazomethanes in pure form in solution; such procedures proceed in 30-60% overall yield starting from inexpensive carbonyl compounds. More important is the discovery that commercial Sc(III) salts are efficient catalysts for net insertion of the diazoalkyl carbon in these nucleophiles into the carbonyl C-C bond of simple cycloalkanones. In a single step, these reactions (1) forge two new C-C bonds under mild conditions, (2) produce molecular nitrogen as the sole stoichiometric byproduct, and (3) afford high yields of complex alpha-tertiary and -quaternary cyclic ketones that are typically accessible only through multistep procedures.

Catalytic Asymmetric Intramolecular Homologation of Ketones with α‐Diazoesters: Synthesis of Cyclic α‐Aryl/Alkyl β‐Ketoesters

“…[1][2][3] Particularly, chemists have applied this methodology to natural product synthesis. [4,5] In contrast, the asymmetric variation, which can directly introduce a chiral tertiary or quaternary stereocenter into the carbonyl compounds to get optically active molecules, has received much less attention so far.…”

“…(3) in Scheme 2]. [18] (+)-1 x (43 % ee) was converted to (À)-3 x with À43 % ee in the presence of Sc(OTf) 3 [Eq. (4) in Scheme 2].…”

The Chemistry of Zirconacycles and 2,6-Diazasemibullvalenes

“…Zirconacyclobutene-silacyclobutene complex 1-20 features the concomitance of two Zr-C bonds and two Si-C bonds as well as two fused 4-membered metallacycles, which are useful for further reaction chemistry and synthetic application [45][46][47][48][49][50][51][52]. In 1995, Takahashi and coworkers reported the reaction of bis(alkynyl) silanes with Cp 2 Zr(II) species (Scheme 1.13).…”

Recent applications of rare-earth metal(III) triflates in cycloaddition and cyclization reactions

“…[78][79][80][81] Sc(OTf) 3 appeared to be a highly active catalyst for the transformation, with the catalyst loadings as low as 0.5 mol% on reaction scales up to 5 mmol. 81 It deserves mentioning that during the initial attempt to identify suitable catalysts for the transformation, various aluminum-and boron-based Lewis acids were screened unsuccessfully.…”

“…81 It deserves mentioning that during the initial attempt to identify suitable catalysts for the transformation, various aluminum-and boron-based Lewis acids were screened unsuccessfully. 78 The enantioselective version of this protocol was reported, allowing access to medium ring 2-aryl cyclic ketones 104 from the respective cyclic ketones 103 in one step in virtually quantitative yields and in up to 96% ee (Scheme 30).…”