Asymmetric Synthesis of Cyclobutanone via Lewis Acid Catalyzed Tandem Cyclopropanation/Semipinacol Rearrangement

Abstract

Chiral Lewis acid catalyzed asymmetric formation of cyclobutanones from α-silyloxyacroleins and α-alkyl or α-aryl diazoesters has been developed. In the presence of a chiral oxazaborolidinium ion catalyst, various α-silyloxycyclobutanones possessing a chiral β-quaternary center were synthesized in high yield (up to 91%) with excellent enantio- and diastereoselectivity (up to 98% ee and up to >20:1 dr) through tandem cyclopropanation/semipinacol rearrangement. The synthetic potential of this method was illustrated by conversion of the product to various cyclic compounds such as γ-lactone, cyclobutanol, and cyclopentanone.

Selective Aerobic Oxygenation of Tertiary Allylic Alcohols with Molecular Oxygen

“…[8c,16] Subsequent OÀObond homolysis,f ollowed by directed radical addition to 1a forms the intermediate C with the formation of the oxygen-centered radical species D.Then, radical epoxidation gives 2a with the regeneration of copper(I) species.Inthe presence of aLewis acid, 2a would undergo rearrangement, delivering 3a. [12] In line with literature reports and our mechanistic studies, B could undergo further fragmentation and reaction with anisic acid to afford 9. [14] In the final step,t he Cu I could be reoxidized to Cu II by O 2 .W ecannot rule out the pathway by which D abstracts the hydrogen from the solvent and regenerates A for the chain reaction.…”

“…To verify the possibility of 2a as the intermediate for the formation of the rearrangement product 3a,akinetic diagram was conducted under standard reaction conditions for the generation of 3a.A sd isplayed in Figure S2, 2a was firstly detected and was consumed after an initial increase,while 3a appeared and gradually increased after ac ertain reaction time.T his clearly demonstrates that epoxides are the key intermediates for the seminal rearrangement. [12] Based on these results,aplausible mechanism is proposed (Scheme 6). Initially,o xidation of 1,4-dioxane by copper(II) by asingle-electron transfer (SET) process occurs to generate ar adical cation, which furnishes the radical intermediate A through deprotonation.…”

“…It is noteworthy that at race amount of byproduct was detected in the above screening reactions. Careful characterization experiments demonstrated that 3a was as emipinacol rearrangement [12] product. This discovery attracted our attention, because a-hydroxymethyl cyclopentanones are useful synthons.W et hen turned to optimize the reaction conditions for the semipinacol rearrangement.…”

Recent Advances in Catalytic Enantioselective Rearrangement

“…Chiral cyclobutane derivatives are valuable building blocks in medicinal chemistry and are present in a variety of natural products . Very recently, Ryu and co‐workers developed a chiral Lewis acid Cat‐8 catalyzed enantioselective annulation of α‐silyloxyacroleins 33 with α‐alkyl or α‐aryl diazoesters 34 for the synthesis of highly functionalized cyclobutanones 35 . Formation of 1‐formyl‐1‐silyloxycyclopropane 36 , which was isolable and characterized, followed by Lewis acid catalyzed rearrangement of the α‐silyloxy aldehyde afforded the substituted cyclobutanone in high yields with excellent diastereo‐ and enantioselectivity (Scheme ).…”

Asymmetric Synthesis of Enantioenriched 2‐Aryl‐2,3‐Dihydrobenzofurans by a Lewis Acid Catalyzed Cyclopropanation/Intramolecular Rearrangement Sequence

“…Recently, our group reported the catalytic asymmetric synthesis of cyclopropane through a Michael‐initiated ring‐closure reaction . Furthermore, we developed additional rearrangement reactions from in situ generated cyclopropanes to synthesize 2,5‐dihydrooxepin and cyclobutanone in the presence of a chiral oxazaborolidinium ion (COBI) as a Lewis acid catalyst. Inspired by these encouraging results, we envisioned that, under similar conditions, the reaction of ortho ‐quinone methides ( o ‐QMs) generated in situ from the reaction of ortho ‐hydroxybenzyl alcohol 1 with a diazoester would generate chiral donor–acceptor cyclopropane 2 , which could rearrange into chiral 2‐aryl‐2,3‐dihydrobenzofuran 3 and 4 through intramolecular rearrangement (Scheme ) .…”