Palladium-Catalyzed Intermolecular Asymmetric Dearomative Annulation of Phenols with Vinyl Cyclopropanes

Abstract

Herein, we report the Pd(0)-catalyzed intermolecular asymmetric dearomative [3 + 2] annulation of phenols with vinyl cyclopropanes via in situ generated ortho-quinone methide intermediates. A series of highly functionalized spiro-[5,6] bicycles which bear three contiguous stereogenic centers including one all-carbon quaternary were obtained with excellent stereoselectivities. Density functional theory (DFT) calculations indicate that the reactions were controlled by thermodynamics.

Asymmetric Dearomatization of Phenols via Ligand‐Enabled Cooperative Gold Catalysis

“…For the ones reporting excellent ee values, [15–24] the substrate scopes are limited (Scheme 1A). For example, in the enantioselective oxidative spiro‐lactonization of phenol derivatives reported by Ishihara, [16] an ortho substitution is required to achieve ≥90 % ee; in the enantioselective fluorinative dearomatization of phenols reported by Toste, both the R group and the C6 substituents need to be H to achieve ≥87 % ee; [15] in the asymmetric hydroxylative phenol dearomatization reported by Pouységu and Quideau, [17] the R group ortho to the phenolic OH group needs to be sterically demanding for high enantioselectivity; several studies focus on specific substrate types including resorcinol‐based aryl ketones/aldehydes [18–19] and alkyl‐/RO substituted phenols of certain patterns [20–24] . Most of the substituents in these studies are limited to electron‐donating alkyl/alkoxy/hydroxy, and no strongly electron‐withdrawing groups are tolerated except in the case of resorcinol substrates [18,19] where the additional phenolic OH group counters the deactivating carbonyl group.…”

“…[1][2] However, the asymmetric dearomatization of ubiquitous phenols affording chiral quaternary centers remains largely underdeveloped and challenging partly due to their higher aromatic stabilization, [7][8][9] and most literature reports in this area exhibit moderate enantioselectivity. [10][11][12][13][14] For the ones reporting excellent ee values, [15][16][17][18][19][20][21][22][23][24] the substrate scopes are limited (Scheme 1A). For example, in the enantioselective oxidative spiro-lactonization of phenol derivatives reported by Ishihara, [16] an ortho substitution is required to achieve � 90 % ee; in the enantioselective fluorinative dearomatization of phenols reported by Toste, both the R group and the C6 substituents need to be H to achieve � 87 % ee; [15] in the asymmetric hydroxylative phenol dearomatization reported by Pouységu and Quideau, [17] the R group ortho to the phenolic OH group needs to be sterically demanding for high enantioselectivity; several studies focus on specific substrate types including resorcinol-based aryl ketones/aldehydes [18][19] and alkyl-/RO substituted phenols of certain patterns.…”

Recent advances in Pd-catalyzed asymmetric cyclization reactions

“…Soon afterwards, employing o-quinone methides generated in situ from the phenol derivative 106, asymmetric [2+3] cycloaddition reactions with VCPs catalyzed by the Pd-PyOX complex to construct highly functionalized spiro- [5,6] bicycles 111 was accomplished by Liu, Bai, Shao and Chu (Scheme 23). 57 The authors also performed DFT calculations to reveal that this [2+3] annulation was more thermodynamically favorable than [4+3] annulation. Very recently, the components of [3+2] cycloaddition with VCPs were further extended to alkenyl Nheteroarenes 112.…”

Brønsted Acid Catalyzed Intramolecular Allylic Substitution Reaction of Allylic Alcohols: A Facile Synthesis of 2-Vinylchromans

“…The Pd-catalyzed oxidation of 2a was achieved in the presence of CuCl, delivering an aldehyde 7 successfully. 13 Additionally, 2-vinyl chroman 2a could undergo the Pd-catalyzed Heck reaction, yielding product 8 smoothly. The chiral Brønsted acid-catalyzed intramolecular asymmetric allylic substitutions of allyl alcohols 1a and 3a was preliminarily examined (Scheme 5).…”

“…Infrared spectra were obtained using a Nicolet AVATAR 370 FT-IR spectrometer. 1 H, 13 C, and 19 F NMR spectra were recorded with a JEOL (400 MHz) or Bruker AV-500 (600 MHz) spectrometer, with chemical shift values being reported in ppm relative to chloroform (δ = 7.26 ppm) or TMS (δ = 0.00 ppm) for 1 H NMR; chloroform (δ = 77.16 ppm) for 13 C NMR. Mass spectra and high resolution mass spectra (HRMS) were recorded with AB SCIEX X500R, LC-Q-TOF with ESI source and Agilent 7250 with EI source.…”