Wittig Rearrangement of Lithiated Allyl Aryl Ethers: A Mechanistic Study

Abstract

At –75 °C, α‐lithiated allyl phenyl ether undergoes mainly the [1,2] Wittig rearrangement to afford, after acidic hydrolysis, 1‐phenyl‐2‐propen‐1‐ol as the main product. A second metalation taking place at one of the ortho positions is the sole competing side reaction. Both, the significant decrease of the isomerization rate upon the introduction of a tert‐butyl substituent in the para position of the aromatic ring and the complete absence of [1.4] rearrangement products suggest an intramolecular addition/elimination process bringing about the aryl migration. The first step, a nucleophilic attack of the α‐ to the ipso‐carbon atom generates a spiro‐connected oxiranylidene‐cyclohexadienyllithium species. This short‐lived intermediate collapses to the final product, a lithium alkoxide, by the nucleofugal departure of the oxygen atom which simultaneously binds the metal atom.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Exploring the Reactivity of α‐Lithiated Aryl Benzyl Ethers: Inhibition of the [1,2]‐Wittig Rearrangement and the Mechanistic Proposal Revisited

“…However, more recently Schlosser and Strunk have studied the Wittig rearrangement of lithiated allyl aryl ethers (Scheme 1, eq 3), suggesting an intramolecular addition / elimination process that accounts for the observed lesser tendency of the 4-t-butylphenyl group to undergo migration in comparison with the parent phenyl group (~10 times slower). [9] In addition, it should also be considered that due to the higher strength of aromatic CH bonds, it is known that phenyl radical is significantly less stable than alkyl radicals, including methyl one (radical stabilization energy for phenyl radical = +32.9 kJ mol 1 vs. 0 kJ mol 1 for methyl or 26.8 kJ mol 1 for isopropyl). [10] Scheme 1.…”

A New One‐Pot Synthetic Approach to the Highly Functionalized (Z)‐2‐(Buta‐1,3‐dienyl)phenols and 2‐Methyl‐2H‐chromenes: Use of Amine, Ruthenium and Base‐Catalysis

“…Structure and regio-chemistry of (Z)-2-(buta-1,3-dienyl)phenols 6 was confirmed by X-ray structure analysis on cis-6a as shown in Figure 1. [5] Some of the (Z)-2-(buta-1,3-dienyl)phenols 6 are unstable at 25°C and slowly rearrange to the 2-methyl-2H-chromenes 7 by [1,7]-sigmatropic hydrogen shift ([1,7]-SHS) followed by rapid cyclization.…”

“…This reaction can be accelerated by heat or addition of silica and CHCl 3 to the crude phenols 6 (see Table 3). With synthetic and pharmaceutical applications in mind, [1] we extended the transformation of other phenols 6 into functionalized 2-methyl-2H-chromenes 7 by a novel thermal or silica-induced [1,7]-SHS reaction followed by rapid cyclization. Reaction of cis-6a in DMF at 120-140°C for 20 h furnished the expected 2-methyl-2H-chromene 7a in 90 % yield, but the same reaction (catalyzed by SiO 2 /CHCl 3 at 25°C for 7 days) furnished 7a with only 50 % conversion (Table 3, entry 1).…”

“…In order to check the general applicability of the RCM/ BIRO/ [1,7]-SHS reaction sequence, we tried to synthesize the C 2 -symmetric 2,8-dimethyl-2,8-dihydro-1,7-dioxachrysene 7oЈЈ [Equation (3)]. RCM reaction of 1,5-diallyl-2,6-bis(allyloxy)naphthalene (4o) at 50°C for 6 h in CH 2 Cl 2 furnished the C 2 -symmetric benzo [b]oxepine 5o in 85 % yield, which on treatment with 1.5 equiv.…”

“…A ruthenium/base/silica-catalyzed one-pot ring-closing metathesis (RCM) and ring-opening/ [1,7]-sigmatropic hydrogen shift reactions are crucial steps in the reaction sequence. Functionalized 2-(buta-1,3-dienyl)phenols are useful materials as additives for rubbers and plastics, antioxidants, antibacterial agents, antibiotics and hair dyeing.…”