Acceleration of Acetal Hydrolysis by Remote Alkoxy Groups: Evidence for Electrostatic Effects on the Formation of Oxocarbenium Ions

Abstract

In contrast to observations with carbohydrates, experiments with 4-alkoxy-substituted acetals indicate that an alkoxy group can accelerate acetal hydrolysis by up to 20-fold compared to substrates without an alkoxy group. The acceleration of ionization in more flexible acetals can be up to 200-fold when compensated for inductive effects.

Influence of Alkoxy Groups on Rates of Acetal Hydrolysis and Tosylate Solvolysis: Electrostatic Stabilization of Developing Oxocarbenium Ion Intermediates and Neighboring-Group Participation To Form Oxonium Ions

“…Scheme 1 shows the route used to prepare acetal trans-5, involving an epoxide ring-opening reaction followed by functionalization. 21 Starting from the appropriate epoxide, acetals trans-6, trans-7, and trans-8 with larger rings were prepared by a similar pathway. The synthesis of the five-and six-membered ring acetals cis-5 and cis-6 The Journal of Organic Chemistry Article followed the general synthetic route but proceeded through alcohols cis-15 and cis-18, which were prepared by inversions of the configurations of the hydroxyl groups on alcohols trans-15 and trans-18 (Scheme 2).…”

“…21 4-Benzyloxybutyraldehyde Dimethyl Acetal (11). To a solution of 4-benzyloxy-1-butane (0.507 g, 2.81 mmol) in CH 2 Cl 2 (14 mL) were added 3 Å molecular sieves (1.41 g), silica (1.33 g), and pyridinium chlorochromate (1.22 g, 5.66 mmol).…”

Participation of Alkoxy Groups in Reactions of Acetals: Violation of the Reactivity/Selectivity Principle in a Curtin–Hammett Kinetic Scenario

“… [a] Rates of acetal hydrolysis [22-23] relative to acetal trans - 2 . [b] Determined by 1 H NMR spectroscopy. [c] Determined by 13 C NMR spectroscopy. [28] …”

“…[27] The low selectivities for the formation of alkenes cis - 4 , trans - 7 , and cis - 7 result from that relatively small interaction. [22-23] …”

Stereoelectronic Model To Explain Highly Stereoselective Reactions of Seven‐Membered‐Ring Oxocarbenium‐Ion Intermediates

“…(1)], and cis - 23 , Chart 2). The benzyloxy group at C4 may be too far from the oxygen and carbon atoms of the oxocarbenium ion intermediate to destabilize it inductively, [33] so reactions proceed via oxocarbenium ions even in the presence of the triflate ion. [31] …”