skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Catalytic Deprotection of Acetals In Strongly Basic Solution Usinga Self-Assembled Supramolecular 'Nanozyme'

Abstract

Acetals are among the most commonly used protecting groups for aldehydes and ketones in organic synthesis due to their ease of installation and resistance to cleavage in neutral or basic solution.[1] The common methods for hydrolyzing acetals almost always involve the use of either Broensted acid or Lewis acid catalysts.[2] Usually aqueous acids or organic solutions acidified with organic or inorganic acids have been used for reconversion of the acetal functionality to the corresponding carbonyl group; however, recently a number of reports have documented a variety of strategies for acetal cleavage under mild conditions. These include the use of Lewis acids such as bismuth(III)[3] or cerium(IV),[4, 5] functionalized silica gel, such as silica sulfuric acid[6] or silica-supported pyridinium p-toluene sulfonate,[7] or the use of silicon-based reagents such as TESOTf-2,6-Lutidine.[8] Despite these mild reagents, all of the above conditions require either added acid or overall acidic media. Marko and co-workers recently reported the first example of acetal deprotection under mildly basic conditions using catalytic cerium ammonium nitrate at pH 8 in a water-acetonitrile solution.[5] Also recently, Rao and co-workers described a purely aqueous system at neutral pH for the deprotection of acetals using {beta}-cyclodextrin as the catalyst.[9] Herein, we report themore » hydrolysis of acetals in strongly basic aqueous solution using a self-assembled supramolecular host as the catalyst. During the last decade, we have used metal-ligand interactions for the formation of well-defined supramolecular assemblies with the stoichiometry M{sub 4}L{sub 6}6 (M = Ga{sup III} (1 refers to K{sub 12}[Ga{sub 4}L{sub 6}]), Al{sup III}, In{sup III}, Fe{sup III}, Ti{sup IV}, or Ge{sup IV}, L = N,N{prime}-bis(2,3-dihydroxybenzoyl)-1,5-diaminonaphthalene) (Figure 1).[10] The metal ions occupy the vertices of the tetrahedron and the bisbidentate catecholamide ligands span the edges. The strong mechanical coupling of the ligands transfers the chirality from one metal center to the other, thereby requiring the {Delta}{Delta}{Delta}{Delta} or {Lambda}{Lambda}{Lambda}{Lambda} configurations of the assembly. While the 12- overall charge imparts water solubility, the naphthalene walls of the assembly provide a hydrophobic environment which is isolated from the bulk aqueous solution. This hydrophobic cavity has been utilized to kinetically stabilize a variety of water-sensitive guests such as tropylium,[11] iminium ions,[12] diazonium ions,[13] and reactive phosphonium species.[14] Furthermore, 1 has been used to encapsulate catalysts[15] for organic transformations as well as act as a catalyst for the 3-aza-Cope rearrangement of enammonium substrates[16] and the hydrolysis of acid-labile orthoformates.[17] Our recent work using 1 as a catalyst for orthoformate hydrolysis prompted our investigation of the ability of 1 to catalyze the deprotection of acetals (Scheme 1). With the ability of 1 to favor encapsulation of monocationic guests, we anticipated that the rates of acetal hydrolysis could be accelerated by stabilization of any of the cationic protonated intermediates along the mechanistic pathway upon encapsulation in 1. In contrast to the stability of 2,2-dimethoxypropane in H{sub 2}O at pH 10, addition of the acetal to a solution of 1 at this pH quickly yielded the products of hydrolysis (acetone and methanol). Addition of a strongly binding inhibitor for the interior cavity of 1, such as NEt{sub 4}{sup +} (log (K{sub a}) = 4.55), inhibited the overall reaction, confirming that 1 is active in the catalysis.« less

Authors:
; ;
Publication Date:
Research Org.:
Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
Sponsoring Org.:
USDOE Director. Office of Science. Basic EnergySciences
OSTI Identifier:
929333
Report Number(s):
LBNL-63259
R&D Project: 402104; BnR: KC0302010; TRN: US200813%%196
DOE Contract Number:  
DE-AC02-05CH11231
Resource Type:
Journal Article
Journal Name:
Angewandte Chemie International Edition
Additional Journal Information:
Journal Volume: 46; Journal Issue: 45; Related Information: Journal Publication Date: 10/09/2007
Country of Publication:
United States
Language:
English
Subject:
37; ACETAL; ACETALS; AMMONIUM NITRATES; AQUEOUS SOLUTIONS; BROENSTED ACIDS; CATALYSTS; HYDROLYSIS; INORGANIC ACIDS; LEWIS ACIDS; SILICA; SILICA GEL; STOICHIOMETRY; SYNTHESIS; WATER

Citation Formats

Pluth, Michael D, Bergman, Robert G, and Raymond, Kenneth N. Catalytic Deprotection of Acetals In Strongly Basic Solution Usinga Self-Assembled Supramolecular 'Nanozyme'. United States: N. p., 2007. Web. doi:10.1002/anie.200703371.
Pluth, Michael D, Bergman, Robert G, & Raymond, Kenneth N. Catalytic Deprotection of Acetals In Strongly Basic Solution Usinga Self-Assembled Supramolecular 'Nanozyme'. United States. https://doi.org/10.1002/anie.200703371
Pluth, Michael D, Bergman, Robert G, and Raymond, Kenneth N. Thu . "Catalytic Deprotection of Acetals In Strongly Basic Solution Usinga Self-Assembled Supramolecular 'Nanozyme'". United States. https://doi.org/10.1002/anie.200703371. https://www.osti.gov/servlets/purl/929333.
@article{osti_929333,
title = {Catalytic Deprotection of Acetals In Strongly Basic Solution Usinga Self-Assembled Supramolecular 'Nanozyme'},
author = {Pluth, Michael D and Bergman, Robert G and Raymond, Kenneth N},
abstractNote = {Acetals are among the most commonly used protecting groups for aldehydes and ketones in organic synthesis due to their ease of installation and resistance to cleavage in neutral or basic solution.[1] The common methods for hydrolyzing acetals almost always involve the use of either Broensted acid or Lewis acid catalysts.[2] Usually aqueous acids or organic solutions acidified with organic or inorganic acids have been used for reconversion of the acetal functionality to the corresponding carbonyl group; however, recently a number of reports have documented a variety of strategies for acetal cleavage under mild conditions. These include the use of Lewis acids such as bismuth(III)[3] or cerium(IV),[4, 5] functionalized silica gel, such as silica sulfuric acid[6] or silica-supported pyridinium p-toluene sulfonate,[7] or the use of silicon-based reagents such as TESOTf-2,6-Lutidine.[8] Despite these mild reagents, all of the above conditions require either added acid or overall acidic media. Marko and co-workers recently reported the first example of acetal deprotection under mildly basic conditions using catalytic cerium ammonium nitrate at pH 8 in a water-acetonitrile solution.[5] Also recently, Rao and co-workers described a purely aqueous system at neutral pH for the deprotection of acetals using {beta}-cyclodextrin as the catalyst.[9] Herein, we report the hydrolysis of acetals in strongly basic aqueous solution using a self-assembled supramolecular host as the catalyst. During the last decade, we have used metal-ligand interactions for the formation of well-defined supramolecular assemblies with the stoichiometry M{sub 4}L{sub 6}6 (M = Ga{sup III} (1 refers to K{sub 12}[Ga{sub 4}L{sub 6}]), Al{sup III}, In{sup III}, Fe{sup III}, Ti{sup IV}, or Ge{sup IV}, L = N,N{prime}-bis(2,3-dihydroxybenzoyl)-1,5-diaminonaphthalene) (Figure 1).[10] The metal ions occupy the vertices of the tetrahedron and the bisbidentate catecholamide ligands span the edges. The strong mechanical coupling of the ligands transfers the chirality from one metal center to the other, thereby requiring the {Delta}{Delta}{Delta}{Delta} or {Lambda}{Lambda}{Lambda}{Lambda} configurations of the assembly. While the 12- overall charge imparts water solubility, the naphthalene walls of the assembly provide a hydrophobic environment which is isolated from the bulk aqueous solution. This hydrophobic cavity has been utilized to kinetically stabilize a variety of water-sensitive guests such as tropylium,[11] iminium ions,[12] diazonium ions,[13] and reactive phosphonium species.[14] Furthermore, 1 has been used to encapsulate catalysts[15] for organic transformations as well as act as a catalyst for the 3-aza-Cope rearrangement of enammonium substrates[16] and the hydrolysis of acid-labile orthoformates.[17] Our recent work using 1 as a catalyst for orthoformate hydrolysis prompted our investigation of the ability of 1 to catalyze the deprotection of acetals (Scheme 1). With the ability of 1 to favor encapsulation of monocationic guests, we anticipated that the rates of acetal hydrolysis could be accelerated by stabilization of any of the cationic protonated intermediates along the mechanistic pathway upon encapsulation in 1. In contrast to the stability of 2,2-dimethoxypropane in H{sub 2}O at pH 10, addition of the acetal to a solution of 1 at this pH quickly yielded the products of hydrolysis (acetone and methanol). Addition of a strongly binding inhibitor for the interior cavity of 1, such as NEt{sub 4}{sup +} (log (K{sub a}) = 4.55), inhibited the overall reaction, confirming that 1 is active in the catalysis.},
doi = {10.1002/anie.200703371},
url = {https://www.osti.gov/biblio/929333}, journal = {Angewandte Chemie International Edition},
number = 45,
volume = 46,
place = {United States},
year = {2007},
month = {7}
}