Borinic acid-catalyzed regioselective acylation of carbohydrate derivatives

Article abstract of DOI:10.1021/ja110332r

Reversible covalent interactions of organoboron compounds are exploited as the basis for regioselective borinic acid-catalyzed acylations of polyols. This catalytic protocol enables differentiation of the secondary OH groups of a wide range of carbohydrat

Full text of DOI:10.1021/ja110332r

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pubs.acs.org/JACS
Borinic Acid-Catalyzed Regioselective Acylation of Carbohydrate
Derivatives
Doris Lee and Mark S. Taylor*
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada
S Supporting Information
b
Scheme 1. Evaluation of Catalysts for Selective Acylation of
cis-Cycloalkanediols
ABSTRACT: Reversible covalent interactions of organo-
boron compounds are exploited as the basis for regioselec-
tive borinic acid-catalyzed acylations of polyols. This catalytic
protocol enables differentiation of the secondary OH groups
of a wide range of carbohydrate derivatives with diverse acid
chloride and chloroformate reagents, using a structurally
simple diarylborinic acid-derived catalyst.
he reversible covalent interactions of organoboron com-
T
pounds with diols have been employed extensively in the
design of receptors for carbohydrates.1 Key features of these
interactions are their tolerance of aqueous medium, favorable
kinetics, and selectivity for cis-vicinal diol moieties, governed by
minimization of angle and torsional strain. Here, we demonstrate
that such interactions may be harnessed to achieve organoboron-
catalyzed monoacylations of carbohydrate derivatives with ro-
bust and general regioselectivity for cis-diol motifs. This method
enables the differentiation of the secondary hydroxy groups of a
wide range of monosaccharide substrates by acylating agents
varying significantly in steric and electronic properties, using a
commercially available and inexpensive borinic ester precatalyst.
The selective protection of carbohydrates has been pursued
intensively for the preparation of value-added intermediates and
building blocks for oligosaccharide synthesis from readily available
sugar feedstocks.2 Strategies based on catalysis are of particular
interest: recent developments include enzyme-catalyzed3 and organo-
catalytic methods,4 Lewis acid-promoted processes,5,6 and tandem
catalytic reactions of persilylated sugar derivatives.7 Despite this
progress, there remains an unmet need for catalysts displaying
the combination of reliable selectivity for a given regiochemical
outcome and generality for a wide range of sugar/protective group
combinations.
a Determined by 1H NMR. b From ref 5a.
We sought to identify organoboron catalysts capable of
promoting selective acylation of cis-diol moieties in carbohy-
drates. Although formation of a boronate ester generally con-
stitutes protection, not activation, of a diol motif,8 Aoyama and
co-workers reported that triethylamine activates fucose- and
arabinose-derived boronate esters toward alkylation through a
putative ate complex.9a In a related strategy, sugar-derived boronate
esters bearing a pendant hydroxy group underwent regioselective
glycosylation.10 Each of these processes required the use of a
stoichiometric quantity of organoboron reagent that was initially
installed in a thermally promoted condensation step, suggesting
that developing catalytic reactivity of this type might be difficult.
Organoboron species were evaluated as catalysts for the
selective benzoylation of 1,2-cis-cyclohexanediol 1a in the pre-
sence of its trans diastereomer 1b (Scheme 1). N,N-Dimethyla-
minopyridine (DMAP) promoted indiscriminate acylation of 1a
and 1b, as did Me2SnCl2, a known catalyst of diol acylation.5
While boronic acids 3a-3d provided varying degrees of rate
enhancement, only modest levels of selectivity for the formation
of 2a were observed.11 In contrast, the ethanolamine ester of
diphenylborinic acid (4a) promoted acylation of 1a with good
activity and superior selectivity. Similar results were obtained
with diphenylborinic acid itself (4b), suggesting that 4a serves
as a precatalyst by benzoylation and displacement of the
Received: November 17, 2010
Published: February 28, 2011
r
2011 American Chemical Society
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ethanolamine ligand.12 Triphenylborane (4c) was also active,
likely by conversion to a borinic acid derivative by either
oxidation or protonolysis of a C-B bond.13 Borinate ester 4a
was chosen as the optimal catalyst due its commercial availability,
stability and ease of handling.14 Although applications of borinic
acids in molecular recognition are rare, they are more acidic than
boronic acids, and readily generate ate adducts with diols at
neutral pH.15 We have previously employed diphenylborinic acid
as a catalyst for direct aldol reactions of pyruvic acids, in which
a similar reversible covalent catalyst-substrate adduct was
proposed.16 Borinic acids have also been employed as catalysts
of mechanistically distinct reactions, including Mukaiyama aldol
reactions,17 Oppenauer oxidations,18 and dehydrations.19
Competition experiments involving cis-diols of varying ring
sizes provide support for the involvement of a covalent borinic
acid-diol adduct in the catalytic pathway (Scheme 1). The
preferential acylations of cis-cyclopentanediol 1c and cis-cyclo-
octanediol 1d over 1a are consistent with the generation of the
less strained boron-diol complex in each case, as assessed by
semiempirical (PM3) calculations (see the Supporting Informa-
tion). The selectivities obtained with 4a are higher than those
observed using boronic acid 3c or the diorganotin catalyst
Bu2SnO (the latter was employed under conditions optimized
byMatsumuraand co-workers:5a K2CO3, THF, 23°C; Scheme 1).
On preparative scale, the borinic acid-catalyzed monobenzoylations
ofcycloalkanediolsproceededin high yield(Table 1, entries1-3);
diacylated products were not detected.20
Table 1. Borinic Acid-Catalyzed Monoacylation of
Cycloalkanediols and Carbohydrate Derivativesa
This catalyst system enables the differentiation of secondary
hydroxy groups in a wide range of carbohydrate derivatives
(Table 1, entries 4-17). Monoacylation was observed only at
cis-vicinal diol moieties, with the equatorial OH group under-
going selective benzoylation in derivatives of arabinose (5a),
galactose (5b, 5c, 5h), lyxose (5d), mannose (5e), fucose (5f),
and rhamnose (5g). The secondary OH groups of carbohydrates
differ in their nucleophilicity as a function of intramolecular
hydrogen bonding, steric, and electronic effects:21 among the
trends observed is a relatively high reactivity of hydroxy groups cis
to adjacent axial hydroxy or alkoxy groups. When a sterically
hindered electrophile such as pivaloyl chloride is employed,
selective monoacylation at a secondary OH group is possible
in certain cases.22 To quantify the magnitude of such preferences,
each substrate from Table 1 was subjected to conditions favoring
controlled monoacylation (1.2 equiv of RCOCl, pyridine, -30 to
23 °C). The yields obtained under these catalyst-free conditions
(indicated in parentheses in Table 1) were less than 50% for 12 of
the 14 carbohydrate monoacylations studied, and less than 25%
for nine of them, due to formation of regioisomeric and/or over-
acylated products. The results indicate that catalyst 4a promotes
monoacylations of challenging substrate combinations, for which
state-of-the-art methods require the use of stoichiometric23 or
catalytic5 quantities of diorganotin reagent.
Consistent with the resultsof Scheme 1, and unlike diorganotin
catalysts, catalyst 4a does not promote acylation of secondary OH
groups in carbohydrates lacking a cis-1,2-diol motif such as
glucose and xylose derivatives. Benzoylation of methyl β-galacto-
pyranoside (5h) occurred competitively at the 3- and 6-positions,
presumably through interactions of the catalyst with the 4,6- and
3,4-diol groups.24 Diacylated product was obtained efficiently in
the presence of excess benzoyl chloride (entry 11). The method is
compatible with a thioglycoside, a functional group absent in
reported examples of tin-catalyzed acylation (entry 5), and is
tolerant of variation of the stereochemistry of the anomeric
a Reaction conditions: substrate (1.0 mmol), catalyst 4a (5-10 mol %),
RCOCl (1.2-2.0 mmol), i-Pr2NEt (1.2-2.0 mmol), CH3CN (0.2 M).
See the Supporting Information. b Isolated yield. Numbers in parenth-
eses are the isolated yields obtained in the absence of catalyst, under
conditions favoring controlled monoacylation (1.2 equiv of RCOCl,
pyridine, -30 f 23 °C). c PhCOCl (4.0 mmol), i-Pr2NEt (4.0 mmol).
d 4b was employed as catalyst.
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the carbohydrate recognition chemistry of organoboron species
for applications in catalysis offers opportunities for the develop-
ment of new stereo- and regioselective processes. Efforts to
expand the scope of boron-catalyzed manipulations of sugars,
and to explore chiral organoboron derivatives for enantioselec-
tive transformations, are underway.
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental procedures and
b
characterization data for all new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
mtaylor@chem.utoronto.ca
Figure 1. DFT-calculated structures, condensed Fukui functions, and
proton affinities of diphenylborinate adducts of representative hexopyr-
anoses (see the text and Supporting Information for details).
’ ACKNOWLEDGMENT
This work was funded by NSERC (Discovery Grants Pro-
gram, Graduate Scholarship to D.L.), the Canadian Foundation
for Innovation, the Province of Ontario, and the University of
Toronto. We are grateful to Prof. M. Nitz for his advice and
valuable comments on this study.
position (entries 5 and 11 vs 6). Acid chlorides and chlorofor-
mates with varied steric and electronic properties reacted regio-
selectively with carbohydrate derivatives in the presence of
catalyst 4a (entries 12-17). The compatibility of this method
with sterically unhindered electrophiles such as R-unbranched
aliphatic acid chlorides (entries 12, 13) and chloroformates
(entries 15-17) is noteworthy, as reagents of this type have
not been employed in Me2SnCl2-catalyzed acylation protocols.
Reactions of chloroformates posed a particular challenge, as the
products were prone to base-catalyzed acyl migration. Although
the formation of regioisomeric byproducts by acyl migrations of
this type resulted in modest yields,25 this represents the first
catalytic method for the selective introduction of these useful
carbonate protective groups.26
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