Site-Selective, Copper-Mediated O-Arylation of Carbohydrate Derivatives

Article abstract of DOI:10.1021/jacs.7b09420

Site-selective functionalization of hydroxy groups in sugar derivatives is a major challenge in carbohydrate synthesis. Methods for achieving this goal will provide efficient access to new sugar-derived chemical building blocks and will facilitate the preparation or late-stage modification of complex oligosaccharides for applications in glycobiology research and drug discovery. Here, we describe site-selective, copper-promoted couplings of boronic acids with carbohydrate derivatives. These reactions generate sugar-derived aryl ethers, a structural class that is challenging to generate by other means and has not previously been accessed in a site-selective fashion. Experimental evidence and computational modeling suggest that the formation of a sugar-derived boronic ester intermediate is crucial to the selectivity of these processes, accelerating the arylation of an adjacent hydroxy group. The results demonstrate how the interactions of sugars with boron compounds can be combined with transition metal catalysis to achieve new chemical reactivity.

Full text of DOI:10.1021/jacs.7b09420

Article
pubs.acs.org/JACS
Cite This: J. Am. Chem. Soc. XXXX, XXX, XXX-XXX
Site-Selective, Copper-Mediated O‑Arylation of Carbohydrate
Derivatives
Victoria Dimakos, Graham E. Garrett, and Mark S. Taylor*
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada
S
* Supporting Information
ABSTRACT: Site-selective functionalization of hydroxy
groups in sugar derivatives is a major challenge in carbohydrate
synthesis. Methods for achieving this goal will provide efficient
access to new sugar-derived chemical building blocks and will
facilitate the preparation or late-stage modification of complex
oligosaccharides for applications in glycobiology research and
drug discovery. Here, we describe site-selective, copper-
promoted couplings of boronic acids with carbohydrate derivatives. These reactions generate sugar-derived aryl ethers, a
structural class that is challenging to generate by other means and has not previously been accessed in a site-selective fashion.
Experimental evidence and computational modeling suggest that the formation of a sugar-derived boronic ester intermediate is
crucial to the selectivity of these processes, accelerating the arylation of an adjacent hydroxy group. The results demonstrate how
the interactions of sugars with boron compounds can be combined with transition metal catalysis to achieve new chemical
reactivity.
esters. Whereas several methods for N- or S-arylation of
functionalized monosaccharides have been developed,17−25
direct arylation of OH groups in sugars remains a challenge
(Scheme 1a). Aryl ethers can be installed with inversion of
configuration by nucleophilic substitution of OH groups in
protected carbohydrate derivatives, through in situ activation as
alkoxyphosphonium26 or alkoxyimidazolium salts.27 Nucleo-
philic aromatic substitution (SNAr) reactions have been used to
generate electron-deficient aryl or heteroaryl ethers from
protected carbohydrates.28 Recently, Olofsson and co-workers
found that electrophilic diaryiodonium salts could be used to
effect O-arylation of carbohydrate-derived substrates.29 The
ability to generate aryl ethers lacking the strong activating
substituents needed for SNAr reactivity (e.g., fluoro or nitro
groups) represented a significant advance. Other arylation
methods that have been applied to OH groups in protected
sugar derivatives include couplings with arylbismuth reagents30
and photoredox substitutions of aryl halides.31 Site-selective
variants of the reactions listed above have not yet been
reported.
In the course of research aimed at employing organoboron
compounds in carbohydrate chemistry,32 our attention was
drawn to the possibility of using copper-mediated Chan−Lam
couplings33−35 to achieve selective O-arylation of sugars
(Scheme 1b). These oxidative couplings employ readily
available boronic acids as arylating reagents, occur under
relatively mild conditions, and are tolerant of diverse organic
functional groups.36 However, couplings of boronic acids with
aliphatic alcoholsespecially secondary alcohols and other
INTRODUCTION
■
Transition-metal-catalyzed methods for coupling of aryl groups
with amines, alcohols, and thiols have provided new ways to
approach the synthesis of pharmaceutical agents, natural
products, and heteroatom-containing polymers.1−3 The pros-
pect of adapting such methods to achieve site-selective
arylations of multiply functionalized substrates has attracted
interest,4 as it could enable access to unprecedented derivatives
of complex biomolecules. Recently reported protocols for
transition-metal-mediated, selective S-arylation of cysteine
motifs,5−9 Se-arylation of selenocysteine derivatives,10 and N-
arylations of lysine groups11 or backbone amide NH groups12
in complex peptide derivatives illustrate the power of this
approach. Analogous methods for site-selective O-arylation
have not been reported, despite the prevalence of biomolecules
bearing multiple hydroxy (OH) groups, of which carbohydrates
are an especially important and widespread class. Here, we
disclose a method for site-selective O-arylation of carbohydrate
derivatives based on the copper-mediated Chan−Lam coupling
of boronic acids. This protocol facilitates the direct preparation
of carbohydrate-derived aryl ethers that would be challenging to
prepare by other means. Crucial to this approach is the in situ
formation of a sugar-derived boronic ester, which serves as a
transient protective group while also accelerating arylation of an
appropriately oriented OH group.
Efficient methods for the preparation of sugar-derived aryl
ethers could facilitate the discovery of medicinal agents,13 chiral
catalysts,14 new protective groups for carbohydrate chemistry,
and metabolically stable tags for glycobiology research. Certain
substitution patterns can be accessed through nucleophilic
substitution reactions of phenols with sugar-derived electro-
philes such as glycosyl donors,15 anhydrosugars,16 and sulfonate
Received: September 3, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/jacs.7b09420
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
Scheme 1. Approaches to Arylation of OH Groups in
Carbohydrate Derivatives: (a) Reported Methods for O-
Arylation of Protected Carbohydrate Derivatives; (b)
Proposed Method Based on Chan−Lam Couplings of
Boronic Acids with Unprotected Glycosides
Scheme 2. Copper-Mediated O-Arylation of Methyl α-L-
a
Rhamnopyranoside with Phenylboronic Acid
a
(a) Site-selective coupling with phenylboronic acid. Proposed
intermediates A and B are shown below the reaction equation. (b)
Coupling with phenylboronic acid neopentyl glycol ester yields a
mixture of O-arylated regioisomers. (c) Competition experiments
gauging the relative reactivity of 1a and protected carbohydrate
derivatives 4a and 4b.
sterically hindered groupsare generally challenging, requiring
distinct conditions from those used for arylations of phenols
and amines.37,38 In the case of carbohydrate derivatives, site-
selectivity poses a significant additional challenge. It is likely
because of these issues that Chan−Lam conditions have not
been explored previously for selective O-arylation of carbohy-
drates, despite the progress that has been made in other
copper-mediated and -catalyzed transformations of sugar
derivatives.39−43
than under argon. See the Supporting Information, Table S1.)
A “phase-switching” workup with aqueous, basic sorbitol
solution was conducted to separate the sugar-derived product
from phenylboronic acid45 and also served to remove the
copper(II) salts prior to further purification. The 4-O-
monoarylated product 3a was obtained in 72% yield and
greater than 20:1 regioselectivity. Analysis of the unpurified
reaction mixture revealed that the primary side products were
three isomeric bis-aryl ethers, which were generated in a
combined 27% yield (see the Supporting Information). The
efficiency of this reaction was noteworthy, given that only a
handful of examples of Chan−Lam arylation of secondary OH
groups have been reported to date.37 The regiochemical
outcome was also intriguing: equatorial OH groups flanked by
other equatorial substituents are sterically encumbered and
show relatively low reactivity with electrophiles.46,47 In keeping
with this trend, direct, selective O-functionalizations of
unprotected α-rhamnopyranosides at the 4-position have not
been reported to date. However, the selectivity shown in
Scheme 2 would be consistent with transient protection of the
rhamnopyranoside as the boronic ester at the cis-diol group,
followed by O-arylation of the free 4-OH group.48 Consistent
RESULTS AND DISCUSSION
■
Reaction Development and Control Experiments.
Methyl α-L-rhamnopyranoside 1a was chosen as a sugar-
derived substrate for investigation of selective O-arylation under
Chan−Lam coupling conditions. This pyranoside-derived triol
was treated with phenylboronic acid (2a) in the presence of
copper(II) acetate, diisopropylethylamine (iPr2NEt), and 4 Å
molecular sieves (MS) in acetonitrile at 40 °C (Scheme 2a).
The reaction was carried out under an inert, argon atmosphere,
and thus two equivalents of Cu(OAc)2 were employed.44
(Attempts to carry out the reaction using catalytic amounts of
copper complex under an oxygen atmosphere resulted in low
yields of O-arylated carbohydrate product, with formation of
the boronic acid-derived diaryl ether being the predominant
side reaction. Furthermore, diminished yield and site-selectivity
were observed when the reaction was conducted under the
optimal conditions, but with an ambient atmosphere rather
B
DOI: 10.1021/jacs.7b09420
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
a
Scheme 3. Copper-Mediated Site-Selective O-Arylation
a
1
Yields after purification by chromatography on silica gel are listed. The isomer ratios were determined by H NMR spectroscopic analysis of
unpurified reaction mixtures. Unless otherwise noted, the selectivity for the isomer depicted was greater than 20:1. For product 3k, treatment with
excess acetic anhydride in pyridine at 23 °C was conducted prior to the phase-switching workup with aqueous Na2CO3/sorbitol solution.
with this hypothesis, treatment of 1a under the reaction
conditions in the absence of the copper(II) salt led to
formation of the 2,3-O-phenylboronate ester (A, Scheme 2).
Moreover, the 4-O-aryl ether-derived boronic ester B was
observed by 1H NMR spectroscopy after passing the unpurified
reaction mixture through a short plug of silica gel in place of the
phase-switching workup. Cleavage of the product-derived
phenylboronic ester thus takes place by transesterification
with sorbitol, as demonstrated previously.48
employed in place of PhB(OH)2, a mixture of isomeric aryl
ethers was obtained. Suppressing the condensation of the
pyranoside with the organoboron reagent thus results in loss of
site-selectivity.
Competition experiments suggested that formation of a
boronic ester under the coupling conditions not only serves to
transiently protect a diol group in the pyranoside substrate but
also accelerates the arylation of the remaining free OH group
(Scheme 2c). When a mixture of 1a and 2,3-O-isopropylidene-
protected derivative 4a was subjected to the conditions for
Chan−Lam coupling, a roughly 11:1 selectivity for the phenyl
ether derived from the free rhamnopyranoside was observed.
Additional evidence for the importance of the formation of a
substrate-derived boronic ester is depicted in Scheme 2b: when
the phenylboronic ester of neopentyl glycol (2b)49 was
C
DOI: 10.1021/jacs.7b09420
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
Since isopropylidene ketal 4a is structurally similar to the
proposed boronic ester intermediate A, this result suggests that
the presence of the 2,3-O-boronate group increases the rate of
arylation of the 4-OH group. A second competition experiment
was conducted using 1a and protected galactose derivative 4b,
having a free primary OH group. The 2:1 selectivity for
arylation of 1a indicates that the rate acceleration provided by
formation of a substrate-derived boronic ester is enough to
overcome the differences in steric demand that would favor the
reaction of 4b under these conditions. Mechanistic hypotheses
related to these observations are provided below.
Scheme 4. Copper-Mediated Site-Selective Installation of
Substituted Aryl Ethers
a
Substrate Scope. Copper-mediated coupling with arylbor-
onic acids provides access to diverse mono-O-arylated pyrano-
side and furanoside derivatives 3b−3m (Scheme 3). For each of
the cases shown, the regiochemical outcome was consistent
with formation of the most stable substrate-derived boronic
ester (structure depicted in square brackets),48,50 followed by
arylation of the remaining free OH group. Analysis of
unpurified reaction mixtures was conducted to assess the site-
selectivity and to identify the major side products of the
reactions (see the Supporting Information). The yields were
generally on par with reported methods for preparation of
phenyl ethers from protected carbohydrate derivatives, and in
the majority of the cases shown (e.g., products 3b−3g), the
OH group that underwent arylation is one that cannot be
functionalized directly by existing methods. For the ribopyrano-
side 1c, the boronic ester group of the product was resistant to
transesterification under the conditions of the phase-switching
workup, and so an oxidative cleavage with basic hydrogen
peroxide solution was employed. The copper-mediated
protocol was also applied to protected myo-inositol derivative
1j and free myo-inositol 1k, yielding O-arylation products
consistent with boronic ester intermediates through complex-
ation of 1,3-diaxial OH groups.51 In the latter case, cleavage of
the product-derived boronic ester was accomplished by
acetolysis rather than by phase-switching workup, to facilitate
isolation of the monoarylated product. Although the yield was
modest, this 2-O-arylation of myo-inositol is a noteworthy
result: direct monofunctionalization of 1k is challenging, with
multistep sequences involving orthoester or acetal-type
intermediates generally being employed.52
In cases where an equilibrium between isomeric substrate-
derived boronic esters was possible, mixtures of products were
obtained. Substrates 1l and 1m, possessing both 4,6-diol and
cis-vicinal diol motifs known to form stable boronic esters,
illustrate this point. In each case, the major product can be
rationalized as arising from one of the two isomeric boronic
esters. For galactopyranoside 1m, it is striking that neither of
the products arises from arylation of the primary OH group:
instead, the reaction of a secondary OH vicinal to the boronic
ester appears to be preferred. A mixture of O-arylated
regioisomers was also obtained when the protocol was applied
to the acyclic triol glycerol (see the Supporting Information).
Substituted arylboronic esters were coupled with rhamno-
pyranoside substrate 1a (Scheme 4). The copper-mediated O-
arylation enabled installation of the para-methoxyphenyl ether
protective group (product 6a),26 as well as functionalized aryl
groups (styrene 6c, haloarenes 6d and 6e, methyl ketone 6f,
dansylamino derivative 6g). A dependence of the level of site-
selectivity on the electronic properties of the arylboronic acid
was observed, with electron-deficient arylboronic acids resulting
in increased proportions of 2-O-arylated side product.
Prestirring the substituted arylboronic acids with 1a prior to
a
Yields after purification by chromatography on silica gel are listed.
The isomer ratios were determined by 1H NMR spectroscopic analysis
of unpurified reaction mixtures.
addition of Cu(OAc)2 had a subtle but reproducible effect on
the level of site-selectivity (Table S3). A rationale for the
reduced site-selectivity with electron-deficient arylboronic acids
is not readily apparent, although it has been noted that
electron-rich congeners undergo more rapid transmetalation to
copper(II).53 Existing methods for O-arylation of carbohydrates
tend to give higher yields for electron-deficient versus electron-
rich aryl coupling partners,28,29 and so the present method is
complementary from this perspective. Other limitations of the
copper-mediated methodology described here include hetero-
aromatic partners such 4-pyridinyl- and N-Boc-2-pyrrolebor-
onic acid, as well as ortho-substituted arylboronic acids (<5%
yields; results not shown). Preliminary attempts at applying this
protocol to more complex substrates resulted in mixtures of
products: the coupling of phenylboronic acid with octyl β-D-
lactoside, having seven free OH groups, generated a complex
mixture of mono- and bis-O-arylated disaccharides, and an
estradiol-derived arylboronic acid54,55 resulted in a roughly
2:1:1 mixture of isomeric ethers upon coupling with 1a (see the
Supporting Information). Further refinements of the protocol
to enable couplings of such highly functionalized partners are
an objective of our ongoing research.
Mechanistic Hypotheses. Stahl and co-workers have used
kinetics and in situ spectroscopy to probe the mechanism of
copper-catalyzed coupling of arylboronic acids with meth-
anol.44,53 The results point toward a reaction pathway involving
formation of an arylcopper(II) species by transmetalation with
the arylboron reagent, followed by disproportionation of two
Cu(II) species to give an arylcopper(III) complex. Reductive
elimination results in formation of the C−O bond and liberates
a copper(I) complex. In the absence of oxygen, the reaction
requires two equivalents of the copper(II) complex, whereas in
the presence of oxygen oxidation of the Cu(I) to Cu(II) closes
the catalytic cycle. Studies of the reactivity of three-coordinate
D
DOI: 10.1021/jacs.7b09420
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
copper(II) aryl complexes are consistent with this general
picture.56 For the copper-catalyzed arylations of methanol
studied by the Stahl group, the transmetalation step was
proposed to be turnover-limiting. It is based on this general
mechanistic framework that we have attempted to understand
the accelerating effect of boronic ester substitution that is
evident from the experiments shown in Scheme 2 and which
underlies the selective arylations shown in Scheme 3.
intermediate capable of C−O bond-forming reductive elimi-
nation to form the aryl ether product.
A distinguishing feature between these proposals is the
nature of the transfer of the aryl group: intramolecular for path
a versus intermolecular for paths b. A crossover experiment was
conducted to probe this issue (Scheme 6). However, because
Scheme 6. Crossover Experiment Using Boronic Esters 7a
and 7b
Possible pathways by which formation of a substrate-derived
boronic ester can facilitate the arylation of a neighboring OH
group are depicted in Scheme 5. Although the rate-determining
Scheme 5. Mechanistic Proposals Consistent with the
Accelerating Effect of an Adjacent Boronic Ester Group on
Copper-Mediated O-Arylation
the two carbohydrate-derived arylboronic esters 7a and 7b
underwent rapid transesterification in the absence of Cu-
(OAc)2, the fact that all four possible 3-O-aryl ether products
(3e, 3f, 8a, and 8b) were obtained could not be used to rule out
a purely intramolecular mechanism (see the Supporting
Information). Further crossover experiments involving sub-
strate-derived boronic esters gave similar inconclusive results
due to competing transesterification.
Given the ambiguity associated with the crossover experi-
ments, computational modeling was used to assess the
feasibility of the two proposed reaction pathways. Density
functional theory (DFT) calculations were carried out using the
dispersion-corrected B97-D3 functional58 and the Def2-TZVP
basis set,59 using the polarized continuum model (PCM) for
acetonitrile. Geometry optimizations and transition state
searches were initially conducted for complexes lacking
coordinated acetonitrile molecules. These geometries were
used as starting points for additional calculations incorporating
one or two acetonitrile ligands. A transition state for
intramolecular transmetalation from a boronate-functionalized,
monosolvated copper alkoxide was identified (Figure 1a),
having a C−B bond distance of 2.16 Å and a C−Cu distance of
2.06 Å. Computational support for the boronic ester-directed
pathway was also obtained: Figure 1b depicts the calculated
transition state for ligand exchange to generate a phenylcopper-
(III) alkoxide (path b, mechanism ii). In both transition state
structures, a Lewis acid−base interaction between the boron
ester group and an acetate ligand is evident, reminiscent of
coordination modes suggested by the Stahl group’s spectro-
scopic studies of Chan−Lam couplings.53 Although further
mechanistic work is warranted, a carboxylate-mediated
interaction between copper and boron centers appears to be
a plausible basis for the accelerating effect of a boronic ester
group on the arylation of a nearby OH group. Consistent with
this idea, when CuBr2 was employed in place of Cu(OAc)2 for
the coupling of 1h and 2a, O-arylation was not observed (see
the Supporting Information).
step has not been identified for the present system, it should be
noted that the depicted steps need not be rate-determining for
selectivity to be observed in a competition experiment of the
type shown in Scheme 2. Path a involves an intramolecular
transmetalation step, in which an aryl group migrates from the
boronic ester to the copper(II) alkoxide. In pathways of type b,
the Lewis acidic boronic ester group serves to direct57 the
formation of the copper alkoxide, either prior to trans-
metalation (i) or at a later stage (e.g., mechanism ii). Of the
latter two possibilities, mechanism i would be most consistent
with Stahl’s studies of the aerobic methoxylation reaction.44,53
The directing effect of a histidine moiety has been invoked to
account for site-selective Chan−Lam-type N-arylations of
backbone amide moieties in peptides.12 Ultimately, each of
these pathways would lead to a copper(III) alkoxide
CONCLUSIONS
■
In summary, we have shown that carbohydrate-derived aryl
ethers can be generated in a site-selective fashion by copper-
mediated couplings of boronic acids with pyranosides or
furanosides. This reactivity enables the selective preparation of
E
DOI: 10.1021/jacs.7b09420
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by NSERC (Discovery Grant and
Canada Research Chairs programs), the McLean Foundation
and University of Toronto (McLean Award to M.S.T.), the
Canada Foundation for Innovation (project nos. 17545 and
19119), and the Ontario Ministry of Research and Innovation.
Computations were performed on resources and with support
provided by the Centre for Advanced Computing (CAC) at
Queen’s University in Kingston, Ontario. The CAC is funded
by: the Canada Foundation for Innovation, the Government of
Ontario, and Queen’s University.
REFERENCES
■
(1) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F; Buchwald, S. L. Acc. Chem.
Res. 1998, 31, 805−818.
(2) Hartwig, J. F. Nature 2008, 455, 314−322.
(3) Bariwal, J.; Van der Eycken, E. Chem. Soc. Rev. 2013, 42, 9283−
9303.
Figure 1. Calculated transition state structures. (a) Boronic ester-
assisted transmetalation. (b) Boronic ester-directed copper(III)
alkoxide formation. Calculations were carried out using density
functional theory with the B97-D3 functional and Def2-TZVP basis
set.
(4) Shafir, A.; Lichtor, P. A.; Buchwald, S. L. J. Am. Chem. Soc. 2007,
129, 3490−3491.
(5) Kung, K. K.-Y.; Ko, H.-M.; Cui, J.-F.; Chong, H.-C.; Leung, Y.-C.;
Wong, M.-K. Chem. Commun. 2014, 50, 11899−11902.
(6) Vinogradova, E.; Zhang, C.; Spokoyny, A. M.; Pentelute, B. L.;
Buchwald, S. L. Nature 2015, 526, 687−691.
functionalized carbohydrate derivatives that would be difficult
to generate by existing methods. Sugars show considerable
potential as scaffolds or linkers in medicinal chemistry,60−62 and
the ability to conduct new types of selective O-functionaliza-
tions may create opportunities in this regard. The efficiency and
site-selectivity of the reactions described here are striking in
light of the challenges associated with copper-mediated O-
arylation of aliphatic alcohols. Both of these features appear to
hinge on the involvement of a boronic ester intermediate
generated by condensation of the boronic acid and
carbohydrate reagents. The formation of the boronic ester
not only transiently protects a diol moiety in the sugar substrate
but also accelerates the arylation of an adjacent hydroxyl group.
The acceleration of O-arylation provided by a neighboring
boronic ester substituent has been probed through competition
experiments, and possible origins of such an effect have been
suggested based on computational modeling of proposed
transition states. These observations have revealed a new facet
of the reactivity of boronic acids with sugar derivatives and may
facilitate applications of sugar-derived aryl ethers in organic
synthesis, medicinal chemistry, and glycobiology.
(7) Willwacher, J.; Raj, R.; Mohammed, S.; Davis, B. G. J. Am. Chem.
Soc. 2016, 138, 8678−8681.
(8) Rojas, A. J.; Zhang, C.; Vinogradova, E. V.; Buchwald, N.; Reily,
J.; Pentelute, B. L.; Buchwald, S. L. Chem. Sci. 2017, 8, 4257−4263.
(9) Zhao, W.; Lee, H. G.; Buchwald, S. L.; Hooker, J. M. J. Am. Chem.
Soc. 2017, 139, 7152−7155.
(10) Cohen, D. T.; Zhang, C.; Pentelute, B. L.; Buchwald, S. L. J. Am.
Chem. Soc. 2015, 137, 9784−9787.
(11) Lee, H. G.; Lautrette, G.; Pentelute, B. L.; Buchwald, S. L.
Angew. Chem., Int. Ed. 2017, 56, 3177−3181.
(12) Ohata, J.; Minus, M. B.; Abernathy, M. E.; Ball, Z. T. J. Am.
Chem. Soc. 2016, 138, 7472−7475.
(13) Ernst, B.; Magnani, J. L. Nat. Rev. Drug Discovery 2009, 8, 661−
677.
(14) Henderson, A. S.; Bower, J. F.; Galan, M. C. Org. Biomol. Chem.
2016, 14, 4008−4017.
(15) Jacobsson, M.; Malmberg, J.; Ellervik, U. Carbohydr. Res. 2006,
341, 1266−1281.
(16) Cerny, M. Chemistry of anhydro sugars. In Advances in
Carbohydrate Chemistry and Biochemistry; Horton, D., Ed.; Elsevier,
2003; Vol. 58, pp 121−198.
̌
́
̌ ̌ ̌ ̌
P.; Leseticky, L.; Smrcek, S.; Tislerova, I.; Stícha, M.
(17) Naus,
Synlett 2003, 14, 2117−2122.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.7b09420.
■
(18) Chida, N. J. Yuki Gosei Kagaku Kyokaishi 2008, 66, 1105−1115.
(19) Brachet, E.; Brion, J.-D.; Messaoudi, S.; Alami, M. Adv. Synth.
Catal. 2013, 355, 477−490.
S
(20) Bruneau, A.; Brion, J.-D.; Alami, M.; Messaoudi, S. Chem.
Commun. 2013, 49, 8359−8361.
(21) Brachet, E.; Brion, J.-D.; Alami, M.; Messaoudi, S. Chem. - Eur. J.
2013, 19, 15276−15280.
(22) Bruneau, A.; Roche, M.; Hamze, A.; Brion, J.-D.; Alami, M.;
Messaoudi, S. Chem. - Eur. J. 2015, 21, 8375−8379.
(23) Chabrier, A.; Bruneau, A.; Benmahdjoub, S.; Benmerad, B.;
Belaid, S.; Brion, J.-D.; Alami, M.; Messaoudi, S. Chem. - Eur. J. 2016,
22, 15006−15010.
(24) Luong, T. T. H.; Brion, J.-D.; Lescop, E.; Alami, M.; Messaoudi,
S. Org. Lett. 2016, 18, 2126−2129.
(25) Al-Shuaeeb, R. A. A.; Montoir, D.; Alami, M.; Messaoudi, S. J.
Org. Chem. 2017, 82, 6720−6728.
Experimental and computational details, characterization
1
data for new compounds, copies of H and 13C NMR
spectra (PDF)
AUTHOR INFORMATION
Corresponding Author
*mtaylor@chem.utoronto.ca
■
ORCID
Graham E. Garrett: 0000-0001-8558-2027
Mark S. Taylor: 0000-0003-3424-4380
F
DOI: 10.1021/jacs.7b09420
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
(26) Petitou, M.; Duchaussoy, P.; Choay, J. Tetrahedron Lett. 1988,
29, 1389−1390.
(27) Shen, X.; Neumann, C. N.; Kleinlein, C.; Goldberg, N. W.;
Ritter, T. Angew. Chem., Int. Ed. 2015, 54, 5662−5565.
(28) Henderson, A. S.; Medina, S.; Bower, J. F.; Galan, M. C. Org.
Lett. 2015, 17, 4846−4849.
(29) Tolani, G. L.; Nilsson, U. J.; Olofsson, B. Angew. Chem., Int. Ed.
2016, 55, 11226−11230.
(30) Barton, D. H. R.; Finet, J.-P.; Motherwell, W. B.; Pichon, C. J.
Chem. Soc., Perkin Trans. 1 1987, 251−259.
(31) Terrett, J. A.; Cuthbertson, J. D.; Shurtleff, V. W.; MacMillan, D.
W. C. Nature 2015, 524, 330−334.
(32) Taylor, M. S. Acc. Chem. Res. 2015, 48, 295−305.
(33) Chan, D. M. T.; Monaco, K. L.; Wang, R. P. Tetrahedron Lett.
1998, 39, 2933−2936.
(34) Evans, D. A.; Katz, J. L.; West, T. R. Tetrahedron Lett. 1998, 39,
2937−2940.
(35) Lam, P. Y. S.; Clark, C. G.; Saubern, S.; Adams, J.; Winters, M.
P.; Chan, D. M. T.; Combs, A. Tetrahedron Lett. 1998, 39, 2941−2944.
(36) Qiao, J. X.; Lam, P. Y. S. Synthesis 2011, 6, 829−856.
(37) Quach, T. D.; Batey, R. A. Org. Lett. 2003, 5, 1381−1384.
(38) El Khatib, M.; Molander, G. A. Org. Lett. 2014, 16, 4944−4947.
(39) Eby, R.; Webster, K. T.; Schuerch, C. Carbohydr. Res. 1984, 129,
111−120.
(40) Osborn, H. M. I.; Brome, V. A.; Harwood, L. M.; Suthers, W. G.
Carbohydr. Res. 2001, 332, 157−166.
(41) Evtushenko, E. V. Carbohydr. Res. 2012, 359, 111−119.
(42) Allen, C. L.; Miller, S. J. Org. Lett. 2013, 15, 6178−6181.
(43) Chen, I.-H.; Kou, K. G. M.; Le, D. N.; Rathbun, C. M.; Dong, V.
M. Chem. - Eur. J. 2014, 20, 5013−5018.
(44) King, A. E.; Brunold, T. C.; Stahl, S. S. J. Am. Chem. Soc. 2009,
131, 5044−5045.
(45) Mothana, S.; Grassot, J. M.; Hall, D. G. Angew. Chem., Int. Ed.
2010, 49, 2883−2887.
(46) Jiang, L.; Chan, T.-H. J. Org. Chem. 1998, 63, 6035−6038.
(47) Huber, F.; Kirsch, S. Chem. - Eur. J. 2016, 22, 5914−5918.
(48) Mancini, R. S.; Lee, J. B.; Taylor, M. S. Org. Biomol. Chem. 2017,
15, 132−143.
(49) Chan, D. M. T.; Monaco, K. L.; Li, R.; Bonne, D.; Clark, C. G.;
Lam, P. Y. S. Tetrahedron Lett. 2003, 44, 3863−3865.
(50) Ferrier, R. J.; Prasad, D. J. Chem. Soc. 1965, 7425−7428.
(51) Salazar-Pereda, V.; Martínez-Martínez, L.; Flores-Parra, A.;
Rosales-Hoz, M.; Ariza-Castolo, A.; Contreras, R. Heteroat. Chem.
1994, 5, 139−143.
(52) Sureshan, K. M.; Shashidhar, M. S.; Praveen, T.; Das, T. Chem.
Rev. 2003, 103, 4477−4504.
(53) King, A. E.; Ryland, B. L.; Brunold, T. C.; Stahl, S. S.
Organometallics 2012, 31, 7948−7957.
(54) Liu, J.; Zheng, S.; Akerstrom, V. L.; Yuan, C.; Ma, Y.; Zhong, Q.;
Zhang, C.; Zhang, Q.; Guo, S.; Ma, P.; Skripnikova, E. V.; Bratton, M.
R.; Pannuti, A.; Miele, L.; Wiese, T. E.; Wang, G. J. Med. Chem. 2016,
59, 8134−8140.
(55) Ahmed, V.; Yong, L.; Silvestro, C.; Taylor, S. D. Bioorg. Med.
Chem. 2006, 14, 8564−8573.
(56) Kundu, S.; Greene, C.; Williams, K. D.; Salvador, T. K.; Bertke,
J. A.; Cundari, T. R.; Warren, T. H. J. Am. Chem. Soc. 2017, 139,
9112−9115.
(57) Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev. 1993, 93,
1307−1370.
(58) Grimme, S.; Ehrlich, S.; Goerigk, L. J. Comput. Chem. 2011, 32,
1456−1465.
(59) Weigend, F.; Ahlrichs, R. Phys. Chem. Chem. Phys. 2005, 7,
3297−3305.
(60) Meutermans, W.; Le, G. T.; Becker, B. ChemMedChem 2006, 1,
1164−1194.
(61) Hirschmann, R. F.; Nicolaou, K. C.; Angeles, A. R.; Chen, J. S.;
Smith, A. B., III Acc. Chem. Res. 2009, 42, 1511−1520.
(62) Lenci, E.; Menchi, G.; Trabocchi, A. Org. Biomol. Chem. 2016,
14, 808−825.
G
DOI: 10.1021/jacs.7b09420
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX