Selective Synthesis of Acylated Cross-Benzoins from Acylals and Aldehydes via N-Heterocyclic Carbene Catalysis

Article abstract of DOI:10.1021/acs.orglett.1c01134

The utility of acylals as building blocks for selective cross-benzoin synthesis was explored in this study. The synthesis of α-acetoxyketones (O-acyl cross-benzoins) was achieved via selective N-heterocyclic carbene-catalyzed cross-benzoin reactions using acylals as aldehyde equivalents. Thus, the combination of ortho-substituted phenyl acylals and aromatic/aliphatic aldehydes as coupling substrates using bicyclic triazolium salts as precatalysts and potassium carbonate as a base in THF at reflux temperature selectively yielded O-acyl cross-benzoins.

Full text of DOI:10.1021/acs.orglett.1c01134

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Letter
Selective Synthesis of Acylated Cross-Benzoins from Acylals and
Aldehydes via N‑Heterocyclic Carbene Catalysis
Kou Onodera, Ryo Takashima, and Yumiko Suzuki*
Cite This: Org. Lett. 2021, 23, 4197−4202
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ABSTRACT: The utility of acylals as building blocks for selective cross-benzoin synthesis was explored in this study. The synthesis
of α-acetoxyketones (O-acyl cross-benzoins) was achieved via selective N-heterocyclic carbene-catalyzed cross-benzoin reactions
using acylals as aldehyde equivalents. Thus, the combination of ortho-substituted phenyl acylals and aromatic/aliphatic aldehydes as
coupling substrates using bicyclic triazolium salts as precatalysts and potassium carbonate as a base in THF at reflux temperature
selectively yielded O-acyl cross-benzoins.
Scheme 1. NHC-Catalyzed Cross-Benzoin Reaction
enzoin condensation is a carbon−carbon bond-forming
Breaction between two aldehyde molecules to furnish an α-
hydroxyketone motif.1 It is a representative example of an
umpolung reaction, in which the polarity of a carbonyl group is
inverted through the catalytic action of a cyanide ion or an N-
heterocyclic carbene (NHC). When two structurally different
aldehydes are mixed and used in the reaction, up to four
benzoin derivativestwo homobenzoins and two cross-
benzoinscan theoretically be produced.
The α-functionalization of ketones2−5 such as Davis
oxidations,2 α-tosyloxylation,3 and Rubottom oxidation via
silyl enol ethers4 has been common strategy to prepare cross-
benzoin-type compounds (α-hydroxyketones). Further, con-
siderable efforts have been made to achieve catalytic cross-
benzoin reactions to construct the motif with good
selectivity.6−10 One example is the cross-acyloin formation
reaction between aromatic aldehydes and alkyl aldehydes
reported by Ming et al.,6 where the use of an excess amount of
alkyl aldehyde allowed the selective synthesis of 1-alkanoyl-1-
aryl alcohols (Scheme 1, a). Gravel and coworkers also
managed the same type of selective cross-acyloin reaction,
mediated by triazole-based NHCs bearing a six-membered
fused ring such as morpholine or piperidine (Scheme 1, a).7
Anand et al. reported the cross-acyloin reactions of aldehydes
and trifluoroacetaldehyde ethyl hemiacetal, also an aldehyde
equivalent, with high yields and chemoselectivities (Scheme 1,
b).8 Connon, Zeitler, and coworkers reported cross-benzoin
reactions using o-substituted aromatic aldehydes as coupling
partners to selectively furnish o-substituted cross-benzoins
(Scheme 1, c).9
Received: April 2, 2021
Published: May 17, 2021
https://doi.org/10.1021/acs.orglett.1c01134
Org. Lett. 2021, 23, 4197−4202
© 2021 American Chemical Society
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These examples and others10 have proven the challenge of
selective catalytic cross-benzoin reactions that afford a wide
range of α-hydroxyketones. In our search for an aldehyde
equivalent for the chemoselective cross-benzoin reaction, the
reactivity of acylals11 inspired us to hypothesize that oxonium
intermediates, presumably generated from acylals by dissoci-
ation of an acyloxyl group, would react with Breslow
intermediates, the key intermediates for benzoin reaction.
Oxonium intermediates derived from acylals behave as
electrophiles in reactions such as the Hosomi−Sakurai
allylation,12 and acylals have also been applied in the selective
protection of formyl groups in the presence of keto groups13
and as reagents for acetylation under mild conditions.14
Although they are readily accessible from aldehydes in one
step15 and are relatively reactive, acylals have not been fully
utilized as building blocks in organic synthesis. Herein, we
report the use of acylals as aldehyde equivalents for the
chemoselective cross-benzoin reaction catalyzed by NHCs to
afford O-acyl-protected benzoins.
Scheme 3. Plausible Reaction Pathways
In preliminary experiments, phenyl acylal 2b and 4-
chlorobenzaldehyde 1a were used as substrates. A screening
of NHCs derived from various precursors such as imidazolium
salts, triazolium salts, and thiazolium salts revealed that bicyclic
triazolium salt 3a and its derivatives possessed potential
catalytic abilities for the reaction between acylals and
aldehydes. (These results, including the optimization of other
reaction conditions and the use of acylals bearing various acyl
groups, may be found in the Supporting Information, Tables
S1−S3). The reaction between 4-chlorobenzaldehyde 1a and 2
equiv of phenyl acylal 2b in the presence of N-(4-methoxy)-
phenyl triazolium salt 3a as a catalyst precursor and potassium
carbonate as a base in refluxing THF for 24 h afforded four O-
acetyl benzoin products, 4ab, 4ba, 4aa, and 4bb (Scheme 2).
We suspected that the lack of selectivity was related to a low
rate of the oxonium intermediate formation. Hence, we
focused on the aryl acylal structure, presuming that
substituents bearing lone-pair electrons at position 2 of the
phenyl ring would stabilize the oxonium intermediates by
resonance (Scheme 4) and facilitate its in situ generation and
Scheme 4. Proposed Stabilization of Positive Charge by
Delocalization
Scheme 2. Preliminary Experiment Using Acylal in Cross-
Benzoin Reaction
the desired reaction. The positive charge of the oxocarbenium
ionthe expected intermediatewould be delocalized among
the central carbon, the adjacent oxygen atom, and the electron-
donating substituent.
The reactions with 2-halogenated phenyl acylals 2c (R = F),
2d (R = Cl), and 2e (R = Br) respectively afforded the desired
O-acetyl-protected cross-benzoin products 4ac, 4ad, and 4ae in
high yields (Scheme 5). In contrast, when 2-(trifluoromethyl)-
phenyl acylal 2f and 2-methoxyphenyl acylal 2g were used,
acetyl homobenzoin 4aa originating from 4-chlorobenzalde-
hyde 1a was the dominant product. In the case of 2f, resonance
stabilization cannot be achieved with the inductively electron-
withdrawing −CF3 group, while the comparative bulk of the
electron-donating −OCH3 group prevents both/either effec-
tive delocalization and/or nucleophilic attack by the Breslow
intermediate. In addition, the methoxy group can increase the
relative reactivity of the acetyl groups, such that the acylal
behaves as an acylating agent. When 4-methoxyphenyl acylal
was employed in the reaction, the desired product was not
obtained; instead, 4,4′-dichlorobenzil, O-acetyl homobenzoin
4aa, O-4-chlorobenzoyl homobenzoin form 1a, and a
substantial amount of 4-anisaldehyde were observed as
products.
a
1
Calculated yield from H NMR spectrum.
The desired cross-benzoin product 4ab was obtained in only
14% yield, and homobenzoin product 4aa was afforded as the
major product. A similar result was obtained using the
dipropionate acylal, and the yields of the O-acyl homobenzoins
were increased when the diisobutyrate acylal was used (Table
S3). In contrast, the dipivaloyl and dibenzoyl acylals were inert
under the same conditions (Table S3).
We expected the oxonium intermediate originating from
acylal B to behave as an electrophile, reacting with the Breslow
intermediate to furnish O-acyl cross-benzoin C (Scheme 3,
route 1). However, the preliminary results indicated the
existence of a competing pathway (route 2), in which
homobenzoin D′ is generated from aldehyde A and acetylated
by B, affording O-acyl homobenzoin D and aldehyde B′. As a
result, both the homo- and cross-benzoin-forming reactions
proceeded, followed by acetylation of the benzoins with B to
afford a mixture of acetylated products.
To examine the scope of aldehyde reaction partners, we
employed 2-chlorophenyl acylal 2d, which afforded the best
yields in the screening of 2-substituted acylals with various
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Scheme 5. Screening of 2-Substituted Acylals
Scheme 7. Cross-Benzoin Reactions between Aldehydes
3-Clorobenzaldehyde 1h afforded the desired cross-benzoin
adduct 4hd in 60% yield. Although an electron-donating 4-
methoxy group on the benzene ring should have increased the
nucleophilicity of its Breslow intermediate, 4-anisaldehyde 1i
afforded compound 4id in low yield. 3-Anisaldehyde 1j
participated in the reaction to afford 4jd in a moderate yield
only in the presence of DMAP (10 mol %); the O-acetyl-
protected homobenzoin product from 1j was also obtained.
The use of 4-formylbenzonitrile 1k resulted in a lower yield,
and the aldehyde was converted to the corresponding O-acetyl-
protected homobenzoin.
Furfural (2l), 2-thiophenecarboxaldehyde (2m), and pico-
linaldehyde (1n) were tolerated to afford the corresponding
products 4ld, 4md, and 4nd in moderate to high yields
(Scheme 6). In the reactions affording 4md and 4nd, the O-
acetyl homobenzoin derivatives from the heteroaromatic
aldehydes were obtained in substantial amounts. The
thermodynamic stability of the homobenzoins caused by
hydrogen bonding between the hydroxy group and the
heteroatoms (sulfur and nitrogen) of the aroyl groups is
thought to drive the reaction toward the homobenzoin
condensation pathway. The reaction with nicotinaldehyde 1o
required DMAP to produce 4od (74% yield), and the O-acetyl
homobenzoin originating from the aldehyde was not obtained.
In the case of N-acetyl-indole-3-carboxyaldehyde N-Ac-1p, N-
deacetylated compound 4pd was obtained, indicating that the
N-acetyl group was removed during the reaction. When indole-
3-carboxyaldehyde 1pwithout an N-acetyl groupwas used,
4pd was obtained in only 20% yield.
a
Yield of O-acetyl homobenzoin 4aa obtained from 1a.
aldehydes (Scheme 6). The reaction with benzaldehyde 1b
afforded the desired cross-benzoin adduct 4bd in 81% yield. In
contrast, when 2-chlorobenzaldehyde 1d was used instead of
2d under the same reaction conditions, the cross-benzoin
product 4bd′ was obtained in 60% yield, along with
homobenzoin 4dd′ obtained from 1d in 36% yield (Scheme
7).
Scheme 6. Screening of Aldehydes
In these reactions, DMAP functions as a cocatalyst and an
initiator to generate 2-chlorobenzaldehyde 1d (as B′ in route
2, Scheme 3) from acylal 2d. When the reaction between the
Breslow and oxonium intermediates from the acylals is
sluggish, the reaction between DMAP and the acylal proceeds
to yield the aldehyde and 1-acetylated 4-dimethylaminopyr-
idinium cation, which behaves as an acetylating agent to afford
O-acetyl benzoins such as 4jd, 4od, and 4pd.
Alkyl aldehydes were also tolerated in this reaction (Scheme
6). The reactions of 2d with primary aldehydes such as n-
hexanal 1q and n-octanal 1r afforded the corresponding cross-
benzoin products 4qd and 4nd in quantitative yields; however,
the branched aldehydes, pivalaldehyde and cyclohexane-
carboxaldehyde, were inert under these conditions.
Mechanistically, we considered whether the present trans-
formation using acylal 2d and the aliphatic aldehydes
proceeded through the in situ generation of 2-chlorobenzalde-
hyde followed by benzoin reaction and acetylation (route 2,
Scheme 3), and if the steric and electronic effects of the 2-
substituent of the aldehyde (from 2d) solely controlled the
a
The yield of O-acetyl homobenzoin 4bb, 4hh, 4jj, 4kk, 4ll, 4mm, or
b
4nn obtained from the corresponding aldehyde 1. 4-Anisaldehyde 1i
(80%) and acylal 2d (73%) were recovered. 10 mol % DMAP was
c
d
added. Nicotinaldehyde 1o (10%) and 2d (35%) were recovered.
e
f
N-acetylindole-3-carboxaldehyde N-Ac-1p was used. Indole-3-
carboxaldehyde 1p was used.
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selectivity. In that case, condensation of the aliphatic and
aromatic aldehydes under the same conditions would
selectively yield cross-benzoin products such as 4qd′ (Scheme
7). However, the reaction of hexanal 1q and 2-chlorobenzal-
dehyde 1d does not yield 4qd, and a trace amount of 2,2′-
dichlorobenzil produced from 1d was obtained with the
recovery of 1q and 1d, indicating that the proposed reaction
pathway through the oxonium intermediate is feasible (route 1,
Scheme 3). It should be mentioned, however, that the
possibility of route 2 (Scheme 3) cannot be completely
excluded, wherein in situ acetylation of the benzoin product
may prevent the retro-reaction, resulting in selective synthesis
in high yields.
convertible, the present method allows facile access to various
α-acetoxy ketones. An enantioselective version of the reaction,
the selective cross-reaction between two structurally different
aliphatic aldehydes, and a computational study to scrutinize the
reaction pathway is currently underway.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c01134.
Detailed experimental procedures, characterization data,
1
and copies of H and 13C NMR spectra of all purified
compounds (PDF)
To examine the effects of substituents on the benzene ring of
phenyl acylal 2, cross-acyloin reactions between several acylals
and 3-phenylpropionaldehyde 1s were conducted (Scheme 8).
AUTHOR INFORMATION
Corresponding Author
■
Scheme 8. Substituent Effects of Phenyl Acylals in Reaction
with 3-Phenylpropionaldehyde
Yumiko Suzuki − Department of Materials and Life Sciences,
Faculty of Science and Technology, Sophia University,
Chiyoda-ku, Tokyo 102-8554, Japan; orcid.org/0000-
0002-8226-5867; Email: yumiko_suzuki@sophia.ac.jp
Authors
Kou Onodera − Department of Materials and Life Sciences,
Faculty of Science and Technology, Sophia University,
Chiyoda-ku, Tokyo 102-8554, Japan
Ryo Takashima − Department of Materials and Life Sciences,
Faculty of Science and Technology, Sophia University,
Chiyoda-ku, Tokyo 102-8554, Japan
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c01134
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
a
We are grateful to Prof. Noriyuki Suzuki of the Department of
Materials and Life Sciences, Faculty of Science and
Technology, Sophia University for the useful discussion on
the present work. We thank Mr. Futa Koyama, a student at the
Graduate School of Science and Technology, Sophia
University, who helped us confirm the experimental
replicability. We also thank Ms. Emiko Okano of the Faculty
of Science and Technology, Sophia University for the mass
spectrometry measurements and Sophia University for
financial support.
Yield of O-acetyl homoacyloin product 4ss from 3-phenyl-
propionaldehyde 1s.
Phenyl acylal 2b without substituents or steric hindrance
afforded the desired cross product 4sb in 45% yield. The
reaction with 2-halogenated phenyl acylals 2c, 2d, and 2e
produced the desired cross-acyloin products 4sc, 4sd, and 4se
in moderate to high yields. In contrast, 2-methoxyphenyl acylal
2g and 4-cyanophenyl acylal 2k furnished 4sg and 4sk in low
yields. These results, together with the results in Scheme 3,
indicate that bulky substituents at position 2 hamper
nucleophilic attack on the oxocarbenium cations (or 2g
behaves as an acylating agent), and that electron-withdrawing
substituents destabilize the intermediates and are unfavorable
for their generation.
In summary, we developed a novel synthetic method for the
selective preparation of O-acetyl cross-benzoins using acylals as
aldehyde equivalents in NHC-catalyzed reactions. A reaction
mechanism involving O-acyl oxocarbenium cations derived
from the acylals as key intermediates was proposed, in which
halogens at the ortho position of the phenyl acylals contributed
to the stabilization of the intermediate cations by the
resonance effect. To the best of our knowledge, this is the
first report of the use of acylals as electrophiles in NHC-
catalyzed reactions. Because halogens are easily removable and
REFERENCES
■
(1) For selected reviews and book chapters, see: (a) Laue, T.;
Plagens, A. Benzoin Condensation. In Named Organic Reactions, 2nd
ed.; John Wiley & Sons, Ltd., 2005; Chapter 2. (b) Langdon, S. M.;
Parmar, K.; Wilde, M. M. D.; Gravel, M. Benzoin Reaction. In N-
Heterocyclic Carbenes in Organocatalysis, Biju, A. T., Ed.; Wiley-VCH
Verlag GmbH & Co. KGaA, 2019; Chapter 2. (c) Menon, R. S.; Biju,
A. T.; Nair, V. Recent advances in N-heterocyclic carbene (NHC)-
catalyzed benzoin reactions. Beilstein J. Org. Chem. 2016, 12, 444−
461. (d) Flanigan, D. M.; Romanov-Michailidis, F.; White, N. A.;
Rovis, T. Organocatalytic Reactions Enabled by N-Heterocyclic
Carbenes. Chem. Rev. 2015, 115, 9307−9387. (e) Bugaut, X.; Glorius,
F. Organocatalytic umpolung: N-heterocyclic carbenes and beyond.
Chem. Soc. Rev. 2012, 41, 3511−3522. (f) Enders, D.; Niemeier, O.;
Henseler, A. Organocatalysis by N-Heterocyclic Carbenes. Chem. Rev.
2007, 107, 5606−5655.
4200
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Org. Lett. 2021, 23, 4197−4202

Organic Letters
pubs.acs.org/OrgLett
Letter
(2) Davis, F. A.; Vishwakarma, L. C.; Billmers, J. G.; Finn, J.
Synthesis of α-hydroxycarbonyl compounds (acyloins): direct
oxidation of enolates using 2-sulfonyloxaziridines. J. Org. Chem.
1984, 49, 3241−3243.
(10) For selected examples and reviews, see: (a) Piel, I.; Pawelczyk,
M. D.; Hirano, K.; Fröhlich, R.; Glorius, F. A Family of Thiazolium
Salt Derived N-Heterocyclic Carbenes (NHCs) for Organocatalysis:
Synthesis, Investigation and Application in Cross-Benzoin Con-
densation. Eur. J. Org. Chem. 2011, 2011, 5475−5484. (b) Jin, M. Y.;
Kim, S. M.; Han, H.; Ryu, D. H.; Yang, J. W. Switching
Regioselectivity in Crossed Acyloin Condensations between Aromatic
Aldehydes and Acetaldehyde by Altering N-Heterocyclic Carbene
Catalysts. Org. Lett. 2011, 13, 880−883. (c) Jin, M. Y.; Kim, S. M.;
Mao, H.; Ryu, D. H.; Song, C. E.; Yang, J. W. Chemoselective and
Repetitive Intermolecular Cross-Acyloin Condensation Reactions
Between a Variety of Aromatic and Aliphatic Aldehydes Using a
Robust N-Heterocyclic Carbene Catalyst. Org. Biomol. Chem. 2014,
12, 1547−1550. (d) Gaggero, N.; Pandini, S. Advances in
chemoselective intermolecular cross-benzoin-type condensation re-
actions. Org. Biomol. Chem. 2017, 15, 6867−6887.
(11) (a) Aggarwal, V. K.; Fonquerna, S.; Vennall, G. P. Sc(OTf)3, an
efficient catalyst for formation and deprotection of geminal diacetates
(acylals); Chemoselective protection of aldehydes in presence of
ketones. Synlett 1998, 1998, 849−852. (b) Sandberg, M.; Sydnes, L.
K. Formation of nitriles by treatment of acylals with trimethylsilyl
azide in the presence of a Lewis acid. Tetrahedron Lett. 1998, 39,
6361−6364. (c) Iranpoor, N.; Firouzabadi, H.; Shaterian, H. R.;
Zolfigol, M. A. New Applications of Solid Silica Chloride (SiO 2 -Cl)
in Organic Synthesis. Efficient Preparation of Diacetals of 2,2-
Bis(Hydroxymethyl)-1,3-propanediol from Different Substrates and
Their Transthioacetalization Reactions. Efficient Regeneration of
Carbonyl Compounds from Acetals and Acylals. Phosphorus, Sulfur
Silicon Relat. Elem. 2002, 177, 1047−1071. (d) Song, Q. Y.; Yang, B.
L.; Tian, S. K. FeSO4·7H2O-Catalyzed Four-Component Synthesis of
Protected Homoallylic Amines. J. Org. Chem. 2007, 72, 5407−5410.
(e) Li, Z.; Duan, Z.; Kang, J.; Wang, H.; Yu, L.; Wu, Y. A simple
access to triarylmethane derivatives from aromatic aldehydes and
electron-rich arenes catalyzed by FeCl3. Tetrahedron 2008, 64, 1924−
1930. (f) Monaco, A.; Szulc, B. R.; Rao, Z. X.; Barniol-Xicota, M.;
Sehailia, M.; Borges, B. M. A.; Hilton, S. T. Short Total Synthesis of
( )-γ-Lycorane by a Sequential Intramolecular Acylal Cyclisation
(IAC) and Intramolecular Heck Addition Reaction. Chem. - Eur. J.
2017, 23, 4750−4755.
(3) For selected examples, see: (a) Boelke, A.; Nachtsheim, B. J.
Evolution of N-Heterocycle-Substituted Iodoarenes (NHIAs) to
Effiecnt Organocatalysits in Iodine(I/III)-Mediated Oxidative Trans-
formations. Adv. Synth. Catal. 2020, 362, 184−191. (b) Lex, T. R.;
Swasy, M. I.; Panda, S.; Brummel, B. R.; Giambalvo, L. N.; Gross, K.
G.; McMillen, C. D.; Kobra, K.; Pennington, W. T.; Whitehead, D. C.
Design and synthesis of Fmoc-SPPS-ready iodoarene amino acid pre-
catalysts and their reactivity in the catalytic oxytosylation of ketones.
Tetrahedron Lett. 2020, 61, 151723. (c) Lex, T. R.; Swasy, M. I.;
Whitehead, D. C. Relative Rate Profiles of Functionalized Iodoarene
Catalysts for Iodine(III) Oxidations. J. Org. Chem. 2015, 80, 12234−
12243. (d) Tanaka, A.; Moriyama, K.; Togo, H. Iodoarene-Mediated
α-Tosyloxylation of Ketones with MCPBA and p-Tolulenesulfonic
Acid. Synlett 2011, 2011, 1853−1858. (e) Yamamoto, Y.; Togo, H.
PhI-Catalyzed α-Tosyloxylation of Ketones with Chloroperbozoic
Acid and p-Tolulenesulfonic Acid. Synlett 2006, 37, 798−800.
(4) Rubottom, G. M.; Vazquez, M. A.; Pelegrina, D. R. Peracid
Oxidation of Trimethylsilyl enol Ethers; A Facile α-Hydroxylation
Procedure. Tetrahedron Lett. 1974, 15, 4319−4322.
(5) For selected recent examples, see: (a) Hasegawa, E.; Nakamura,
S.; Oomori, K.; Tanaka, T.; Iwamoto, H.; Wakamatsu, K. Competitive
Desulfonylative Reduction and Oxidation of α-Sulfonylketones
Promoted by Photoinduced Electron Transfer with 2-Hydroxyaryl-
1,3-dimethylbenzimidazolines under Air. J. Org. Chem. 2021, 86,
2556−2569. (b) Hasegawa, E.; Yoshioka, N.; Tanaka, T.;
Nakaminato, T.; Oomori, K.; Ikoma, T.; Iwamoto, H.; Wakamatsu,
K. Sterically Regulated α-Oxygenation of α-Bromocarbonyl com-
pounds Promoted Using 2-Aryl-1,3-dimethylbenzimidazolines and
Air. ACS Omega 2020, 5, 7651−7665. (c) Liu, W.; Chen, C.; Zhou, P.
N-dimethylformamide (DMF) as a Source of Oxygen To Access α-
Hydroxy Arones via the α-Hydroxylation of Arones. J. Org. Chem.
2017, 82, 2219−2222. (d) Liang, Y.-F.; Wu, K.; Song, S.; Li, X.;
Huang, X.; Jiao, N. I2- or NBS-Catalyzed Highly Efficient α-
Hydroxylation of Ketones with Dimethyl Sulfoxide. Org. Lett. 2015,
17, 876−879.
(6) (a) Jin, M. Y.; Kim, S. M.; Han, H.; Ryu, D. H.; Yang, J. W.
Switching Regioselectivity in Crossed Acyloin Condensations
between Aromatic Aldehydes and Acetaldehyde by Altering N-
Heterocyclic Carbene Catalysts. Org. Lett. 2011, 13, 880−883. (b) Jin,
M. Y.; Kim, S. M.; Mao, H.; Ryu, D. H.; Song, C. E.; Yang, J. W.
Chemoselective and repetitive intermolecular cross-acyloin condensa-
tion reactions between a variety of aromatic and aliphatic aldehydes
using a robust N-heterocyclic carbene catalyst. Org. Biomol. Chem.
2014, 12, 1547−1550.
(7) Langdon, S. M.; Wilde, M. M. D.; Thai, K.; Gravel, M.
Chemoselective N-Heterocyclic Carbene-Catalyzed Cross-Benzoin
Reactions: Importance of the Fused Ring in Triazolium Salts. J. Am.
Chem. Soc. 2014, 136, 7539−7542.
(12) (a) Larsen, C. H.; Ridgway, B. H.; Shaw, J. T.; Woerpel, K. A. A
Stereoelectronic Model to Explain the Highly Stereoselective
Reactions of Nucleophiles with Five-Membered-Ring Oxocarbenium
Ions. J. Am. Chem. Soc. 1999, 121, 12208−12209. (b) Smith, D. M.;
Tran, M. B.; Woerpel, K. A. Nucleophilic Additions to Fused Bicyclic
Five-Membered Ring Oxocarbenium Ions: Evidence for Preferential
Attack on the Inside Face. J. Am. Chem. Soc. 2003, 125, 14149−
14152. (c) Ayala, L.; Lucero, C. G.; Romero, J. A. C.; Tabacco, S. A.;
Woerpel, K. A. Stereochemistry of Nucleophilic Substitution
Reactions Depending upon Substituent: Evidence for Electrostatic
Stabilization of Pseudoaxial Conformers of Oxocarbenium Ions by
Heteroatom Substituents. J. Am. Chem. Soc. 2003, 125, 15521−15528.
(d) Larsen, C. H.; Ridgway, B. H.; Shaw, J. T.; Smith, D. M.;
Woerpel, K. A. Stereoselective C-Glycosylation Reactions of Ribose
Derivatives: Electronic Effects of Five-Membered Ring Oxocarbe-
nium Ions. J. Am. Chem. Soc. 2005, 127, 10879−10884.
(13) (a) Jung, M.; Yoon, J.; Kim, H. S.; Ryu, J. S. Mild and
Chemoselective Synthesis and Deprotection of Geminal Diacetates
Catalyzed by Titanium(IV) Halides. Synthesis 2010, 16, 2713−2720.
(b) Khazaei, A.; Manesh, A. A.; Alavi-Nik, H. A.; Roosta, Z. T. SnCl2·
2H2O and Ni(OAc)2·4H2O: Efficient Heterogeneous Inorganic
Catalysts for the Chemoselective Synthesis of Geminal Diacetates
(Acylal) Under Solvent-Free Conditions. Asian J. Chem. 2011, 23,
627−630.
(8) Ramanjaneyulu, B. T.; Mahesh, S.; Anand, R. V. N-Heterocyclic
Carbene Catalyzed Highly Chemoselective Intermolecular Crossed
Acyloin Condensation of Aromatic Aldehydes with Trifluoroacetalde-
hyde Ethyl Hemiacetal. Org. Lett. 2015, 17, 6−9.
(9) (a) Delany, E. G.; Connon, S. J. Enantioselective N-heterocyclic
carbene-catalysed intermolecular crossed benzoin condensations:
improved catalyst design and the role of in situ racemization. Org.
Biomol. Chem. 2021, 19, 248−258. (b) Delany, E. G.; Connon, S. J.
Highly chemoselective intermolecular cross-benzoin reactions using
an ad hoc designed novel N-heterocyclic carbene catalyst. Org. Biomol.
Chem. 2018, 16, 780−786. (c) O’Toole, S. E.; Rose, C. A.; Gundala,
S.; Zeitler, K.; Connon, S. J. Highly Chemoselective Direct Crossed
Aliphatic−Aromatic Acyloin Condensations with Triazolium-Derived
Carbene Catalysts. J. Org. Chem. 2011, 76 (2), 347−357. (d) Rose, C.
A.; Gundala, S.; Connon, S. J.; Zeitler, K. Chemoselective Crossed
Acyloin Condensations: Catalyst and Substrate Control. Synthesis
2011, 2011, 190−198.
(14) Chapman, R. S. L.; Tibbetts, J. D.; Bull, S. D. 1,1-Diacyloxy-1-
phenylmethanes as versatile N-acylating agents for amines. Tetrahe-
dron 2018, 74, 5330−5339.
(15) (a) Kochhar, K. S.; Bal, B. S.; Deshpande, R. P.; Rajadhyaksha,
S. N.; Pinnick, H. W. Conversion of aldehydes into geminal
diacetates. J. Org. Chem. 1983, 48, 1765−1767. (b) Hirao, T.;
4201
https://doi.org/10.1021/acs.orglett.1c01134
Org. Lett. 2021, 23, 4197−4202

Organic Letters
pubs.acs.org/OrgLett
Letter
Santhitikul, S.; Takeuchi, H.; Ogawa, A.; Sakurai, H. eductive
esterification of aromatic aldehydes using Zn/Ac2O/imidazole or
Zn/Yb(OTf)3/(RCO)2O system. Tetrahedron 2003, 59, 10147−
10152. (c) Shelke, K. F.; Gadekar, L. S. Titaniumdioxide as an eco-
friendly and recyclable catalyst for the synthesis of 1,1-diacetate under
solvent-free conditions. Org. Chem. An Ind. J. 2015, 11, 102−107.
4202
https://doi.org/10.1021/acs.orglett.1c01134
Org. Lett. 2021, 23, 4197−4202