Boron-Templated Dimerization of Allylic Alcohols to Form Protected 1,3-Diols via Acid Catalysis

Article abstract of DOI:10.1021/acs.orglett.9b03760

We report an unprecedented boron-templated dimerization of allylic alcohols that generates a 1,3-diol product with two stereogenic centers in high yield and diastereoselectivity. This acid-catalyzed reaction is achieved via in situ formation of a boronic ester intermediate that facilitates selective cyclization and formation of a cyclic boronic ester product. High yields are observed with a variety of allylic alcohols, and mechanistic studies confirm the role of boron as a template for the reaction.

Full text of DOI:10.1021/acs.orglett.9b03760

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Boron-Templated Dimerization of Allylic Alcohols To Form
Protected 1,3-Diols via Acid Catalysis
S. Hadi Nazari,†,§ Kelton G. Forson,§ Erin E. Martinez, Nicholas J. Hansen,‡ Kyle J. Gassaway,
Nathan M. Lyons, Karissa C. Kenney, Gabriel A. Valdivia-Berroeta, Stacey J. Smith,
and David J. Michaelis*
Brigham Young University, Provo, Utah 84602, United States
S
* Supporting Information
ABSTRACT: We report an unprecedented boron-templated
dimerization of allylic alcohols that generates a 1,3-diol product
with two stereogenic centers in high yield and diastereoselectiv-
ity. This acid-catalyzed reaction is achieved via in situ formation
of a boronic ester intermediate that facilitates selective
cyclization and formation of a cyclic boronic ester product.
High yields are observed with a variety of allylic alcohols, and
mechanistic studies confirm the role of boron as a template for
the reaction.
emplated organic transformations are reminiscent of
Tenzyme-mediated processes because, like enzymes, they
rely on the preorganization of reacting substrates in close
proximity to achieve high yield and high selectivity. Various
innovative and efficient strategies that employ substrate
preorganization for organic catalysis have recently been
reported and include the use of organic or metal ion
templates,1−5 porous coordination frameworks (e.g.,
MOFs),6−10 removable covalent tethers such as silicon
tethers,11−14 and work from our group in bifunctional peptide
catalysis.15 These types of templated processes can enable
selective intramolecular cyclizations such as macrocycliza-
tion,16,17 as well as achieve selective dimerization/trimerization
Figure 1. Boron-tethered transformations.
with unique regio- or stereoselectivity.6,18,19 Boron-based
1b). In this unprecedented transformation, the boronic acid is
incorporated into the structure of the product (2), but can be
easily removed under basic conditions to reveal a new 1,3-diol
structure (3). Herein, we report the development of this new
selective dimerization of allylic alcohols, demonstrate good
substrate tolerance, and confirm the necessity and role of the
boronic acid template in forming the dimerized product. We
also demonstrate that the resulting boron-protected 1,3-diol
product is a versatile intermediate for chemical synthesis
through a series of derivatization studies.
In our early optimization studies, we found that copper(II)
triflate facilitated the formation of dimerization product 2 in
moderate yield (Table 1, entry 1). Due to difficulty in isolating
the boronic ester product early on, we subsequently cleaved
the boronic ester under basic aqueous conditions and isolated
the diol product 3. We next screened various Cu(II) and Cu(I)
salts and found that only copper(II) triflate enabled product
tethers are particularly attractive because the dynamic nature
of B−O bonds under acidic or basic conditions can enable
boronic ester formation as a route to activate allylic and
benzylic alcohols20 and enable templated reactions.21−23
Indeed, Morgan and co-workers recently reported boron-
tethered, enantioselective Diels−Alder reactions that rely on a
boron-based tether between the diene and dienophile (1,
Figure 1a).24−29 Boron-tethered radical cyclizations,30,31
carboborations of alkenes and alkynes,32−34 and cyclo-
trimerizations18,19 have also been reported. Boronic ester
tethers can also be easily removed under basic conditions, and
B−C bonds are readily transformed to new C−O bonds upon
oxidation.
Our research group is interested in the use of simple allylic
alcohol substrates as coupling partners for transition-metal-
catalyzed reactions.35,36 Recently, while investigating the use of
nickel catalysts for Suzuki reactions with unprotected allylic
alcohol electrophiles,36 we discovered that copper(II) triflate
catalyzed a unique dimerization of allylic alcohols to form new
C−C and C−O bonds (red) across one of the alkenes (Figure
Received: October 23, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b03760
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
presumably due to the low nucleophilicity of the conjugated
alkene. In all cases, the product was isolated in ∼10:1
diastereoselectivity. The reaction is also readily scalable and
when performed on 11.2 mmol scale, product 2a (3.65 g) was
isolated in 96% yield. The structure of the boronic ester
product and the trans diastereoselectivity of the reaction were
confirmed by single crystal X-ray analysis of 2a (Figure 2).
Table 1. Optimization Studies
a
b
entry
catalyst
solvent
temp
% yield (3)
c
1
2
3
4
5
6
7
Cu(OTf)2 + dppf
CuCl2 + dppf
Cu(OAc)2 + dppf
CuI + dppf
TfOH
toluene
toluene
toluene
toluene
toluene
toluene
DCE
60 °C
60 °C
60 °C
60 °C
60 °C
rt
rt
rt
rt
rt
42
0
0
0
90
96
90
0
30
0
TfOH
TfOH
8
9
TfOH
TfOH
THF
DCE
d
10
11
None
TfOH
DCE
DCE
e
rt
0
a
Reactions run with 1 mmol of cinnamyl alcohol, 0.5 mmol of
PhB(OH)2, and 10 mol % catalyst in solvent (0.06 M) for 12 h.
b
Isolated yields of 3 (∼10:1 dr) after hydrolysis of the boronic ester
c
d
e
with aq. KOH. After 16 h. Reaction run with 5 mol % TfOH. No
PhB(OH)2 was added.
formation (entries 2−4). These latter results made us question
whether triflic acid (TfOH) was not in fact responsible for the
catalysis we observed.37 When TfOH was employed as the sole
catalyst instead of copper triflate, the identical product was
formed in improved yield (entry 5). Thus, our continuing
optimization studies focused on the use of TfOH as catalysts.
We next screened temperature (entries 5, 6), solvents (entries
6−8), and acid catalyst loading (entries 9, 10) and found that
high yields (>90%) could be obtained with just 10% TfOH in
DCE or toluene as solvent at room temperature. In control
studies, we found that no reaction occurs in the absence of
triflic acid (entry 10) and that the boronic acid was necessary
for formation of the 1,3-diol product (entry 11). Furthermore,
the addition of molecular sieves to soak up the water formed in
the reaction had no impact on the rate or yield of the reaction,
suggesting that triflic acid is indeed acting as a catalyst and that
the reaction is not likely under boronic acid promoted
hydronium catalysis.20,39 In all of our optimization studies,
the cyclization product was obtained with a high diastereo-
meric ratio (∼10:1 dr), favoring the anti isomer.
The high yield and selectivity observed in this new
transformation, and the versatility of the 1,3-diol product as
a synthetic intermediate, led us to explore the substrate scope
of the transformation. For these studies, we found that
purification of the boronic ester product directly on silica gel
that was deactivated with Et3N allowed us to isolate this
intermediate (2) without the need to hydrolyze the boronic
ester and reveal the diol product (3). When exploring
variations of the allylic alcohol structure, we found that a
variety of aryl substituents were tolerated in the reaction,
including substituents at the para (2a−2i), meta (2j, 2k), and
ortho positions (2l, 2m). Various electron donating (2c−2g,
2m) and electron withdrawing (2b, 2h) substituents could also
be employed, as well as heterocyclic (2r) and polycyclic
aromatic substrates (2n). We also found that trisubstituted
nonaryl allylic alcohols worked well in the reaction (2s), but
disubstituted nonconjugated allylic alcohols did not (2t).
Cinnamyl alcohols with strong electron-withdrawing groups
(2i, 2q) react slowly and provide low yields in the reaction,
Figure 2. Substrate scope for acid-catalyzed dimerization.
Having established the generality of this reaction for
selective alcohol dimerization, we next investigated the
mechanism of the transformation. We hypothesize that the
phenylboronic acid used in the reaction condenses with 2
equiv of the allylic alcohol. This boronic ester intermediate
then facilitates selective cyclization and product formation.
When the boronic ester of cinnamyl alcohol was formed
stoichiometrically (4) and then treated with TfOH, the desired
dimerization product (2a) was isolated in 98% yield (Figure
3a). We also considered the possibility of boronic acid
promoted hydronium catalysis, which is a possible mechanism
in the presence of the water formed in the reaction.38,39
However, when molecular sieves were added to the reaction to
sequester the water formed, no decrease in rate or yield was
observed, as previously noted. We next asked whether the
boronic ester tether was a strict requirement or if other tethers
such as a silicon tether could be employed. However, when we
employed silicon tether cinnamyl alcohol (5), no product was
observed (Figure 3b). An additional mechanistic consideration
is the fact that only styrenyl or trisubstituted allylic alcohols
participate in the reaction, which suggests that stabilization of a
B
DOI: 10.1021/acs.orglett.9b03760
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Regeneration of the acid catalyst and formation of 2a
terminates the cycle.
Next, we wondered whether we could generate enantioen-
riched 1,3-diol product via use of a chiral acid or incorporation
of a chiral auxiliary. As such, (R)-camphorsulfonic acid ((R)-
CSA) was employed in the reaction and the product was
isolated in 33% yield after 12 h (Figure 5a). Unfortunately, no
Figure 3. Tether studies.
cationic intermediate might be necessary for efficient reaction
to occur.
Based on our observations about the requirements for this
new transformation, we proposed the mechanism shown in
Figure 4. An acid-catalyzed boronic ester formation leads to
Figure 5. Attempts at stereoinduction.
enantioselectivity was observed in the process, and therefore,
the approach was not pursued further. We also synthesized
enantiopure 1,1′-binaphthylboronic acid and subjected it to
the reaction. The product was isolated in 70% yield, but as a
1:1 mixture of diastereomers, indicating that no diastereoin-
duction was achieved in the process (Figure 5b).
Due to the potential synthetic value of our protected 1,3-diol
product, we also desired to demonstrate that the product could
be readily derivatized and that the boronic ester protecting
group could survive various reaction conditions for function-
alization of the olefin (Figure 6). Oxidative cleavage of the
Figure 4. Proposed catalytic cycle.
the boronic ester intermediate (A), which we know converts to
the desired product. We believe protonation of the boronic
ester by triflic acid (B) is followed by attack of one of the
olefins onto the activated C−O bond to generate intermediate
C. The electron-withdrawing ability of boron could help
explain why boron tethers facilitate the transformation but
silicon tethers do not.38 Formation of carbocation intermediate
C could also help explain the substrate requirements of the
reaction, where styryl alcohols and trisubstituted olefins
perform efficiently in the reaction due to formation of
stabilized benzylic or tertiary carbocations. Subsequent
rotation of the C−C bond and addition of the boronic acid
OH to the carbocation would then generate cyclized product
D. The high preference for trans diastereoselectivity in the
reaction is likely due to formation of a cyclic six-membered
transition state that places both the phenyl and cinnamyl
substituents on C in the equatorial position (see Supporting
Information for proposed structure). In addition, participation
by the boronic acid OH as a nucleophile in this fashion is
similar to the mechanism of the Nagata reaction, where a
boronic acid adds to an ortho-quinone methide.20,21,23
Figure 6. Derivitization studies. (a) OsO4, NaIO4, 98% yield; (b) H2,
10% Pd/C, 91% yield; (c) Hoveyda−Grubbs 2nd Gen (5 mol %),
C2H4 (balloon), 72% yield; (d) DMDO, acetone, 71% yield, 1:1 dr.
alkene with OsO4 and sodium periodate (Lemieux−Johnson
oxidation) provided the aldehyde product (8) in 98% yield.
While the dimerization reaction necessitates that two
equivalent phenyl groups be incorporated into the product,
this transformation allows for removal of the second phenyl
group for further derivatization studies. Hydrogenation of 2a
with palladium on carbon also proceeded smoothly to provide
a saturated product (9) without loss of the boronic ester
protecting group (91% yield). Olefin cross metathesis with a
Hoveyda−Grubbs second generation catalyst and ethylene
afforded the corresponding terminal alkene (10) in good yield
(72%). Finally, epoxidation of the alkene with dimethyldiox-
C
DOI: 10.1021/acs.orglett.9b03760
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(3) Rezaeivala, M.; Keypour, H. Schiff base and non-schiff base
macrocyclic ligands and complexes incorporating the pyridine moiety
− The first 50 years. Coord. Chem. Rev. 2014, 280, 203−253.
(4) Inthasot, A.; Tung, S.-T.; Chiu, S.-H. Using alkali metal ions to
template the synthesis of interlocked molecules. Acc. Chem. Res. 2018,
51, 1324−1337.
irane (DMDO) afforded the corresponding epoxide (11) as a
1:1 mixture of diastereomers (71% yield).
In conclusion, we have developed an expeditious route to
1,3-diol products via a boron-templated dimerization of allylic
alcohols. This transformation provides access to highly
versatile protected 1,3-diol building blocks for organic
synthesis, which contain a dense arrangement of alcohol and
alkene functional groups and two stereogenic centers. The
reaction also proceeds with high diastereoselectivity, and we
confirmed the necessity of both the boron tether and the acid
catalyst in the reaction. Future work on this transformation is
focused on achieving high enantioselectivity in the formation
of the two stereogenic centers.
(5) Tan, K. L. Induced Intramolecularity: An Effective Strategy in
Catalysis. ACS Catal. 2011, 1, 877−886.
(6) Wei, Y.-S.; Zhang, M.; Liao, P.-Q.; Lin, R.-B.; Li, T.-Y.; Shao, G.;
Zhang, J.-P.; Chen, X.-M. Coordination templated [2 + 2+2]
cyclotrimerization in a porous coordination framework. Nat. Commun.
2015, 6, 8348.
(7) Chen, Y.-Z.; Zhang, R.; Jiao, L.; Jiang, H.-L. Metal-organic
framework-derived porous materials for catalysis. Coord. Chem. Rev.
2018, 362, 1−23.
(8) Hong, C. M.; Bergman, R. G.; Raymond, K. N.; Toste, F. D. Self-
Assembled Tetrahedral Hosts as Supramolecular Catalysts. Acc. Chem.
Res. 2018, 51, 2447−2455.
ASSOCIATED CONTENT
* Supporting Information
■
S
(9) Bender, T. A.; Morimoto, M.; Bergman, R. G.; Raymond, K. N.;
Toste, F. D. Supramolecular Host-Selective Activation of Iodoarenes
by Encapsulated Organometallics. J. Am. Chem. Soc. 2019, 141, 1701−
1706.
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.9b03760.
Experimental procedures and compound characteriza-
tions (PDF)
(10) Xu, C.; Fang, R.; Luque, R.; Chen, L.; Li, Y. Functional metal−
organic frameworks for catalytic applications. Coord. Chem. Rev. 2019,
388, 268−292.
Accession Codes
CCDC 1922366 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
(11) Fensterbank, L.; Malacria, M.; Sieburth, S. McN . Intra-
molecular reactions of temporarily silicon-tethered molecules. Syn-
thesis 1997, 1997, 813−854.
(12) Bracegirdle, S.; Anderson, E. A. Recent advances in the use of
temporary silicon tethers in metal-mediated reactions. Chem. Soc. Rev.
2010, 39, 4114−4129.
(13) Cusak, A. Temporary silicon-tethered ring-closing metathesis:
Recent advances in Methodology development and natural product
synthesis. Chem. - Eur. J. 2012, 18, 5800−5824.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: dmichaelis@chem.byu.edu.
ORCID
(14) Zhang, W.-X.; Zhang, S.; Xi, Z. Zirconocene and Si-tethered
diynes: A happy match directed toward organometallic chemistry and
organic synthesis. Acc. Chem. Res. 2011, 44, 541−551.
(15) Kinghorn, M. J.; Valdivia-Berroeta, G. A.; Chantry, D. R.;
Smith, M. S.; Ence, C. C.; Draper, S. R. E.; Duval, J. S.; Masino, B. M.;
Cahoon, S. B.; Flansburg, R. R.; Conder, C. J.; Price, J. L.; Michaelis,
D. J. Proximity-Induced Reactivity and Selectivity with a Rationally
Designed Bifunctional Helical Peptide Catalyst. ACS Catal. 2017, 7,
7704−7708.
David J. Michaelis: 0000-0003-3914-5752
Present Addresses
†Current location: Acme Bioscience Inc., 3941 E. Bayshore Rd,
Palo Alto, CA 94303, USA.
‡Home institution: Department of Chemistry, Marquette
University, Milwaukee, WI 53233.
(16) Martí-Centelles, V.; Pandey, M. D.; Burguete, M. I.; Luis, S. V.
Macrocyclization Reactions: The Importance of Conformational,
Configurational, and Template-Induced Preorganization. Chem. Rev.
2015, 115, 8736−8834.
(17) Batiste, S. M.; Johnston, J. N. Evidence for ion-templation
during macrocyclooligomerization of desipeptides. J. Am. Chem. Soc.
2018, 140, 4560−4568.
(18) Yamamoto, Y.; Ishii, J.-I.; Nishiyama, H.; Itoh, K. Cp*-RuCl-
catalyzed Formal Intermolecular cyclotrimerization of three unsym-
metrical alkynes through a boron temporary tether: regioselective
four-component coupling synthesis of phthalides. J. Am. Chem. Soc.
2005, 127, 9625−9631.
Author Contributions
§S.H.N. and K.G.F. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Acknowledgment is made to the donors of the American
Chemical Society Petroleum Research Fund for support of this
research (PRF No. 56371-DNI1). Financial support was also
provided by the National Science Foundation (CHE-
1665015). Funding for Nicholas Hansen was provided by
the National Science Foundation Chemistry and Biochemistry
REU Site to Prepare Students for Graduate School and an
Industrial Career under Award CHE-1757627.
(19) Yamamoto, Y.; Ishii, J.-I.; Nishiyama, H.; Itoh, K. Ru(II)-
catalyzed Chemo- and Regioselective Cyclotrimerization of three
unsymmetrical alkynes through boron temporary tether. One-pot
four-component coupling via cyclotrimerization/Suzuki−Miyaura
coupling. J. Am. Chem. Soc. 2004, 126, 3712−3713.
́ ́
(20) For a leading reference, see: Estopina-Duran, S.; Donnelly, L. J.;
̃
Mclean, E. B.; Hockin, B. M.; Slawin, A. M. Z.; Taylor, J. E. Aryl
Boronic Acid Catalysed Dehydrative Substitution of Benzylic Alcohols
for C−O Bond Formation. Chem. - Eur. J. 2019, 25, 3950−3956.
(21) Hall, D. G. Boronic acid catalysis. Chem. Soc. Rev. 2019, 48,
3475−3496.
REFERENCES
■
(1) Laughrey, Z. R.; Gibb, B. C. Macrocycle synthesis through
templation. Top. Curr. Chem. 2005, 249, 67−125.
(2) Evans, N. H.; Beer, P. D. Advances in Anion supramolecular
chemistry: from recognition to chemical applications. Angew. Chem.,
Int. Ed. 2014, 53, 11716−11754.
(22) Peer, H. G. The reaction of phenol with formaldehyde. III.
selective hydroxymethylation of phenols at the ortho-position. Recl.
Trav. Chim. Pays-Bas. 1960, 79, 825−835.
D
DOI: 10.1021/acs.orglett.9b03760
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(23) Nagata, W.; Okada, K.; Aoki, T. ortho-Specific α-Hydrox-
yalkylation of Phenols with Aldehydes. Synthesis 1979, 1979, 365−
368.
(24) Scholl, K.; Dillashaw, J.; Timpy, E.; Lam, Y.-H.; De Ratt, L.;
Benton, T. R.; Powell, J. P.; Houk, K. N.; Morgan, J. B. Quinine-
promoted, enantioselective boron-templated Diels-Alder reaction by
anomeric control of transition-state conformation. J. Org. Chem. 2018,
83, 5756−5765.
(25) Batey, R. A.; Thadani, A. N.; Lough, A. J. Alkenylboronate
tethered intramolecular Diels-Alder Reactions. J. Am. Chem. Soc.
1999, 121, 450−451.
(26) Batey, R. A.; Thadani, A. N.; Lough, A. J. Diels-Alder reactions
of dienylboron compounds with unactivated dienophiles: an
application of boron tethering for substituted cyclohexanol synthesis.
Chem. Commun. 1999, 475−476.
(27) Batey, R. A.; Lin, D.; Wong, A.; Hayhoe, C. L. S.
Intromolecular Diels-Alder reactions of alkenylboranes − A stereo-
selective route to functionalized bicyclo[4.3.0]nonenes. Tetrahedron
Lett. 1997, 38, 3699−3702.
(28) Narasaka, K.; Shimada, S.; Osoda, K.; Iwasawa, N. Phenyl-
boronic Acid as a Template in the Diels-Alder Reaction. Synthesis
1991, 1991, 1171−1172.
(29) Nicolaou, K. C.; Liu, J. J.; Hwang, C.-K.; Dai, W.-M.; Guy, R.
K. Synthesis of a fully functionalized CD ring system of taxol. J. Chem.
Soc., Chem. Commun. 1992, 1118−1120.
(30) Batey, R. A.; Smil, D. V. The first boron-tethered radical
cyclizations and intramolecular homolytic substitutions at boron.
Angew. Chem., Int. Ed. 1999, 38, 1798−1800.
(31) Batey, R. A.; Smil, D. V. Tethered α-boryl radical cyclizations of
haloalkyl boronates. Tetrahedron Lett. 1999, 40, 9183−9187.
(32) Daini, M.; Yamamoto, A.; Suginome, M. Palladium-catalyzed
trans- and cis-carboboration of alkynes tethered to chloroborane with
organozirconium reagents: ligand-dependent complementary stereo-
selectivity. J. Am. Chem. Soc. 2008, 130, 2918−2919.
(33) Daini, M.; Suginome, M. Palladium-catalyzed, stereoselective,
cyclizative alkenylboration of carbon−carbon double bonds through
activation of a boron−chlorine bond. J. Am. Chem. Soc. 2011, 133,
4758−4761.
(34) Nogami, M.; Hirano, K.; Kanai, M.; Wang, C.; Saito, T.;
Miyamoto, K.; Muranaka, A.; Uchiyama, M. Transition metal-free
trans-selective alkynylboration of alkynes. J. Am. Chem. Soc. 2017, 139,
12358−12361.
(35) Nazari, S. H.; Tiempos-Flores, N.; Forson, K. G.; Bourdeau, J.
E.; Michaelis, D. J. C−N Bond Formation from Allylic Alcohols Via
Cooperative Nickel and Titanium Catalysis. J. Org. Chem. 2018, 83,
10646−10654.
(36) Nazari, S. H.; Bourdeau, J. E.; Talley, M. R.; Valdivia-Berroeta,
G. A.; Smith, S. J.; Michaelis, D. J. Nickel-Catalyzed Suzuki Cross
Couplings with Unprotected Allylic Alcohols Enabled by Bidentate
NHC/Phosphine Ligands. ACS Catal. 2018, 8, 86−89.
(37) Taylor, J. G.; Whittall, N.; Hii, K. K. Copper-Catalyzed
Intermolecular Hydroamination of Alkenes. Org. Lett. 2006, 8, 3561−
3564.
(38) Zheng, H.; Hall, D. G. Zirconium-catalyzed Nagata reaction for
the synthesis of 2-aryl-1,3,2-aryldioxaborins via a mild three-
component condensation of phenols, aldehydes, and boronic acid.
Tetrahedron Lett. 2010, 51, 4256−4259.
(39) Ang, H. T.; Rygus, J. P. G.; Hall, D. G. Two-component
boronic acid catalysis for increased reactivity in challenging Friedel−
Crafts alkylations with deactivated benzylic alcohols. Org. Biomol.
Chem. 2019, 17, 6007−6014.
E
DOI: 10.1021/acs.orglett.9b03760
Org. Lett. XXXX, XXX, XXX−XXX