Regioselective trans-Carboboration of Propargyl Alcohols

Article abstract of DOI:10.1021/acs.orglett.9b01225

Proper choice of the base allowed trans-diboration of propargyl alcohols with B₂(pin)₂ to evolve into an exquisitely regioselective procedure for net trans-carboboration. The method is modular as to the newly introduced carbon substituent (aryl, methyl, allyl, benzyl, alkynyl), which is invariably placed distal to the a'OH group.

Full text of DOI:10.1021/acs.orglett.9b01225

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Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Regioselective trans-Carboboration of Propargyl Alcohols
̈
Hongming Jin and Alois Furstner*
Max-Planck-Institut fu
̈
̈
r Kohlenforschung, 45470 Mulheim/Ruhr, Germany
S
* Supporting Information
ABSTRACT: Proper choice of the base allowed trans-diboration
of propargyl alcohols with B2(pin)2 to evolve into an exquisitely
regioselective procedure for net trans-carboboration. The method
is modular as to the newly introduced carbon substituent (aryl,
methyl, allyl, benzyl, alkynyl), which is invariably placed distal to
the −OH group.
s a substructure of polyketide origin, allylic alcohols of type
Scheme 2
A
B are prominently featured in innumerous natural
products. Our group has recently devised a new entry into this
important motif based on a sequence commencing with a
stereochemically unorthodox trans-hydrometalation of a prop-
argyl alcohol followed by C-methylation of the resulting product
A by formal cross-coupling (Scheme 1).1,2 This methodology is
Scheme 1. Regio-complementary Functionalization of
Propargyl Alcohols: Access to Polyketide Motifs B and D
subjected to subsequent Suzuki coupling12 with 4-tolyl iodide in
the presence of catalytic palladium and aqueous KOH as a
promoter. In the present context, it is important to note that both
boron sites of 2a reacted under these conditions to give the
tetrasubstituted alkene 4a in 64% yield.4 Because ate-complexes
per se are competent intermediates for cross-coupling,12 we
surmised that addition of excess base might actually be
unnecessary. Rather, advantage could be taken of the distinct
chemical character to the two boron centers in a compound of
type 2: cross-coupling should occur selectively at the endocyclic
borate site, whereas the tricoordinate boron moiety is expected
to persist in the absence of external base; if so, many
opportunities for downstream functionalization can be
envisaged. As the borate site does not survive workup (see the
formation of product 3a), any such selective derivatization is
contingent on the ability to generate and manipulate an ate-
complex of type 2 in “one pot”.
very functional group tolerant and has already stood the test of
total synthesis.3 For its exquisite regioselectivity, however, the
procedure does not broker formation of the isomeric motif D (R
= Me), which is equally prominent in the polyketide estate.
Inspired by a literature report,4 we saw an opportunity to
attain compounds of type D via formal trans-carboboration,
although broadly applicable manifestations of this type of
reactivity are exceedingly rare.5−10 Specifically, it is known that
propargyl alcohols such as 1a, on deprotonation with nBuLi,
followed by reaction with B2(pin)2 in THF at increased
temperature, undergo trans-selective diboration to give 4-
borylated 1,2-oxaborolol derivatives 3a after hydrolytic workup
(Scheme 2).4,11 The reaction likely passes through the mixed
ate-complex 2a; in one case, this putative intermediate has been
However, our initial efforts to intercept the putative
intermediate 2 derived from the model substrate 1b by simply
Received: April 8, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b01225
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
complementing the original recipe for trans-diboration4 with an
appropriate electrophilic partner (PhI, PhOTf, [Ph2I]OTf, MeI,
allyl bromide), a catalytic amount of a palladium source
(Pd(OAc)2, Pd2(dba)3, Pd(PPh3)4), and an adequate phos-
phine ligand (PPh3, PCy3, P(o-tol)3, P(2-furyl)3, X-Phos, dppf,
Xantphos, etc.) basically met with failure (Table 1, entries 1−4).
from an inherently much less Lewis acidic RB(OR)2 entity.15
Under this premise, a lithium counterion is unlikely to be the
ideal escort as the neutral boron species 2′ might be favored,
which will not engage in cross-coupling in the absence of an
external base. Therefore, we rescreened different counterions
with the hope of stabilizing the critical borate intermediate 2,
even though the original report on trans-diboration had
identified nBuLi as the optimal promoter.4
a
Table 1. Optimization of the trans-Arylboration
In accord with the empirical order observed in our previous
study,13,14 replacement of nBuLi by NaHMDS16 opened the
doorway to the desired net trans-carboboration chemistry
(Table 1; for further details, see the Supporting Information).
In a first foray, trans-diboration was merged with classical
Suzuki-type sp2−sp2 coupling: to this end, the use of
diaryliodonium salts in combination with Pd2(dba)3/P(2-
furyl)3 proved optimal. Although the reaction proceeded well
in 1,4-dioxane in many cases, the use of 1,2-dichloroethane/
THF (10 equiv) was found to be more general (Figure 1). The
entry
base
BuLi
PhX
[Pd]
ligand
dppf
dppf
5b (%)
b
1
2
3
4
5
6
7
PhOTf
PhOTf
PhI
Ph2IOTf
Ph2IOTf
Ph2IOTf
Ph2IOTf
Pd(OAc)2
Pd(OAc)2
Pd(PPh3)4
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
0
c
LiHMDS
LiHMDS
LiHMDS
NaHMDS
NaHMDS
NaHMDS
<10
0
P(o-tol)3
P(o-tol)3
P(2-furyl)3
P(2-furyl)3
31
d
62
d
81
e
82
a
Unless stated otherwise, the reactions were performed in THF at 70
b
c
°C (bath temperature). 73% of 3b was obtained after workup. 62%
of 3b and 9% of 4b were formed. In 1,4-dioxane. In 1,2-
d
e
dichloroethane + THF (10 equiv).
In most cases, the boracycle 3b was formed as the major
product; it was accompanied by varying amounts of the proto-
deborylated compound 4b but only tracesif anyof the
desired product 5b.
In an attempt to rationalize this renitence, we wondered
whether the borate subunit in 2 actually subsists under the
chosen conditions. Earlier work from this laboratory on the “9-
MeO-9-BBN variant” of the Suzuki reaction showed that the
stability of ate-complexes of type 7 derived from the highly
Lewis acidic 6 and polar organometallic reagents R−M is
strongly cation-dependent (Scheme 3).13,14 The ease of
scrambling complex 7 as the competent nucleophile for cross-
coupling into unproductive 8 and 9 roughly follows the order:
Na+ ≈ K+ < Li+ ≪ MgX+, ZnX+. The analogous equilibration of
the borate unit in 2 is arguably more facile because it derives
Figure 1. Products 5 formed by trans-arylboration of propargyl
alcohols. aReagents and conditions: NaHMDS (1 equiv), B2(pin)2 (1.1
equiv), Pd2(dba)3 (5 mol %), P(2-furyl)3 (20 mol %), [Ar2I]OTf (2
equiv), 1,2-dichloroethane/THF, 60 °C. bIn 1,4-dioxane.
crude products are usually very clean, but partial loss of material
upon flash chromatography on silica diminishes the isolated
yields. In the case of tert-propargyl alcohols as the substrates, the
basic conditions can entail retro-alkynylation, leading to the
formation of the corresponding ketones as minor impurities.
The functional group compatibility is remarkable in that pre-
existing aryl bromides or chlorides remained intact, regardless
whether they originate from the propargyl alcohol substrate or
from the transferred aryl substituent; conceivable oligomeriza-
tion of the resulting products carrying a C−X as well as a C−B
unit was not observed. This favorable outcome shows that the
residual tricoordinate boron substituent in the product formed is
“silent” in the absence of an external base, whereas the ate site of
transient 2 (M = Na) readily engages in cross-coupling.17 The
excellent regioselectivity harnessed in reactions of 1,3-enyne or
even 1,3-diyne substrates is an additional asset: only the
propargylic triple bond undergoes carbometalation, whereas an
additional site of unsaturation does not interfere.
Scheme 3. Presumed Equilibration of the 1,2-Oxaborolol
a
Intermediate
The new procedure also lends itself to the introduction of a
methyl substituent at the distal propargylic C atom; a slightly
modified catalyst system (Pd2(dba)3/P(1-nap)3 in 1,4-dioxane)
in combination with MeI gave the best results (Figure 2 and
Supporting Information). In all cases investigated, C−C bond
a
The cation- and solvent-dependent scrambling of ate-complexes in
the 9-BBN series provides relevant precedent.
B
DOI: 10.1021/acs.orglett.9b01225
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 4
Figure 2. Products 10 formed by trans-methylboration of propargyl
alcohols. aReagents and conditions: NaHMDS (1 equiv), B2(pin)2 (1.1
equiv), Pd2(dba)3 (5 mol %), P(1-naphthyl)3 (20 mol %), MeI (3
equiv), 1,4-dioxane, 60 °C. bWith KHMDS.
formation occurred exclusively distal to the alcohol substituent.
Extensive NMR investigations and crystallographic data
confirmed connectivity and double bond geometry of the
products (for the structures of compounds 3b, 5b,n, and 10i in
the solid state, see the Supporting Information). Once again, the
observed regio- and stereoselectivities were excellent as were the
functional group tolerance; moreover, the method scales well. It
is important to note that O-methylation of the propargylic
alcohol substrate did not interfere with productive trans-
methylboration to any noticeable extent, which indicates a
perfect orchestration of events along the reaction coordinate.
For this very reason, other reactive electrophiles are equally
competent partners (Figure 3). Specifically, allyl and benzyl
the important polyketide motif D cited in the introduction; as
shown for product 14, the reaction can be readily achieved using
catalytic AgNO3.19 (ii) Addition of aq NaOH “arms” the
remaining boron atom in 10 for cross-coupling with a second
electrophilic partner. In this manner, two different hydrocarbyl
residues can be stitched trans to each other across the triple
bond;20 the resulting tetrasubstituted alkenes such as 15 are
difficult to make in rigorously stereodefined format by other
means.21 This aspect is highlighted by the concise approach to
compound 22, which is a key metabolite of the nonsteroidal
estrogen receptor modulator idoxifen (Scheme 5);22 this
a
Scheme 5
Figure 3. Additional trans-carboboration reactions. aReagents and
conditions: NaHMDS (1 equiv), B2(pin)2 (1.1 equiv), Pd2(dba)3 (5
b
mol %), supplemented by Pd(PtBu3)2 (10 mol %), allyl bromide (3
c
equiv), 1,4-dioxane, 75 °C; P(1-naphthyl)3 (20 mol %), BnBr (3
equiv), 1,4-dioxane, 60 °C; dP(2-furyl)3 (20 mol %), (R3Si)CCBr (3
equiv), toluene/THF, 75 °C.
a
Reagents and conditions: (a) Pd2(dba)3 (5 mol %), Pd(2-furyl)3 (20
mol %), NaHMDS, B2(pin)2, (4-BrC6H4)2IOTf, THF/1,2-dichloro-
ethane, 60 °C, 62%; (b) PhI, aq KOH, (dppf)PdCl2 (5 mol %), THF,
97%; (c) (i) pyrrolidine, EtOH, reflux; (ii) CuI, NaI, N,N′-
dimethylethane,1,2-diamine, 1,4-dioxane, 110 °C, 75%
bromide could be used without O-alkylation intervening.
Likewise, the incorporation of an alkynyl substituent was
successful; the resulting enynes 13 are regioisomeric to the
products formed by the transition-metal-free trans-alkynylbora-
tion using RCC−B(pin) as the reagent recently described in
the literature.5 Overall, these data show that the concept
underlying this new trans-carboboration manifold is pleasingly
general, although its different incarnations require some catalyst
optimization. Further extensions are subject to ongoing
investigations in our laboratory.
The alkenyl boronate products thus formed lend themselves
to numerous downstream transformations;18 only a few
possibilities are shown in Scheme 4: (i) Although proto-
deborylation of 10 “wastes” the valuable C−B bond, it leads to
example further substantiates the compatibility of the method
with alkyl as well as aryl halides. (iii) Oxidation of the C−B
bond23 in 10 unmasks the corresponding acyloin 16, whereas
directed epoxidation affords the building block 17 with high
diastereoselectivity.24 (iv) Addition of catalytic amounts of
Sc(OTf)3 as an oxophilic Lewis acid activates the allylic −OH
group of 5c without damaging the C−B bond as evident from
the intramolecular Friedel−Crafts alkylation, furnishing the
borylated indene 18.25 (v) Finally, we note that the triple bond
of compounds 13 constitutes yet another valuable handle for
functionalization; the formation of the tetrasubstituted bory-
C
DOI: 10.1021/acs.orglett.9b01225
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(5) For related trans-alkynylboration, in which the boron reagent
delivers the alkynyl substituent, see: 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.
lated furan 19 with the aid of AuCl3 as a carbophilic catalyst
illustrates this aspect.26,27
In summary, a robust yet modular procedure for net
carboboration of propargyl alcohols is reported. The trans-
formation is distinguished by the unorthodox trans-addition
mode and benefits from exquisite regio- and chemoselectivity.
For these virtues and for the multifaceted character of the
resulting products, we expect that the new method qualifies for
many applications. Studies along these lines are currently
ongoing in our laboratory.
(6) For pioneering studies on trans-carboboration, see the following
and references cited therein: (a) Suginome, M.; Yamamoto, A.;
Murakami, M. Palladium- and Nickel-Catalyzed Intramolecular
Cyanoboration of Alkynes. J. Am. Chem. Soc. 2003, 125, 6358−6359.
(b) Daini, M.; Yamamoto, A.; Suginome, M. Palladium-Catalyzed
trans- and cis-Carboboration of Alkynes Tethered to Chloroborane with
Organzirconium Reagents: Ligand Dependent Complementary Stereo-
selectivity. J. Am. Chem. Soc. 2008, 130, 2918−2919. (c) Daini, M.;
Yamamoto, A.; Suginome, M. Nickel-Catalyzed Cyclizative trans-
Carboboration of Alkynes through Activation of Boron-Chlorine Bonds
by Using Organometallic Reagents as Donors or Organic Groups. Asian
J. Org. Chem. 2013, 2, 968−976. (d) Suginome, M. Catalytic
Carboborations. Chem. Rec. 2010, 10, 348−358.
(7) For trans-carboborations of strongly polarized or tailored internal
alkynes, see: (a) Nagao, K.; Ohmiya, H.; Sawamura, M. Phosphine-
Catalyzed Anti-Carboboration of Alkynoates with Alkyl-, Alkenyl-, and
Arylboranes. J. Am. Chem. Soc. 2014, 136, 10605−10608. (b) Roscales,
S.; Csaky, A. G. Transition-Metal-Free Direct anti-Carboboration of
Alkynes with Boronic Acids to Produce Alkenylheteroarenes. Org. Lett.
2015, 17, 1605−1608.
(8) For other trans-carbometalations of internal alkynes, see the
following and literature cited therein: (a) Asao, N.; Matsukawa, Y.;
Yamamoto, Y. trans-Allylstannation of Certain Acetylenes Catalyzed by
ZrCl4. Chem. Commun. 1996, 1513−1514. (b) Miura, K.; Itoh, D.;
Hondo, T.; Saito, H.; Ito, H.; Hosomi, A. Allylstannylation of Alkynes
via a Radical Process: Stereoselective Synthesis of Di- and Tri-
substituted Vinylstannanes. Tetrahedron Lett. 1996, 37, 8539−8542.
(c) Zhao, J.; Liu, S.; Marino, N.; Clark, D. A. Regio- and Stereoselective
trans-Silylvinylation of Internal Alkynes Catalyzed by RuHCl(CO)-
(PCy3)2. Chem. Sci. 2013, 4, 1547−1551. (d) Iwamoto, T.; Nishikori,
T.; Nakagawa, N.; Takaya, H.; Nakamura, E. Iron-Catalyzed anti-
Selective Carbosilylation of Internal Alkynes. Angew. Chem., Int. Ed.
2017, 56, 13298−13301. (e) Wang, S.; Zhang, J.; Kong, L.; Tan, Z.; Bai,
Y.; Zhu, G. Palladium-Catalyzed anti-Selective Fluoroalkylboration of
Internal and Terminal Alkynes. Org. Lett. 2018, 20, 5631−5635.
(f) Guo, W.-H.; Zhao, H.-Y.; Luo, Z.-J.; Zhang, S.; Zhang, X.
Fluoralkylation-Borylation of Alkynes: An Efficient Method to Obtain
(Z)-Tri- and Tetrasubstituted Fluoroalkylated Alkenylboronates. ACS
Catal. 2019, 9, 38−43. (g) Nishimoto, Y.; Kang, K.; Yasuda, M. Regio-
ans Dtereoselective Anti-Carbozincation of Alkynyl Ethers Using ZnBr2
toward (Z)-β-Zincated Enol Ether Synthesis. Org. Lett. 2017, 19,
3927−3930.
(9) For cyclization reactions thought to involve a trans-carbometa-
lation step, see the following for leading references and literature cited
therein: (a) Zhang, X.; Xie, X.; Liu, Y. Nickel-Catalyzed Cyclization of
Alkyne-Nitriles with Organoboronic Acids Involving anti-Carbometa-
lation of Alkynes. Chem. Sci. 2016, 7, 5815−5820. (b) Clarke, C.;
Incerti-Pradillos, C. A.; Lam, H. W. Enantioselective Nickel-Catalyzed
anti-Carbometallative Cyclizations of Alkynyl Electrophiles Enabled by
Reversible Alkenylnickel E/Z Isomerization. J. Am. Chem. Soc. 2016,
138, 8068−8071. (c) Reding, A.; Jones, P. G.; Werz, D. B. trans-
Carbocarbonation of Internal Alkynes through a Formal anti-
Carbopalladation/C-H Activation Cascade. Angew. Chem., Int. Ed.
2018, 57, 10610−10614.
(10) For trans-hydroboration of internal alkynes, see: Sundararaju, B.;
̈
Furstner, A. A trans-Selective Hydroboration of Internal Alkynes.
Angew. Chem., Int. Ed. 2013, 52, 14050−14054.
(11) For related trans-diboration (silaboration) of strongly polarized
alkynes, see: (a) Nagao, K.; Ohmiya, H.; Sawamura, M. Anti-Selective
Vicinal Silylboration and Diboration of Alkynoates through Phosphine
Organocatalysis. Org. Lett. 2015, 17, 1304−1307. (b) Verma, A.; Snead,
R. F.; Dai, Y.; Slebodnick, C.; Yang, Y.; Yu, H.; Yao, F.; Santos, W. L.
Substrate-Assisted, Transition-Metal-Free Diboration of Alkynamides
with Mixed Diboron: Regio- and Stereoselective Access to trans-1,2-
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.9b01225.
Experimental section including characterization data,
NMR spectra of new compounds, and supporting
crystallographic data (PDF)
Accession Codes
CCDC 1895345−1895348 contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif, or by email-
ing data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road, Cam-
bridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: fuerstner@kofo.mpg.de.
ORCID
Alois Furstner: 0000-0003-0098-3417
̈
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Generous financial support by the MPG is gratefully acknow-
ledged. We thank Prof. C. W. Lehmann and Mr. J. Rust, at this
institute, for solving the X-ray structures in the Supporting
Information.
REFERENCES
■
(1) Fu
̈
rstner, A. trans-Hydrogenation, gem-Hydrogenation and trans-
Hydrometalation of Alkynes. An Interim Report on an Unorthodox
Reactivity Paradigm. J. Am. Chem. Soc. 2019, 141, 11−24.
(2) Huwyler, N.; Radkowski, K.; Rummelt, S. M.; Furstner, A. Two
̈
Enabling Strategies for the Stereoselective Conversion of Internal
Alkynes into Trisubstituted Alkenes. Chem. - Eur. J. 2017, 23, 12412−
12419.
(3) (a) Rummelt, S. M.; Preindl, J.; Sommer, H.; Furstner, A. Selective
̈
Formation of a Trisubstituted Alkene Motif by trans-Hydrostannation/
Stille Coupling: Application to the Total Synthesis and Late-Stage
Modification of 5,6-Dihydrocineromycin B. Angew. Chem., Int. Ed.
2015, 54, 6241−6245. (b) Meng, Z.; Souillart, L.; Monks, B.; Huwyler,
N.; Herrmann, J.; Muller, R.; Furstner, A. A, ,Motif-Oriented“ Total
̈ ̈
Synthesis of Nannocystin Ax. Preparation and Biological Assessment of
Analogues. J. Org. Chem. 2018, 83, 6977−6994. (c) Kwon, Y.;
Schulthoff, S.; Dao, Q. M.; Wirtz, C.; Furstner, A. Total Synthesis of
̈
Disciformycin A and B: Unusually Exigent Targets of Biological
Significance. Chem. - Eur. J. 2018, 24, 109−114.
(4) Nagashima, Y.; Hirano, K.; Takita, R.; Uchiyama, M. trans-
Diborylation of Alkynes: Pseudo-Intramolecular Strategy Utilizing a
Propargylic Alcohol Unit. J. Am. Chem. Soc. 2014, 136, 8532−8535.
D
DOI: 10.1021/acs.orglett.9b01225
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Vinyldiboronates. Angew. Chem., Int. Ed. 2017, 56, 5111−5115.
(c) Fritzemeier, R.; Santos, W. L. Brønsted Base-Mediated Regio-
and Steroselective trans-Silaboration of Propargylamides: Access to 1,2-
Vinylborasilanes. Chem. - Eur. J. 2017, 23, 15534−15537.
(12) (a) Suzuki, A. Cross-Coupling Reactions of Organboranes: An
Easy Way to Construct C-C Bonds. Angew. Chem., Int. Ed. 2011, 50,
6722−6737. (b) Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-
Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95,
2457−2483.
(27) Du, X.; Song, F.; Lu, Y.; Chen, H.; Liu, Y. A General and Efficient
Synthesis of Substituted Furans and Dihydrofurans via Gold-catalyzed
Cyclization of (Z)-2-en-4-yn-1-ols. Tetrahedron 2009, 65, 1839−1845.
(13) (a) Furstner, A.; Seidel, G. Palladium-Catalyzed Arylation of
̈
Polar Organometallics Mediated by 9-Methoxy-9-Borabicyclo[3.3.1]-
nonane: Suzuki Reactions of Extended Scope. Tetrahedron 1995, 51,
̈
11165−11176. (b) Furstner, A.; Nikolakis, K. Ethynylation of Aryl
Halides by a Modified Suzuki Reaction: Application to the Syntheses of
Combretastatin A-4, A-5 and Lunularic Acid. Liebigs Ann. 1996, 1996,
2107−2113.
(14) Seidel, G.; Furstner, A. Suzuki Reactions of Extended Scope: The
̈
‘9-MeO-9-BBN Variant’ as a Complementary Format for Cross
Coupling. Chem. Commun. 2012, 48, 2055−2070.
(15) For a review concerning such issues and how they impact cross-
coupling, see: Lennox, A. J. J.; Lloyd-Jones, G. C. Transmetalation in
the Suzuki-Miyaura Coupling: The Fork in the Trail. Angew. Chem., Int.
Ed. 2013, 52, 7362−7370.
(16) KHMDS can also be used; in most cases, the yields are
comparable or marginally lower. NaH instead of NaHMDS, however,
proved much less adequate, which suggests that the released
hexamethyldisilazane also plays a role in the reaction; see the
Supporting Information.
(17) 11B NMR confirms the presence of a tricoordinate (δB ∼ 31 ppm,
br) and a tetracoordinate boron center (δB = 11 ppm) in the putative
intermediate 2b formed from 1b on treatment with NaHMDS and
B2(pin)2; for details, see the Supporting Information.
́
(18) (a) Carreras, J.; Caballero, A.; Perez, P. J. Alkenyl Boronates:
Synthesis and Applications. Chem. - Asian J. 2019, 14, 329−343.
(b) Boronic Acids: Preparation, Applications in Organic Synthesis and
Medicine, 2nd ed.; Hall, D. G., Ed.; Wiley-VCH:Weinheim, Germany,
2011.
(19) Ping, Y.; Chang, T.; Wang, K.; Huo, J.; Wang, J. Palladium-
catalyzed Oxidative Borylation of Conjugated Enynones through
Carbene Migratory Insertion: Synthesis of Furyl-substituted Alkenyl-
boronates. Chem. Commun. 2019, 55, 59−62.
(20) For a special case of trans-addition of two carbon residues to
terminal alkynes, see the following and literature therein: Li, Z.; Garcia-
Dominguez, A.; Nevado, C. Pd-Catalyzed Stereoselective Carboper-
fluoroalkylation of Alkynes. J. Am. Chem. Soc. 2015, 137, 11610−11613.
(21) For an alternative, consisting of a cascade comprising a Suzuki
reaction, see: Gomes, F.; Echeverria, P.-G; Furstner, A. Iron- or
̈
Palladium-Catalyzed Reaction Cascades Merging Cycloisomerization
and Cross-Coupling Chemistry. Chem. - Eur. J. 2018, 24, 16814−
16822.
(22) Hardcastle, I. R.; Horton, M. N.; Osborne, M. R.; Hewer, A.;
Jarman, M.; Phillips, D. H. Synthesis and DNA Reactivity of α-
Hydroxylated Metabolites of Nonsteroidal Antiestrogens. Chem. Res.
Toxicol. 1998, 11, 369−374.
(23) Kabalka, G. W.; Shoup, T. M.; Goudgaon, N. M. Sodium
Perborate: A Mild and Convenient Reagent for Efficiently Oxidizing
Organoboranes. J. Org. Chem. 1989, 54, 5930−5933.
(24) Hussain, M. M.; Hernandez Toribio, J.; Carroll, P. J.; Walsh, P. J.
Synthesis of 2-Keto-anti-1,3-diols by Chemoselective Tandem
Oxidation of 3-B(pin)-Substituted Allylic Alcohols. Angew. Chem., Int.
Ed. 2011, 50, 6337−6340.
(25) Guo, S.; Liu, Y. A Facile Zr-mediated Multicomponent Approach
to Arylated Allylic Alcohols and its Application to the Synthesis of
Highly Substituted Indenes and Spiroindenes. Org. Biomol. Chem. 2008,
6, 2064−2070.
(26) Furstner, A.; Davies, P. W. Catalytic Carbophilic Activation:
̈
Catalysis by Platinum and Gold π-Acids. Angew. Chem., Int. Ed. 2007,
46, 3410−3449.
E
DOI: 10.1021/acs.orglett.9b01225
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