Cyclic (Alkyl)(amino)carbene Ligands Enable Cu-Catalyzed Markovnikov Protoboration and Protosilylation of Terminal Alkynes: A Versatile Portal to Functionalized Alkenes**

Article abstract of DOI:10.1002/anie.202106107

Regioselective hydrofunctionalization of alkynes represents a straightforward route to access alkenyl boronate and silane building blocks. In previously reported catalytic systems, high selectivity is achieved with a limited scope of substrates and/or rea

Full text of DOI:10.1002/anie.202106107

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How to cite:
International Edition: doi.org/10.1002/anie.202106107
German Edition: doi.org/10.1002/ange.202106107
CAACs
Cyclic (Alkyl)(amino)carbene Ligands Enable Cu-Catalyzed
Markovnikov Protoboration and Protosilylation of Terminal Alkynes:
AVersatile Portal to Functionalized Alkenes**
Yang Gao+, Sima Yazdani+, Aaron Kendrick IV, Glen P. Junor, Taeho Kang,
Douglas B. Grotjahn, Guy Bertrand,* Rodolphe Jazzar,* and Keary M. Engle*
Abstract: Regioselective hydrofunctionalization of alkynes
represents a straightforward route to access alkenyl boronate
and silane building blocks. In previously reported catalytic
systems, high selectivity is achieved with a limited scope of
substrates and/or reagents, with general solutions lacking.
Herein, we describe a selective copper-catalyzed Markovnikov
hydrofunctionalization of terminal alkynes that is facilitated by
strongly donating cyclic (alkyl)(amino)carbene (CAAC) li-
gands. Using this method, both alkyl- and aryl-substituted
alkynes are coupled with a variety of boryl and silyl reagents
with high a-selectivity. The reaction is scalable, and the
products are versatile intermediates that can participate in
various downstream transformations. Preliminary mechanistic
experiments shed light on the role of CAAC ligands in this
process.
species are more limited.[4] Among existing procedures, few
are highly Markovnikov-selective across different terminal
alkynes and diverse boron sources. In a seminal study,
Hoveyda demonstrated that Cu complexes bearing NHC
ligands (namely SIMes and SIPr) catalyze a-selective proto-
boration of terminal alkynes using bis(pinacolato)diboron
(B2pin2) as a boron source (Scheme 1A).[4a] However, the
substrate scope was limited to alkyl-substituted alkynes
bearing heteroatom substituents at the propargylic position
(which have an inductively electron-withdrawing effect) and
aryl-substituted alkynes bearing electron-withdrawing or
-neutral substituents. Mechanistic studies indicate that the
regiochemical outcomes in this system are governed by
competing steric and electronic influences in the migratory
Introduction
Alkenyl boronic acids and their derivatives are employed
in a variety of stereospecific transformations, making them
useful reagents in organic synthesis.[1] Hydro- and protobora-
tion of terminal alkynes are among the most straightforward
approaches to prepare alkenyl boronic acid derivatives.[2]
Various transition metal catalysts have been developed to
furnish linear E-alkenyl boron species with high b-selectiv-
ity,[3] whereas methods to access branched a-alkenyl boron
[*] Dr. Y. Gao,[+] A. Kendrick IV, T. Kang, Prof. K. M. Engle
Department of Chemistry, The Scripps Research Institute
10550 N Torrey Pines Road, La Jolla, CA 92037-1000 (USA)
E-mail: keary@scripps.edu
S. Yazdani,[+] G. P. Junor, Prof. G. Bertrand, Dr. R. Jazzar
Department of Chemistry and Biochemistry
University of California, San Diego
UCSD-CNRS Joint Research Laboratory (IRL 3555)
La Jolla, CA 92093-0358 (USA)
E-mail: guybertrand@ucsd.edu
rjazzar@ucsd.edu
S. Yazdani,[+] Prof. D. B. Grotjahn
Department of Chemistry and Biochemistry
San Diego State University
5500 Campanile Drive, San Diego, CA 92182-1030 (USA)
[+] These authors contributed equally to this work.
[**] A previous version of this manuscript has been deposited on
a preprint server (http://doi.org/10.26434/chemrxiv.14368607).
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
https://doi.org/10.1002/anie.202106107.
Scheme 1. Overview of carbene-ligated Cu-catalyzed a-selective proto-
boration of terminal alkynes.
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Table 1: Optimization of reaction conditions.[a]
ꢀ
insertion step, where the copper boryl species adds across the
ꢁ
C C bond of the terminal alkyne (Scheme 1B). When
alkynes bearing electron-donating substituents are used, the
addition of the highly Lewis acidic boron moiety to the
terminal carbon (Cb) is favored to allow partial positive
charge to accumulate at the more substituted internal carbon
atom (Ca), leading to anti-Markovnikov selectivity. With
electron-deficient alkynes (e.g., propargyl alcohol and amine
derivatives), the two transition states are less differentiated
on electronic grounds, and in this case steric factors predom-
inate, with copper transferred to the less hindered terminal
position (Cb) to furnish the Markovnikov product. By
attenuating the Lewis acidity of the boryl moiety with
a diaminato substituent, Yoshida developed a sterically
controlled a-selective protoboration of terminal alkynes
where selectivity is independent of the electronic and steric
properties of the alkyne (Scheme 1A).[4c] However, this
method requires the use of the expensive masked diboron
ꢀ
reagent pinB Bdan (dan = naphthalene-1,8-diaminato), and
[a] Yields of products (a+b) and regioselectivity (ꢂ2%) were deter-
ꢀ
the alkenyl Bdan products normally require an extra un-
mined by 1H NMR (600 MHz) using CH2Br2 as the internal standard.
masking step before further transformation.
Inspired by Yoshidaꢀs boryl-controlled strategy, we rea-
soned that a more strongly s-donating ancillary ligand could
partially quench the Lewis acidity of Bpin and other more
commonly used boryl groups, decreasing the electronic
preference for boryl transfer to the terminal position (akin
to Bdan). The reaction would then be expected to proceed
under steric control, providing a means of controlling
Markovnikov selectivity in a manner that is independent of
the electronic nature of both the alkyne substrate and the
diboron reagent (Scheme 1B). Over the past several years,[5]
the Bertrand lab has developed a number of cyclic (alkyl)-
(amino)carbene (CAAC) ligands,[6–9] which show unique
reactivity and selectivity profiles in several transition-metal-
catalyzed reactions.[10] Given that these ligands are known to
be stronger s-donors than analogous NHC ligands,[11,12] we
hypothesized that the corresponding LCu(BX2) species would
undergo preferential Markovnikov-selective addition to ter-
minal alkynes via a-TS. Herein we describe a highly a-
selective protoboration of terminal alkynes catalyzed by
CAAC-ligated Cu complexes (Scheme 1C). In addition to
tolerating a wide range of alkyl- and aryl-substituted alkynes,
the protocol can also be applied to install a variety of boron
moieties. The generality of this CAAC-controlled Markovni-
To our delight, EtCAAC5-ligated Cu complex (L1CuCl)
promoted the transformation with 92% a-selectivity. Re-
placement of the ethyl groups on the a-carbon of L1 with
either an electron-withdrawing group (L2) or a more sterically
bulky group (L3) did not lead to further improvement.
EtCAAC6 ligand (L4), a much stronger electron-donor than
L1, gave the highest a:b ratio (94:6). Along these lines,
BiCAAC ligands, i-PrBiCAAC (L5) and PhEtBiCAAC (L6),
which are also strong electron-donors, furnished the desired
product 2a with high, although slightly attenuated, a-selec-
tivity of 86% and 93%, respectively. For comparison, an
NHC variant, namely SIPr-ligated Cu complex L7CuCl, only
delivered 22% of the a-isomer 2a under identical reaction
conditions.
Substrate scope. We then evaluated the scope with respect
to alkyl-substituted alkynes using L4CuCl as the precatalyst
(Table 2). Alkynes containing different primary alkyl chains
readily underwent efficient Markovnikov-selective protobo-
ration (2a and 2c). A wide range of functional groups,
including halide (2b), cyano (2d), carboxy (2e), and hydroxy
(2j) groups, were tolerated, with products isolated in ex-
cellent yields and high regioselectivity. Substrates containing
different methylene spacer lengths (n = 1–4) between the
kov-selectivity is demonstrated through the realization of an
[13]
ꢀ
analogous protosilylation method with pinB SiMe2Ph,
ꢁ
whereas NHC ligands, such as SIMes and SIPr, gave exclusive
C C bond and a heteroatom group, such as ethers (2k–2o) or
b-selectivity.[14]
protected amino groups (2p–2s), all underwent protobora-
tion with 94–98% a-selectivity and in 74–94% yield.[15] The
reactions of alkynes bearing secondary alkyl groups at the a-
position (2g–2i) gave especially high Markovnikov selectivity.
However, increasing steric hindrance further with a tertiary
alkyl group is deleterious, as seen with the reactivity of the
tert-butyl acetylene under the optimal conditions (2v).
Alkynes with functional groups like pendant piperidine,
azetidine, and glycine, commonly found in medicinally
relevant molecules, were all competent reactants (2g, 2h,
and 2u). Notably, catalytic protoboration of a non-conjugated
enyne substrate took place selectively at the alkyne group to
Results and Discussion
Reaction optimization. To initiate our study, we first
selected 5-phenyl-1-pentyne (1a) as the model substrate,
B2pin2 as the boron coupling partner, MeOH as the proton
source, NaOt-Bu as the base, and THF as the solvent and
carried out the reaction at room temperature. As summarized
in Table 1, a select number of CAAC-ligated Cu complexes
were examined for their ability to promote formation of 2a.
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Table 2: Scope of a-selective protoboration of terminal alkyl-substituted
alkynes.
used, the yield of 2aa was improved to 90% with the same a:b
ratio observed. A range of diboron esters performed well,
allowing the highly regioselective synthesis of a-alkenyl
boronates (2ab–2ad). The reaction using B2nep2 also required
L1CuCl as the catalyst to obtain a good yield. It is worth
noting that B2(OH)4 was a competent partner, furnishing 2ae
with 98:2 a:b ratio under slightly modified reaction conditions
in which EtOH was added as co-solvent to dissolve
B2(OH)4.[16] Subsequent conversion of the B(OEt)2 group
into BMIDA and BF3K groups furnished 2af (74% yield) and
2ag (85% yield), respectively, over two steps.
We next sought to develop a method for Markovnikov-
selective protoboration of terminal aryl-substituted alkynes.
After a brief screening of CAAC and BiCAAC ligands,
PhEtBiCAAC (L6) was found to give the highest a:b ratio
(94:6) with phenylacetylene (1w) as substrate (see SI for
additional data). The effect of aromatic substituents on L6Cu-
catalyzed protoboration was examined and further compared
with that of (SIPr)Cu-catalyzed reactions (Table 3). To our
delight, L6CuCl consistently gave the branched compounds as
the major products with high yields, whereas variable
Table 3: Scope of a-selective protoboration of terminal aryl-substituted
alkynes.[a]
[a] Ratios of a:b (ꢂ2%) were determined via 1H NMR (600 MHz) of the
crude reaction mixture. Percentages represent isolated yields of the a-
borylated products. [b] Conditions: 1 (0.10 mmol), B2pin2 (0.11 mmol),
L4CuCl (0.004 mmol), NaOt-Bu (0.008 mmol), MeOH (0.12 mmol), and
THF (0.50 mL), r.t. [c] NaOt-Bu (1.1 equiv); the product was esterfied
before isolation. [d] 98% ee obtained from 1s of 99% ee. [e] Percentage
represents 1H NMR (600 MHz) yield of the a-borylated isomer using
CH2Br2 as the internal standard. [f] Conditions: 1a (0.10 mmol), diboron
reagent (0.11 mmol), L4CuCl (0.004 mmol), NaOt-Bu (0.008 mmol),
MeOH (0.12 mmol), and THF (0.50 mL), r.t. [g] L1CuCl (2.0 mol%) and
ꢀ
NaOt-Bu (4.0 mol%). [h] pinB Bdan (1.1 equiv). [i] B2nep2 (1.1 equiv).
[j] B2(dmpd)2 (1.1 equiv). [k] Bis[(ꢀ)-pinanediolato]diboron (1.1 equiv).
[l] L1CuCl (2.0 mol%), NaOt-Bu (0.3 equiv), B2(OH)4 (1.2 equiv), EtOH
(0.25 mL) and THF (0.25 mL), r.t., 6 h. [m] Conditions: methyliminodi-
acetic acid (3.0 equiv), toluene/DMSO, 1058C. [n] Conditions: KHF2
aqueous solution (6.0 equiv), MeOH, 08C!r.t.
[a] Conditions: 1 (0.10 mmol), B2pin2 (0.11 mmol), L6CuCl
(0.005 mmol), NaOt-Bu (0.010 mmol), MeOH (0.12 mmol), and THF
1
(0.50 mL), r.t. Ratios of a:b (ꢂ2%) were determined via H NMR
(600 MHz) of the crude reaction mixtures. Percentages represent
isolated yields of the a-borylated products. [b] Reported results from
Ref. [4a]. [c] Results using reaction conditions from Ref. [4a]; percen-
tages represent 1H NMR yields of the a-borylated products. [d] KOt-Bu
(10 mol%) and toluene (0.50 mL). [e] Percentages represent 1H NMR
(600 MHz) yields of the a-borylated products using CH2Br2 as the
internal standard. The isolated yield was not obtained due to compli-
cations during the isolation.
afford 2t with > 98% a-selectivity and excellent chemo-
selectivity.
The generality of this reaction was further evaluated by
ꢀ
exploring a range of diboron reagents. pinB Bdan was
subjected to the reaction conditions, affording product 2aa
in 64% yield and with 97% a-selectivity. When L1CuCl was
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regioselectivity and yields were observed in (SIPr)Cu-cata-
lyzed reactions. This difference in performance is most
evident in the case of p-NMe2-phenylacetylene as substrate,
where 74:26 a:b ratio and 68% yield were observed in the
L6Cu-catalyzed reaction, while the NHC-ligated L7CuCl
catalyst led to only 23:77 a:b ratio and 15% yield (2zb).
Reactions with aryl alkynes that bear an o-Me or o-Br
performed well with 91–94% a-selectivity observed (2zg–
2zh). 2-Ethynylnaphthalene and 3-ethynylthiophene under-
went efficient a-selective protoboration (2zi–2zj), while
reaction of 2-ethynylpyridine gave a slightly lower a-selec-
tivity of 81% (2zk).
Scheme 3. Selected examples of Cu-catalyzed protosilylation of termi-
Product transformations. Upon scaling up the reaction
using 1a (4.0 mmol) as the substrate, two representative
protoboration reactions proceeded smoothly, furnishing 2a in
81% yield and 2af in 60% yield over two steps. The Bpin
group of 2a is readily converted to a variety of functional
groups, enabling access to other valuable a-substituted
alkenes, including a-halogenated alkenes (3aa–3ab) and a-
arylated alkenes (3ac). Moreover, the resulting alkene is
amenable to a variety of diversifications. We were able to
synthesize a 1,3-bis(boryl)alkane 3ad via a boronic ester-
induced bis-1,2-migration pathway, following Studerꢀs proce-
dure.[17] In addition, Fe-catalyzed HAT olefin cross-coupling
reaction between 2a and N,N-dimethylacrylamide gave 3ae
in useful yield under Baranꢀs conditions with slight modifi-
cations.[18] Finally, with mCPBA as an oxidant, epoxidation of
2af giving 3af was achieved in 89% yield (Scheme 2).[19]
Protosilylation. To further explore the CAAC/BiCAAC-
controlled regioselectivity in Cu-catalyzed hydrofunctionali-
zation chemistry, we turned our attention to protosilylation of
terminal alkynes.[20] Though the NHC-ligated copper com-
plex, (SIMes)CuCl, has been demonstrated to catalyze such
a reaction, exclusive anti-Markovnikov-selectivity was ob-
nal alkynes.
heteroatom groups at the propargylic or homopropargylic
position and significantly decreased regioselectivity with
phenylacetylene as substrate.
In our initial experiments we attempted to adapt the
reaction conditions for protoboration to protosilylation by
ꢀ
enlisting pinB SiMe2Ph as the nucleophilic silyl source.
Different CAAC and BiCAAC ligands were examined, and
L4 was found to give the highest a:b ratio (97:3), providing
product 4a in 55% yield (see SI for additional data). After
brief optimization, we identified conditions for a-selective
protosilylation of terminal alkynes (Table 4). Heteroatom
groups like an ether or a protected amine group on the
propargylic or homopropargylic position had little effect on
reactivity, with products (4b–4c) obtained in excellent yields
(86–93%) and high a-selectivity (91–95%). We then tested
the scope of aryl-substituted alkynes. The L4CuCl-catalyzed
protosilylation of phenylacetylene delivered the branched
product 4d with 91% a-selectivity. Reactions of p-, m-, and o-
tolylacetylene proceed with excellent yield (75–93%) and
high a-selectivity (89–95%; 4 f, 4i and 4k). In contrast to what
served across
a broad collection of terminal alkynes
(Scheme 3).[14] On the other hand, Markovnikov-selective
Cu-catalyzed protosilylation of aliphatic alkynes was reported
by Loh, using JohnPhos as the ligand.[21] Although highly
enabling in its own right, Lohꢀs method has notable draw-
backs, including modest performance with alkynes bearing
Table 4: Scope of a-selective protosilylation of terminal alkynes.[a]
ꢀ
[a] Conditions: 1 (0.10 mmol), pinB SiMe2Ph (0.11 mmol), L4CuCl
(0.004 mmol), KOt-Bu (0.008 mmol), MeOH (0.12 mmol), and toluene
1
Scheme 2. Scale up and diversification. Conditions: [a] CuX2, MeOH/
H2O, 908C. [b] 10% Pd(PPh3)4, Cs2CO3, p-iodotoluene, THF, 658C.
[c] n-BuLi, Et2O, 08C!r.t., then ICH2Bpin, MeCN, r.t. [d] 5% Fe(acac)3,
Na2HPO4, Ph(i-PrO)SiH2, N,N-dimethylacrylamide, EtOH, 658C.
[e] mCPBA, DCM, 08C!r.t. under air.
(0.50 mL), r.t. Ratios of a:b (ꢂ2%) were determined via H NMR
(600 MHz) of the crude reaction mixtures. Percentages represent
combined yields of the two regioisomers, which were inseparable and
isolated together. [b] Results using method in Ref. [21]. [c] Reported
results from Ref. [21].
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we observed in our study of protoboration, electron-deficient
aryl groups have a negative impact on the selectivity for
formation of the a-silylated products. For instance, reactions
of aryl alkynes bearing p-CF3 or m-Cl groups gave 54:46 and
72:28 a:b ratios, respectively. Electron-donating aryl sub-
stituents, such as p-OMe and p-NMe2, on the other hand, gave
rise to higher a-selectivity (4e and 4g).[22] 2-Ethynylnaphtha-
lene and 3-ethynylthiophene were also competent partners
(4m and 4n), though the latter gave only moderate yield.
Mechanistic studies. As previously reported, site selectiv-
ity in (NHC)Cu-catalyzed protoboration of terminal alkynes
is governed by the structure of the NHC ligand and the
substrate.[4] To better understand the conspicuous catalytic
differences observed with CAAC ligands, a preliminary
mechanistic study was performed.
that is more amenable to substrate modularity.[6,26,27] It is
noteworthy that these observations contrast with previous
reports using NHC ligands in which the a- vs. b-selectivity was
rationalized through the respective electronic properties of
the ligands (i.e. b-selectivity for SIAd: HOMO = ꢀ5.34 eV; a-
selectivity for SIMes: HOMO = ꢀ5.70 eV).[28] While more
studies will be needed to clarify these competing effects, it is
possible that steric hindrance is also at play in this scenario.[29]
Alkyne effects. As noted previously, our results suggest
that CAAC ligands are more impervious to the nature of the
reagents compared to NHCs. To confirm this trend, a Ham-
mett correlation study was performed to quantify the
electronic influence of the substrates in the protoborylation
of arylacetylenes catalyzed by copper complexes of L6
(
PhEtBiCAAC) and L7 (SIPr) (Scheme 5).[30] In either catalytic
Ligand effects. Contrasting with our initial hypothesis and
as highlighted in Scheme 4A using L1, L3, L4, and L5, a trend
rationalizing the a-selectivity obtained across CAAC motifs
from their respective s-donating properties alone is not
straightforward.[23] Intrigued by the reversed selectivity ob-
served with the rigid and bulky adamantyl CAAC5 L3
(Table 1), we wondered if the steric and the electronic
environment of the CAAC ligands could have conflicting
influences. To deconvolute these effects, we first considered
the CAAC5 ligands L1–L3, bearing comparable electronic
environments and noted that the a-selectivity rose with
decreasing steric hindrance (Scheme 4B).[24,25] We next ex-
amined CAAC ligands L3–L5 with comparable steric environ-
ments, and in this case confirmed that increasing s-donation
of the CAAC ligands favors a-selectivity (Scheme 4C). Taken
together these observations clarify the higher a-selectivity
obtained with the more donating BiCAAC and CAAC6
ligands, which also benefit from a flexible steric environment
system, high a-selectivity was observed in the presence of
electron-neutral or -deficient aryl groups (s ꢃ 0), while it
dropped when electron-rich aryl groups were used. As a result,
positive values for D1 (1aꢀ1b) were obtained with both SIPr
and PhEtBiCAAC ligands. Though there does seem to be some
influence as one moves from electron-neutral to highly
electron-donating, the significantly smaller D1 obtained with
BiCAAC (D1BiCAAC = 0.43 vs. D1SIPr = 1.2), together with
a weaker log(a/b) vs. s correlation (R2BiCAAC = 0.38 vs.
R2SIPr = 0.90), supports the notion that with CAAC ligands
there is no longer as strong of a relationship between the
variables of electronic character and regioselectivity.
Stoichiometric reactions. While the mechanism of the
ꢀ
protoboration involving copper boryl intermediates has been
thoroughly studied with NHC ligands,[4] much less is known
about the corresponding protosilylation reaction, and nothing
is known yet about either of these reactions with CAAC-
based catalysts. It is generally accepted, however, that both
Scheme 4. Highlighting the influence of steric and electronic parameters in the (CAAC)copper-catalyzed protoboration of alkynes.
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selectivity. To confirm these results under pseudo-catalytic
conditions, complex A’ was reacted with a mixture of B2Pin2,
1a, and MeOH, affording the same selectivity.
Turning our attention to the protosilylation reaction, we
ꢀ
found that reaction of A with pinB SiMe2Ph afforded the
ꢀ
comparatively more stable copper silyl intermediate BSi,
which could be characterized by NMR spectroscopy (Sche-
me 6B).[33] More interestingly, addition of alkyne 1a to this
complex led to the formation of 99:1 mixture of a- and b-
silylorganocopper intermediates CSi and CSi’, respectively.
Subsequent protonolysis with MeOH afforded the corre-
sponding protosilylated products 4a and 4a’ in the same ratio.
Note that protonolysis with [D4]MeOH led to selective
deuteration in the same positions, supporting a similar
mechanism as seen for the protoboration reaction. Here also
we could recapitulate these results under pseudo-catalytic
ꢀ
conditions by reacting complex A with a mixture of pinB
SiMe2Ph, 1a, and MeOH. Beyond supporting the postulated
catalytic cycle, these preliminary mechanistic studies suggest
that in this system the steric and electronic environment of the
CAACs governs the regiochemical outcome by controlling
the coordination of the alkyne substrate and the ensuing
migratory insertion step.
Scheme 5. Compared to SIPr, the PhEtBiCAAC copper catalyst is more
impervious to alkynes’ electronic properties.
pathways proceed through the same catalytic sequence as
highlighted in Scheme 6A starting from L4CuCl.[31] To further
our understanding of (CAAC)Cu-catalyzed hydrofunctional-
ization of alkynes, stoichiometric reactions were performed.
As shown in Scheme 6B reaction of L4CuCl with one Conclusion
ꢀ
equivalent of KOPh afforded the corresponding copper
phenoxide A’, which underwent anion metathesis with B2Pin2
We have developed a selective method for accessing
ꢀ
to generate the corresponding copper boryl BBpin with
Markovnikov alkenyl boronate and silane building blocks. It
tolerates both electron-rich and electronic-deficient alkynes
as well as a range of boryl and silyl reagents. Gram-scale
synthesis allowed for the diversification of these building
blocks into value-added chemicals. Furthermore, preliminary
a characteristic 11B NMR signal at 43.5 ppm.[32] In our hands
ꢀ
the copper boryl BBpin proved too reactive to be handled;
however, upon addition of alkyne 1a and MeOH (2 equiv),
the desired a-borylated product 2a was obtained with 99%
Scheme 6. Proposed mechanism (A) and mechanistic studies (B and C).
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environments of the ligand have competing effects, with the
Markovnikov hydrofunctionalization preferring the sterically
flexible and most donating BiCAAC and CAAC6 ligands. The
ability of CAAC ligands to control regioselectivity in LCu-
(BX2) additions to p-bonds has significant implications given
the wide array of electrophilic reaction partners that partic-
ipate in this mode of catalysis[34] and its demonstrated use as
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Acknowledgements
This work was financially supported by the National Institutes
of Health (5R35GM125052-04 and diversity supplement,
5R35GM125052-04S1) and an ACS PRF Doctoral New
Investigator Grant (K.M.E.). We gratefully acknowledge the
Kwanjeong Educational Foundation (Graduate Fellowship to
T.K.). This work was also supported by the U.S. Department
of Energy, Office of Science, Basic Energy Sciences, Catalysis
Science Program, under Award No. DE-SC0009376 (G.B.),
National Science Foundation Award No. CHE-1800598
(D.B.G.), and the Agence Nationale de la Recherche Award
No. ANR-19-276 CE07-0017 (R.J). Thanks are due to San
Diego State University for initial support of this work by
a SDSU University Graduate Fellowship (S.Y.) and the
Alfred P. Sloan Foundations University Centre for Exemplary
Mentoring (G.P.J.). This material is based upon work sup-
ported by the National Science Foundation Graduate Re-
search Fellowship Program under Grant No. DGE-1650112
(G.P.J.). We also acknowledge the Keck Foundation for
provided computational resources.
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Conflict of Interest
The authors declare no conflict of interest.
Keywords: alkyne functionalization · copper catalysis ·
cyclic (alkyl)(amino)carbene · protoboration · protosilylation
ꢀ
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Manuscript received: May 6, 2021
Revised manuscript received: June 11, 2021
Accepted manuscript online: June 22, 2021
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Version of record online: && &&
,
&&&&
Angew. Chem. Int. Ed. 2021, 60, 2 – 10
ꢀ 2021 Wiley-VCH GmbH
www.angewandte.org
&&&&
These are not the final page numbers!

Angewandte
Research Articles
Chemie
Research Articles
CAACs
Y. Gao, S. Yazdani, A. Kendrick IV,
G. P. Junor, T. Kang, D. B. Grotjahn,
G. Bertrand,* R. Jazzar,*
K. M. Engle*
&&&& — &&&&
Cyclic (Alkyl)(amino)carbene Ligands
Enable Cu-Catalyzed Markovnikov
Protoboration and Protosilylation of
Terminal Alkynes: A Versatile Portal to
Functionalized Alkenes
Copper catalysts bearing cyclic (alkyl)-
(amino)carbene (CAAC) ligands exhibit
remarkably high Markovikov selectivity in
the protoboration and -silylation of ter-
minal alkynes. This work demonstrates
the ability of this strongly s-donating
family of ligands to perturb regiose-
ꢀ
lectivity in the addition of copper boryl
ꢀ
species to C C p-bonds.
&&&&
www.angewandte.org
ꢀ 2021 Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 2 – 10
These are not the final page numbers!