Synergistic Catalysis by Br?nsted Acid/Carbodicarbene Mimicking Frustrated Lewis Pair-Like Reactivity

Article abstract of DOI:10.1002/anie.202107127

Carbodicarbene (CDC), unique carbenic entities bearing two lone pairs of electrons are well-known for their strong Lewis basicity. We demonstrate herein, upon introducing a weak Br?nsted acid benzyl alcohol (BnOH) as a co-modulator, CDC is remolded into a Frustrated Lewis Pair (FLP)-like reactivity. DFT calculation and experimental evidence show BnOH loosely interacting with the binding pocket of CDC via H-bonding and π-π stacking. Four distinct reactions in nature were deployed to demonstrate the viability of proof-of-concept as synergistic FLP/Modulator (CDC/BnOH), demonstrating enhanced catalytic reactivity in cyclotrimerization of isocyanate, polymerization process for L-lactide (LA), methyl methacrylate (MMA) and dehydrosilylation of alcohols. Importantly, the catalytic reactivity of carbodicarbene is uniquely distinct from conventional NHC which relies on only single chemical feature of nucleophilicity. This finding also provides a new spin in diversifying FLP reactivity with co-modulator or co-catalyst.

Full text of DOI:10.1002/anie.202107127

A Journal of the Gesellschaft Deutscher Chemiker
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Accepted Article
Title: Synergistic Catalysis via Brønsted Acid Modulated Frustrated
Lewis Pair-Like Reaction in Carbodicarbene
Authors: Tiow-Gan Ong, Yi-Chen Chan, Yuna Bai, Wen-Ching Chen,
Hsing-Yin Chen, Chen-Yu Li, Ying-Yann Wu, Mei-Chun
Tseng, Glenn P. A. Yap, Lili Zhao, and Hsuan-Yin Chen
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10.1002/anie.202107127
Angewandte Chemie International Edition
RESEARCH ARTICLE
Synergistic Catalysis by Brønsted Acid/Carbodicarbene
Mimicking Frustrated Lewis Pair-Like Reactivity
Yi-Chen Chan,[a,b,d] Yuna Bai,[c] Wen-Ching Chen,[a] Hsing-Yin Chen,[e] Chen-Yu Li,[e] Ying-Yann Wu,[a]
Mei-Chun Tseng,[a] Glenn P. A. Yap,[f] Lili Zhao,*[c] Hsuan-Ying Chen,*[e,g] Tiow-Gan Ong*[a,h]
Dedication ((optional))
[a]
Y.-C. Chan, Dr. W.-C. Chen, Dr. Y.-Y. Wu, Dr. M.-C. Tseng, Prof. T.-G. Ong
Institute of Chemistry, Academia Sinica
Taipei, Taiwan, R.O.C.
E-mail: tgong@gate.sinica.edu.tw
[b]
[c]
Y.-C. Chan
Department of Applied Chemistry, National Yang Ming Chiao Tung University
Hsinchu, Taiwan, R.O.C.
Y. Bai, Prof. L. Zhao
Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University
Nanjing, China
E-mail: ias_llzhao@njtech.edu.cn
[d]
[e]
Y.-C. Chan
Taiwan International Graduate Program (TIGP), Sustainable Chemical Science and Technology (SCST), Academia Sinica
Taipei, Taiwan, R.O.C.
Prof. H.-Y. Chen, C.-Y. Li, Prof. H.-Y. Chen
Department of Medicinal and Applied Chemistry, Drug Development and Value Creation Research Center, Kaohsiung Medical University
Kaohsiung, 80708, Taiwan, R.O.C.
E-mail: hchen@kmu.edu.tw
[f]
G. P. A. Yap
The Department of Chemistry and Biochemistry, University of Delaware
Newark, Delaware, United States
Prof. H.-Y. Chen
Department of Medicinal Research, Kaohsiung Medical University Hospital
Kaohsiung, 80708, Taiwan, R.O.C.
Prof. T.-G. Ong
[g]
[h]
Department of Chemistry, National Taiwan University
Taipei, Taiwan, R.O.C.
Supporting information for this article is given via a link at the end of the document.((Please delete this text if not appropriate))
Abstract: Carbodicarbene (CDC), unique carbenic entities bearing
two lone pairs of electrons are well-known for their strong Lewis
basicity. We demonstrate herein, upon introducing a weak Brønsted
acid benzyl alcohol (BnOH) as a co-modulator, CDC is remoulded into
a Frustrated Lewis Pair (FLP)-like reactivity. DFT calculation and
experimental evidence show BnOH loosely interacting with the
binding pocket of CDC via H-bonding and - stacking. Four distinct
reactions in nature were deployed to demonstrate the viability of
proof-of-concept as synergistic FLP/Modulator (CDC/BnOH),
demonstrating enhanced catalytic reactivity in cyclotrimerization of
isocyanate, polymerization process for L-lactide (LA), methyl
methacrylate (MMA) and dehydrosilylation of alcohols. Importantly,
the catalytic reactivity of carbodicarbene is uniquely distinct from
conventional NHC which relies on only single chemical feature of
nucleophilicity. This finding also provides a new spin in diversifying
FLP reactivity with co-modulator or co-catalyst.
reactive chemical behavior caused by a long-range attractive
force between Lewis acid and base components that are sterically
prevented from forming classical Lewis acid–base adducts.
Today, this conceptual stochiometric reactivity has expanded into
metal-free catalytic processes with a plethora of FLP derivatives
such as hydrogenation,[3] CO2 reduction,[4] hydrosilylation,[5]
borylation of heteroarenes,[6] amination of carbonyl compounds[7]
and others.[8]
In considering many examples of FLP, we organize the FLP
systems based on the number of bonds (n) in between the Lewis
acid and base units. The most common FLP like
phosphane/borane Lewis pair and its other variants can be
classified as class I with an infinite number of bonding (n = , see
Chart 1) and are frequently coined as the intermolecular or non-
bridging FLPs.[9] Steric substituents are generally introduced and
precluded the association and formation of a classical Lewis acid–
base adduct. Meanwhile, bridging FLPs (class II-IV) contain
conformationally rigid backbone tethering both the Lewis acid and
base units. They can generally be categorized according to the
number of bonding in between the acid-base units that are n 
3[10], n = 2[11] and n = 1[12]. They were designed with the aim of
addressing the unfavorable entropic term associated with a small
molecule capture that is lacking in traditional class I.
Introduction
Frustrated Lewis Pairs (FLPs), a unique concept first proposed in
1942,[1] have been adopted by Stephan[2] et al. in 2006 for their
breakthrough studies in activating a small molecule like H2. The
ability of FLP to break up small molecules is attributed to its highly
Carbodicarbenes (CDCs) are classified into the family of
carbones (CL2) that feature a dicoordinated central carbon (C0)
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10.1002/anie.202107127
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RESEARCH ARTICLE
bearing two lone pairs of electrons with N-heterocyclic carbenes
(NHCs) as flanking ligands (L).[13] Owing to the two lone-pairs on
the central carbon, CDCs have been regarded as ligands with a
strong -donation, allowing them to promote a myriad of metal-
mediated catalysis[14] and serve as organic catalysts in CO2
functionalization.[15] Apart from lone pairs residing at the central
Cb site (Chart 1), our group also recently uncovered that CDCs
possess low-lying empty p-orbitals at the Ca site after sequential
activation of the electron-rich Cb site, rendering CDCs capable of
1,2-addition reactions with a series of organic molecules.[16] Such
chemical behavior bears certain degree of resemblance to those
FLP of class IV,[17] but their reactivity might be less practical for
catalysis, presumably due to quenching effect generated from the
short distance with -delocalization between Ca (Lewis acid) and
Cb (Lewis base) sites.
attuning a rather weak π-acidity locates at the Ca site.
Simultaneously, the second lone pair at Cb is still available for
nucleophilic reaction. It should be noted CDC/Brønsted acid can
be considered as a Brønsted acid modulated synergistically FLP-
like reactivity from CDC, which has a chemical uniqueness that is
remarkably distinct from the traditional NHC as organic catalyst.
In this work, we successfully applied carbodicarbene/benzyl
alcohol (BnOH) to reactions of isocyanate cyclotrimerization, ring
opening polymerization of L-lactide, methyl methacrylate
polymerization and dehydrosilylation of alcohol. In addition, we
also carried out mechanistic studies experimentally and
computationally to delineate the synergistic nature of this new
FLP-like behavior of CDC modulated by BnOH.
Results and Discussion
Chart 1. Frustrated Lewis Pairs (FLPs) and Their Classifications.
Identification of “co-modulator” molecule. Prior to examining
CDC for any catalytic application based on synergistic FLP model,
one should identify a suitable co-modulator molecule. Ideally,
such a molecule would feature a non-permanent non-bonding
interaction with its hosting catalyst. In line with this thought, we
selected a target molecule bearing a weakly acidic proton that
would have a loose interaction with one of the electron lone-pairs
of CDCs, thus enhancing the -acidity at Ca. To find an
appropriate candidate, we elected to perform NMR experiments
on each C1-CDC mixture with benzyl amine, BnOH and t-butanol.
1H NMR shows no interaction of C1-CDC with benzyl amine and
t-butanol (see Figure S3). For BnOH, we observed subtle NMR
shift changes at the methylene signal ( 4.325.06 ppm) and
methine signal of C1-CDC ( 4.494.51 ppm). Importantly, the
hydroxy peak of BnOH became broad centered around  9.50
ppm, explicitly shifted downfield from its origin sharp triplet at 
1.70 ppm (Figure S3b).
Figure 1. 1H-1H NOESY NMR mixture of C1-CDC and BnOH in 1:1 ratio.
To further verify such a non-covalent interaction, we carried out
a NOESY experiment. Two concomitant peaks of BnOH were
correlated with the two side arm peaks of C1-CDC (CH3 of
isopropyl and CH3 of methyl (Figure 1)), implying those protons
were closely associated in space. Again, downfield shift in 13C
NMR (Figure S4) with an average value of 4.9 ppm attributed to
the flanking NHC fragment was consistent with the reduction of
electron density at Ca site. This is due to the non-bonding
interaction of the hydrogen of BnOH with one of the lone-pairs of
To circumvent the impasse within CDCs, we sought an
inspiration from Nature’s enzyme/cofactor for which we
introduced a specific assisting molecule so-called co-modulator
that would mitigate or amplify the ambiphilic behavior within CDC
through weak non-covalent interactions. In the course of
investigation, we found Brønsted acid like alcohol is a suitable co-
modulator, as it can lock-down on one of the lone pairs of CDCs,
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C1-CDC. Finally, we detected no protonated C1-CDC species after
prolonged exposure to BnOH in solution for 18 hours, indicating
the chemical stability of C1-CDC against any chemical or
structural transformation by BnOH.
cyclotrimerization without BnO- or H+, but also a further indication
that BnOH may act as co-modulator in this reaction.
Scheme 1. Cyclotrimerization of Isocyanate 1.[a]
Cyclotrimerization of isocyanate as model reaction. Next, we
selected cyclotrimerization of isocyanate as a simple model
reaction to test the feasibility of concept using “C1-CDC/BnOH” in
reaction. First, the cyclotrimerization of 1-methoxy-4-
isocyanatobenzene 1a was attempted against a series of
carbodicarbenes at ambient temperature (Scheme 1A, entries 1-
6). The cyclotrimerization of 1a using 1.0 mol% C1-symmetric
carbodicarbene (C1-CDC) as a catalyst afforded the cyclic product
2a in 59% yield within 30 mins in THF solution (entry 1). When the
reaction was conducted with the addition of 1.0 mol% BnOH
(entry 2), the catalytic activity of CDC increased dramatically to
92% yield under the same reaction time, hinting at the CDC
mediated FLP-like reactivity promoted by BnOH. Subsequently,
C2-symmetric C2-CDC was also examined and found to be an
active catalyst with 74% yield (entry 3). Considering similarity in
the electronic feature for both CDCs, we attributed the slightly
lower reactivity to the higher steric demand of C2-CDC. For
comparison, typical NHC derivatives like L1 and IPr (entries 4-5)
were also evaluated under similar conditions, showing no sign of
reactivity. The negative outcome of L1 had also ruled out the
possibility that the catalytic activity was generated by the
decomposition of CDC. Notably, the presence of BnOH does not
impose any beneficial effect on IPr catalytic activity (Figure S5),
implying activity unique to the CDC-type framework.[18] Finally, a
carbone flanked by triphenylphosphine (CPC, entry 6) also served
as excellent catalyst for cyclotrimerization process with 86% yield.
Utilizing the optimized process from Scheme 1A which led to
92% yield, we expanded the scope of isocyanates in Scheme 1B.
Chloro (1b) and nitro (1c) electron-withdrawing derivatives
afforded nearly quantitative yield (>~95%) in only 5 mins (entries
2-3). Meanwhile, electron-neutral phenyl isocyanate 1d furnished
a good yield (89%) of cyclotrimeric product (entry 4). Electron-rich
derivatives like 3-methyl (89%, 1e) were also effective in this
reaction (entry 5). 1f possessing steric encumbrance at the ortho
position required more than 3 h to achieve 92% yield (entry 6).[19]
[a] Each reaction carried out in the mixture of 0.5 M isocyanate, 1.0 mol% C1-
CDC (or catalyst) and 1.0 mol% BnOH in 5 mL THF at 25 C. All yields are
isolated unless otherwise mentioned. [b] NMR yield with 1,3,5-
trimethoxybenzene as Internal Standard. [c] 2.5 mL of THF was used to make
a 1.0 M reaction mixture.
Mechanistic investigations and determination of the role of
BnOH. A series of experiments were conducted to gain more
insight into the reaction mode of isocyanate based with CDC.
Performing a reaction in the presence of BnOH or combination of
NBu4OBn and protonated C1-CDC showed no sign of reactivity,
illustrating that BnO- or H+ were not active species (Figure 2A).
We managed to obtain a single crystal X-ray structure of 3c
derived from the stoichiometric reaction of C1-CDC with 1c in the
absence of BnOH. A nucleophilic attack of C1-CDC via Cb site
onto 4-nitrophenyl isocyanate generated an organic zwitterion
bearing a cationic sp2 type of C(3)-C(1)-C(12) (1.398 and 1.445
Å) and N(1) with anionic feature (Figure 2B). Upon closer
investigation of 3c, one would also find an unexpected close non-
bonding interaction at N(1)---C(12) with 2.723 Å, which is shorter
than the sum of van der Waals radii of C---N with ~3.25 Å.[20]
Indeed, the short contact could be rationalized by a -acidity
feature which exists at the Ca site of CDC, working synergistically
with the nucleophilic site at Cb to promote the catalytic
cyclotrimerization. These experimental evidences also suggest
that C1-CDC manifests FLP-like character in isocyanate
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Figure 2. (A). Experiments for mechanism study. (B) Solid-state structure of 3c
with thermal ellipsoids set at 30% probability. All hydrogen atoms and THF
solvent molecules have been omitted for clarity. Selected bond lengths [Å],
interatomic distances [Å] and bond angles [o]: C(1)-C(12) 1.445(3), C(1)-C(3)
1.398(3), C(1)-C(2) 1.482(3), C(2)-O(1) 1.248(3), C(2)-N(1) 1.362(3), C(12)-
C(1)-C(3) 119.34(19), C(12)-C(1)-C(2) 117.33(17), C(3)-C(1)-C(2) 123.3(2),
C(12)∙∙∙N(1) 2.723(3).
equivalent of 1d generates the zwitterionic complex IM3 and IM4
via the transition states TS3 and TS4, respectively. Again, these
two barriers related to C-N bond formation with 13.8 and 10.7
kcal/mol, respectively, were in the range of experimental
realization under mild conditions. Note that, the second equivalent
of BnOH can further reduce the C-N coupling barrier of TS4 via
weak interactions, which is detailed in Figure S45. After crossing
a smaller barrier of 6.9 kcal/mol, the ring-closure step can be
readily achieved via the six-membered-ring transition state TS5
forming intermediate IM5. Subsequently, the final product 2d can
be easily released via a very small barrier of 1.0 kcal/mol (i.e., IM5
→TS6), to regenerate the intermediate IM1 for the next catalytic
cycle. The highest barrier along the reaction pathway, measured
from the most stable intermediate IM2, is predicated to be 16.5
kcal/mol, which should be the rate-determining step (RDS) for the
catalytic cycle. It should be emphasized that the favorable
interactions between N-anion species and the electron-deficient
-acidity at the Ca site of CDC, as well as the hydrogen bonds and
- stacking interactions between the BnOH and CDC species,
play important roles in stabilizing the geometry of the stationary
points during catalysis. The whole reaction is exergonic by 38.6
kcal/mol, which can provide enough thermodynamic driving force
for moving the reaction forward. On the other hand, we have also
explored the reaction without addition of BnOH, which is less
favorable in terms of both kinetics and thermodynamics (see
Figure S46). This suggests the addition of BnOH can accelerate
the reaction rate, which is in good agreement with the
experimental observations.
Based on the structural evidence of 3c and experimental
outcomes, we next carried out DFT calculations to gain insight
into the positive influence of BnOH upon the rate as well as
mechanistic insight of this reaction. As detailed in Figure 3, the
reaction initiates from the coupling step of 1d and C1-CDC via the
transition state TS1 with the assistance of BnOH, leading to the
thermodynamically more stable zwitterionic complex IM1. This is
in line with the experimentally observed molecule 3c. Therein, the
weak interactions between the electron rich N-center of simplified
substrate 1d and the electron-deficient -acidity at the Ca site of
CDC
CDC, as indicated by the OCNN---Ca
distance of 2.787 Å,
provides a stabilizing effect to TS1. This means the CDC behaves
as both a -donor at Cb-center and -accepter at Ca site, hence
the appropriation of synergistic FLP-like behavior. In addition, the
favorable Cb---H-O hydrogen bonding (1.928 Å) and - stacking
interactions between the BnOH and CDC species (3.718 Å) also
play important roles as witnessed in TS1 and other reaction
pathways. After overcoming a small barrier of 10.6 kcal/mol (i.e.,
IM1→TS2), the second equivalent 1d will insert easily into IM1 via
the electron-rich N-anion site to generate IM2 that is 4.5 kcal/mol
lower than IM1. Similarly, the addition of the third and fourth
Figure 3. calculated energy profile at M06-2x+D3/6-311+G(d,p)(CPCM,solvent=toluene)//M06-2x+D3/6-31G(d)(CPCM, solvent=toluene) level for the addition of
carbodicarbene C1-CDC to phenyl isocyanate (1d) leading to product 2d. Key interatomic distances are given in Ångstroms, while other geometries are given in
Figure S44. Non-interacting hydrogen atoms have been omitted for clarity. (color code, C: gray, O: red, N: blue, H: white)
4
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L-Lactide ring opening polymerization and methyl
methacrylate polymerization based on CDC/BnOH. Following
the above mechanistic studies, we wondered if this synergistic
CDC/BnOH could be further extended to other catalytic reactions.
Several carbodicarbenes were tested for ring-opening
polymerization (ROP) of L-lactide (LA) in the presence of BnOH
in toluene at ambient temperature (Scheme 2A). C1-CDC
exhibited the best activity with almost 90% conversion within 1
min with a good dispersity (Đ) of 1.44 (entry 1). C2-CDC, which
possesses similar electronic features, but with a bulkier steric
environment gave 87% conversion with a longer reaction time (65
mins) and slight increase in Đ of 1.53 (entry 2). CPC performed
poorly with 57% conversion and higher Đ of 2.18 value (entry 3).
To better optimize the polymerization process, we also tested
various conditions affecting the catalytic behavior of C1-
CDC/BnOH. First, we examined solvent scope and toluene
appeared to be the ideal solvent (entries 1-3, Scheme 2B). No
conversion occurred in THF, implying that coordinating solvents
may compete with LA for CDC, hence reducing the catalytic
activity drastically.[21] Whereas, CH2Cl2 posed a vulnerability to
C1-CDC catalyst, as it ceased to operate after 1 min with only 53%
conversion (Đ = 1.10). The control experiment showed that the
presence of BnOH is crucial to the efficiency and narrow
molecular weight distribution (entries 2 vs 4); as it would take a
longer time (27 mins) to reach 91% conversion accompanying
with large Đ value (1.60) in the absence of BnOH. We also
discovered that pre-mixing C1-CDC and BnOH prior to the LA
addition leads to narrower dispersity (Đ =1.26, entry 5), while
maintaining the high activity of polymerization.
[a] Mixture of LA & BnOH prepared prior to catalyst addition. [LA] = 0.5 M in 5
mL solution at 25 C. [b] Determined by NMR. [c] Values by Gel Permeation
Chromatography (GPC) × 0.58 of PLA. [d] Dispersity index by GPC. [e] C1-CDC
and BnOH were mixed for 5 mins prior to LA addition. [f] Initial with each addition
[LA] : [Cat.] : [BnOH] = 200 : 1.5 : 30, [Cat.] = 3.25 mM, 10 mL. Final tally =
1200: 1.5: 30. [g] [Cat.] = 50 mM in 0.5 mL solution at 0 C.
The tolerance of C1-CDC towards monomer loading was also
evaluated. The reaction was initiated with [LA]:[Cat]:[BnOH] =
200:1.5:30 to reach 90% conversion in 10 mins duration and the
polymerization process could be carried out for nearly 10
successive additions of 100 equivalent of LA until the solution
could not be further mechanically stirred, making the final tally of
this experiment with a record of [LA]:[Cat]:[BnOH] of 1200:1.5:30
(entry 6). Interestingly, this strategy based on fragmentation
additions could also be used to improve the dispersity of polymer
(Đ=1.38). Several advantageous aspects of CDC are noteworthy.
First, C1-CDC possesses an immortality feature in polymerization
process, as the excessive BnOH loading does not affect its
catalytic activity (entry 6, also see Table S2).[22] Generally, most
organometallic catalyst mediated PLA process are not tolerant to
protic reagents like alcohol.[23] Second, C1-CDC took a much
shorter time to accomplish the catalytic ROP of LA than its
counterparts (classical NHCs).[24] Third, the good controllability of
C1-CDC in the PLA polymerization process was reflected in the
linear relationship plot of MnGPC and [LA]/[BnOH] with acceptable
Đ values (see Figure S2).
Tacticity of the resulting PLAs was investigated, and
epimerization occurred in the absence of BnOH (entry 4, Pm =
0.66, Figure S7). It implied the strong basicity of C1-CDC and
deprotonation of L-LA took place, causing the loss of optical purity
of the monomer and therefore affecting tacticity of the
corresponding polymer. Similar situation was also observed in
other highly basic catalysts like NHCs.[25] However, PLA with high
isotacticity was obtained in the presence of sufficient BnOH (entry
6, see Figure S8); indicating the modulating effect by BnOH on
the basicity of C1-CDC. Additionally, we performed a small scale
reaction with [LA]:[C1-CDC] of 10:1.5 for MALDI-TOF MS analysis
in order to understand the nature of ROP process. The mass
analysis showed peaks corresponding to fragment C1-CDC + 2LA
as well as nLA monomer repeating units (see Figure S9). This
indicated that C1-CDC initiated the polymerization and later stage
transesterification (back-biting) on the propagating species
occurred to give cyclic PLAs. However, only linear PLAs with
benzyl alkoxide (BnO) end-chain group was observed for entry 6
when high ratio of BnOH presented (also see Figure S10). Again,
adequate amount of BnOH as co-modulator is critical in
minimizing transesterification side reaction.
Scheme 2. CDC Mediated Polymerization Process.
The CDC/BnOH mediated-reaction could also be applied to
polymerization of methyl methacrylate; a different reaction
pathway from PLA polymerization (Scheme 2C). Initially, we
performed the reaction in 0.5 mL toluene with 100:1:1 of
[MMA]:[C1-CDC]:[BnOH] to generate polymeric product with Mn
of 17500 and Đ of 1.79 in a short time (12 mins, entry 1). The
narrow Đ of 1.36 and high molecular weight of 55100 could be
achieved by incrementally increasing the amount of MMA (entries
2-6) without sacrificing the rate of the reaction. On the contrary,
[MMA]:[C1-CDC] with 100:1 without BnOH additive gave a
relatively large Mn (~180,000) with broad Đ value of 3.50 (entry 7).
This outcome indicated the BnOH had played a co-modulating
role by moderating the rate of polymerization for better dispersity.
5
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To better understand the nature of the polymerization, MALDI-
TOF mass analysis was carried out to examine the small-scale
reaction. The feed of monomer/catalyst/BnOH in 10:1:1 (Figure
S12) showed mass series of oligomers with analogous pattern
having signal interval that coincide with MMA repeating unit (MW
= 100) and incorporation of one C1-CDC (MW = 360), implying
that CDC is responsible for the initiation of the chain addition in
polymerization. Mass analysis also illustrated some of the
pendant group (COOMe) dangled on oligomers had been
converted to COOBn, which was attributed to the CDC-promoted
transesterification in presence of BnOH. In lower molecular mass
analysis, the feed of monomer/catalyst/BnOH in 2:1:1 (Figure
S13) again consistently showed that the CDC unit was
incorporated into a series of oligomers with m/z = 561, 661, 761
and 861. However, the feed of 2:1:0; in the absence of BnOH
revealed only major peak corresponded to m/z of 561 (Figure
S14), hinting the propagation rate is relatively greater than
initiation rate for which we would not be able to detect the other
low mass oligomers. Hence, BnOH does affect the nucleophilicity
of CDC and its presence is necessary to slow down the
propagation rate of polymerization and thus for improved
dispersity of the resulting polymer. Finally, it is noteworthy to
mention that the catalytic polymerization of MMA by C1-CDC is
distinctly unique. No additional strong Lewis acid like Al(C5F6)3 is
required, that is usually present in NHC-promoted PMMA
polymerization.[26] Moreover, no NHC were found to polymerize
MMA in toluene and yet the catalytic property of NHC is highly
dependent on its structures.[27]
tertiary alcohols (eg. t-butanol, Figure S3c and 2-phenyl-2-
propanol, Figure S6); probably due to steric interference; no
silylated products were obtained. These findings further validate
the synergistic model of CDC/BnOH through non-bonding
interactions.
Scheme 3. CDC-mediated Dehydrosilylation of Alcohols.[28]
Extension of the reaction model: Dehydrosilylation of
alcohols. BnOH has been shown to serve as an effective co-
modulator for CDC to promote the FLP-like reactivity in
cyclotrimerization of isocyanate, PLA and MMA polymerizations.
We sought to further exploit the BnOH---CDC interaction for
chemical transformations in the presence of a suitable substrate.
Yet, in situ formation of H[C1-CDC]+ generated from the reaction
with BnOH should not be the active species responsible for these
catalytic reactions. Dehydrosilylation of alcohols, important
methodology in organic synthesis appeared to be a perfect
reaction model to rule out this possibility and 4a was selected as
the test candidate along with several hydrosilanes (Scheme 3).
The reaction proceeds smoothly in THF solution with 2.5 mol% of
C1-CDC catalyst at ambient temperature to furnish desired benzyl
silyl ether, 5a in quantitative yield using Et3SiH. More sterically
bulky and robust hydrosilanes like (t-Bu)Me2SiH and (i-Pr)3SiH
posed no problem in this catalytic reaction with excellent yields;
albeit under longer reaction times. It is noteworthy to mention that
no catalytic activity was observed for C1-CDC if both BnOH and
Et3SiH were not added together, indicative of a synergistic
interaction among these substrates with CDC.
Next, we also examined the scope of alcohols. A variety of
electron-deficient and rich benzyl alcohols (4a-f) and naphthyl
alcohols (4g-h) were amenable to the CDC-catalyzed reaction
(Scheme 3B). Other primary alcohols, containing functionality of
alkyl (4i), heteroaryl (4j) and allylic (4k) underwent
dehydrosilylation smoothly. We were pleased to find that a series
of secondary alcohols (4l-r) reacted well with the desired silyl
ethers without any side products. Finally, this catalytic reaction
could also be applied to biologically active compounds like
cholesterol (4s) and sugar derivative (4t) with excellent yields.
Since there is no obvious loose interaction between C1-CDC and
Conclusion
In summary, our findings bring to light a FLP-like feature in
carbodicarbene attuned by a co-modulator BnOH to direct
isocyanate cyclotrimerization. Moreover, this proof-of-concept
could be expanded to other different catalytic reactions such as
6
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10.1002/anie.202107127
Angewandte Chemie International Edition
RESEARCH ARTICLE
Sapsford, D. J. Scott, N. J. Allcock, M. J. Fuchter, C. J. Tighe, A. E.
Ashley, Adv. Synth. Catal. 2018, 360, 1066-1071.
ring opening polymerization of L-lactide, methyl methacrylate
polymerization and dehydrosilylation of alcohols. DFT calculation
and NMR analysis indicated that - stacking and weak Brønsted
acid/Lewis base pair interactions between the BnOH and CDC
played a major role to generate this subtle synergistic FLP
behavior in catalysis. Undeniably, several aspects of this work
should have broad future impacts on (i) carbone-like organic
catalysts based on Frustrated Lewis Pairs (ii) enriching and
diversifying the reactivity of FLP reactions by adding different “co-
modulator” molecules bearing variable functionalities and (iii)
catalytic reactivities of carbone is uniquely distinct from
conventional NHC, as carbone can access its second lone-pair
and -acceptability, which are lack in NHC. Ongoing application
of this FLP reactive behavior of C1-CDC with the assistance of co-
modulator is currently one of the focus of our group.
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Acknowledgements ((optional))
This work was financially supported by the Ministry of Science &
Technology of Taiwan (MOST-107-2113-M-001-034-MY2,
MOST-109-2113-M-001-038,
MOST-109-2113-M-037-006,
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MOST-109-2113-M-037-017 and MOST-108-2113-M-001-026-
MY3 grant) and Academia Sinica Investigator Award (AS-IA-108-
M04). Y.-C. Chan thanks Academia Sinica and TIGP for financial
and technical supports. L. Zhao acknowledges the high-
performance center of Nanjing Tech University for supporting the
computational resources, the financial support from National
Natural Science Foundation of China (grant no. 21973044),
Nanjing Tech University (grant number 39837123), and the State
Key Laboratory of Materials-oriented Chemical Engineering
(project No. KL19-11). Finally, we are grateful to Dr. Yuh-Sheng
Wen for assistance with X-ray diffraction data collection.
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Keywords: Carbodicarbene • Benzyl alcohol, BnOH • Frustrated
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8
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RESEARCH ARTICLE
Entry for the Table of Contents
In the present of co-modulator alcohol, the putative strong  donor, CDC is reshaped into Frustrated Lewis Pair-like reactivity. The
unique synergistic FLP behavior of CDC; unachievable by its counterpart NHCs, shown to have beneficial and complementary effects
on isocyanate cyclotrimerization, LA polymerization, MMA polymerization and dehydrosilylation of alcohols.
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