Photochemical Carbene Transfer Reactions of Aryl/Aryl Diazoalkanes—Experiment and Theory**

Article abstract of DOI:10.1002/anie.202100299

Controlling the reactivity of carbene intermediates is a key parameter in the development of selective carbene transfer reactions and is usually achieved by metal complexes via singlet metal-carbene intermediates. In this combined experimental and computational studies, we show that the reactivity of free diaryl carbenes can be controlled by the electronic properties of the substituents without the need of external additives. The introduction of electron-donating and -withdrawing groups results in a significant perturbation of singlet triplet energy splitting of the diaryl carbene intermediate and of activation energies of consecutive carbene transfer reactions. This strategy now overcomes a long-standing paradigm in the reactivity of diaryl carbenes and allows the realization of highly chemoselective carbene transfer reactions with alkynes. We could show that free diaryl carbenes can be readily accessed via photolysis of the corresponding diazo compounds and that these carbenes can undergo highly chemoselective cyclopropenation, cascade, or C?H functionalization reactions. Experimental and theoretical mechanistic analyses confirm the participation of different carbene spin states and rationalize for the observed reactivity.

Full text of DOI:10.1002/anie.202100299

Angewandte
Research Articles
Chemie
How to cite:
International Edition: doi.org/10.1002/anie.202100299
German Edition: doi.org/10.1002/ange.202100299
Metal-Free Photochemistry
Photochemical Carbene Transfer Reactions of Aryl/Aryl
Diazoalkanes—Experiment and Theory**
Sripati Jana+, Chao Pei+, Claire Empel, and Rene M. Koenigs*
Abstract: Controlling the reactivity of carbene intermediates is
a key parameter in the development of selective carbene
transfer reactions and is usually achieved by metal complexes
via singlet metal-carbene intermediates. In this combined
experimental and computational studies, we show that the
reactivity of free diaryl carbenes can be controlled by the
electronic properties of the substituents without the need of
external additives. The introduction of electron-donating and
-withdrawing groups results in a significant perturbation of
singlet triplet energy splitting of the diaryl carbene intermediate
and of activation energies of consecutive carbene transfer
reactions. This strategy now overcomes a long-standing
paradigm in the reactivity of diaryl carbenes and allows the
realization of highly chemoselective carbene transfer reactions
with alkynes. We could show that free diaryl carbenes can be
readily accessed via photolysis of the corresponding diazo
compounds and that these carbenes can undergo highly
metal-stabilized carbene intermediates, which in the vast
majority exist as singlet carbenes.[7] Latest developments
demonstrate the importance of modern metal carbene
À
chemistry to access site- and enantioselective C H function-
alization reactions of unreactive hydrocarbon frameworks.[8]
On the contrary, the triplet carbene, bearing two unpaired
electrons, has only received little attention in carbene transfer
reactions due to the requirements of specific metal com-
plexes[9] and as such the reactivity of triplet carbenes in
organic synthesis is vastly underdeveloped.
The spin state of free carbene intermediates is an
important area of research in physical organic chemistry
and of prime importance to understand the chemical proper-
ties and reactivity of carbenes.[10] Matrix-isolation, ultrafast
spectroscopy, or latest developments in computational
chemistry represent important state-of-the-art techniques to
characterize such short-lived intermediates.[11–17] These stud-
ies demonstrated that the electronic properties of the carbene
substituents significantly impact on the spin state of carbenes
and their singlet triplet splitting. For example, donor/acceptor
carbenes exhibit a singlet ground state in chlorinated solvent
as demonstrated both experimentally and computationally.[12]
This free singlet carbene can be selectively accessed via the
photolysis of donor/acceptor diazoalkanes and utilized in
singlet carbene transfer reactions, as demonstrated only
recently (Scheme 1a).[6,18] Contrarily, the spin state of diaryl
carbenes is much more dependent on the nature of the
electronic properties of the substituents of the aromatic ring.
While for diphenyl carbene 5b the triplet state is favored over
the singlet state by 4.6 kcalmolÀ1,[17] the energies of the singlet
and triplet state of electron-rich bis(4-methoxyphenyl)car-
bene 5c are almost degenerate with the singlet state being
0.3 kcalmolÀ1 energetically favored.[13] Moreover, 5c can be
selectively switched from triplet to singlet state at 3 K by
irradiation with 450 nm blue light and reverted back with
365 nm light. This intersystem crossing can already occur
under thermal conditions at very low temperature by heating
of the singlet carbene 5c to 25 K.[13] In 1976, Rabinow already
concluded that rapidly occurring ISC prevents the separation
of singlet and triplet diaryl carbene intermediates and—as
a consequence—the application in synthesis.[19]
À
chemoselective cyclopropenation, cascade, or C H function-
alization reactions. Experimental and theoretical mechanistic
analyses confirm the participation of different carbene spin
states and rationalize for the observed reactivity.
Introduction
Carbenes are one of the key reactive intermediates in
synthesis to leverage a broad variety of important trans-
formations, ranging from cycloaddition towards site-selective
[1–6]
À
C H functionalization reactions.
Since the initial discov-
ery of metal-catalyzed carbene transfer reactions in 1950,[3] it
is regarded a necessity to use transition metal catalysts to
access, stabilize and control the carbene intermediate and to
make them viable intermediates for synthesis applications.[4,5]
Research in this area has been devoted to the development of
new catalysts and ligand design to implement reactions of
[*] S. Jana,[+] C. Pei,[+] C. Empel, Prof. Dr. R. M. Koenigs
Institute of Organic Chemistry, RWTH Aachen University
Landoltweg 1, 52074 Aachen (Germany)
E-mail: rene.koenigs@rwth-aachen.de
[+] These authors contributed equally to this work.
[**] A previous version of this manuscript has been deposited on
a preprint server (https://doi.org/10.26434/chemrxiv.13159994.v1).
The development of chemoselective and efficient syn-
thesis methods via free diaryl carbenes would thus overcome
a long-standing paradigm and represents an important
advancement in modern carbene chemistry. We hypothesized
that the electronic properties of the carbene intermediate
could serve as a suitable handle to address this challenge.
Specifically, we assumed that the introduction of electron-
donating or -withdrawing groups to the aromatic rings of
diaryl carbenes influences the spin state and thus allows for
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.202100299.
ꢀ 2021 The Authors. Angewandte Chemie International Edition
published by Wiley-VCH GmbH. This is an open access article under
the terms of the Creative Commons Attribution Non-Commercial
License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited and is not used
for commercial purposes.
&&&&
ꢀ 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 2 – 11
These are not the final page numbers!

Angewandte
Research Articles
Chemie
Scheme 1. Carbene Transfer Reactions. a) and b) singlet reactivity vs. c) electronic control on singlet and triplet carbenes.
spin-dependent reactions of photochemically generated, free Experimental Studies
carbene intermediates. This approach should thus enable
orthogonal reaction pathways of carbene intermediates that
can be controlled by the electronic properties under other-
wise identical conditions (Scheme 1c).
We initiated our studies by exploring the reaction of aryl/
aryl diazoalkanes with phenyl acetylene (6a) and evaluated
the reaction of electron-poor aryl/aryl diazoalkane 3a first.[21]
We assumed that the introduction of one electron-withdraw-
ing group could be utilized to control the reactivity of the
carbene intermediate and that this carbene more resembles
a classic donor/acceptor carbene. Indeed, under blue light
conditions the cyclopropene product 7a was obtained in
excellent yield after only 20 minutes reaction time (Sche-
me 2a), which is in line with the reactivity of donor/acceptor
carbenes.[18c] Noteworthy, the synthesis of diaryl cyclopro-
penes represents even today a challenge in cyclopropene
chemistry and only singular examples are known in the
literature.[27]
Results and Discussion
As part of our ongoing research interest in photochemical
applications of diazoalkanes,[18c,20] we observed a marked
dependency of the visual appearance and absorption proper-
ties of aryl/aryl diazoalkanes on their electronic properties
(Scheme 1c). While the electron-poor, para-NO2-substituted
aryl/aryl diazoalkane 3a absorbs visible light in the purple
light region (lmax = 409 nm), the absorption maxima of
electron-neutral diphenyl diazomethane 3b is red-shifted
towards the dark green light region (lmax = 522 nm).[21]
Introduction of electron-donating groups results in a further
bathochromic shift towards the light green region of the
visible part of the electromagnetic spectrum (lmax = 543 nm).
This observation prompted us to further study aryl/aryl
diazoalkanes to access donor/donor carbene intermediates
via photolysis reactions. The carbene intermediates them-
selves differ in their electronic properties that we hypothesize
to be applicable in chemoselective, orthogonal organic trans-
formations (5-S, 5-T, Scheme 1c).[5]
In a similar context, yet using transition metal cata-
lysts,[22,23] the Davies group recently reported on the effect of
electron-donating and -withdrawing groups on the reactivity
of aryl/aryl diazoalkanes in RhII-catalyzed stereoselective
cyclopropanation reactions.[24] Shortly thereafter, the Zhou
and Franz groups reported on similar observations in RhII-
catalyzed Si-H insertion reactions.[25,26] In these cases the
reactivity of the carbene intermediate is controlled by the RhII
catalyst and thus represents the singlet carbene reactivity
(Scheme 1b).
We next turned our attention towards electron-neutral
aryl/aryl diazoalkane 3b in the reaction with phenyl acetylene
(Scheme 2b). No cyclopropenation reaction occurred under
identical conditions, instead a highly selective cascade reac-
tion occurred and indene product 8a was obtained in
excellent yield as the sole product. Finally, we probed the
reactivity of electron-rich aryl/aryl diazoalkane 3c (Sche-
me 2c). Neither the cyclopropene nor the indene product was
À
observed, instead a selective C H functionalization of the
À
terminal alkynyl C(sp) H bond (9a) occurred with excellent
yield, which represents an intriguing reactivity of free
carbenes, which can otherwise only be accessed from N-
heterocyclic carbenes.[28]
To probe, if the absorption properties of diazoalkanes 3a–
c (cf. Scheme 1c) influence the efficiency and synthetic
applicability of this photochemical carbene transfer reaction,
we studied all above reactions under green or UV light
conditions. Under UV light conditions, the cyclopropene
product 7a was not observed and 3a underwent decomposi-
tion to a complex mixture. In the case of diazoalkanes 3b and
À
3c the yield of indene 8a and C(sp) H functionalization
product 9a, respectively, was significantly decreased and
a complex mixture of by-products was observed. Photo-
chemical decomposition pathways of either the diazoalkane
Angew. Chem. Int. Ed. 2021, 60, 2 – 11
ꢀ 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
www.angewandte.org
&&&&
These are not the final page numbers!

Angewandte
Research Articles
Chemie
Further studies on the compatibility of solvent showed
a strong solvent dependency and only chlorinated solvents are
compatible with the present reaction conditions. In all other
solvent either decomposition of the diazoalkane or signifi-
cantly reduced yields were observed (please see Table S1 in
Supporting Information). Importantly, when studying the
reaction of aryl/aryl diazoalkanes 3a–c with phenyl acetylene
in the presence of RhII- or CuI-based catalysts only the
decomposition of diazoalkane was observed (Scheme 2d),
which showcases the complementarity and orthogonality of
photochemical and metal-catalyzed carbene transfer reac-
tions.
We subsequently studied the application of the photolysis
reaction of aryl/aryl diazoalkanes in electronic-controlled
carbene transfer reactions with alkynes (Scheme 3). Different
terminal aromatic alkynes smoothly reacted with electron-
poor aryl/aryl diazoalkane 3a in a very efficient cycloprope-
nation reaction, with diminutive amounts of indene as by-
product (7a–i, r.r. up to > 20:1). Contrarily, aliphatic alkynes
À
reacted in selective C H functionalization of the propargylic
À
C H bond in high yield (10a–c). We then turned our attention
to the reaction of electron-neutral aryl/aryl diazoalkane 3b
with aryl and alkyl alkynes. An almost quantitative yield of
the corresponding indene products (8a–j) were obtained in
the case of aryl acetylenes bearing halogen or electron-
withdrawing groups in all positions of the aromatic ring.
Slightly reduced yields were obtained, when electron-donat-
ing groups, such as alkyl- or methoxy-groups were introduced
(8c, 8h, 8i). In all cases the indene products were obtained as
the only reaction product. Similarly, aliphatic, terminal
alkynes gave indene products (8k–o). Finally, we studied
Scheme 2. Carbene transfer reactions of electronically distinct aryl/aryl
diazoalkanes with phenyl acetylene. Reaction conditions: In an oven
dried reaction tube the diazoalkane (0.2 mmol, 1 equiv.) was added
and DCM was added. Phenyl acetylene (2 mmol, 10 equiv.) was
dissolved in 0.5 mL of DCM and added to the reaction tube by syringe
and then irradiated as indicated at room temperature. The crude
reaction mixture was purified by silica gel column chromatography.
À
electron-rich aryl/aryl diazoalkane 3c that underwent C(sp)
H insertion reaction into a variety of different terminal aryl
alkynes in very good to almost quantitative yield (9a–i).
Under the present reaction conditions, TMS-acetylene
À
smoothly reacted to give the C H functionalization product
in excellent yield (9i). Aliphatic alkynes however, did not
3
À
À
itself or of reaction products can reason the by-product
formation and reduced efficiency under UV light conditions.
When irradiated with green light, a considerable influence of
the absorption properties of the diazoalkanes on the reaction
yield was observed. Electron-poor aryl/aryl diazoalkanes,
which absorb only poorly in the green light range, reacted in
low yield to the corresponding cyclopropene. In contrast,
electron-neutral and electron-rich aryl/aryl diazoalkanes
absorb in the green light range (Scheme 1c) and significantly
higher yields were obtained, with the best yields for the most
red-shifted and electron-rich aryl/aryl diazoalkane 3c. Last, it
should be noted that no reaction between the aryl/aryl
diazoalkane and phenylacetylene was observed in the dark.
In contrast to the reaction of donor/acceptor diazoal-
kanes,[6,18,20] the photolysis of aryl/aryl diazoalkanes needs to
be performed under an inert atmosphere and exclusion of air
and moisture are required to obtain high reaction yields.
However, it should be noted that electron-poor diazoalkane
3a reacts in reasonable yield (78%) to the cyclopropene
product in air, while electron-rich substrate 3c requires strict
exclusion of air.
undergo C(sp) H insertion, instead a highly efficient C(sp )
H insertion in the propargylic position was observed in high
3
À
yields (10d–f). It should be noted that this C(sp ) H
functionalization can be readily applied to install a quaternary
carbon center in the direct proximity of an alkyne group that
are valuable building blocks for further derivatization.
This observation prompted us to study the electronic
properties of diaryl carbenes experimentally (Scheme 4 and
Scheme 5). First, we investigated the reaction of E-b-methyl
styrene and Z-b-methyl styrene with aryl/aryl diazoalkanes
(Scheme 4). 3a reacted under the present reaction conditions
in a fully stereospecific reaction with both E-b-methyl styrene
and Z-b-methyl styrene without loss of stereochemical
information of the olefin geometry in the starting material
(15a, 16a). Contrarily, the reaction of electron-neutral and
electron-rich aryl/aryl diazoalkanes was significantly ham-
pered for both E-b-methyl styrene and Z-b-methyl styrene.
The electron-poor methyl acrylate reacted preferentially with
electron-rich or electron-neutral diaryl carbenes and no
reaction was observed with electron-poor diazoalkane 3a.
Next, we studied the reaction of aryl/aryl diazoalkanes with
sulfides in rearrangement reactions. An excellent yield of the
&&&&
www.angewandte.org
ꢀ 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 2 – 11
These are not the final page numbers!

Angewandte
Research Articles
Chemie
Scheme 3. Investigations on the photochemical reaction of aryl/aryl diazoalkanes with alkynes. Reaction conditions: In an oven dried reaction tube
the diazoalkane (0.2 mmol, 1 equiv.) was added and the reaction tube was purged with argon for three times then 0.5 mL of degassed and dry
DCM was added. Alkyne (2 mmol, 10 equiv.) was dissolved in 0.5 mL of degassed and dry DCM and added to the reaction tube by syringe and
then irradiated with blue LED (470 nm, 3 W) for 30 minutes at room temperature under argon atmosphere. The crude reaction mixture was
purified by silica gel column chromatography.
rearrangement products 18a and 19a
were obtained for electron-poor aryl/
aryl diazoalkane 3a in the reaction
with allyl phenyl sulfide 13 and phenyl
benzyl sulfide 14. A significantly re-
duced yield of 18b and 19b was
observed for the electron-neutral
aryl/aryl diazoalkane 3b. Electron-rich
diazoalkane 3c gave the products 18c
and 19c in good isolated yield.
In a second set of control experi-
ments, we probed the reaction of
diazoalkanes 3a–c with terminal al-
kynes in the presence of TEMPO as
a trapping reagent. In the presence of
Scheme 4. Reactions with different carbene trapping reagents; for compounds a R1 =OMe,
R2 =NO2; b R1 =R2 =H; c R1 =R2 =OMe.
TEMPO all of the photochemical
carbene transfer reactions were (al-
Angew. Chem. Int. Ed. 2021, 60, 2 – 11
ꢀ 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
www.angewandte.org
&&&&
These are not the final page numbers!

Angewandte
Research Articles
Chemie
reaction of carbene intermediates 5a–c with phenyl acetylene
and 3-methyl but-1-yne.
We set out our investigations by studying geometrical and
electronic properties of carbenes 5a–c. Specifically, we
performed calculations using the B3LYP-D3 functional to
obtain a first data set on the singlet triplet energy splitting,
which could provide a reasonable approximation for subse-
quent investigations on the reaction mechanism.[29] For
benchmarking of B3LYP-D3 calculations, we next performed
coupled cluster calculations with the DLPNO-CCSD(T)
method[30] that was recently demonstrated as a viable method
to obtain an accurate singlet triplet energy splitting.[31,32]
With the B3LYP-D3 functional, we observed a significant
difference in the singlet triplet energy splitting of carbenes
5a–c, which strongly depends on the substitution pattern of
the aromatic ring (Table 1). For diphenyl carbene (5b), this
Scheme 5. Reactions with a carbene trapping reagent and with deute-
rium-labeled alkynes.
Table 1: Theoretical calculations on the singlet triplet splitting.
most) completely inhibited for both phenyl acetylene and 3-
methyl-1-butyne (for details, please see Scheme S4 in Sup-
porting Information).[21] The only exception was observed for
the reaction of diazoalkane 3a with phenyl acetylene; in this
case only a slightly reduced yield (89%) of the cyclopropene
product was observed (Scheme 5a).
[a]
#
Functional/ method DES/T/ DGS/T (kcalmolÀ1
)
5b
(Ph/Ph)
B3LYP-D3
DLPNO-CCSD(T)
CCSD(T)
Experimental
B3LYP-D3
3.0 (4.5)
4.6 (4.0)
3.2[13]
4.6[17]
5c
À1.5 (0.4)
1.1 (0.1)
À0.3[13]
This observation is now indicative of a singlet carbene
intermediate in the cyclopropenation reaction, while triplet
(4-MeOPh/4-MeOPh) DLPNO-CCSD(T)
CCSD(T)
5a
(4-NO2Ph/4-MeOPh) DLPNO-CCSD(T)
CCSD(T)
À
B3LYP-D3
À0.8 (À0.3)
3.3 (1.7)
0.3 (À1.4)
carbenes are viable intermediates in indene formation or C
H functionalization reactions.
We next examined the reaction of deuterium-labeled
alkyne substrates with diazoalkanes 3a–c under the optimized
reaction conditions. Importantly, the deuterium label was
preserved with > 95% for most substrates (for details, please
see S5 in Supporting Information);[21] only in the case of the
[a] Calculations were performed at the following levels of theory: B3LYP-
D3/def2-tzvp(DCM)//B3LYP-D3/def2-svp(DCM); DLPNO-CCSD(T)/cc-
PVDZ// B3LYP-D3/def2-tzvp; CCSD(T)/cc-PVDZ//B3LYP-D3/def2-tzvp.
Positive values indicate an energetically favored triplet state, negative
values indicate an energetically favored singlet state. DGS/T is the Gibbs
energy gap calculated in DCM.
À
C(sp) H functionalization reaction of the electron-rich
diazoalkane 3c with phenyl acetylene, a significant erosion
of the deuterium label was observed (Scheme 5b), which
suggests either proton or hydrogen atom transfer to occur in
energy gap was calculated to be 4.5 kcalmolÀ1, which is close
to the CCSD(T) calculations that showed an energy gap of
3.2 kcalmolÀ1.[13] The data obtained on B3LYP-D3 level is
reasonably close to the experimentally observed energy gap
of 4.6 kcalmolÀ1.[17] For the more electron-rich bis(4-methox-
yphenyl)carbene a smaller energy gap of only 0.4 kcalmolÀ1
(0.1 kcalmolÀ1 for DLPNO-CCSD(T)) was calculated, which
is an overestimation of the calculation using CCSD(T).[13] In
the case of the (4-nitrophenyl)(4-methoxyphenyl)carbene 5a,
an energy gap of À0.3 kcalmolÀ1 was calculated with the
B3LYP functional, while a slightly larger DGS/T was obtained
when using the DLPNO-CCSD(T) method (DGS/T = 1.7 kcal
molÀ1).
Although singlet triplet splitting energies from calcula-
tions using the B3LYP-D3 functional do not perfectly reflect
experimentally observed or high level CCSD(T) calculations,
an important aspect can be deduced: In the case of diphenyl
carbene 5b, DGS/T is the largest and can thus provide
a rationale for the observed reactivity. For carbenes 5a and
5c the singlet triplet splitting is significantly smaller, which
can rationalize for the coexistence of both spin states in
solution and a facile intersystem crossing and thus for the
markedly different reactivity of 5a and 5c. In this context,
À
the C(sp) H functionalization reaction. This observation can
now rationalize for the missing reactivity of 3c with phenyl
acetylene in the presence of spin trapping reagents due to
side-reactions of ionic intermediates with the trapping
reagent.
The above experimental evidence is suggesting the
participation of either singlet or triplet carbene intermediates
in this photochemical carbene transfer reaction. For further
validation of the above data, additional experiments using
time-resolved spectroscopy would provide important addi-
tional insight. In contrast to the Rabinow report from 1976,
we could show that the reaction of diaryl carbenes can be
differentiated by electronic properties to enable a high
chemoselectivity in the reaction with terminal alkynes.
Theoretical Studies
To gain a better understanding of the underlying reaction
mechanism and the involvement of singlet or triplet carbene
intermediates, we performed computational studies on the
&&&&
www.angewandte.org
ꢀ 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 2 – 11
These are not the final page numbers!

Angewandte
Research Articles
Chemie
Sander reported on the reversible switching of spin states of
positive charge on the singlet carbene carbon, which indicates
5c by different light sources or temperature annealing in Ar
matrices at temperatures between 3 and 25 K.[13] However, it
is important to note that thermal relaxation at temperatures
as low as 25 K resulted in an equilibrium shift towards the
singlet carbene of 5c. We therefore consider that thermally
induced intersystem crossing via a low intersystem crossing
barrier (DG° = 1.4 kcalmolÀ1 for 5c)[13] rationalizes for the
observed reactivity of 5a and 5c. While the low barrier for 5c
was already determined experimentally in argon matrices,[13]
similar experimental evidence is not yet available for 5a.
As part of these calculations, we also studied the geo-
metric properties and electron-distribution by NBO analysis
of all possible carbene intermediates. The geometries of the
triplet state of all carbene intermediates 5a–c are remarkably
close and only small deviations in bond or torsion angles were
observed. However, in singlet state the influence of the
electron-withdrawing nitro group in (4-nitrophenyl)(4-me-
thoxy-phenyl)carbene 5a-S leads to a rotation of the electron-
poor 4-nitrophenyl group to a near orthogonal position, while
the other aryl ring rotates to a near-coplanar orientation with
the carbene empty p-orbital. It is remarkable that this free
singlet carbene now shows similar structural features as the
singlet donor/acceptor carbenes (20, Table S7 in the Support-
ing Information)[21] or aryl/aryl carbenes in the corresponding
Rh-carbene complexes as recently described by Davies and
co-workers.[24] NBO analysis of these carbene intermediates
shows that singlet carbene 5c-S is significantly more nucle-
ophilic than 5a-S and 5b-S. Furthermore, 5a-S has a more
that it is more electrophilic and thus facilitates cycloprope-
nation, similar to a phenyl-(carbomethoxy)carbene singlet
carbene 20 (Table S7 in the Supporting Information)[21] or the
2-naphthyl-(carbomethoxy)carbene, which was studied by
McMahon.[16]
Calculations on the Reaction of Diphenyl Carbene
We next studied both spin states of the diphenyl carbene
intermediate in the reaction with terminal alkynes on the
B3LYP-D3 level of theory. In the reaction of singlet diphenyl
carbene 5b-S with phenyl acetylene, two transition states
were identified that lead to the direct formation of the
cyclopropene (via TS1S, DG° = 10.5 kcalmolÀ1) and the
°
À1
À
insertion into the C(sp) H (via TS2S, DG = 12.7 kcalmol ).
In the case of triplet diphenyl carbene 5b-T two further
transition states could be located. The relatively high lying
À1
À
TS2T (27.5 kcalmol ) can account for C(sp) H functionali-
zation, yet is not feasible due to its high barrier. The addition
of triplet carbene 5b-T to the distal acetylene carbon atom
proceeds via the lowest-lying transition state TS1T (DG° =
11.4 kcalmolÀ1) to give INT1T. As the triplet carbene inter-
mediate is energetically favored over the singlet carbene
intermediate, the addition pathway via INT1T leading to the
indene product is energetically preferred. INT1T further
undergoes a radical cyclization via TS4T followed by inter-
system crossing to give INT2S. Final [1,2]-hydrogen shift and
Scheme 6. Theoretical calculations on the reaction mechanism of diphenyl carbene with phenyl acetylene and analysis of all possible reaction
pathways. Level of theory: B3LYP-D3/def2-tzvp(PCM)// B3LYP-D3/def2-svp(PCM).
Angew. Chem. Int. Ed. 2021, 60, 2 – 11
ꢀ 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
www.angewandte.org
&&&&
These are not the final page numbers!

Angewandte
Research Articles
Chemie
rearomatization gives the desired indene product as the
preferred reaction product in the reaction of diphenyl
carbene with aromatic alkynes (Scheme 6, right part), which
is consistent with the experimental data.
preferred, depending on the alkyne reaction partner (Ta-
ble 2).[21] The presence of two electron-donating methoxy
groups leads to a significant increase of electron density at the
carbene atom (please also see the NBO analysis in Supporting
À
In the reaction with 3-methyl but-1-yne we considered all
of the above transition states and identified two additional
Information) and thus facilitates a formal C H functionali-
zation mechanism via the low lying transition state TS2S
(DG° = 9.8 kcalmolÀ1) to give a carbocation and acetylide
ion pair INT1S that is stabilized by weak hydrogen-bonding
and p-p stacking between alkynyl anion and diaryl cation.
Subsequent, barrierless nucleophilic addition results in the
3
À
transition states that can account for C(sp ) H functionaliza-
tion.[21] In this case, calculations with the B3LYP-D3 func-
tional gave data that is partially in line with the experimental
results. These calculations gave consistent results regarding
transition states on the singlet spin surface, which are high in
activation free energy and do not account for product
formation.[21] Contrarily, calculations on the triplet spin
surface gave slightly contradictory results, which suggest
C(sp ) H functionalization (DG = 12.7 kcalmol ) being
slightly favored by 0.9 kcalmolÀ1 over indene formation
(DG° = 13.6 kcalmolÀ1), which can be attributed to spin
contamination in the triplet state (Table 2).[31]
À
formation of the new C C bond (Scheme 7a). Transition
states leading to cyclopropene or C(sp ) H functionalization
are disfavored on the singlet spin surface. Similarly, transition
states leading to formation of the indene or C H function-
alization are disfavored on the triplet spin surface (Table 2).
The reaction profile with 3-methyl but-1-yne is similarly
influenced.[21] In this case, bis(4-methoxyphenyl)carbene re-
acts on the triplet spin surface via TS3T (DG° = 12.7 kcal
molÀ1) and hydrogen atom abstraction to give two radicals
(INT4T) that undergo a radical recombination and intersys-
tem crossing to the C(sp ) H functionalization product
(Scheme 7b). Importantly, other reaction pathways are
disfavored and proceed via relatively high lying transition
states (See Table 2 and Supporting Information).
3
À
À
3
°
À1
À
To better rationalize for the reaction pathways of diphenyl
carbene on the triplet spin surface, we performed calculations
using the DLPNO-CCSD(T) method. These provide more
accurate calculations in the case of unpaired electrons and
indeed provide a good rationale on the reaction of triplet
diphenyl carbene 5b-Twith 3-methyl but-1-yne and show that
3
À
transition state TS1T that leads to indene formation is
The introduction of the electron-withdrawing group in the
case of (4-nitrophenyl)(4-methoxyphenyl)carbene 5a-S and
5a-T (Table 2) had a similar influence on the energies of
transition states.[21] In this case, calculations on the singlet
triplet splitting with the B3LYP-D3 functional suggest a more
stabilized singlet state (cf. Table 2). Indeed, for the reaction
with phenyl acetylene, the calculated energies of transition
states suggest that cyclopropene formation is almost identical
to indene formation. However, as the singlet carbene is the
energetically preferred intermediate, the cyclopropene is thus
formed as the main reaction product. Contrarily, in the
3
0.8 kcalmolÀ1 lower in energy compared to the C(sp ) H
À
functionalization (DG° = 14.0 kcalmolÀ1 for indene vs.
3
DG° = 14.8 kcalmolÀ1 for C(sp ) H functionalization).
À
Calculations on the Reaction of Bis(4-methoxyphenyl) Carbene
and (4-Nitrophenyl)(4-methoxy-phenyl)carbene
A significant perturbation of transition state free energies
was observed when studying the reaction of bis(4-methox-
yphenyl)carbene 5c. This variation in the electronic structure
of the carbene intermediate and the almost degenerate singlet
and triplet state result have a major effect on the activation
free energy of the first bond-forming event for most reaction
pathways and as a result, different reaction pathways are
reaction with 3-methyl but-1-yne, the lowest activation free
3
À
energy was calculated for C(sp ) H functionalization via
a similar pathway as for the reaction of bis(4-methoxyphe-
nyl)carbene and is thus the favored pathway on the triplet
spin surface (Table 2).
Table 2: Activation free energies of the first transition state in the reaction of bis(4-methoxyphenyl)carbene and (4-nitrophenyl)(4-methoxyphenyl)-
carbene with phenyl acetylene or 3-methyl but-1-yne.
Singlet spin state
Triplet spin state
Carbene[a]
R
TS1S
Cyclopropene
10.6
15.5
12.0
TS2S
C(sp) H
17.2
20.4
9.8
TS3S
C(sp ) H
–
14.0
–
TS1T
indene
10.2
12.9
11.3
14.1
TS2T
C(sp) H
27.4
33.5
27.5
33.1
TS3T
C(sp ) H
–
12.3
–
3
3
(Ar1/ Ar2)
À
À
À
À
5a (4NO2/4MeO)
Ph
iPr
Ph
iPr
5c (4,4’MeO)
15.7
13.0
13.8
12.7
[a] Calculations were performed at the following levels of theory: B3LYP-D3/def2-tzvp(PCM)// B3LYP-D3/def2-svp(PCM). The relative Gibbs energies
are shown in kcalmolÀ1 as DG° against the respective carbene intermediate.
&&&&
www.angewandte.org
ꢀ 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 2 – 11
These are not the final page numbers!

Angewandte
Research Articles
Chemie
Scheme 7. Theoretical calculations on the reaction mechanism of bis(4-methoxyphenyl)carbene with phenyl acetylene and 3-methylbut-1-yne at the
B3LYP-D3/def2-tzvp(DCM)//B3LYP-D3/def2-svp(DCM) level of theory.
These computational studies now provide a rationale for
the observed reactivity. The distinct reactivity of aryl/aryl
diazoalkanes 3a–c under photochemical conditions with
alkynes can be reasoned by two factors: First, singlet triplet
energy splitting of diaryl carbene intermediates 5a–c is
significantly affected by the introduction of electron-donating
or electron-withdrawing groups, leading to almost degenerate
energies of both carbene intermediates in the case of 5a and
5c. Moreover, the electronic properties of the diaryl carbene
intermediates influences the transition state energies and can
the geometric and electronic properties of the diaryl carbene
intermediate, and on the activation free energy in the reaction
with alkynes. This strategy now overcomes classic limitations
in the reaction of diaryl carbenes and now enables applica-
tions of aryl/aryl diazoalkanes in electronically controlled
photochemical carbene transfer reactions via singlet and
triplet spin states. Future studies are expected to concern
mechanistic details and at the experimental identification of
intermediate species involved in these reactions, for example,
by time-resolved spectroscopy.
À
facilitate for example, C(sp) H functionalization via a depro-
tonation/addition reaction mechanism or cyclopropenation
via a classic cyclopropenation reaction mechanism similar to
a donor/acceptor carbene. Thus both the singlet triplet
splitting energies and electronics result in distinct reaction
pathways and allow the access of orthogonal reaction path-
ways of diaryl carbene intermediates, for which further
experimental support of highly reactive intermediate species,
for example, by time-resolved spectroscopy, would be bene-
ficial to experimentally validate the above theoretical calcu-
lations.
Acknowledgements
RMK thanks the German Science Foundation for financial
support. CP gratefully acknowledges the China Scholarship
Council for generous support. CE thanks RWTH Aachen
University for support with a PhD scholarship. Open access
funding enabled and organized by Projekt DEAL.
Conflict of interest
Conclusion
The authors declare no conflict of interest.
We herein report on the photochemical reaction of aryl/
aryl diazoalkanes with alkynes via diaryl carbene intermedi-
ates. Visible light photolysis furnishes the diaryl carbene
intermediate that, depending on the electronic properties of
Keywords: carbene · DFT calculations · photochemistry ·
singlet · triplet
[1] A. Ford, M. Miel, A. Ring, C. N. Slattery, A. R. Maguire, M. A.
McKervey, Chem. Rev. 2015, 115, 9981 – 10080.
[2] M. P. Doyle, R. Duffy, M. Ratnikov, L. Zhou, Chem. Rev. 2010,
110, 704 – 724.
[3] R. Casanova, T. Reichstein, Helv. Chim. Acta 1950, 33, 417 – 422.
[4] H. M. L. Davies, K. Liao, Nat. Rev. Chem. 2019, 3, 347 – 360.
À
the substituents, selectively reacts in cyclopropenation, C H
functionalization, or cascade reactions. We could show by
detailed computational and experimental studies that elec-
tronic properties of the diaryl carbene intermediate have
a significant influence on the singlet triplet energy splitting,
Angew. Chem. Int. Ed. 2021, 60, 2 – 11
ꢀ 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
www.angewandte.org
&&&&
These are not the final page numbers!

Angewandte
Research Articles
Chemie
[5] D. Zhu, L. Chen, H. Fan, Q. Yao, S. Zhu, Chem. Soc. Rev. 2020,
49, 908 – 950.
Koenigs, Angew. Chem. Int. Ed. 2020, 59, 5562 – 5566; Angew.
Chem. 2020, 132, 5608 – 5613.
[6] Z. Yang, M. L. Stivanin, I. D. Jurberg, R. M. Koenigs, Chem. Soc.
Rev. 2020, 49, 6833 – 6847.
[7] H. M. L. Davies, D. Morton, Chem. Soc. Rev. 2011, 40, 1857 –
1869.
[8] J. Fu, Z. Ren, J. Bacsa, D. G. Musaev, H. M. L. Davies, Nature
2018, 564, 395 – 399.
[21] For details, please see the supporting information.
[22] Selected recent review articles: a) G. Bertrand, J. Organomet.
Chem. 2005, 690, 5397 – 6252; b) D. Qian, J. Zhang, Chem. Soc.
Rev. 2015, 44, 677 – 698; c) Y. Xia, J. Wang, Chem. Soc. Rev. 2017,
46, 2306 – 2362; d) M. Jia, S. Ma, Angew. Chem. Int. Ed. 2016, 55,
9134 – 9166; Angew. Chem. 2016, 128, 9280 – 9313.
[9] C. te Grotenhuis, N. van den Heuvel, J. I. van der Vlugt, B.
de Bruin, Angew. Chem. Int. Ed. 2018, 57, 140 – 145; Angew.
Chem. 2018, 130, 146 – 151.
[10] a) M. Jones, Jr., R. A. Moss, in Reactive Intermediates Chemistry
(Eds.: R. A. Moss, M. S. Platz, M. Jones, Jr.), Wiley, Hoboken,
2003, pp. 273 – 328; b) H. Timeoka, in Reactive Intermediates
Chemistry (Eds.: R. A. Moss, M. S. Platz, M. Jones, Jr.), Wiley,
Hoboken, 2003, pp. 375 – 461.
[23] C. Werlꢀ, R. Goddard, A. Fꢁrstner, Angew. Chem. Int. Ed. 2015,
54, 15452 – 15456; Angew. Chem. 2015, 127, 15672 – 15676.
[24] M. Lee, Z. Ren, D. G. Musaeev, H. M. L. Davies, ACS Catal.
2020, 10, 6240 – 6247.
[25] L.-L. Yang, D. Evans, B. Xu, W.-T. Li, M.-L. Li, S.-F. Zhu, K. N.
Houk, Q.-L. Zhou, J. Am. Chem. Soc. 2020, 142, 12394 – 12399.
[26] J. R. Jagannathan, J. C. Fettinger, J. T. Shaw, A. K. Franz, J. Am.
Chem. Soc. 2020, 142, 11674 – 11679.
[11] J. Wang, J. Kubicki, E. F. Hilinski, S. L. Mecklenburg, T. L.
Gustafson, M. S. Platz, J. Am. Chem. Soc. 2007, 129, 13683 –
13690.
[12] J. L. Wang, I. Likhotvorik, M. S. Platz, J. Am. Chem. Soc. 1999,
121, 2883 – 2890.
[13] P. Costa, T. Lohmiller, I. Trosien, A. Savitsky, W. Lubitz, M.
Fernandez-Oliva, E. Sanchez-Garcia, W. Sander, J. Am. Chem.
Soc. 2016, 138, 1622 – 1629.
[14] P. Costa, W. Sander, Angew. Chem. Int. Ed. 2014, 53, 5122 – 5125;
Angew. Chem. 2014, 126, 5222 – 5225.
[15] I. Trosien, E. Mendez-Vega, T. Thomanek, W. Sander, Angew.
Chem. Int. Ed. 2019, 58, 14855 – 14859; Angew. Chem. 2019, 131,
14997 – 15001.
[16] Z. Zhu, T. Bally, L. L. Stracener, R. J. McMahon, J. Am. Chem.
Soc. 1999, 121, 2863 – 2874.
[17] K. B. Eisenthal, N. J. Turro, E. V. Sitzmann, I. R. Gould, G.
Hefferon, J. Langan, Y. Cha, Tetrahedron 1985, 41, 1543 – 1554.
[18] Selected articles on photochemical singlet carbene transfer
reactions: a) I. Jurberg, H. M. L. Davies, Chem. Sci. 2018, 9,
5112 – 5118; b) T. Xiao, M. Mei, Y. He, L. Zhou, Chem.
Commun. 2018, 54, 8865 – 8868; c) R. Hommelsheim, Y. Guo,
Z. Yang, C. Empel, R. M. Koenigs, Angew. Chem. Int. Ed. 2019,
58, 1203 – 1207; Angew. Chem. 2019, 131, 1216 – 1220; d) Z.
Zhang, D. Yadagiri, V. Gevorgyan, Chem. Sci. 2019, 10, 8399 –
8404.
[27] a) M. A. Bartucci, P. M. Wierzbicki, C. Gwengo, S. Shajan, S. H.
Hussain, J. W. Ciszek, Tetrahedron Lett. 2010, 51, 6839 – 6842;
b) V. A. Vasin, Y. A. Popkova, Y. V. Bezrukova, V. V. Razin,
N. V. Somov, Russ. J. Org. Chem. 2018, 54, 1189 – 1199; c) H.
Dꢁrr, G. Klauck, K. Peters, H. G. von Schnering, Angew. Chem.
Int. Ed. Engl. 1983, 22, 332 – 333; Angew. Chem. 1983, 95, 321.
[28] A. J. Arduengo III, J. C. Calabrese, F. Davidson, H. V. D.
Rasika, J. R. Goerlich, R. Krafczyk, W. J. Marshall, M. Tamm,
R. Schmutzler, Helv. Chim. Acta 1999, 82, 2348 – 2364.
[29] For references on methods used for the calculations, see:
a) A. D. Becke, J. Chem. Phys. 1993, 98, 5648 – 5652; b) C. Lee,
W. Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785 – 789; c) S.
Grimme, J. Antony, S. Ehrlich, H. Krieg, J. Chem. Phys. 2010,
132, 154104; d) F. Weigend, R. Ahlrichs, Phys. Chem. Chem.
Phys. 2005, 7, 3297 – 3305; e) G. Scalmani, M. J. Frisch, J. Chem.
Phys. 2010, 132, 114110; f) K. Raghavachari, G. W. Trucks, J. A.
Pople, M. Head-Gordon, Chem. Phys. Lett. 1989, 157, 479 – 483;
g) T. H. Dunning, J. Chem. Phys. 1989, 90, 1007 – 1023.
[30] Y. Guo, C. Riplinger, U. Becker, D. G. Liakos, Y. Minenkov, L.
Cavallo, F. Neese, J. Chem. Phys. 2018, 148, 011101.
[31] J. Xu, J. Mieres-Perez, E. Sanchez-Garcia, J. K. Lee, J. Org.
Chem. 2019, 84, 7685 – 7693.
[32] R. Ghafarian Shirazi, F. Neese, D. A. Pantazis, J. Chem. Theory
Comput. 2018, 14, 4733 – 4746.
[19] C. L. Closs, B. E. Rabinow, J. Am. Chem. Soc. 1976, 98, 8190 –
8198.
Manuscript received: January 7, 2021
[20] a) C. Empel, R. M. Koenigs, Synlett 2019, 30, 1929 – 1934; b) S.
Jana, Z. Yang, C. Pei, X. Xu, R. M. Koenigs, Chem. Sci. 2019, 10,
10129 – 10134; c) S. Jana, Z. Yang, F. Li, C. Empel, J. Ho, R. M.
Revised manuscript received: March 8, 2021
Accepted manuscript online: March 9, 2021
Version of record online: && &&
,
&&&&
&&&&
www.angewandte.org
ꢀ 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 2 – 11
These are not the final page numbers!

Angewandte
Research Articles
Chemie
Research Articles
Metal-Free Photochemistry
Aryl/aryl diazoalkanes undergo distinct,
chemoselective reactions with alkynes
upon blue light photolysis. This report
showcases how electronic properties and
spin state influence the reaction outcome
of metal-free carbene transfer reactions
by experimentation and theory.
S. Jana, C. Pei, C. Empel,
R. M. Koenigs*
&&&& — &&&&
Photochemical Carbene Transfer
Reactions of Aryl/Aryl Diazoalkanes—
Experiment and Theory
Angew. Chem. Int. Ed. 2021, 60, 2 – 11
ꢀ 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
www.angewandte.org
&&&&
These are not the final page numbers!