Nickel-Catalyzed Anionic Cross-Coupling Reaction of Lithium Sulfonimidoyl Alkylidene Carbenoids With Organolithiums

Article abstract of DOI:10.1002/chem.201904862

The mechanistic platform for a novel nickel⁰-catalyzed anionic cross-coupling reaction (ACCR) of lithium sulfonimidoyl alkylidene carbenoids (metalloalkenyl sulfoximines) with organometallic reagents is reported herein, affording substituted alkenylmetals and lithium sulfinamides. The Ni⁰-catalyzed ACCR of three different types of metalloalkenyl sulfoximines, including acyclic, axially chiral and exocyclic derivatives, with sp² organolithiums and sp² and sp³ Grignard reagents has been studied. The ACCR of metalloalkenyl sulfoximines with PhLi in the presence of the Ni⁰-catalyst and precatalyst Ni(PPh₃)₂Cl₂ afforded alkenyllithiums, under inversion of configuration at the C atom and complete retention at the S atom. In a combination of experimental and DFT studies, we propose a catalytic cycle of the Ni⁰-catalyzed ACCR of lithioalkenyl sulfoximines. Computational studies reveal two distinctive pathways of the ACCR, depending on whether a phosphine or 1,5-cyclooctadiene (COD) is the ligand of the Ni atom. They rectify the underlying importance of forming the key Ni⁰-vinylidene intermediate through an indispensable electron-rich Ni⁰-center coordinated by phosphine ligands. Fundamentally, we present a mechanistic study in controlling the diastereoselectivity of the alkenyllithium formation via the key lithium sulfinamide coordinated Ni⁰-vinylidene complex, which consequently avoids an unselective formation of an alkylidene carbene Ni-complex and ultimately racemic alkenyllithium.

Full text of DOI:10.1002/chem.201904862

A Journal of
Accepted Article
Title: Nickel-Catalyzed Anionic Cross-Coupling Reaction of Lithium
Sulfonimidoyl Alkylidene Carbenoids With Organolithiums
Authors: Irene Erdelmeier, Joonghee Won, Steve Park, Jürgen Decker,
Gerd Bülow, Mu-Hyun Baik, and Hans-Joachim Gais
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201904862
Link to VoR: http://dx.doi.org/10.1002/chem.201904862
Supported by

10.1002/chem.201904862
Chemistry - A European Journal
Nickel-Catalyzed Anionic Cross-Coupling Reaction of Lithium
Sulfonimidoyl Alkylidene Carbenoids With Organolithiums
Irene Erdelmeier,[a, b, f] Joonghee Won,[c, d] Steve Park,[d] Jürgen Decker,[e, g] Gerd Bülow,[b, e, h] Mu-Hyun Baik*[d, c]
and Hans-Joachim Gais*[a, b, e]
ABSTRACT
Herein we report the mechanistic platform for a novel nickel(0)-catalyzed anionic cross-coupling reaction (ACCR)
of lithium sulfonimidoyl alkylidene carbenoids (metalloalkenyl sulfoximines) with organometallic reagents,
affording substituted alkenylmetals and lithium sulfinamides. The Ni(0)-catalyzed ACCR of three different types of
metalloalkenyl sulfoximines, including acyclic, axially chiral and exocyclic derivatives, with sp2 organolithiums and
sp2 and sp3 Grignard reagents has been studied. The ACCR of metalloalkenyl sulfoximines with PhLi in the
presence of the Ni(0)-catalyst and precatalyst Ni(PPh3)2Cl2 afforded alkenyllithiums, under inversion of
configuration at the C atom and complete retention at the S atom. In a combination of experimental and DFT
studies, we propose a catalytic cycle of the Ni(0)-catalyzed ACCR of lithioalkenyl sulfoximines. Computational
studies reveal two distinctive pathways of the ACCR, depending on whether phosphine or COD is the ligand of
the Ni atom. They rectify the underlying importance of forming the key Ni(0)-vinylidene intermediate through an
indispensable electron-rich Ni(0)-center coordinated by phosphine ligands. Fundamentally, we present a
mechanistic study in controlling the diastereoselectivity of the alkenyllithium formation via the key lithium
sulfinamide coordinated Ni(0)-vinylidene complex, which consequently avoids an unselective formation of an
alkylidene carbene Ni-complex and ultimately racemic alkenyllithium.
[a] Dr. I. Erdelmeier, Prof. Dr. H.-J. Gais
Institute of Organic Chemistry and Biochemistry
Technische Universität Darmstadt, Petersenstrasse 22, 64287 Darmstadt (Germany)
E-mail: gais@RWTH-Aachen.de
[b] Dr. I. Erdelmeier, Dr. G. Bülow, Prof. Dr. H.-J. Gais
Institute of Organic Chemistry
Albert-Ludwigs-Universität Freiburg, Albertstrasse 21, 79104 Freiburg (Germany)
[c] J. Won, Prof. Dr. M.-H. Baik
Department of Chemistry
Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141 (Republic of Korea)
E-mail: mbaik2805@kaist.ac.kr
[d] J. Won, S. Park, Prof. Dr. M.-H. Baik
Center for Catalytic Hydrocarbon Functionalization, Institute for Basic Science (IBS), Daejeon 34141 (Republic of
Korea)
[e] Dr. J. Decker, Dr. G. Bülow, Prof. Dr. H.-J. Gais
Institute of Organic Chemistry
1
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
RWTH Aachen University, Landoltweg 1, 52056 Aachen (Germany)
Present Address
[f] Dr. I. Erdelmeier
Innoverda, 38 Rue Dunois, 75013 Paris (France)
E-Mail: irene.erdelmeier@innoverda.com
[g] Dr. J. Decker
Salierstrasse 30, 67373 Dudenhofen (Germany)
E-mail: juergende@gmx.de
[h] Dr. G. Bülow
Kurze Maräcker 1, 67133 Maxdorf/Pfaltz (Germany)
E-mail: gerd.buelow@t-online.de
Introduction
Myriads of studies of nickel and palladium have extensively expanded not only the research spectrum on
organometallic catalysis but also their utilization in cross-coupling reactions. Cross-coupling reactions catalyzed
by late transition metals such as Pd and Ni have been widely exploited for the introduction of various functional
groups into unsaturated substrates such as alkenes and aromatic rings.[1] Whilst chemists have shed much light
on the nature of catalysis by interchanging transition metals that share isoelectronic properties to mimic their
respective complex systems, Ni and Pd have flourished in many other pairs/trios of transition metals in producing
fruitful insight to chemists.[1d] Anionic Pd complexes have proven to play a crucial role in cross-coupling or Heck
reactions through high catalytic activity.[2] In a similar vein, anionic Ni-ate complexes showed promise in
overcoming the less efficient oxidative addition of alkyl halides as a Ni-catalyzed cross-coupling partner than that
of aryl or alkenyl halide.[3] Especially, Kambe described the formation of anionic Ni-ate complexes from
organometallic reagents, which show an enhanced nucleophilicity in the cleavage of the C(sp3)–X bond of alkyl
halides.[4] Cornella recently reported that highly reduced Ni-precatalysts, which are stabilized by simple olefinic
ligands, exhibit an increased catalytic activity in the Kumada-Corriu-Negishi (KCN) cross-coupling.[5] Despite
these advances in anionic cross-coupling reactions (ACCR) and pervasive usage of interchanging Ni and Pd to
their respective complex systems, fundamental aspects of electron-rich Ni-ate complexes have not been well-
understood and studies in this field remain relatively scarce.
2
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
Scheme 1. (a) Metallo alkylidene carbenoids. (b) Lithium sulfonimidoyl alkylidene carbenoids. (c) Ni-catalyzed
ACCR.
The ubiquitous use of Ni-catalysts in modern chemistry and the increased interest they received in recent
years instigated us to carefully examine the mechanism of the Ni-catalyzed ACCR of metalloalkenyl sulfoximines
with organolithium or Grignard reagents, yielding substituted alkenylmetals.[6,7] In these reactions, metalloalkenyl
sulfoximines react under inversion of configuration at the C atom and complete retention at the S atom.
Combining experimental and computational techniques, we found a new catalytic cycle that includes an anionic
Ni(0)-ate intermediate induced by organolithium that traverses a putative Ni(0)-vinylidene intermediate via α-
elimination of the sulfonimidoyl group, which is a nucleofugal leaving group. In this paper, we disclose a complete
and detailed mechanism of Ni-catalyzed ACCR of metalloalkenyl sulfoximines.
Metallo alkylidene carbenoids 1, carrying an electrofugal and a nucleofugal leaving group at the Cα atom,
are an intriguing class of compounds (Scheme 1a).[8,9] Key reactivity features of 1 are electrophilic and
nucleophilic substitution at the Cα atom, Fritsch-Buttenberg-Wiechell (FBW) rearrangement, α-elimination and

formation of transition metal-ate complexes, for example. Lithioalkenyl sulfoximines Li-2[6,7,10 12] are a new group
3
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
of non-classical alkylidene carbenoids, displaying characteristic ambiphilic reactivity (Scheme 1b). For example,
while electrophilic substitution of Li-2 gives alkenyl sulfoximines 3,[6,10,12] nucleophilic substitution of Li-2 with
cuprates furnishes alkenyl cuprates 4 via 1,2-metalate shift of higher order cuprates.[13] Unlike the classical
alkylidene carbenoids 1, Li-2 carry a chiral nucleofuge, are generally stable in solution up to 0 °C, and do not
undergo FBW rearrangement or nucleophilic substitution with organolithiums.[14] According to experimental and
theoretical studies, lithioalkenyl sulfoximines Li-2, which are obtained by lithiation of alkenyl sulfoximines H-2, are
monomeric in etheral solution and dimeric in the crystal (bridging OLi bonds), contain a fluxional C–Li bond and
a Li atom being coordinated by the N atom or in case of a N-sulfonyl group by one of its O atoms.[15,16]
We observed an interesting stereoselective C–C bond formation of metalloalkenyl sulfoximines using
organolithium reagents RLi to form alkenyllithiums 5. It traverses through a Ni-vinylidene intermediate, which is
synthetically derived from either anionic or dianionic Ni(0)-ate intermediates, where the sulfonimidoyl group acted
as a nucleofuge as described in Scheme 1c. Of particular interest was the role of the anionic Ni(0)-ate complex
that leads to the Ni(0)-vinylidene intermediate under reduction of the S(VI) atom of the sulfonimidoyl group to S(IV)
and extrusion of PhS(O)N(Li)Me. Herein, the extremely electron-rich nickel center is necessary for pushing the
electron density to the α-carbon to form a putative Ni(0)-vinylidene intermediate. In cases of vinylidene-mediated
catalysis, there have been plenty of studies of metal-vinylidene complexes in reaction pathways.[17] These studies
generally demonstrate that the rearrangement of an acetylene to a vinylidene in the coordination sphere of a
transition metal is a thermodynamically favorable process and henceforth has been widely employed for
approaching the metal-vinylidene complex. In closer scrutiny, however, there have been very few examples of
metal-vinylidene complexes involving group 10 metals,[18] because they have preferred modes of reactivity with
alkynes that do not easily allow formation of metal-vinylidene intermediates during the reaction. Instead,
Ni2(vinylidenoid) intermediates have been accessed in vinylidene transfer reactions from dinuclear Ni-catalysts
and 1,1-dichloroalkenes as vinylidene precursors.[19] Herein, we demonstrate that metalloalkenyl sulfoximines can
also lead to Ni(0)-vinylidenes, where the nickel center is highly reduced.
During synthetic studies of carbocyclic prostacyclin analogs,[20] we made the intriguing observation that
the exocyclic magnesioalkenyl sulfoximines (E/Z)-M-6, obtained through metallation of (E)-H-6,[21] seemingly
partake in a Ni-catalyzed ACCR with PhMgBr, affording the phenyl-substituted alkenylmagnesiums (E/Z)-M-7
(Scheme 2).[6] Furthermore, the acyclic lithioalkenyl sulfoximines (E)-Li-8,[11a] prepared by lithiation of (Z)-H-8,[22]
were found to apparently participate in a Ni-catalyzed ACCR with PhLi, furnishing alkenyllithiums (E/Z)-Li-9 as
intermediates.[7] In the absence of the Ni-precatalyst no ACCR took place between the metalloalkenyl
sulfoximines and PhM.
4
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
Scheme 2. Nickel-catalyzed anionic cross-coupling reaction (ACCR) of metalloalkenyl sulfoximines wtih PhM (M
= MgBr, Li).
Shortly after the publication of our preliminary observation with the exocyclic magnesioalkenyl
sulfoximines (E/Z)-Mg-6, Kocieńsky reported that cyclic α-lithioalkenyl ethers engage in a copper-catalyzed
ACCR with organolithiums.[23] To date, Ni- and Pd-catalyzed ACCRs of metallo alkylidene carbenoids with
organometallic reagents have not been described with the exception of the examples depicted in Scheme 2,
however. This prompted us to carry out a comprehensive study of the Ni-catalyzed ACCR of metalloalkenyl
sulfoximines M-2 using experimental and computational techniques.
Result and Discussion
The magnesioalkenyl sulfoximines (E/Z,R)-Mg-6 (X = Br) (50:50 dr), which were obtained through
metallation of the alkenyl sulfoximine (E,R)-H-6[24] with PhMgBr, engaged in an ACCR with PhMgBr (3 equiv) and
Ni(dppp)Cl2 (dppp = 1,3-bis(diphenylphosphino)propane) (610 mol%) in ether at 0 C for 3 h and gave
alkenylmagnesiums (E/Z)-Mg-7a (X = Br), which after quenching with CF3CO2D furnished the deuteriated alkenes
(E/Z)-D-7a (93% D) in 80% yield and 50:50 dr (Scheme 3a). A similar ACCR of the lithioalkenyl sulfoximines
(E/Z,R)-Li-6 (50:50 dr), which were prepared from (E,R)-H-6 upon treatment with MeLi, with PhLi (3 equiv) and
Ni(dppp)Cl2 (10 mol%) in ether at 0 C for 35 h afforded alkenyllithiums (E/Z)-Li-7a. Quenching of the
alkenyllithiums with CF3CO2H gave alkenes (E)-H-7a and (Z)-H-7a in 80% yield and 50:50 dr. The ACCR of
(E/Z,R)-Mg-6 (X = Br) with ClMg(CH2)4OSitBuPh2[6] (4.3 equiv) in the presence of Ni(dppp)Cl2 (6 mol%) in ether at
0 °C for 3 d furnished alkenylmagnesiums (E/Z)-Mg-7b (X = Br, Cl). Quenching of the alkenylmagnesiums with
CF3CO2H gave alkenes (E)-H-7b and (Z)-H-7b in 27% yield and 50:50 dr.
5
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
Scheme 3. (a) Ni-catalyzed ACCR of exocyclic metalloalkenyl sulfoximines. (b) Ni-catalyzed ACCR of acyclic (E)-
configured lithioalkenyl sulfoximines. (c) Proposed pathway via [1,5]-retro-Brook rearrangement of δ-silyloxy
alkenyllithiums. (d) Synthesis of acyclic and cyclic aryl-substituted homoallylic alcohols, carrying a (Z)-configured
alkenylsilane group.
6
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
The acyclic (E)-configured lithioalkenyl sulfoximine (E)-Li-8a, which was obtained from alkenyl
sulfoximine (Z)-H-8a[11] through metallation with MeLi, engaged in an ACCR with PhLi (2 equiv) and Ni(PPh3)2Cl2
(5 mol%) in ether at 0 C. To our surprise, quenching of the reaction mixture with CF3CO2H furnished the (Z)-
configured alkenylsilane (Z)-H-10a (≥98:2 dr) in 82% yield instead of the corresponding alkene derived from
protonation of alkenyllithium (Z)-Li-9a or (E)-Li-9a (Scheme 3b). The (E)-configured lithioalkenyl sulfoximine rac-
(E)-Li-8b, which was obtained through metallation of (Z)-H-8b[11] with MeLi, similarly engaged in an ACCR with
PhLi and Ni(PPh3)2Cl2 and afforded the (Z)-configured alkenylsilane rac-(Z)-H-10b (≥98:2 dr) in 59% yield
(Scheme 3c). The ACCR of (E)-Li-8a and rac-(E)-Li-8b had initially given alkenyllithiums Li-9a and rac-Li-9b
either as (Z)- or (E)-configured isomers or mixtures of both isomers. Regardless of the selectivity of the ACCR,
the establishment of an equilibrium between the (E)- and (Z)-isomers of alkenyllithiums Li-9a and rac-Li-9b has to
be assumed, since the α-phenyl alkenyllithiums should have a low configurational stability under the reaction
conditions.[25] For example, (Z)-(2-isopropyl-1-phenylvinyl)lithium experienced under ACCR conditions a fast
(Z,E)-isomerization in ether at 0 C (see the SI for details). From the equilibrium mixture of the isomeric
alkenyllithiums the (E)-configured isomers selectively reacted via migration of the silyl group from the O to the C
atom under formation of the (Z)-configured alkenylsilanes (Z)-Li-10a and rac-(Z)-Li-10b. Silyl migration in the (Z)-
configured isomers should be prohibited because of steric reasons. The formation of alkenylsilanes (Z)-Li-10a
and rac-(Z)-Li-10b from the corresponding alkenyllithiums (E)-Li-9a and rac-(E)-Li-9b are examples of a [1,5]-
retro-Brook rearrangement involving sp2-hybridized
C
atoms.[26] While examples of [1,4]-retro-Brook
rearrangement has been frequently been described,[26,27] those of [1,5]-retro-Brook rearrangement are
scarce.[26,28] The alternative route to (Z)-H-10a and rac-(Z)-H-10b commencing with a [1,5]-retro-Brook
rearrangement of (E)-Li-8a and rac-(E)-Li-8b followed by a Ni-catalyzed CCR of the corresponding -silyl alkenyl
sulfoximines[24] can be excluded, because of the inertness of the lithioalkenyl sulfoximines towards silyl migration.
Ultimately, the Ni-catalyzed ACCR of (E)-Li-8 with aryllithiums followed by a [1,5]-retro Brook rearrangement of
the intermediate alkenyllithiums provides a stereoselective route to acyclic homoallylic alcohols (Z)-10, carrying a
synthetically valuable (Z)-alkenylsilane group[29] (Scheme 3(d)), from allylic sulfoximines and aldehydes. Because
of the availability of the exocyclic lithioalkenyl sulfoximines (E)-Li-11,[12g] this route should also give access to the
exocyclic silyl-substituted homoallylic alcohols (Z)-12.
Although we initially observed a Ni-catalyzed ACCR of (E/Z,R)-M-6, its stereoselectivity remained unclear
since we could not differentiate in diastereoselectivity between (E,R)-M-6 and (Z,R)-M-6 or (Z,S)-M-6 and (E,S)-
M-6 as illustrated in Scheme 4a. Although the exocyclic metalloalkenyl sulfoximines are configurationally stable at
70 °C in ether and ether/HMPA and can be trapped with electrophiles, isomerization is fast at 35 °C, forming
1:1 mixtures of the diastereomers (see the SI for details). In addition, the ACCR of the acyclic lithioalkenyl
sulfoximines (E)-Li-8 led to a C–C coupling and an intriguing [1,5]-retro-Brook rearrangement to form the (Z)-
alkenylsilanes as described in Schemes 2 and 3. However, the ACCR of the (Z)-configured lithioalkenyl
o
sulfoximines (Z)-Li-8 could not be studied, because of a fast and complete isomerization at –35 C to the
corresponding (E)-configured diastereomers (E)-Li-8 (see the SI for details),[12] as revealed by trapping
7
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
experiments (Scheme 4b). Thus, we had to employ a new class of metalloalkenyl sulfoximines as illustrated in
Scheme 4c, in order to investigate the mechanism and stereoselectivity of the ACCR.
Scheme 4. Isomerization of exocyclic metalloalkenyl sulfoximines (a), acyclic metalloalkenyl sulfoximines (b), and
axially chiral lithioalkenyl sulfoximines (c).
The axially chiral lithioalkenyl (N-methyl)sulfoximines (aS,S)-Li-13a and (aR,S)-Li-13a, which are
accessible through metallation of the corresponding alkenyl sulfoximines (aS,S)-H-13a and (aR,S)-H-13a[24] with
MeLi, exist as equilibrium mixtures in which the composition and the rate of isomerization are strongly solvent
dependent. While the dr of the lithioalkenyl (N-methyl)sulfoximines (aS,S)-Li-13a and (aR,S)-Li-13a is 97:3 in
ether at 70 C (95:5 at 0 C) and 97:3 in dimethoxyethane (DME) at 50 C, it is 33:67 in THF at 70 C to 0 C.
Lithioalkenyl sulfoximine (aS,S)-Li-13a is configurationally stable in ether and DME at low temperatures for a
prolonged period of time (see the SI for details). Isomerization of the lithioalkenyl sulfoximines is in THF
significantly faster than in ether (see the SI for details). However, at low temperatures both lithioalkenyl
8
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
sulfoximines (aS,S)-Li-13a and (aR,S)-Li-13a can be efficiently trapped with electrophiles in ether/HMPA or THF.
Isomerization of the lithioalkenyl sulfoximines, which are expected to contain a C–Li bond and Li atom being
coordinated by the N atom or N-sulfonyl O atom, most likely involves a solvent assisted cleavage of the C–Li
bond and formation of N,Li or O,Li contact ion pairs, which undergo inversion at the anionic C atom and rotation
around the C–S bond followed by the formation of the C–Li bond to give the corresponding diastereomer.[15] The
unresolved issue within this dynamic scheme is the strong solvent dependency of the equilibrium between (N-
methyl)alkenyllithiums (aS,S)-Li-13a and (aR,S)-Li-13a and rate of isomerization. The (N-silyl)sulfoximine (aR,S)-
Li-13c is configurationally stable at 70 °C in ether, but forms a 1:1 mixture of diastereomers (aR,S)-Li-13c and
(aS,S)-Li-13c at 0 °C. The substituent at the N atom of the axially chiral lithioalkenyl sulfoximines exerts a strong
influence on the rate of isomerization. In contrast to the (N-methyl)- and (N-silyl)sulfoximines, the (N-
sulfonyl)sulfoximine (aR,S)-Li-13b experiences even at 70 C in ether and THF a fast isomerization to give a
mixture of (aR,S)-Li-13b and (aS,S)-Li-13b in 50:50 dr. The origin of the difference in configurational stability of
the (N-methyl)- and (N-sulfonyl)alkenyllithiums is unknown.
Table 1. Ni-catalyzed ACCR of lithioalkenyl sulfoximine (aS,S)-Li-13a using PhLi.
o
o
a
Reaction conditions: (aS,S)-Li-13a, catalyst/precatalyst (5 mol%), PhLi (2 equiv.), 3 h, –65 C to –50 C. Not
b
c
o
determined. 1.5 h. Reaction was conducted with (aR,S)-Li-13a for 4 h at –65 C, and er represents the ratio of
(aS)-D-14a : (aR)-D-14a.
The axially chiral metalloalkenyl sulfoximine (aS,S)-Li-13a was considered to be a good stereochemical
probe, because it carries diastereotopic methylene groups at the double bond and ACCR will afford enantiomeric
alkenes. Moreover, the three types of metalloalkenyl sulfoximines, (aS,S)-Li-13a, (aR,S)-Li-13b and (aR,S)-Li-13c
should also serve to explore the substrate specificity of the ACCR. Finally, the axially chiral metalloalkenyl
sulfoximines, which carry sulfonimidoyl groups of different nucleofugacity and Lewis basicity,[15,30] were intended
to be probes for the influence of the nucleofuge upon the ACCR.
9
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
The dependency of the ACCR of metalloalkenyl sulfoximines on a number of variables, including the Ni-
catalyst, Ni-precatalyst, ligands of the Ni atom, sulfonimidoyl group and reaction conditions, was studied by using
(aS,S)-Li-13a as substrate. Generally, ACCR was run in ether, because of the high dr and the configurational
stability of the lithioalkenyl sulfoximine in this solvent at low temperatures. Treatment of lithioalkenyl sulfoximine
(aS,S)-Li-13a of 96:4 dr in ether with Ni(COD)2[31] (5 mol%) and salt-free PhLi (2 equiv)[32] at –60 °C to –55 °C for
3 h followed by quenching the mixture with CF3CO2D afforded alkenes (aR)-D-14a and (aS)-D-14a with 97% D in
1
82% yield and 84:16 er (Table 1, entry 1). The er of (aR)-D-14a and (aS)-D-14a was determined by H NMR
spectroscopy in the presence of AgFOD (FOD = 7,7-dimethyl-1,1,1,2,2,3,3-heptafluoro-octan-4,6-dionato) and
[33]
Pr(tfc)3
(tfc = (3-trifluoroacetyl-d-camphorato) and by GC on a chiral stationary phase. The absolute
configuration of (aR)-D-14a was determined based on a comparison of its chirotropic properties with those
reported in the literature for (aS)-H-14a and structurally closely related compounds.[34] In addition to (aR)-D-14a
and (aS)-D-14a sulfinamide (S)-H-15[35,36] was isolated in 73% yield and ≥98:2 er. Repetition of the above ACCR
experiment with salt-containing PhLi gave similar results.
Because of the difference in the 96:4 dr of (aS,S)-Li-13a (equilibrium ratio) (see, Table S3, Supporting
Information) and the 84:16 er of (aR)-H-14a and (aS)-H-14a found in the ACCR, control experiments with (aS,S)-
Li-13a (96:4 dr), Ni(COD)2 and PhLi in ether were run at –65 °C to –55 °C. First, the reaction mixture was
quenched after 1.5 h and the alkenyl sulfoximine (aS,S)-H-13a was isolated, the dr of which was 92:8. In a
second experiment the reaction mixture was quenched after 15 min and the alkenes (aR)-H-14a and (aS)-H-14a
were isolated, the er of which was 85:15, showing that no racemization of (aR)-Li-14a occurred during the
reaction. Racemization of (aR)-Li-14a in ether is slow. For example, (aR)-Li-14a with 62:38 er had after being
kept in ether at 0 °C for 6 h an er of 59:41.
To reveal the possible influence of phosphines, reaction of (aS,S)-Li-13a (97:3 dr) with PhLi was
conducted with in situ prepared Ni(PPh3)2(COD)[37] (5 mol%) in ether at –60 to –55 °C for 3 h followed by
quenching the mixture with CF3CO2D, which gave (aR)-D-14a and (aS)-D-14a in 85:15 er and 93% yield (entry 2).
In further experiments, the ligand for the Ni atom was further varied in the ACCRs of (aS,S)-Li-13a (97:3 dr) with
PhLi and Ni(COD)2 (entries 3 and 4), and different Ni(II)-precatalysts were tested (entries 57). Complex
Ni(PPh3)2Cl2 proved to be an excellent precatalyst (entry 5), which is converted by PhLi to a Ni(0)-complex.[38]
Alkenes (aR)-H(D)-14a and (aS)-H(D)-14a were isolated in 8094% yield and 82:18 to 85:15 er. ACCR of (aS,S)-
Li-13a (97:3 dr) with PhLi and Ni(PPh3)2Cl2 in ether at 0 °C was less selective. After a reaction time of only 2 min
(aR)-D-14a and (aS)-D-14a were isolated in 62:38 er and 84% yield. Table 1 reveals that the catalyst, the
precatalyst(s) and the ligands of the Ni atom have only a minor influence upon the ACCR. We also studied the
ACCR of (aR,S)-Li-13a, which is configurationally less stable than (aS,S)-Li-13a. ACCR of (aR,S)-Li-9a of
approximately 95:5 dr with PhLi in ether in the presence of Ni(PPh3)2Cl2 at 65 C for 4 h followed by quenching
the mixture with CF3CO2D gave alkenes (aS)-D-10a and (aR)-D-10a (98% D) in 64:36 er and 82% yield (entry 8).
The selectivity of the ACCR of (aR,S)-Li-13a is lower than that of diastereomer (aS,S)-Li-13a. Responsible for the
lower selectivity is most likely the competing isomerization of (aR,S)-Li-13a to the more stable diastereomer
(aS,S)-Li-13a and its respective ACCR.
10
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
Previously, alkenyl sulfoximines (E)-H-6 and (aS,S)-H-13a were found to be subject to a highly
stereoselective Ni(0)-catalyzed and Lewis acid promoted cross-coupling reaction with diorganozincs,[6,24,39,40]
which most likely proceeds by a KCN catalytic cycle.[3,24] The adaption of this cycle to the ACCR involved (i) an
oxidative addition of (aS,S)-Li-13a to the Ni(0)-catalyst to afford a Ni(II)-complex, (ii) a transmetallation with PhLi,
and (iii) a reductive elimination to furnish alkenyllithium (aS)-Li-14a as described in Scheme 5 with the dotted red
line. Whilst the KCN cycle leads under retention of configuration to alkenyllithium (aS)-Li-14a, the alkenyllithium
obtained experimentally in ACCR had the (aR)-configuration, under inversion of configuration. The observed
difference in stereoselectivity led us to deduce that the KCN cycle is not applicable to the ACCR of metalloalkenyl
sulfoximines. Moreover, our density functional theory (DFT) calculations indicate that the barrier of the oxidative
addition pathway is 27.7 kcal/mol, which is too high for the given experimental conditions to be mechanistically
relevant (see the SI for details). Therefore, we considered an unconventional and intriguing mechanism, as
illustrated in Scheme 5. We imagined that the highly reduced nickel center of the complex, containing a CNi
bond, may be compelled to form the Ni(0)-vinylidene complex that is stabilized by lithium sulfinamide coordination
and which we were able to locate in our DFT calculations. Our calculations suggest that the reaction may proceed
further by coordination of the phenyl anion to the Ni-center of the Ni(0)-vinylidene to form a Ni(II)-intermediate
with carbanionic character, which requires stabilization by two Li+. Finally, reductive elimination of the Ni(II)-
intermediate extrudes alkenyllithium (aR)-Li-14a.
Scheme 5. Solid lines represent the newly proposed reaction pathway of the Ni-catalyzed ACCR. Dotted lines
represent the oxidative addition pathway, which is of opposite stereoselectivity (OA, oxidative addition; TM,
transmetallation; RE, reductive elimination).
Figure 1 illustrates the computed free energy profile for the proposed mechanism. In our computer model,
Ni(PMe3)2Cl2 was used as the precatalyst and (aS,S)-Li-13a was employed as representative substrate. Notably,
11
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
the electron-rich Ni-center in the anionic Ni(0)-ate intermediate A1 is stabilized by π-back-donation to the anti-
bonding orbital of the C=C moiety in the lithioalkenyl sulfoximine, leading to a notable lengthening of the C=C
bond from 1.35 Å to 1.44 Å (see the SI for details). The carbenoid addition from A1 to the dianionic Ni(0)-ate
complex A10 at 25.1 kcal/mol is energetically too high to be mechanistically relevant, as indicated in red. This
finding is easy to understand given that in the putative intermediate A10 there is no appropriate electron acceptor
that may allow for delocalizing the high electron density of the highly reduced nickel center. Of course, the
phosphine ligands are notorious for being excellent π-acceptors and, thus, we also tested if the arylphosphine
ligand PPh3 could act as an effective electron-acceptor. Our calculations indicate that compared to the model
ligand PMe3 the PPh3-analogue of A10 is indeed lower, but still too high in energy at 20.6 kcal/mol to be
meaningful for the overall chemical reaction (see the SI for details).
Figure 1. Free energy profile for stereoselective ACCR via lithium coordinated Ni(0)-vinylidene intermediate.
Black and blue traces represent the stereoselective and non-stereoselective pathway, respectively.
12
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
We propose that the productive mechanistic pathway involves the neutral Ni(0) intermediate A2 located
at 4.2 kcal/mol, which can form the anionic Ni(0)-ate intermediate A3 via nucleophilic attack of the carbanion
substrate mediated by Li. We found that this process only requires the passage through the transition state A2-
TS at 16.3 kcal/mol. Subsequently, the transient intermediate A3 must undergo an α-elimination via A3-TS at
20.4 kcal/mol to form intermediate A4. And again, the presence of Li+ is important for this step, as the barrier is
would be nearly 6 kcal/mol higher in energy without it (see SI for details). Intriguingly, Li+ also plays a critical role
in determining the stereoselectivity. Lithium sulfinamide coordinated Ni(0)-vinylidene A4 is energetically preferred
over the non-coordinated Ni(0)-vinylidene A7, a finding which is ultimately responsible for the observed
stereoselectivity. The geometry of A4 exposes only one possible site for the addition of a PhLi reagent to the Ni-
center, rendering intermediate A5, stabilized by two Li+ and located at 17.2 kcal/mol, the only plausible adduct.
Formation of A5 with the opposite configuration at the chiral axis requires a prior isomerization of the Ni(0)-
vinylidene intermediate A4. Attempts to locate a transition state for the putative isomerization of A4 were
unsuccessful, but the conversion of A4 to A5 having the aR configuration should be fast given the driving force of
G  17 kcal/mol and should only be limited by diffusion and collision of A4 with PhLi.
Figure 2. Optimized structures of Ni-complexes A4 and A5 (bond lengths are represented in Å, and hydrogen
atoms have been omitted for clarity).
Figure 2 illustrates the optimized structures of A4 and A5, intermediates featuring structural and
energetic stabilization by Li+-coordination. Ni(0)-vinylidene A4 shows a Ni–C1 bond length of 1.74 Å, clearly
indicating a double bond character. Relatively weak Ni-Li interaction is indicated by the calculated bond length of
2.58 Å. Similar metal-lithium interactions have been previously observed in lithiated Fe- Co-, and Ni-complexes.[41]
The short distance between the vinylidene carbon and the Li-center of 2.26 Å suggests a strong interaction and is
analogous to interactions previously reported for metal carbene complexes stabilized by alkali metals.[42] Taken
together, this structural pattern demonstrates why the three-center interaction of Ni–Li–C1 cannot be easily
overcome to afford the free Ni(0)-vinylidene intermediate A7. Moreover, the two Li+ interact covalently with C1 as
shown in A5 with bond lengths of C1–Li1 (2.13 Å) and C1–Li2 (2.10 Å). The elongated bond length of Ni–C1 of
1.85 Å shows that the two Li+ stabilize C1, allowing it to formally remain a carbanion center instead of becoming
13
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
part of a Fischer-type metal–carbon double bond. Consequently, the Ni-center of A5 has a formal oxidation state
of Ni(II). Intermediate A5 easily undergoes reductive elimination to form the C–C bond of A6 with a barrier of only
7.6 kcal/mol, which is 3 kcal/mol lower than the barrier of 10.5 kcal/mol associated with the alternative transition
state A8-TS. Furthermore, transition state A5-TS illustrates the impact of the second Li+. It facilitates the
reductive elimination by temporarily increasing the positive charge of the Ni-center without actively participating in
the redox process. Finally, alkenyllithium (aR)-Li-14a coordinated by (S)-Li-15 is extruded from A6 via ligand
exchange with (aS,S)-13a to give A2, which can start a new catalytic cycle.
Scheme 6. Attempted Ni-catalyzed ACCR of lithioalkenyl sulfoximine (aS,S)-Li-13a with PhLi in DME using PPh3
as ligand.
In summary, our computational study suggests an intriguing mechanistic role of Li+ and proposes that the
stereoselectivity of ACCR is determined by the electrostatic stabilization of the putative Ni(II)-complex A5 via
coordination of two Li+, which is in accordance with the experimental observations. To test this hypothesis, we
examined the decreasing effect of the Li+ when DME is used as the solvent. It is well known that DME can
chelate Li+ by formation of Li–O interactions and thereby give rise to the formation of solvent-separated ion
pairs.[43] In DME treatment of (aS,S)-Li-13a (97:3 dr) with PhLi and Ni(PPh3)2Cl2 (5 mol%) at –60 to –55 °C for 3 h
followed by quenching the mixture with MeI at –55 °C to 0 °C gave a mixture of the methylated alkenyl
sulfoximines (aS,R)-Me-13a and (aR,R)-Me-13a in 50:50 dr in 74% yield, but only traces of the methylated alkene
derived from a methylation of alkenyllithium (aR)-Li-14a (vide infra) (Scheme 6). Formation of the mixture of the
diastereomeric methylated alkenyl sulfoximines in 50:50 dr indicates that the Ni(0)-vinylidene intermediate A7 and
two different isomer of A7/Li-sulfinamide (Scheme 6) exist in the reaction path and Li+ is chelated by DME instead
of forming A4 (see the SI for details). Moreover, it is likely that the carbanion intermediate A4 is formed to afford
the Ni(II) intermediate A5 that undergoes reductive elimination and advances the C–C bond formation with PhLi.
However, because of the reduced activity of Li+ it may not accelerate the formation of the Ni(II) intermediate A5
from A7 or (aR)- and (aS)-A7/Li-sulfinamide intermediates, which might be generated because of the different
reaction conditions with DME as solvent.
14
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
Scheme 7. Control experiment of (aS,S)-Li-13a with Ni(PPh3)2(COD) in the absence of PhLi.
The anionic Ni(0)-ate mediated catalytic pathway was established with Ni(2PPh3)Cl2 as precatalyst.
However, we also obtained experimental results when employing Ni(PPh3)2(COD) as the precatalyst that were
inconsistent with the aforementioned mechanism. Scheme 7 represents a control experiment with (aS,S)-Li-13a
(96:4 dr) and stoichiometric amounts of Ni(PPh3)2(COD)[37] at –55 °C in ether/cyclohexene for 2 h in the absence
of PhLi. The Ni-complex did not cause a decomposition of the lithioalkenyl sulfoximine at low temperatures.
Instead, the decomposition took place when the temperature was increased to 0 oC,[44] indicating that the reaction
pathway of A2➝A3➝A3-TS does not occur when COD is present as innocent ligand. In this case, the C–S bond
cleavage of the lithioalkenyl sulfoximine will be accelerated by the existence of the PhLi reagent at low
temperature. Computational studies show that PhLi is not necessary for the Ni(PPh3)2Cl2 system where the
dianionic Ni(0) intermediate A10 is located at high energy of 25.1 kcal/mol, whereas in the Ni(COD)2 system the
dianionic Ni(0) intermediate B3 (vide infra) has a relatively low energy. Thus, the use of olefinic ligands such as
COD for the Ni-catalyzed ACCR gave the same product with a similar yield (cf. Table 1) but to our surprise, the
reaction path seemed to be different. Recently, formation of anionic Ni(0) complexes has been described when
COD was employed as innocent ligand.[5] In these complexes, which display an intriguing catalytic activity, the
highly reduced Ni(0) atom is stabilized by π-back-donation to the C=C bond of the olefinic ligand. As we sensed
for the reaction pathway of the ACCR with Ni(COD)2 disparities in comparison with the aforementioned one
based on Ni(PPh3)2Cl2, we decided to further examine the elusive mechanism of the ACCR via dianionic Ni(0)-ate
intermediates with theoretical methods.
DFT calculations of the ACCR of (aS,S)-Li-13a with PhLi in the presence of Ni(COD)2 represented in
Figure 3 began with the neutral Ni(0) intermediate B1 that coordinates the lithioalkenyl sulfoximine. In the
absence of PhLi, the carbenoid addition traversing the transition state B6-TS is associated with a reaction barrier
of 23.7 kcal/mol. This barrier suggests that the decomposition of the lithioalkenyl sulfoximine via Ni(0)-vinylidenes
B7 and B8 is not feasible at low temperatures, when the olefinic ligand is employed, as observed in the control
experiment mentioned above. On the other hand, the addition of PhLi to B1 leads to the anionic Ni(0)-ate
complex B2, which is stabilized by two olefinic ligands, COD and the lithioalkenyl sulfoximine. Next, the carbenoid
addition to the Ni atom generates the dianionic Ni(0)-ate complex B3 at 1.5 kcal/mol.
15
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
Figure 3. Free energy profile for the stereoselective ACCR via dianionic Ni(0)-ate intermediate. Black and red
traces represent the reaction pathway via dianionic Ni(0)-ate and anionic Ni(0)-ate intermediates.
Optimized structures of B2 and B3 are shown in Figure 4. Although the anionic Ni(0)-ate complex could
be stabilized by the C=C bond of the lithioalkenyl sulfoximine for both ligands PMe3 (A1) and COD (B2), only the
dianionic Ni(0)-ate complex B3, carrying COD as ligand, was located at relatively low energy. This differentiates
the two distinct mechanisms of the Ni-catalyzed ACCR with the different innocent ligands since the analogous
dianionic Ni(0)-ate A10 is associated with a high barrier. Electron-rich [Ni(0)]–1 in B2 engages in π-backdonation
to the C=C bond of the lithioalkenyl sulfoximine that displays an elongated C3–C4 bond length of (1.43 Å) as a
consequence. This orbital interaction is also present in A1, where the alkenyl double bond is found to be 1.44 Å
(see the SI for details). On the way from B2 to the dianionic Ni(0)-ate complex B3, the interaction between the Ni
atom and C=C bond of the lithioalkenyl sulfoximine is resolved and instead the Ni–C3 σ-bond is formed. The
other olefinic ligand, COD, accepts an electron from the highly reduced [Ni(0)]2– metal center, which is indicated
by the elongated bond length of C1–C2 (1.45 Å) in B3, whereas there is no more proper electron acceptor in the
PMe3 coordinated system (A10). The proposed formation of the Ni(0)-ate complexes B2 and B3 is supported by
the synthesis of lithium and dilithium Ni(0)-ate complexes from Ni(0) complexes including Ni(COD)2 and
organolithiums.[45] Furthermore, the highly electron-rich [Ni(0)]2– metal center of B3 can easily push some electron
density to the alkenyl sulfoximine group, consequently transpiring the C–S bond cleavage with the reduction of
16
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
sulfur from S(VI) to S(IV). The overall barrier associated with B3-TS is 16.4 kcal/mol. The transformation of B3 to
the Ni(II) complex B4 is mediated by two Li+ in an exogenic process. Finally, reductive elimination of B4 via
transition state B4-TS affords alkenyllithium (aR)-Li-14a, as observed when Ni(PPh3)2Cl2 was used as precatalyst.
Figure 4. Optimized structures of Ni-complexes B2 and B3 (bond lengths are represented in Å, and hydrogen
atoms have been omitted for clarity).
In order to gain information about the observed lack of a competing ACCR of the lithioalkenyl sulfoximine
with alkenyllithium (aR)-Li-14a, ACCRs of (aS,S)-Li-13a (97:3 dr) with vinyllithium and α-phenyl vinyllithium as
model compounds for (aR)-Li-14a were performed (Table 2, entry 14). ACCR of (aS,S)-Li-13a (96:4 dr) with
vinyllithium in the presence of Ni(PPh3)2Cl2 (5 mol%) in ether was slow at low temperatures (entries 1 and 2). It
took place with reasonable rate only at 0 °C and gave after quenching the reaction mixture with CF3CO2D diene
rac-D-14b (83% D) in 86% yield (entry 3). A similar ACCR of (aS,S)-Li-13a (96:4 dr) with -phenyl vinyllithium in
the presence of Ni(PPh3)2Cl2 (5 mol%) at 0 °C in ether for 1.5 h followed by treatment of the reaction mixture with
CF3CO2D afforded diene rac-D-14c (42% D) in only 30% yield (entry 4). The rate of the ACCR of (aS,S)-Li-13a
with the sp2-organolithiums strongly decreases in the order PhLi >> vinyllithium > α-phenyl vinyllithium. These
data suggest that the ACCR of (aS,S)-Li-13a with alkenyllithium (aR)-Li-14a should be even slower than with α-
phenyl vinyllithium. Isolation of rac-D-14c and rac-D-14c, having a low D-content, appears to be the result of a
lithiation of the corresponding lithioallyl sulfoximine, resulting from a vinyl-allyl-isomerization of (aS,S)-Li-13a, by
the dienyllithium under formation of the corresponding dilithioallyl sulfoximine and the protonated diene (see the
SI for details). On the other hand, attempts to achieve a Ni-catalyzed ACCR of (aS,S)-Li-13a with alkyllithiums,
including MeLi, n-BuLi, and LiCH2SiMe3, were unsuccessful.
17
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
Table 2. Ni-catalyzed ACCR based on different lithioalkenyl sulfoximines and alkenyllithiums
aA mixture of (aS,S)-D-13a and (aR,S)-D-13a (70:30 dr) and the corresponding diastereomeric allylic sulfoximines
b
in a ratio of 92:8 was recovered in 47% yield. A mixture of (aS,S)-D-13a and (aR,S)-D-13a (75:25 dr) and the
corresponding diastereomeric allylic sulfoximines (200% D at the α-position) in a ratio of 92:8 was recovered in
12% yield. cAmount of unreacted sulfoximine was not determined.
In further experiments with axially chiral lithioalkenyl sulfoximines, we studied the influence of the
substituent at the N atom upon the ACCR. In stark contrast to the (N-methyl)sulfoximine (aS,S)-Li-13a, the (N-
sulfonyl)sulfoximines (aR,S)-Li-13b and (aS,S)-Li-13b (50:50 dr), which were synthesized through metallation of
alkenyl sulfoximine (aR,S)-H-13b[24] with nBuLi, did not undergo an ACCR with PhLi at –75 °C in ether for 1 h in
the presence of Ni(PPh3)2Cl2 (5 mol%) (Table 2, entry 5). Quenching the reaction mixture with CF3CO2D led to a
recovery of the deuteriated sulfoximines (aR,S)-D-13b and (aS,S)-D-13b (95% D) in 50:50 dr. Under these
conditions, already 30% of the (N-methyl)sulfoximine (aS,S)-Li-13a had been converted to alkenyllithium (aR,S)-
Li-14a (vide supra). Correspondingly, no ACCR was observed between the (N-silyl)sulfoximine (aR,S)-Li-13c,
which was obtained from alkenyl sulfoximine (aR,S)-H-13c on reaction with MeLi, and PhLi in the presence of
Ni(PPh3)2Cl2 (5 mol%) at –75 °C (entry 6). After the temperature of the reaction mixture was raised to –5 °C and
the mixture quenched with CF3CO2D, alkene rac-D-14a (77% D) was isolated in only 12% yield. Alkenyl
sulfoximines (aR,S)-D-13c and (aS,S)-D-13c (98% D) were recovered in 73% yield and 50:50 dr (entry 7).
So far the phenyl-substituted alkenyllithiums (aS,S)-Li-14a and (aR,S)-Li-14a were trapped by
protonation and/or deuteriation. It was of interest to see, however, whether the alkenyllithiums can also be
intercepted with other electrophiles. Therefore experiments were carried out by using methyl iodide,
dibromoethane, and isobutyraldehyde as trapping reagents (Scheme 8).
18
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
Scheme 8. Trapping of axially chiral alkenyllithiums with electrophiles.
First, the ACCR of (aS,S)-Li-13a (97:3 dr) with PhLi was run in the presence of Ni(PPh3)2Cl2 or
Ni(PPh3)2(COD)[37] (5 mol%). Treatment of thus obtained alkenyllithiums (aR)-Li-14a and (aS)-Li-14a (85:15 er)
with MeI at 55 C to 0 C afforded the disubstituted axially chiral alkenes (aR)-14d and (aS)-14d in 82% yield
and 85:15 er. Determination of the er was done by GC on a chiral stationary phase and by 1H NMR spectroscopy
in the presence of AgFOD and Pr(tfc)3.[33] The absolute configuration of (aR)-14d was assigned based on its
chirotropic properties in comparison with those of (aR)-H-14a. Addition of a cold (55 C) solution of (aR)-Li-14a
and (aS)-Li-14a in ether to a solution of 1,2-dibromoethane in ether at 0 C gave the axially chiral bromo alkenes
(aS)-14e and (aR)-14e in 68% yield and 78:22 er. Determination of the er was made by 1H NMR spectroscopy in
the presence of AgFOD and Pr(tfc)3.[33] The absolute configuration of (aR)-14e was assigned based on its
chiroptical properties in comparison with those of (aR)-H-14a. Trapping of (aR)-Li-14a and (aS)-Li-14a in ether at
i
50 C to 0 C with PrCHO furnished a mixture of diastereomeric alcohols, (aS,R)-14f and (aS,S)-14f, in a ratio
of 54:46 in 79% yield, which were separated by MPLC. The configuration of the stereogenic center of the alcohols
1
was not determined. The minor diastereomer had an er of 84:16 as determined by H NMR spectroscopy in the
presence of AgFOD and Pr(tfc)3.[33] The configuration of the chiral axis of (aS,R)-14f and (aS,S)-14f was assigned
in analogy to that of (aR)-14a.
CONCLUSION
The ACCR of metalloalkenyl sulfoximines with PhLi in the presence of the Ni(0)-catalyst yielded
alkenyllithiums and lithium sulfinamide under inversion of configuration at the C atom and complete retention at
o
the S atom. Utilizing NiCl2 as the precatalyst at optimal conditions of –60 C, COD and phosphine ligands or
Ni(COD)2 as catalyst proved to be ideal in attaining a favorable yield and er. In search of establishing the first
ACCR with nickel, we discovered an interesting feature in which the oxidative addition step does not initiate the
ACCR catalytic cycle, further supported by computational studies. Moreover, in conjunction with DFT calculations,
we were able to differentiate the distinct pathways with respect to the two different innocent ligands PPh3 and
COD for the reaction system. Fundamentally, the role of Li+ is vital. On the one hand, it stabilizes the electron-rich
metal center in the Ni(0)-intermediates and on the other hand it participates in controlling the reaction barriers that
lead to the key Ni(0)-vinylidene and dianionic Ni(0)-ate intermediates of the ACCR pathways. The mechanism of
the Ni catalyzed ACCR of lithioalkenyl sulfoximines is distinctly different from that of the Cu catalyzed ACCR of
19
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
lithioalkenyl ethers[8c,8d,23] and Cu mediated ACCR of litthioalkenyl sulfoximines,[13] which feature as key step a
1,2-metalate shift[8] of higher order cuprates under displacement of the nucleofuge at the sp2 C atom.
Supporting Information
The Supporting Information is available free of charge at DOI: xxxxxxxxx. Experimental details, NMR spectra,
determination of er values, computational details, Cartesian coordinates of all computed structures and energy
components (PDF).
ORCID
Joonghee Won: 0000-0002-2487-8788
Mu-Hyun Baik: 0000-0002-8832-8187
Hans-Joachim Gais: 0000-0003-2716-6898
Conflicts of interest
The authors declare no competing financial interest.
ACKNOWLEDGMENT
Financial support of this research by the Deutsche Forschungsgemeinschaft, VW Foundation and Fonds der
Chemischen Industrie is gratefully acknowledged. The analytic and spectroscopic laboratories of the institutes of
organic chemistry of Technische Universität Darmstadt, Albert-Ludwigs Universität Freiburg and RWTH Aachen
University are gratefully acknowledged for support of this work. We thank Cornelia Vermeeren for GC analysis
and Professors Dr. Helmut Vorbrüggen and Dr. Werner Skuballa for generous support and helpful discussions.
This research was supported by the Institute for Basic Science (IBS-R010-A1) in South Korea.
Keywords: carbenoids, nickel, nickel-vinylidene, organolithium, diastereoselectivity
REFERENCES
[1] a) N, Hazari, P. R. Melvin, M. M. Beromi, Nat. Rev. Chem. 2017, 1, 25; b) A. Biffis,
P. Centomo, A. D. Zotto, M. Zecca, Chem. Rev. 2018, 118, 2249-2295; c) K. C. Nicolaou, P. G. Bulger, D. Sarlah,
Angew. Chem. 2005, 117, 4516-4563; Angew. Chem. Int. Ed. 2005, 44, 4442-4489; d) F.-S. Han, Chem. Soc.
Rev. 2013, 42, 5270-5298.
[2] a) C. Amatore, A. Jutand, Acc. Chem. Res. 2000, 33, 314-321; b) S. Kozuch, C. Amatore, A. Jutand, S. Shaik,
Organometallics 2005, 24, 2319-2330; c) F. Schroeter, J. Soellner, T. Strassner, ACS Catal. 2017, 7, 3004-3009;
20
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
d) A. F. Schmidt, A. A. Kurokhtina, E. V. Larina, E. V. Yarosh, N. A. Lagoda, Organometallics 2017, 36, 3382-
3386.
[3] R. Jana, T. P. Pathak, M. S Sigman, Chem. Rev. 2011, 111, 1417-1492.
[4] a) J. Terao, N. Kambe, Acc. Chem. Res. 2008, 41, 1545-1554; b) J. Terao, H. Watanabe, A. Ikumi, H.
Kuniyasu, N. Kambe, J. Am. Chem. Soc. 2002, 124, 4222-4223.
[5] L. Nattmann, S. Lutz, P. Ortsack, R. Goddard, J. Cornella, J. Am. Chem. Soc. 2018, 140, 13628-13633.
[6] I. Erdelmeier, H.-J. Gais, J. Am. Chem. Soc. 1989, 111, 1125-1126.
[7] H.-J. Gais, H. Müller, J. Decker, R. Hainz, Tetrahedron Lett. 1995, 36, 7433-7436.
[8] a) G. Köbrich, A. Akhtar, F. Ansari, W. E. Breckoff, H. Büttner, W. Drischel, R. H. Fischer, K. Flory, H. Fröhlich,
W. Goyert, H. Heinemann, I. Hornke, H. R. Merkle, H. Trapp, W. Zündorf, Angew. Chem. 1967, 79, 15-27; Angew.
Chem. Int. Ed. Engl. 1967, 6, 41-52; b) G. Köbrich, Angew. Chem. 1972, 84, 557-596; Angew. Chem. Int. Ed.
Engl. 1972, 11, 473-485; c) P. Kocieński, C. Barber, Pure Appl. Chem. 1990, 62, 1933-1940; d) P. Kocieński, -
Heteroalkenyl Metallate Rearrangements in Organic Synthesis. In Organic Synthesis via Organometallics; D.
Enders, H.-J. Gais, W. Eds. Keim, Vieweg: Braunschweig/Wiesbaden, 1993, pp 203-223; e) M. Braun, Angew.
Chem. 1998, 110, 444-465; Angew. Chem. Int. Ed. 1998, 37, 430-451; f) G. Boche, J. C. W. Lohrenz, Chem. Rev.
2001, 101, 697-756; g) R. W. Friesen, J. Chem. Soc., Perkin Trans. 1 2001, 1969-2001; h) T. Kurahashi, T. Hata,
H. Masai, H. Kitagawa, M. Shimizu, T. Hiyama, Tetrahedron 2002, 58, 6381-6395; i) S. Dixon, R. J. Whitby,
Elaboration of Organozirkonium Species by Insertion of Carbenoids. In Titanium and Zirkonium in Organic
Synthesis; Marek, I., Ed.; Wiley-VCH: Weinheim, 2002; pp 86-109; j) T. Satoh, A. Kondo, J. Musashi,
Tetrahedron 2004, 60, 5453-5460; k) R. Knorr, Chem. Rev. 2004, 104, 3795-3850; l) M. Braun, Lithium
Carbenoids. In The Chemistry of Organolithium Compounds; Z. Rappoport, I. Eds Marek, Wiley: Chichester, 2004;
pp 829-900; m) T. Satoh, Chem. Soc. Rev. 2007, 36, 1561-1572; n) S. Chiba, K. Ando, K. Narasaka, Synlett
2009, 2549-2564; o) R. S. Grainger, K. R. Munro, Tetrahedron 2015, 71, 7795-7835; p) T. Kimura, Synthesis
2017, 49, 5105-5119; q) M. Zhu, L. Liu, H.-T. Yu, W.-X. Zhang, Z. Xi, Chem. Eur. J. 2018, 24, 19122-19135.
[9] a) P. Bichler, W. A. Chalifoux, S. Eisler, A. L. K. Shi Shun, E. T. Chernik, R. R. Tykwinski, Org. Lett. 2009, 11,
519-522; b) T. Kimura, T. Satoh, Tetrahedron 2013, 69, 6371-6374; c) F. Chemla, F. Dulong, F. Ferreira, A.
Perez-Luna, Beilstein J. Org. Chem. 2013, 9, 236-245; d) R. Lhermet, M. Ahmad, C. Fressigne, B. Silvi, M.
Durandetti, J. Maddaluno, Chem. Eur. J. 2014, 20, 10249-10254; e) T. O. P. Hayes, B. Slater, R. A. J. Horan, M.
Radigois, J. D. Wilden, Org. Biomol. Chem. 2017, 15, 9895-9902.
[10] a) M. Harmata, Tetrahedron Lett. 1988, 29, 5229-5232; b) R. F. W. Jackson, A. D. Briggs, P. A. Brown, W.
Clegg, M. R. J. Elsegood, C. Frampton, J. Chem. Soc., Perkin Trans. 1 1996, 1673-1682; c) M.-A. Virolleaud, V.
Sridharan, D. Mailhol, D. Bonne, C. Bressy, G. Chouraqui, L. Commeiras, Y. Coquerel, J. Rodriguez, Tetrahedron
21
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
2009, 65, 9756-9764; d) N. Yongpruksa, S. Pandey, G. A. Baker, M. Harmata, Org. Biomol. Chem. 2011, 9,
7979-7982.
[11] H.-J. Gais, R. Hainz, H. Müller, P. R. Bruns, N. Giesen, G. Raabe, J. Runsink, S. Nienstedt, J. Decker, M.
Schleusner, J. Hachtel, R. Loo, C.-W. Woo, P. Das, Eur. J. Org. Chem. 2000, 3973-4009.
[12] a) H.-J. Gais, R. Loo, D. Roder, P. Das, G. Raabe, Eur. J. Org. Chem. 2003, 1500-1526; b) M. Lejkowski, H.-
J. Gais, P. Banerjee, C. Vermeeren, J. Am. Chem. Soc. 2006, 128, 15378-15379; c) M. Lejkowski, P. Banerjee, J.
Runsink, H.-J. Gais, Org. Lett. 2008, 10, 2713-2716; d) V. Mahajan, H.-J. Gais, Chem. Eur. J. 2011, 17, 6187-
6195; e) M. Lejkowski, P. Banerjee, S. Schüller, A. Münch, J. Runsink,V Vermeeren, H.-J. Gais, Chem. Eur. J.
2012, 18, 3529-3548; f) M. Lejkowski, P. Banerjee, G. Raabe, J. Runsink, H.-J. Gais, Eur. J. Org. Chem. 2014,
529-553.
[13] H.-J. Gais, C. V. Rao, R. Loo, Chem. Eur. J. 2008, 14, 6510-6528.
[14] In contrast, the corresponding alkylidenecarbene (dimethylamino)sulfoxonium ylides undergo FBW
rearrangement and α-elimination: a) L. R. Reddy, H.-J. Gais, C.-W. Woo, G. Raabe, J. Am. Chem. Soc. 2002,
124, 10427-10434; b) H.-J. Gais, L. R. Reddy, G. S. Babu, G. Raabe, J. Am. Chem. Soc. 2004, 126, 4859-4864.
[15] A. W. Giesen, G. Raabe, J. Runsink, H.-J. Gais, Chem. Eur. J. 2017, 23, 14231-14247.
[16] M. Zehnder, J. F. K. Müller, M. Neuburger, Acta Cryst. 1997, C53, 419-422.
[17] a) C. Bruneau, P. H. Dixneuf, Acc. Chem. Res. 1999, 32, 311-323; b) B. M. Trost, D. Toste, A. B. Pinkerton,
Chem. Rev. 2001, 101, 2067-2096; c) B. M. Trost, A. McClory, Chem. Asian J. 2008, 3, 164-194; d) J. M. Lynam,
Chem. Eur. J. 2010, 16, 8238-8247; e) D. G. Johnson, J. M. Lynam, N. S. Mistry, J. M. Slattery, R. J. Thatcher, A.
C. Whitwood, J. Am. Chem. Soc. 2013, 135, 2222-2234; f) O. J. S. Pickup, I. Khazal, E. J. Smith, A. C. Whitwood,
J. M. Lynam, Organometallics 2014, 33, 1751-1761; g) S. W. Roh, K. Choi, C. Lee, Chem. Rev. 2019, 119, 4293-
4356.
[18] a) G. B. Bajracharya, N. K. Pahadi, I. D. Gridnev, Y. Yamamoto, J. Org. Chem. 2006, 71, 6204-6210; b) M.
Tobisu, H. Nakai, N. Chatani, J. Org. Chem. 2009, 74, 5471-5475.
[19] S. Pal, Y.-Y. Zhou, C. Uyeda, J. Am. Chem. Soc. 2017, 139, 11686-11689.
[20] a) J. Bund, H.-J. Gais, I. Erdelmeier, J. Am. Chem. Soc. 1991, 113, 1442-1444; b) H.-J. Gais, G. Schmiedl, R.
K. L. Ossenkamp, Liebigs Ann/Rec. 1997, 2419-2431; c) R. K. L. Ossenkamp, H.-J. Gais, Liebigs Ann./Rec. 1997,
2433-2441; d) I. Vaulont, H.-J. Gais, N. Reuter, E. Schmitz, R. K. L. Ossenkamp, Eur. J. Org. Chem. 1998, 805-
826; e) J. Bund, H.-J. Gais, E. Schmitz, I. Erdelmeier, G. Raabe, Eur. J. Org. Chem. 1998, 1319-1335; f) M. van
Bergen, H.-J. Gais, J. Am. Chem. Soc. 2002, 124, 4321-4328; g) M. Lerm, H.-J. Gais, K. Cheng, C. Vermeeren, J.
Am. Chem. Soc. 2003, 125, 9653-9667; h) G. J. Kramp, M. Kim, H. J. Gais, C. Vermeeren, J. Am. Chem. Soc.
22
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
2005, 127, 17910-17920; i) H.-J. Gais, G. J. Kramp, D. Wolters, L. R. Reddy, Chem. Eur. J. 2006, 12, 5610-5617;
j) M. van de Sande, H.-J. Gais, Chem. Eur. J. 2007, 13, 1784-1795.
[21] H.-J. Gais, I. Erdelmeier, H. J. Lindner, J. Vollhardt, Angew. Chem. 1986, 98, 914-915; Angew. Chem. Int. Ed.
Engl. 1986, 25, 938-939.
[22] H.-J. Gais, R. Hainz, H. Müller, P. R. Bruns, N. Giesen, G. Raabe, J. Runsink, S. Nienstedt, J. Decker, M.
Schleusner, J. Hachtel, R. Loo, C.-W. Woo, P. Das, Eur. J. Org. Chem. 2000, 3973-4009.
[23] P. Kocieński, S. Wadman, K. Cooper, J. Am. Chem. Soc. 1989, 111, 2363-2365.
[24] I. Erdelmeier, G. Bülow, C.-W. Woo, J. Decker, G. Raabe, H.-J. Gais, Chem. Eur. J. 2019, 25, 8371-8386.
[25] a) E. J. Panek, B. L. Neff, H. Chu, M. G. Panek, J. Am. Chem. Soc. 1975, 97, 3996-4000; b) R. Knorr, K.-O.
Hennig, P. Böhrer, B. Schubert, J. Organomet. Chem. 2014, 767, 125-135.
[26] W. H. Moser, Tetrahedron 2001, 57, 2065-2084.
[27] a) S. Yamago, K. Fujita, M. Miyoshi, M. Kotani, J.-I. Yoshida, Org. Lett. 2005, 7, 909-911; b) K. D. Kim, P. A.
Magriotis, Tetrahedron Lett. 1990, 31, 6137-6140.
[28] Y. He, B. Ma, J. Yang, X. Xie, X. She, Tetrahedron 2013, 69, 5545-5549.
[29] D. S. W. Lim, E. A. Anderson, Synthesis 2012, 44, 983-1010.
[30] a) C. R. Johnson, Acc. Chem. Res. 1973, 6, 341-347; b) C. R. Johnson, Sulphoximides In Comprehensive
Organic Chemistry; D. H. Barton, W. D. Ollis, Eds. Pergamon Press: Oxford, Vol. 3, 1979; pp 223-232; c) C. R.
Johnson, Aldrichimica Acta 1985, 18, 3-10; d) Pyne, S. G. Sulfur Rep. 1992, 12, 57–89; e) S. G. Pyne, Sulfur Rep.
1999, 21, 281–334; f) M. Reggelin, C. Zur, Synthesis 2000, 1–64; g) H. Okamura, C. Bolm, Chem. Lett. 2004, 33,
482-487; h) C. Bolm, Sulfoximines as ligands in asymmetric metal catalysis In Asymmetric synthesis with
Chemical and Biological Methods; Enders, D.; Jaeger, K.-F.; Wiely-VCH: Weinheim, 2007, pp 149-176; i) H.-J.
Gais, Heteroatom Chem. 2007, 18, 472–481.
[31] B. Bogdanovic, M. Kröner, Wilke, G. Liebigs Ann. Chem. 1966, 699, 1-23.
[32] M. Schlosser, V. Ladenberger, J. Organometal. Chem. 1967, 8, 193-197.
[33] T. J. Wenzel, R. E. Sievers, Anal. Chem. 1981, 53, 393-399.
[34] a) S. Hanessian, S. Beaudoin, Tetrahedron Lett. 1992, 33, 7655-7658; b) S. E. Denmark, C.-T. Chen, J. Am.
Chem. Soc. 1992, 114, 10674-10676; c) S. E. Denmark, C.-T. Chen, Heteroatom Chem. 1995, 6, 133-144; d) S.
Nakamura, T. Aoki, T. Ogura, L. Wang, T. Toru, J. Org. Chem. 2004, 69, 8916-8923.
23
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
[35] E. U. Jonsson, C. R. Johnson, J. Am. Chem. Soc. 1971, 93, 5308-530.
[36] H.-J. Gais, H. Müller, J. Bund, M. Scomomoda, J. Brandt, G. Raabe, J. Am. Chem. Soc. 1995, 117, 2453-
2466.
[37] H. Maciejewski, A. Sydor, B. Marciniec, M. Kubicki, P. B. Hitchcock, Inorg. Chim. Acta 2006, 359, 2989-2997.
[38] a) D. G. Morrell, J. K. Kochi, J. Am. Chem. Soc. 1975, 97, 72627270; b) J. F. Fauvarque, A. Jutand, J.
Organometal. Chem. 1981, 209, 109114; c) S. Saito, S. Oh-Tani, N. Miyaura, J. Org. Chem. 1997, 62,
80248030.
[39] H.-J. Gais, G. Bülow, Tetrahedron Lett. 1992, 33, 461-464.
[40] H.-J. Gais, Bülow, G. Tetrahedron Lett. 1992, 33, 465-468.
[41] a) A. Fꢀrstner, K. Majima, R. Martin, H. Krause, E. Kattnig, R. Goddard, C. W. Lehmann, J. Am. Chem. Soc.
2008, 130, 1992-2004; b) A. Fꢀrstner, R. Martin, H. Krause, G. Seidel, R. Goddard, C. W. Lehmann, J. Am.
Chem. Soc. 2008, 130, 8773-8787; c) H. Bꢀnnemann, C. Krꢁger, Y.−H. Tsay, Angew. Chem. 1976, 88, 50-51;
Angew. Chem., Int. Ed. 1976, 15, 46-47; d) K. Jonas, L. Schieferstein, C. Krꢀger, Y.-H. Tsay, Angew. Chem.
1979, 91, 590; Angew. Chem., Int. Ed. 1979, 18, 549-550; e) K. Jonas, C. Krꢀger, J. C. Sekutowski, Angew.
Chem. 1979, 91, 520-521; Angew. Chem. Int. Ed. 1979, 18, 487-488.
[42] a) H. Osseili, K.-N. Truong, T. P. Spaniol, L. Maron, U. Englert, J. Okuda, Titanium Carbene Complexes
Stabilized by Alkali Metal Amides. Angew. Chem. 2019, 131, 1847-1851; Angew. Chem. Int. Ed. 2019, 58, 1833-
1837; b) J. A. R. Schmidt, S. A. Chmura, J. Arnold, Organometallics 2001, 20, 1062-1064; c) J. A. R. Schmidt, J.
Arnold, J. Am. Chem. Soc. 2001, 123, 8424-8425.
[43] a) E. Niecke, M. Nieger, O. Schmidt, D. Gudat, W. Schoeller, J. Am. Chem. Soc. 1999, 121, 519522; b) S.
Krieck, H. Görls, M. Westerhausen, Organometallics 2010, 29, 67906800; c) S. Tsuzuki, W. Shinoda, S. Seki, Y.
Umebayashi, K. Yoshida, K. Dokko, M. Watanabe, ChemPhysChem 2013, 14, 1993-2001.
[44] The experiments were run in the presence of cyclohexene in order to trap the (4-tert-
butyl)cyclohexylidenecarbene (M. Topolski, H. M. Walborsky, J. Org. Chem. 1994, 59, 5506-5510), which might
have been generated in the decomposition of the Ni-complex derived from (aS,S)-13a and Ni(PPh3)2(COD).
However, formation of 7-(4-(tert-butyl)cyclohexylidene)-bicyclo[4.1.0]heptane was not observed. Instead, 1,2-
bis(4-(tert-butyl)cyclohexylidene)ethane (see the SI for details) could be detected by GC MS analysis besides
several unidentified compounds.
[45] a) K. Jonas, K.-R. Pörschke, C. Krüger, Y.-H. Tsay, Angew. Chem. 1976, 88, 682; Angew. Chem. Int. Ed.
Engl. 1976, 15, 621-622; b) E. Uhlig, B. Hipler, Z. Chem. 1977, 17, 272-273; c) R. Taube, N. Stransky, W.
24
This article is protected by copyright. All rights reserved.

10.1002/chem.201904862
Chemistry - A European Journal
Höboldt, Z. Chem. 1979, 19, 412-413; d) K. Jonas, C. Krüger, Angew. Chem. 1980, 92, 513-531; Angew. Chem.
Int. Ed. Engl. 1980, 19, 520-537; e) P. W. Jolly, Nickel Hydride, Alkyl and Aryl Complexes In Comprehensive
Organometallic Chemistry; G. Wilkinson, F. G. A. Stone, Eds.; Pergamon Press: Oxford, 1982; Vol. 6, pp 37-100;
f) K.-L. Pörschke, K. Jonas, G. Wilke, R. Benn, R. Mynott, R. Goddard, C. Krüger, Chem. Ber. 1985, 118, 275-
297; g) G. Wilke, Angew. Chem. 1988, 100, 189-211; Angew. Chem. Int. Ed. Engl. 1988, 24, 185-206; h) K.-R.
Pörschke, K. Jonas, G. Wilke, Chem. Ber. 1988, 121, 1913-1919; i) W. Kaschube, K.-R. Pörschke, K. Angermund,
C. Krüger, G. Wilke, Chem. Ber. 1988, 121, 1921-1929.
TOC graphic
25
This article is protected by copyright. All rights reserved.