Formation of macrocyclic ring systems by carbonylation of trifunctional p/b/b frustrated lewis pairs

Article abstract of DOI:10.1039/c7sc04394e

The trifunctional P/B/B frustrated Lewis pairs 11a-c featuring bulky aryl groups at phosphorus [Dmesp (a), Tipp (b), Mes? (c)] react with H₂ by heterolytic hydrogen splitting followed by cleavage of HB(C₆F₅)₂ to give the zwitterionic six-membered heterocyclic PH phosphonium/borate products 14a-c. Compounds 11a,b react with carbon monoxide by means of a Lewis acid induced CO insertion/rearrangement sequence that eventually results in the formation of the macrocyclic dimers 17a,b. The respective carbonylation reaction of the Mes?P/B/B FLP gives the macrocyclic trimer 18c. The new products were characterized spectroscopically and by X-ray diffraction and the reaction mechanism was analyzed by DFT calculations.

Full text of DOI:10.1039/c7sc04394e

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Formation of Macrocyclic Ring Systems by Carbonylation of
Trifunctional P/B/B Frustrated Lewis Pairs
Long Wang,a Shunxi Dong,a Constantin G. Daniliuc,a Lei Liu,b Stefan Grimme,b Robert Knitsch,c
Hellmut Eckert,c,d Michael R. Hansen,c Gerald Kehra and Gerhard Erkera*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
The trifunctional P/B/B frustrated Lewis pairs 11a-c featuring bulky aryl groups at phosphorus [Dmesp (a), Tipp (b), Mes*
(c)] react with H2 by heterolytic hydrogen splitting followed by cleavage of HB(C6F5)2 to give the zwitterionic six-membered
heterocyclic PH phosphonium/borate products 14a-c. Compounds 11a,b react with carbon monoxide by means of a Lewis
acid induced CO insertion/rearrangement sequence that eventually results in the formation of the macrocyclic dimers
17a,b. The respective carbonylation reaction of the Mes*P/B/B FLP gives the macrocyclic trimer 18c. The new products
were characterized spectroscopically and by X-ray diffraction and the reaction mechanism was analyzed by DFT
calculations.
www.rsc.org/
Introduction
Results and discussion
Macrocyclic compounds have very interesting structural
features.1,2 Many such systems play significant roles in
medicine and biology3-7 and many serve as important chemical
reagents8-12. Macrocyclic ring closure is often difficult to
achieve selectively since ring closure principally competes with
entropically favoured formation of the linear oligomers.
Chemical synthesis of macrocycles, therefore, has relied on a
variety of specific measures in order to achieve the required
chemoselectivity; high dilution is one important and often
used principle13-15 as is template directed synthesis.
Conformational features as well as electrostatic effects may
play a role.16-19 There are some reactions that seem to bear a
“natural” tendency for macrocyclic ring formation.20-28
Alkyl boranes are important building blocks in organic
synthesis. Many such systems are readily available by
convenient hydroboration routes.29-31 Many alkyl boranes
insert carbon monoxide into the boron-carbon bond. This
reaction type has been used for the preparation of CO derived
ketones, aldehydes or alcohols.32 Hydroboration of alkenes
with Piers’ borane [HB(C6F5)2] (
resulting products, such as the respective styrene
hydroboration compound PhCH2CH2B(C6F5)2 ), however, do
2
) occurs readily.33-34 The
(1)
(3
not readily insert CO at ambient conditions (r.t., 1.5 bar CO
pressure, see Scheme 1, see the ESI for details). CO insertion
was not observed even in the presence of additional B(C6F5)3.
The difference is even more pronounced with vicinal P/B
We have now found that Lewis pair formation might favor
intermolecular cyclooligomerization in cases where the direct
internal interaction of the Lewis acid and base functionalities is
effectively precluded by specific geometric restrictions. We
have found that this may selectively lead to cyclodimeric and
frustrated Lewis pairs (FLPs), such as compound
6, which
readily reacts with CO, but does not form the CO insertion
product into the [B]-CH2- linkage but rather undergoes
cooperative 1,1-P/B addition to the carbon atom of carbon
monoxide to yield the CO-bridged product
related P/B FLPs show a similar behavior.35-40
7. A number of
even cyclotrimeric ring systems in
a
rather simple
experimental procedure. First examples will be presented and
discussed in this account.
a.Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster,
Corrensstr. 40, 48149 Münster (Germany). E-mail: erker@uni-muenster.de
b.Mulliken Center for Theoretical Chemistry, Institut für Physikalische und
Theoretische Chemie, Universität Bonn, Beringstr. 4, 53115 Bonn (Germany).
c. Institut für Physikalische Chemie, Westfälische Wilhelms-Universität Münster,
Corrensstr. 28/30, 48149 Münster (Germany).
d.Institute of Physics in Sao Carlos, University of Sao Paulo, CEP 369, Sao Carlos SP
13566-590 (Brazil).
† Electronic Supplementary Informaꢀon (ESI) available: additional experimental
details, further spectral and crystallographic data, additional data from the solid
state NMR and theoretical studies. CCDC deposition numbers are 1549697 to
1549702. See DOI: 10.1039/x0xx00000x
Scheme 1. Behavior of strongly electrophilic pentafluorophenyl containing boranes
toward carbon monoxide.
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We reasoned that this behavior might originate from the very product 14a (Ar: Dmesp) and HB(C6F5)2. The latter was
special properties of the strong B(C6F5)2 Lewis acid unit making removed from the mixture by the hydroboration reaction with
the alkyl migration step to carbon monoxide unfavorable. 1-pentene converting it to pentane soluble pentyl-B(C6F5)2. It
Introduction of a second B(C6F5)2 group into the system might was isolated and identified as its pyridine adduct 15py (for
potentially provide a way out of this behavior: specifically details see the ESI). The heterocycle 14a was eventually
located it could function as an activator for the P/B bonded isolated as a white solid in 78% yield. Its X-ray crystal structure
carbonyl unit and thus initiate the otherwise unfavorable CO analysis (see Figure 1) showed the presence of the chair-
insertion reaction in such systems. This turned out to be a shaped 1,4-P/B heterocycle with tetracoordinated boron and
successful concept and, in addition, it opened an easy pathway the PH(Dmesp) phosphonium unit being part of it. In solution,
to several rather unusually structured macrocyclic ring compound 14a shows a typical borate 11B NMR feature at δ -
systems. Three such examples with some of their remarkable 14.6 and a phosphonium 31P NMR signal at δ 9.0 (1H: δ 5.56,
characteristic features will be reported in this account.
1JPH = 463.0 Hz). The 13C NMR spectrum shows signals of the
1
six-membered core unit at δ 19.0 (PCH2, JPC = 43.1 Hz) and δ
20.8 (broad, BCH2), respectively (see Scheme 3, also see the
ESI for details).
HB(C6F5)2
Ar: Mes*
Mes*P
[B]
ArP
Mes*P
10c
[B]
8aꢀc
9c
2 HB(C6F5)2
[B]H
[B]
[B]
Mes*
H2
PtBu3
Ar: Mes*
P
ArP
[B]
[B]
ArP
HPtBu3
[B]H
H
11a-c
12c
[B]: B(C6F5)2
iPr
tBu
Mes
Scheme 3. Reaction of the P/B/B FLPs 11 with dihydrogen; evidence for facile σ-bond
Mes:
2,4,6ꢀtrimethylꢀ
phenyl
iPr
tBu
metathesis.
Ar :
iPr
tBu
(Mes*)
Mes
(Dmesp)
a
(Tipp)
b
c
Scheme 2. Formation and some previously reported reactions of the P/B/B FLP systems
11.
We have prepared the aryldivinylphosphanes 8a-c by
treatment of the respective ArPCl2 precursors41-47 with two
molar equiv. of vinyl magnesium bromide. We had reported
the reaction of compound 8c with one molar equiv. of
HB(C6F5)2 which had given the unique zwitterionic methylene
phosphonium product 10c via internal B(C6F5)2 addition to the
adjacent vinyl phosphane (see Scheme 2).48 Addition of a
second equiv. of Piers’ borane had given the P/B/B49a-e system
11c, for which we had observed a dynamic equilibrium of the
P···B/B coordination by dynamic 19F NMR spectroscopy (see
Scheme 2).49f We have now also prepared the P/B/B systems
Figure 1. A view of the molecular structure of the P/B/B hydrogenation product 14a
(thermal ellipsoids are shown with 50 % probability). Selected bond lengths (Å) and
angles (°): P1-C1 1.786(3), P1-C3 1.786(3), C1-C2 1.540(4), C3-C4 1.546(5), C2-B1
1.648(5), C4-B1 1.652(5), C1-P1-C3 106.7(2), C2-B1-C4 107.5(3), ΣP1CCC 339.2(5).
11a,b featuring the bulky 2,6-dimesitylphenyl (Dmesp) and
2,4,6-triisopropylphenyl (Tipp) aryl groups at phosphorus,
respectively. Both also feature equilibrating dynamic
structures in solution analogous to the previously described
behavior of 11c. We had shown that the P/B/B system 11c
The P/B/B compounds 11b
,
c
reacted analogously with
. We
dihydrogen with formation of the PH/B products 14b
,
c
isolated them both in ca. 70% yield; both were characterized
by spectroscopy and by X-ray diffraction (see the ESI for
details). We assume a reaction pathway (see Scheme 3) that is
initiated by heterolytic splitting of dihydrogen by using a P/B
pair50-58 of the P/B/B FLP 11 to give the PH+/BH-/B
intermediates 13. We assume that the additional -B(C6F5)2
Lewis acid becomes actively involved and forms the six-
membered P/B heterocycles 14 by a σ-bond metathesis type
reaction59-61 with concomitant formation of HB(C6F5)2. The
t
splits dihydrogen in the presence of the external base Bu3P to
give 12c 49f
.
We have now exposed the small series of P/B/B FLPs 11a-c to
dihydrogen in the absence of the external base and found a
markedly different behavior which indicated a surprising mode
of participation of the extra -B(C6F5)2 Lewis acid. Typically, the
in situ generated system 11a was exposed to a H2 atmosphere
(1.5 bar) in dichloromethane solution for 30 min at r.t. to give
a mixture of the zwitterionic heterocyclic phosphonium/borate
formation of the products 14 and HB(C6F5)2 (2) gave us a
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strong indication of the active role of the additional -B(C6F5)2 energy calculations at the PW6B95-D3 level of theory65,67,68
Lewis acid in the compounds 11. This we used advantageously with a Gaussian AO def2-TZVP basis set.64,66 The COSMO-RS
in the reaction of the P/B/B FLPs 11a
We generated the P/B/B system 11b (Ar: Tipp) in situ (24 h, model62,63 (with toluene as the solvent) was used to compute
r.t., see Scheme 2) and then exposed the solution to a carbon solvation free energies. Endergonic opening of the P———
monoxide atmosphere (1.5 bar, r.t.). After 30 min reaction linkage of 11b yields the reactive P/B/B intermediate 11open
-c
with carbon monoxide
.
(Conductor-like Screening Model for Real Solvents) solvation
B
,
time a white precipitate of the cyclodimeric CO insertion which may undergo the typical 1,1-P/B FLP addition reaction to
product 17b had formed. It was isolated as a white solid in 54 carbon monoxide.35-36 Carbonyl activation by the remaining
% yield (for details see the ESI). Compound 17b is thermally pendent -B(C6F5)2 functionality70-71 via 16A might initiate the
quite stable in solution. However, it lost carbon monoxide kinetically facile and thermodynamically feasible formation of
upon heating for 6h at 80°C in benzene-d6 solution to re-form the CO insertion product32 16B. Isomerization forms the P/B
the starting material 11a
.
Lewis pair. In 16C the direct internal interaction of the
carbonyl oxygen with the pendent borane Lewis acid is
geometrically precluded; the system may serve as an active
C=O/B frustrated Lewis pair. This leads to dimerization giving
the observed macrocyclic reaction product 17b
.
The X-ray crystal structure analysis confirmed the sixteen-
membered cyclodimeric heterocyclic ring structure. The
monomeric units are connected by
a pair of carbonyl
C=O···borane interactions. The remaining boron atoms form
Lewis pair interactions with their adjacent phosphane Lewis
bases. In this situation two diastereoisomers are possible due
to the phosphorus chirality;72-73 we found the near to C2-
symmetric rac-structure in the crystal (see Figure 2, also see
the ESI for details).
In solution, compound 17b shows the NMR features of the
symmetry-equivalent monomeric subunits. We monitored
eight separate 1H NMR sp3-CH signals of the methylene
groups. the 19F NMR signals of four different C6F5 substituents
at boron and a single 31P NMR signal at δ 21.0. From a 13C
labelled sample we located the 13C NMR carbonyl resonance at
Scheme 4. Carbonylation reaction of the P/B/B FLPs 11a,b. with computed reaction
Gibbs free energies at PW6B95-D3/def2-TZVP (COSMO-RS, toluene)//PBEh-3c level of
the theory. The energy of 11b + CO is selected as the reference and all values are given
in kcal mol‒1 at 298 K. The value of the dimer 17b refers to the monomeric subunit for
the purpose of comparability.
δ 269.0.70-71 Compound 17b shows a
ῦ
(CO) = 1588 cm-1
[ῦ
(13CO) = 1547 cm-1] carbonyl stretching band.
The Dmesp substituted P/B/B system 11a reacts analogously
with CO. We isolated the C2-symmetrical dimer 17a in 61%
yield and characterized it by C,H-elemental analysis, by NMR
(10B: δ 7.8, -10.0; 31P: δ 19.1) and IR spectroscopy (
ῦ(CO) =
1579 cm-1) and by X-ray diffraction (for details see the ESI). It is
thermally slightly less stable than 17b. Compound 17a lost CO
upon heating to 50°C (12h) in dichloromethane solution to give
the starting material 11a
.
The carbonylation reaction of the Mes*P/B/B system 11c took
a slightly different course. Exposure of the in situ generated
Mes*P/B/B system 11c to CO (1.5 bar, r.t. 30 min) gave
compound 18c (81% isolated) (see Scheme 5, for details see
the ESI). The compound was stable in the solid state but lost
carbon monoxide with re-formation of the starting material
11c in solution (CD2Cl2). Therefore, the solution NMR data
were monitored using in situ generated samples at low
temperature (for details see the ESI). Single crystals of
compound 18c for the X-ray crystal structure analysis were
Figure 2. A view of the structure of the framework of macrocyclic dimer 17b (the bulky
substituents at boron and phosphorus were omitted for clarity; thermal ellipsoids are
shown with 50 % probability). Selected bond lengths (Å) and angles (°): P1-B1 2.063(2),
B1-C3A 1.632(3), C3A-O1 1.254(2), O1-B4 1.609(2), P2-B3 2.067(2), B3-C3B 1.648(3),
C3B-O2 1.255(2), O2-B2 1.618(2), B1-C3A-O1 120.8(2), C3A-O1-B4 129.6(1), B3-C3B-O2
122.7(2), C3B-O2-B2 130.8(1).
obtained from
a dichloromethane solution in a carbon
monoxide atmosphere at -5oC. Compound 18c shows a
macrocyclic twentyfour-membered core structure. It is
composed of three monomeric subunits that were probably
formed by a CO insertion/ rearrangement sequence analogous
to the one described in Scheme 4; this was supported by DFT
We assume a reaction pathway as it is depicted in Scheme 4,
which was supported by the results of a DFT calculation62-69
(for details see the ESI). All structures were optimized with a
composite DFT method PBEh-3c,69 followed by single point
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calculation (for details see the ESI). The presence of the three Arylphosphanes usually have the C(aryl)-P vector oriented in
phosphorus chirality centers would principally allow for two line with the aryl plane. Very bulky arylphosphanes may
diastereoisomers, an all-cis- (of averaged C3-symmetry) and a deviate from this behavior (which may be expressed by the P1-
cis-,trans-,trans-isomer. The latter structural situation is found C11-C14 angle as schematically shown in Figure 4 for one of
in the crystal of compound 18c. Each of the three symmetry the three Mes*-P units of the trimer 18c). We note an almost
inequivalent but chemically closely related subunits features a co-linear arrangement for the pair of Tipp-P units in the dimer
five-membered P/B containing heterocyclic carbonyl moiety. 17b
. The respective P1-C11-C14 angles for the pair of
The C=O group is used for bridging to the pendent -B(C6F5)2 crystallographically independent Tipp-P subunits were found
Lewis acid of the next monomeric subunit (see Figure 3).
at 174.4° and 173.1°. We find a slightly bent structure for the
more bulky Dmesp-P groups in compound 17a with P1-C11-
C14 angles of 171.0° and 166.2°, respectively, but we note a
rather extreme bending of the Mes*-P moiety. In the Mes*-
PCl2 reagent the P1-C11-C14 type angle amounts to 156°.46 In
the three Mes*-P subunits in our trimer 18c we find this
distortion of the (aryl)C-P moieties being increased further by
ca 10° to P1-C11-C14 values of 144.1°, 147.9°, and 146.1°,
respectively. Figure 4 shows a side-on projection of one out of
the three Mes*-P moieties of compound 18c, which visualizes
this strong distortional effect. This might actually have created
in an overall conformational situation that may have
contributed to determining the observed chemistry of this
system to a considerable extent, especially the specific
association behaviour of the monomeric subunits forming the
Scheme 5. Formation of the cyclotrimeric carbonylation product 18c.
observed cyclotrimer 18c
.
Figure 5. 31P MAS NMR spectra obtained for the C1-symmetric macrocyclic trimer 18c.
Left: (a) 31P{1H} CP/MAS NMR spectrum of 18c with 1H and 11B decoupling, (b) 31P MAS
NMR spectrum with 1H decoupling only and corresponding simulations, based on the
indirect 31P-11B and/or 31P-10B spin-spin interactions. The symbol + marks a suspected
impurity. Right: 31P, 31P{1H}, and 31P{1H,11B} NMR spectra of compound 18c in solution
(CD2Cl2, 203 K).
Figure 3. A view of the core structure of the macrocyclic P/B/B carbonylation trimer 18c
(the substituents at boron and phosphorus are omitted for clarity; thermal ellipsoids
are shown with 15 % probability). Selected bond lengths (Å) and angles (°) of the
molecular: P1-B1 2.096(5), C3A-O1 1.253(5), O1-B6 1.590(6), P3-B5 2.110(5), C3C-O3
1.245(5), O3-B4 1.603(6), P2-B3 2.094(5), C3B-O2 1.239(5), O2-B2 1.625(6), B1-C3A-O1
117.7(4), C3A-O1-B6 133.7(3), B5-C3C-O3 119.6(4), C3C-O3-B4 133.4(3), B3-C3B-O2
118.3(4), C3B-O2-B2 131.9(4).
The solid-state 31P MAS NMR spectra confirmed the
asymmetric (C1) structure of the cyclotrimer 18c containing
three different phosphorus atoms. Consequently, three 31P
NMR signals at 12, 13 and 15 ppm were observed which are
broadened and additionally split by the indirect 31P-11B spin-
spin coupling (1J(31P-11B) ~ 80 Hz). As illustrated in Figure 5 (a),
simultaneous 11B and 1H decoupling enhances the resolution
(see Figure 5, left, for further details including the11B{31P}
REDOR and 2D-INEPT experiments see the ESI). Compound 18c
also showed three equal intensity 31P NMR resonances in
solution (Figure 5, right). It showed 22 different 1H NMR
signals (two with relative intensity two, all others with
intensity one at 243K) of the 12 pairs of diastereotopic CH2
hydrogen atoms as well as 12 methylene 13C NMR signals of
the core ring carbons. There are nine separate 1H NMR t-Bu
Figure 4. Side view of a 2,4,6-tri-tbutylphenyl-P (i.e. Mes*-P) unit of the macrocyclic
trimer 18c. The P1-C11-C14 angle of this unit amounts to 144.1°.
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singlets and the 19F NMR signals of 12 C6F5 groups at the boron introduced by the very bulky aryl Mes* substituent into this
atoms of compound 18c. The 13CO derived isotopologue chemistry.
2
showed three 13C NMR carbonyl signals [δ 273.3 (d, JPC = 23.6 The formation of the macrocyclic dimers and trimers from our
2
Hz), 272.0 d, JPC = 29.9 Hz) and 271.9 d, JPC = 29.9 Hz] (for carbonylated P/B/B FLP systems may place some frustrated
2
details see the ESI).
Lewis pair reactions into the group of macrocyclic ring closure
procedures that show a “natural” tendency of favoring the
internal bond formation in cases of a suitable general design.20-
26
Conclusions
This unique behavior of the carbonylation chemistry of the
P/B/B systems 11 emphasizes the potential that frustrated
Lewis pair chemistry has for discovering surprisingly facile
pathways to unusual products formed under mild reaction
conditions.
It seems that the presence of the additional B(C6F5)2 Lewis acid
function influences the reaction of the internal ethylene-
bridged P/B FLP functionality of the compounds 11 in two
decisive ways: activation of the carbonyl group at the stage of
the conventional cooperative P/B CO addition intermediate
16A35-36 by the reactive boron Lewis acid probably makes the
CO insertion reaction into the adjacent –CH2-B(C6F5)2 group
Acknowledgements
feasible. Our DFT analysis of the CO insertion step of the Financial support from the European Research Council and the
Mes*P/B/B system revealed an exergonic ( G ca -4 kcal mol ) Deutsche Forschungsgemeinschaft (SFB 858; Leibniz Award to
∆
formation of the intermediate 16Bc (the intermediate S.G.) is gratefully acknowledgment.
analogous to 16Bb in the Tipp system shown in Scheme 4). In
contrast the hypothetical CO insertion reaction from Mes*-
(see Scheme 1) was computed by the DFT calculation as
markedly endergonic [ G( ) = 0].
G ca. +11 kcal mol-1, rel.
Once the carbonyl compound is formed by C-C bond formation
it is prone to rearrangement generating monomeric
7
Notes and references
∆
∆ 6
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