Silanediol versus chlorosilanol: Hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

Article abstract of DOI:10.3762/bjoc.15.17

Biphenyl-2,2’-bisfenchyloxydichlorosilane (7, BIFOXSiCl₂) is synthesized and employed as precursor for the new silanols biphenyl-2,2’-bisfenchyloxychlorosilanol (8, BIFOXSiCl(OH)) and biphenyl-2,2’-bisfenchyloxysilanediol (9, BIFOXSi(OH)_2<

Full text of DOI:10.3762/bjoc.15.17

Silanediol versus chlorosilanol: hydrolyses and
hydrogen-bonding catalyses with fenchole-based silanes
Falco Fox1, Jörg M. Neudörfl2 and Bernd Goldfuss*1
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2019, 15, 167–186.
1Department für Chemie, Institut für Organische Chemie,
Greinstrasse 4, 50939 Köln, Germany and 2Department für Chemie,
Institut für Organische Chemie, Greinstrasse 6, 50939 Köln, Germany
doi:10.3762/bjoc.15.17
Received: 26 September 2018
Accepted: 22 December 2018
Published: 18 January 2019
Email:
Bernd Goldfuss* - goldfuss@uni-koeln.de
Associate Editor: M. Rueping
* Corresponding author
© 2019 Fox et al.; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
hydrogen bonds; hydrolysis; ion pairs; organocatalysis; silanediol
Abstract
Biphenyl-2,2’-bisfenchyloxydichlorosilane (7, BIFOXSiCl2) is synthesized and employed as precursor for the new silanols
biphenyl-2,2’-bisfenchyloxychlorosilanol (8, BIFOXSiCl(OH)) and biphenyl-2,2’-bisfenchyloxysilanediol (9, BIFOXSi(OH)2).
BIFOXSiCl2 (7) shows a remarkable stability against hydrolysis, yielding silanediol 9 under enforced conditions. A kinetic study
for the hydrolysis of dichlorosilane 7 shows a 263 times slower reaction compared to reference bis-(2,4,6-tri-tert-
butylphenoxy)dichlorosilane (14), known for its low hydrolytic reactivity. Computational analyses explain the slow hydrolyses of
BIFOXSiCl2 (7) to BIFOXSiCl(OH) (8, Ea = 32.6 kcal mol−1) and BIFOXSiCl(OH) (8) to BIFOXSi(OH)2 (9,
Ea = 31.4 kcal mol−1) with high activation barriers, enforced by endo fenchone units. Crystal structure analyses of silanediol 9 with
acetone show shorter hydrogen bonds between the Si–OH groups and the oxygen of the bound acetone (OH···O 1.88(3)–2.05(2) Å)
than with chlorosilanol 8 (OH···2.16(0) Å). Due to its two hydroxy units, the silanediol 9 shows higher catalytic activity as hydro-
gen bond donor than chlorosilanol 8, e.g., C–C coupling N-acyl Mannich reaction of silyl ketene acetals 11 with N-acylisoquino-
linium ions (up to 85% yield and 12% ee), reaction of 1-chloroisochroman (18) and silyl ketene acetals 11 (up to 85% yield and 5%
ee), reaction of chromen-4-one (20) and silyl ketene acetals 11 (up to 98% yield and 4% ee).
Introduction
Silanediols are attractive target molecules due their hydrogen- groups at the silicon atom are converted by acids (e.g., TFA or
bonding capabilities [1-6]. Two synthetic routes are available TfOH) and following aqueous work-up into silanediols
for syntheses of organosilanediols: If diphenylsilanes are used [2,4,7-11]. Another route employs dichlorosilanes, which
as building blocks, this route is well suited for syntheses of hydrolyze directly with nucleophiles (e.g., water [12-17] or
silanediols with electrophilic functions. In this case, the phenyl hydroxide [18-22]) to the corresponding silanediols. While
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Beilstein J. Org. Chem. 2019, 15, 167–186.
hydrolyses of dichlorosilanes have been studied extensively two new hydrogen bonding scaffolds for anion recognition [37]
[23-25], hydrolyses of alkoxy dichlorosilanes are much less and ion-pair catalysis [6,38]. Since Kondo et al. established
explored.
silanediol 1 [39] as HBD for anion recognition in 2006, new
chiral and achiral silanediols with organosilicon units have been
Hydrogen bond donor (HBD) catalysis is an emerging field in developed by the groups of Franz (2) [40-44] and Mattson (3, 4)
organic synthesis [26-28], employing, e.g., squaramides [29], [45-49] (Figure 1, Scheme 1). While these new catalysts have
(thio)ureas [30,31] and phosphoric acid derivatives [27]. been proven to be potent HBD catalysts, the syntheses are chal-
Cyclodiphosph(V)azanes [32-35] and silanediols [1,28,36] are lenging [47]. Compared to these stable carbon-connected silane-
Figure 1: Hydrogen-bonding silanediols, i.e., di(1-naphthyl)silanediol (1) [39], silanediols 2 [41-43], binaphthylsilanediol derivatives 3 [45,46] and 4
[47,48] and novel biphenyl-2,2’-bisfenchyloxydichlorosilane (7), biphenyl-2,2’-bisfenchyloxychlorohydroxysilane (8) and biphenyl-2,2’-bisfenchyloxysi-
lanediol (9) with precursor BIFOL (5) [52] and phosphite derivative BIFOP-Cl (6) [53].
Scheme 1: Hydrogen-bond-catalyzed N-acyl Mannich reaction of in situ-generated isoquinolin derivative 10 with different silyl ketene acetals 11
yielding C–C coupling product 12 [45,47].
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Beilstein J. Org. Chem. 2019, 15, 167–186.
diols, the readily accessible alkoxy silanediols undergo fast con-
densation reactions which often lead to unknown and insoluble
polysiloxanes [50,51].
Table 1: Hydrolysis of BIFOXSiCl2 (7) to BIFOXSi(OH)2 (9)
(Scheme 3) in different solvent mixtures, with or without KOH at differ-
ent temperatures.
yielda [%] in solvent:
Previously, our group reports syntheses and applications of
symmetric biphenyl-2,2`-bisfenchol (5, BIFOL, Figure 1)
[52,54] and it´s derivative, the chiral chlorophosphite ligand 6
(BIFOP-Cl, Figure 1), e.g., in Cu-catalyzed 1,4-additions [53],
in Pd-catalyzed alkyl–aryl cross coupling reactions [55,56], as
well as for organoaluminum fencholate reagents [57]. Unex-
pected stability against hydrolysis [58] makes BIFOL (5) a
potentially promising chiral backbone for new organo silicates,
e.g., silanediol 9 (Figure 1). As a silicic acid ester, silanediol 9
should show increased acidity in comparison to C–Si(OH)2
derivates, e.g., 1–4 [40]. In this work the syntheses of
a)
b)
c)
d)
T
H2O H2O/KOH H2O/THF
H2O/THF/KOH
20 °C
50 °C
refluxb
<1
<1
<1
<1
<1
<1
<1
32
84
14
64
53
aIsolated yields, reaction conditions: 0.09 mmol 7, 2.5 mL solvent,
0.9 mmol KOH, H2O/THF 1:1. breflux conditions are: H2O ≈ 100 °C,
H2O/KOH ≈ 107 °C, H2O/THF ≈ 77 °C, H2O/THF/KOH ≈ 80 °C.
BIFOXSiCl2 (7), BIFOXSi(OH)2 (9) and BIFOXSiCl(OH) (8) nucleophile to yield BIFOXSi(OH)2 (9) at 20 °C (14% yield,
are described. The hydrolytic stability of dichlorosilane 7 is in- Table 1, Scheme 3d). By increasing the temperature to 50 °C
vestigated in a kinetics study and is compared to analogue the hydrolysis increases, resulting in 32% yield in H2O/THF
dichlorosilanes, i.e., 13 and 14 (Scheme 4). UV–vis titration ex- and 64% yield in H2O/THF/KOH (Table 1, Scheme 3).
periments and catalyses are carried out with chlorosilanol 8 and
silanediol 9, to assess catalytic and anion binding characteris-
tics.
Results and Discussion
Enantiopure dichlorosilane 7 is readily accessible by lithiation
of BIFOL (5) [28,52,54,59] and subsequent reaction with tetra-
chlorosilane (92% yield, Scheme 2).
Scheme 2: Synthesis of BIFOXSiCl2, starting with BIFOL (5) [52,54]
yielding dichlorosilane 7.
Unlike the hydrolysis of BIFOP-Cl (6) to BIFOP-OH, the
dichlorosilane 7 is not hydrolyzed by aqueous potassium
Scheme 3: Hydrolysis of BIFOXSiCl2 (7) yielding the corresponding
silanediol 9 and controlled hydrolysis of BIFOXSiCl2 (7) to
hydroxide solution [53]. The heterolytic reaction of solid
BIFOXSiCl(OH) (8). For solvent mixtures and temperatures see
Table 1.
BIFOXSiCl2 (7) in an aqueous KOH solution is negligible
(<1% yield, Table 1, Scheme 3 in a) H2O and b) H2O/KOH).
The reluctance against hydrolysis of BIFOXSiCl2 (7) can be ex-
plained by the hydrophobic aryl backbone and the fenchyl
groups, which result in a decrease of the solubility of
BIFOXSiCl2 (7) in water. Thus, a H2O/THF mixture is used to
increase solubility and yields (Table 1, Scheme 3c). While the
solubility of BIFOXSiCl2 (7) in H2O/THF greatly increases
(clear solution), potassium hydroxide is needed as a strong
At reflux conditions in H2O/THF, but without potassium
hydroxide, BIFOXSi(OH)2 (9) is isolated in 89% yield, while
with KOH, just 53% yield is achieved (Table 1). The lower
yield of silanediol 9, at H2O/THF/KOH reflux conditions, can
be explained by the further hydrolysis to BIFOL (5, Scheme 3).
Under the conditions described in Table 1, the monohydroxy
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Beilstein J. Org. Chem. 2019, 15, 167–186.
compound BIFOXSiCl(OH) (8) cannot be isolated as an inter-
mediate. For the synthesis of chlorosilanol 8 optimized reaction
conditions are necessary. Here, 1 equiv of water and 2 equiv of
triethylamine (relative to dichlorosilane 7) are added to a THF
solution at 20 °C. BIFOXSiCl(OH) (8) is isolated in 67% yield
(Scheme 3).
Hydrolysis studies
To assess the stability of dichlorosilane 7, its hydrolysis
relative to established silanediol motifs, i.e., di-tert-
butoxydichlorosilane (((CH3)3CO)2SiCl2) [50], di(1-naphthyl)-
dichlorosilane (13) [39] and bis(2,4,6-tri-tert-butylphenoxy)di-
chlorosilane (14) [60,61] is examined (Scheme 4). In close
analogy to BIFOXSiCl2 (7), di-tert-butoxydichlorosilane is
substituted with tertiary alkoxy groups. While the close analogy
of BIFOXSiCl2 (7) and ((CH3)3CO)2SiCl2 would make a com-
parison of these two dichlorosilanes preferable, the instability of
the latter against hydrolyses and temperature resulting in further
condensation products [50,51], leaves no comparison possible.
Scheme 4: Hydrolysis of dichlorosilanes 13 and 14 to their corre-
sponding silanediols 1 and 15 [51,60].
At H2O/THF reflux conditions, the hydrolysis of dichlorosilane
13 yields silanediol 1 with >99% yield, after a reaction time of tions (H2O/THF reflux) resulting in >99% yield after 100 min
two seconds (Scheme 4, addition of H2O, with instant extrac- (Figure 2, red squares). The hydrolysis of dichlorosilanes 7 and
tion with Et2O). The stability of dichlorosilane 14, which has 14 to the corresponding silanediols 9 (Scheme 3) and 15
been previously reported by Spirk et al. [60], has been found to (Scheme 4) is investigated further (Figure 2). The conversion of
be higher than that of dichlorosilane 13 under the same condi- dichlorosilane 14 to silanediol 15 is completed (yield >99%)
Figure 2: Hydrolyses of dichlorosilane 7 and 14 to BIFOXSi(OH)2 (9, green circle) and bis(2,4,6-tri-tert-butylphenoxy)silanediol (15, red square) in
H2O/THF reflux and BIFOXSi(OH)2 (9, blue triangle) in H2O/THF/KOH reflux conditions. Isolated yields are plotted against reaction time (Table 1,
Scheme 3 and Scheme 4). Reflux conditions are: H2O/THF ≈ 77 °C, H2O/THF/KOH ≈ 80 °C.
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Beilstein J. Org. Chem. 2019, 15, 167–186.
after 100 minutes at H2O/THF reflux conditions (Figure 2, red To remove the influence of the decomposition of silanediol 9,
square). The hydrolysis of BIFOXSiCl2 (7) on the other hand is just the reaction time from 0 to 600 min is considered. Com-
slower at the same conditions (24 h for 84% yield of pared to established dichlorosilanes, the observed stability of
BIFOXSi(OH)2 (9, Figure 2, green circle). With H2O/THF/ BIFOXSiCl2 (7) is clearly apparent from those studies (Figure 2
KOH reflux conditions the initial reaction is found to be slightly and Figure 3). Dichlorosilane 14, which is known to show a
faster, but resulting in a saturation at a lower yield of comparably high resistancy against hydrolysis [60], exhibits a
BIFOXSi(OH)2 (9, Figure 2, blue triangle, 70% yield), caused much faster hydrolysis reaction (krel = 263 min−1, Table 2) at
by a starting decomposition of BIFOXSi(OH)2 (9) to BIFOL (5) H2O/THF reflux conditions than BIFOXSiCl2 (7). With KOH,
and Si(OH)4 (Scheme 3). To quantify the reactivity of the the reaction rate of the hydrolysis of BIFOXSiCl2 (7) is just
dichlorosilanes 7 and 14, a higher concentration of water (sol- slightly increased (krel = 1.5 min−1, Table 2).
vent) or hydroxide (10 equiv) is used (Table 2), resulting in a
pseudo first order reaction.
Computational analyses
Nucleophilic substitution at silicon is already discussed with
SN2 mechanism, following a backside attack opposite of the
leaving group, as well as a front side attack near the leaving
group [62-68]. A backside attack at the silicon in dichlorosilane
7 and monochlorosilanol 8 is blocked by the backbone, making
a consideration of the mechanism not necessary. A mechanism
with a pentacoordination at the silicon is assumed for the hydro-
lyses of BIFOXSiCl2 (7) to BIFOXSiCl(OH) (8) as intermedi-
ate and BIFOXSI(OH)2 (9) as product [65-67]. Two pathways
(front attack mechanism (front) or side attack mechanism
(side)) for the approaching water molecule are considered
(Scheme 5).
Table 2: Hydrolyses of dichlorosilanes 7 and 14 to the corresponding
silanediols 9 and 15 (Figure 3, Scheme 3 and Scheme 4, absolute
reaction constant k and relative reaction constant krel).
reaction
ka [min−1]
krelb [min−1]
14 H2O/THF refluxc
7 H2O/THF/KOH refluxc
7 H2O/THF refluxc
0.848
0.005
0.003
263
1.5
1
ak is determined with ln ([A0]/[At]) = k * t and plotted in Figure 3. bkrel is
normalized on the slowest hydrolysis reaction of BIFOXSiCl2 (7) in
H2O/THF reflux conditions (Scheme 2, Scheme 3). cReflux conditions
are: H2O/THF ≈ 77 °C, H2O/THF/KOH ≈ 80 °C.
Figure 3: Hydrolyses of BIFOXSiCl2 (7) to BIFOXSi(OH)2 (9, green circle), bis(2,4,6-tri-tert-butylphenoxy)dichlorosilane (14) to bis(2,4,6-tri-tert-
butylphenoxy)silanediol (15, red square) in H2O/THF reflux and BIFOXSiCl2 (7) to BIFOXSi(OH)2 (9, blue triangle) H2O/THF/KOH reflux conditions
(Scheme 3 and Scheme 4). Reaction constants are evaluated with ln ([A0]/[At]) = k·t for a pseudo-first-order reaction plotted against reaction time
(Table 2). Reflux conditions are: H2O/THF ≈ 77 °C, H2O/THF/KOH ≈ 80 °C.
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Beilstein J. Org. Chem. 2019, 15, 167–186.
Geometry optimizations and frequency computations are per-
formed in gas phase with B3LYP-D3BJ/6-31G(d) at 298 K. For
single point energies, M06-2X-D3/6-311++G(d,p) in the sol-
vent THF with the PCM model is used [69,70]. The free Gibbs
energies of the respective structures are discussed. The activa-
tion energy (Ea) is the difference between the educt and the TS
and the reaction energy (Er) is the difference between the educts
and products of the respective steps. The mechanism of hydro-
lysis, only one molecule of water per hydrolysis step is consid-
ered. Additional interactions by THF and water are only consid-
ered by the PCM model. Starting with BIFOXSiCl2 (7), the side
and front1 attack mechanism are resulting in BIFOXSiCl(OH)
8eq. The front2 attack mechanism results in BIFOXSiCl(OH)
8ax (Figure 5).
For the TS of the front1 attack mechanism, the lowest activa-
tion energy (Ea = 32.6 kcal mol−1, Table 3, entry 1, Figure 5
and Figure 6) is found, closely followed by the front2 attack
mechanism (Ea = 33.2 kcal mol−1, Table 3, entry 2, Figure 5
and Figure 7). The side attack mechanism leads to the highest
TS for the first hydrolysis step of BIFOXSiCl2 (7) to
BIFOXSiCl(OH) 8eq (Ea = 37.3 kcal mol−1, Table 3, entry 3,
Figure 5 and Figure 8). BIFOXSiCl(OH) 8ax is found to
Scheme 5: Two investigated pathways for the hydrolysis of the
dichlorosilanes. Front attack mechanism (front) between the two chloro
substituents or side attack mechanism (side) between one chloro and
both additional substituents (TS = transition structure) [62-68].
In both, front attack and side attack, the attacking water mole- be the more stable isomer with a reaction energy Er of
cule is in plane with the Cl–Si–Cl unit for the first hydrolysis −4.4 kcal mol−1, compared to BIFOXSiCl(OH) 8eq with a Er of
step. For the second hydrolysis step, analogue pathways −1.7 kcal mol−1 (ΔEr = 2.7 kcal mol−1, Table 3, entries 1 and 2,
are considered. These trajectories lead to three transition struc- Figure 5), as it is found as the only isomere in crystal structure
tures each, for the hydrolysis of BIFOXSiCl2 (7) and analysis (Figure 13). For the second hydrolysis step from
BIFOXSiCl(OH) (8, Figure 4).
BIFOXSiCl(OH) 8ax to BIFOXSi(OH)2 (9), the side attack
Figure 4: Three transition structures each, for the hydrolysis of BIFOXSiCl2 (7) and BIFOXSiCl(OH) (8) considering two possible configuration
isomers of BIFOXSiCl(OH) (8). For 8ax the OH group is parallel situated to the biaryl axis. For 8eq the OH group is orthogonal oriented to the biaryl
axis. The fenchyl groups are abbreviated with (*) for more clarity.
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Figure 5: Computed hydrolyses of BIFOXSiCl2 (7) to BIFOXSiCl(OH) 8ax and BIFOXSiCl(OH) 8eq and subsequent computed hydrolysis to
BIFOXSi(OH)2 (9) and comparison with glycoxydichlorosilane. The activation energy (Ea) is the difference of the free Gibbs energy of the educt and
the TS and the reaction energy (Er) is the difference the free Gibbs energies of the educts and products of the respective steps side and front1 result-
ing in BIFOXSiCl(OH) 8eq, front2 results in BIFOXSiCl(OH) 8ax. From BIFOXSiCl(OH) 8eq only front2 is a possible path to BIFOXSi(OH)2 (9). From
BIFOXSiCl(OH) 8ax front1 and side are possible paths to BIFOXSi(OH)2 (9, Table 3, Figure 4, Scheme 5). Reaction energies are (Er) in kcal mol−1,
activation energies are (Ea) in kcal mol−1 and italic.
Table 3: Computeda activation energies and reaction energies (Ea and Er [kcal mol−1]) and imaginary frequencies (ν [cm−1]) of the transition struc-
ture (TS) for the hydrolysis of dichlorosilane 7, 8, 13, [CH2O]2SiCl2 and SiCl4 to the corresponding mono- and diols.
entry
reaction
TS
ν
Ea
Er
1b
2
7 to 8eq
TSfront1 7
TSfront2 7
–206.23
–221.44
–189.66
–208.01
–242.41
–162.28
–167.52
–176.02
–137.30
−119.75
–542.44
–189.64
–415.78
–209.82
–145.49
–128.55
32.6
33.2
37.3
33.4
40.2
31.4
27.7
35.4
29.1
29.9
23.6
21.1
28.4
25.0
20.9
20.8
−1.7
−4.4
−1.7
−5.3
−5.3
−5.3
−1.1
−1.1
1.5
7 to 8ax
3
7 to 8eq
TSside 7
4
8ax to 9
TSfront1 8ax
TSfront2 8eq
TSside 8ax
TSfront 13
TSside 13
5
8eq to 9
6b
7b
8
8ax to 9
13 to 13ClOH
13 to 13ClOH
9b
10
11
12
13
14
15
16
13ClOH to 1
TSfront 13ClOH
TSside 13ClOH
13ClOH to 1
1.5
[CH2O]2SiCl2 to [CH2O]2SiClOH
[CH2O]2SiClOH to [CH2O]2Si(OH)2
Cl2SiCl2 to Cl2SiClOH
Cl2SiClOH to Cl2Si(OH)2
(OH)2SiCl2 to (OH)2SiClOH
(OH)2SiClOH to (OH)2Si(OH)2
−4.0
−4.7
−5.4
−9.3
−3.4
−4.8
aM06-2X-D3/6-311++G(d.p)(PCM=THF)//B3LYP-D3BJ/6-31G(d) at 298 K. bFavored reaction structures are bolted.
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Beilstein J. Org. Chem. 2019, 15, 167–186.
mechanism leads to the lowest TS (Ea = 31.4 kcal mol−1, dotted lines in TSfront2 7, Figure 7, five dotted lines in TSfront1
Table 3, entry 6, Figure 5, Figure 9), followed by the front1 7, Figure 6).
attack mechanism (Ea = 33.4 kcal mol−1, Table 3, entry 4,
Figure 5, Figure 10) leading to product BIFOXSi(OH)2 (9).
From BIFOXSiCl(OH) 8eq only the front attack mechanism
TSfront2 8eq is possible, which also leads to BIFOXSi(OH)2 (9),
but with the highest Ea (40.2 kcal mol−1, Table 3, entry 5,
Figure 5 and Figure 11). In accordance with the crystal struc-
ture analysis of BIFOXSiCl(OH) (8, Figure 13), it can be seen
that the more stable isomer BIFOXSiCl(OH) 8ax corresponds to
the synthesized isomer. Considering the lowest Ea for both
steps, the first hydrolysis step is the rate-determining step (7 to
8eq, TSfront1 7 Ea = 32.6 kcal mol−1 vs 8ax to 9, TSside 8ax
Ea = 31.4 kcal mol−1, Table 3, entries 1 and 6, Figure 6 and
Figure 9), which agrees with the experimental hydrolysis.
Under H2O/THF reflux conditions, no BIFOXSiCl(OH) (8) has
been isolated, but has to be synthesized separately (Scheme 3,
Figure 2 and Figure 3). Both front attack TS have much lower
energy, than the TS resulting by side attack mechanism, for the
Figure 7: Transition state leading to 8ax following front2 attack
(Ea = 33.2 kcal mol−1, Figure 5, Table 3, entry 2). Breaking and
first hydrolysis step (TSfront2 7 Ea = 33.2 kcal mol−1, TSfront1 7
Ea = 32.6 kcal mol−1 vs TSside 7 Ea = 37.3 kcal mol−1, Table 3,
entries 1–3, Figures 6–8). Responsible for the lower Ea is an ad-
ditional stabilization by an interaction of the remaining chloro
atom to the attacking water (dotted line to the Cl(ax) Figure 6
forming bonds in dashed lines, additional C–H-interactions with dotted
lines (M06-2X-D3/6-311++G(d,p)(PCM=THF)//B3LYP-D3BJ/6-31G(d)
at 298 K).
and Cl(eq) Figure 7). The small energy difference for the Through the approach of the attacking water molecule in the
TSfront1 7 and TSfront2 7 is to explained by additional C–H inter- side attack mechanism, the chloro atoms are forced to get closer
actions between the fenchyl groups to the leaving chloride (four to each other leading to electrostatic repulsion (Figure 8). Stabi-
lizing C–H interaction from the fenchyl group to the exiting
chloride can be found as well (one dotted line in TSside 7,
Figure 8).
At the second step, the side mechanism leads to a lower energy
barrier (TSside 8ax Ea = 31.4 kcal mol−1, Table 3, entry 6,
Figure 9) than the front attack mechanisms (TSfront1 8ax
Ea = 33.4 kcal mol−1, TSfront2 8eq Ea = 40.2 kcal mol−1,
Table 3, entries 4 and 5, Figure 10 and Figure 11). In the former
mechanism the chloro atom comes closer to the already present
hydroxy group (Figure 9).
A contact between the OH(ax) and the Cl(eq) is found, in addi-
tion to the C–H interaction (dotted line, Figure 9), which stabi-
lized the leaving Cl ion with a weak hydrogen bond. In the front
attack mechanisms for the second hydrolytic step only stabi-
lizing C–H interactions from the fenchyl group to the chloro
atom occur (dotted line, Figure 10 and Figure 11).
Figure 6: Transition state leading to 8eq following front1 attack
(Ea = 32.6 kcal mol−1, Figure 5, Table 3, entry 1). Breaking and
forming bonds in dashed lines, additional C–H-interactions with dotted
The highest energy barriers of the computed molecules are
found for BIFOXSiCl2 for the first step (Ea = 32.6 kcal mol−1,
lines (M06-2X-D3/6-311++G(d,p)(PCM=THF)//B3LYP-D3BJ/6-31G(d)
at 298 K).
Ea = 33.2 kcal mol−1, Ea = 37.3 kcal mol−1, Table 3, entries
1–3, Figures 6–8) and for BIFOXSiCl(OH) (8) for the second
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Beilstein J. Org. Chem. 2019, 15, 167–186.
Figure 8: Transition state leading to 8eq following side attack
(Ea = 37.4 kcal mol−1, Figure 5, Table 3, entry 3). Breaking and
forming bonds in dashed lines, additional C–H-interactions with dotted
lines (M06-2X-D3/6-311++G(d,p)(PCM=THF)//B3LYP-D3BJ/6-31G(d)
at 298 K).
Figure 10: Transition state leading to 9 following front1 attack
(Ea = 33.4 kcal mol−1, Figure 5, Table 3, entry 4). Breaking and
forming bonds in dashed lines, additional C–H-interactions with dotted
lines (M06-2X-D3/6-311++G(d,p)(PCM=THF)//B3LYP-D3BJ/6-31G(d)
at 298 K).
Figure 9: Transition state leading to 9 following side attack
(Ea = 31.4 kcal mol−1, Figure 5, Table 3, entry 6). Breaking and
forming bonds in dashed lines, additional C–H-interactions with dotted
lines (M06-2X-D3/6-311++G(d,p)(PCM=THF)//B3LYP-D3BJ/6-31G(d)
at 298 K).
Figure 11: Transition state leading to 9 following front2 attack
(Ea = 40.2 kcal mol−1, Figure 5, Table 3, entry 5). Breaking and
forming bonds in dashed lines, additional C–H-interactions with dotted
lines (M06-2X-D3/6-311++G(d,p)(PCM=THF)//B3LYP-D3BJ/6-31G(d)
at 298 K).
step (Ea = 33.4 kcal mol−1, Ea = 31.4 kcal mol−1,
Ea = 40.2 kcal mol−1, Table 3, entries 4–6, Figures 9–11),
which also confirms the kinetics study of BIFOXSiCl2 (7) and
BIFOXSiCl(OH) (8) as the most stable dichlorosilane and Table 3, entry 8). The second hydrolysis, 13ClOH to 1 has a
chlorosilanol (Figure 2 and Figure 3, Table 2). In comparison higher energy barrier (Ea = 29.1 kcal mol−1 for front attack
the front attack mechanism for dichlorosilane 13 mechanism (Table 3, entry 9) and Ea = 29.9 kcal mol−1 for side
(Ea = 27.7 kcal mol−1, Table 3, entry 7) has a lower energy attack mechanism (Table 3, entry 10)) than the first. In accor-
barrier than side attack mechanism (Ea = 35.4 kcal mol−1, dance with the kinetic study, dichlorosilane 13 hydrolysed
175

Beilstein J. Org. Chem. 2019, 15, 167–186.
faster than BIFOXSiCl2 (7, Scheme 4). In addition, the hydroly- A hydrogen bridge is a displacement of electrons (lp or π) from
sis of glycol-based dichlorosilane (Table 3, entries 11 and 12) a donor into the σ* orbital of an H–X bond. NBO analyses can
and tetrachlorosilane (Table 3, entries 13 to 16) is computed as be used to calculate the energy of such an interaction. With the
model system. The first hydrolytic step of SiCl4 has a higher shift of the electron density of a lone pair into the σ* orbital, the
energy barrier (Ea = 28.4 kcal mol−1, Table 3, entry 13) than 13 O–H bond of the HB donor is weakened. This causes a change
to 13ClOH (Ea = 27.7 kcal mol−1, Table 3, entry 7) and 13ClOH in the O–H stretching frequency of the bond. A strong hydro-
to 1 (Ea = 29.1 kcal mol−1, Table 3, entry 9). The glycol-substi- gen bridge results from strong lone pair···σ* orbital interactions,
tuted dichlorosilane has a smaller energy barrier to the TS resulting in a weakening of the O–H bond, which in turn results
(Ea = 23.6 kcal mol−1, Table 3, entry 11, Figure 5 and in a decrease of the O–H stretching frequency [71]. An alterna-
Ea = 21.1 kcal mol−1, Table 3, entry 12, Figure 5). The step- tive method is to determine the relaxed force constant [72].
wise hydrolysis of tetrachlorosilane shows that the energy In the following, the stretching frequency und the NBO
barrier for the first step is higher (Ea = 28.4 kcal mol−1, Table 3, analyses were calculated for different acceptors and water
entry 13), than the second step (Ea = 25.0 kcal mol−1, Table 3, (Table 4).
entry 14). With two hydroxy substituents, the energy barrier for
the third TS is Ea = 20.9 kcal mol−1 (Table 3, entry 15) and for The silanol group is a better hydrogen bond acceptor than an
the fourth step (Ea = 20.8 kcal mol−1, Table 3, entry 16). For the alcohol group for single hydrogen bonds (CH3OH
computed values, it should be noted that THF is used for the (11.88 kcal mol−1) vs SiH3OH (16.43 kcal mol−1), Table 4,
PCM solvent correction, but the reactions are carried out in a entries 1 and 2), which is more acidic and inconsistent with the
1/1 mixture of water/THF.
results of West et al. [73]. In case of double hydrogen bonds in
Table 4: Computeda stretching frequencies (ν [cm−1]), lp···σ* [kcal mol−1] and donor acceptor distances (D [Å]) of silanes 7, 8, [CH2O]2SiCl(OH),
[CH2O]2Si(OH)2, (OH)2SiCl(OH), Si(OH)4, methanol and [CH2O]2C(OH)2.
entry
νO-H
[cm−1]
lp-σ* energy
[kcal mol−1]
D O···X
[Å]
1
2
3
CH3-OH···OH2
SiH3-OH···OH2
3741
3602
11.88
16.43
2.785
2.793
Si(OH)3-OH···OH2
H2O···OH-Si(OH)3
3441
3608
20.39
12.05
2.732
2.797
4
5
SiCl(OH)2-OH···OH2
H2O···OH-SiCl(OH)2
3450
3649
19.44
7.78
2.727
2.862
SiCl(OH)2-OH···OH2
SiCl(OH)2-OH···OH2
H2O···Cl-Si(OH)3
3725
3701
3832
6.78
6.82
1.58
2.865
2.863
2.804
6
(CH2)2O2Si-(OH)2···OH2
3745b
3717b
3691c
7.62
7.59
2.855
2.857
7
(CH2)2O2SiCl-OH···OH2
H2O···Cl-Si(OH)O2(CH2)2
3377
3819c
3707b
22.16
1.58
2.705
3.331
8
(CH2)2O2C-(OH)2···OH2
(CH2)2O2C-(OH)2···OH2
H2O···O2(CH2)2C(OH)2
3678c
3631c
3604c
6.57
8.69
8.96
2.844
2.816
2.715
9
BIFOXSiCl-OH···OH2
BIFOXSi(OH)-Cl···H2O
3445
3691b
3811c
24.90
5.19
2.734
3.273
10
BIFOXSi(OH)2···OH2
3733b
3703c
3685c
9.73
10.15
2.878
2.834
11
12
BIFOXSiCl-OH···Cl-
BIFOXSi(OH)2···Cl-
3165
36.87
2.994
3421
3151
17.36
33.61
3.082
2.927
13
BIFOXSi(OH)2 – dimer
3670
3490
7.55
21.63
2.880
2.752
aComputed with B3LYP-D3BJ/6-31G(d) at 298 K; bsymmetric stretching frequency νs; casymmetric stretching frequency νas.
176

Beilstein J. Org. Chem. 2019, 15, 167–186.
the glyoxal based system, both are equally strong, because of a
third hydrogen bond, a rebond from where water is the acceptor
and the oxygen in the ring is the donor ((CH2)2O2Si(OH)2
(15.21 kcal mol−1) vs (CH2)2O2C(OH)2 (15.26 kcal mol−1),
Table 4, entries 6 and 8), Two possible geometries can be ob-
served for SiCl(OH)3. On the one hand with two hydrogen
bridges to water (13.60 kcal mol−1, Table 4, entry 5) or with
one hydrogen bridge to water (19.44 kcal mol−1, Table 4, entry
4), with an additional rebond of the oxygen of one of the SiOH
groups to water H–O (7.78 kcal mol−1, Table 4, entry 4). The
trend of the stronger single hydrogen bridge compared to the
double hydrogen bridge is also reflected in the systems glycolic
(22.16 kcal mol−1 vs 15.21 kcal mol−1, Table 4, entries 6 and 7)
and BIFOSi (24.90 kcal mol−1 vs 19.88 kcal mol−1, Table 4,
entries 9 and 10). As was to be expected, the energies of the
O–H bonds decreases with increasing lone pair···σ* orbital
interactions (3502 cm−1 to 22.16 kcal mol−1 vs 3830 cm−1 to
3.06 kcal mol−1, Table 4, entries 5 and 7). With a stronger elec-
tron donor, as the chloride ion, the lone pair···σ* orbital interac-
tions rises (36.87 kcal mol−1 vs 50.97 kcal mol−1, Table 4,
entries 11 and 12). In here, the BIFOXSi(OH)2 (9) binds the
chlorid stronger with two hydrogen bridges, than
BIFOXSiCl(OH) (8) with just one hydrogen bridge. The
BIFOXSi(OH)2 (9) dimer forms hydrogen bridges, which are
stronger than hydrogen bridges with water, but less stronger
than hydrogen bridges to chloride (50.97 kcal mol−1 vs
29.18 kcal mol−1 vs 19.88 kcal mol−1, Table 4, entries 13, 12,
and 10).
Figure 12: X-ray crystal structure of BIFOXSiCl2 (7). H atoms on the
chiral backbone are omitted for clarity issues and the ellipsoids are
shown with 65% probability.
X-ray analyses
Dichlorosilane 7 (Figure 12), as well as chlorosilanol 8
(Figure 13) crystallize as monomers from n-hexane.
BIFOXSiCl(OH) (8) is obtained as the 8ax isomer, which is
computed to be the more stable isomer (Table 3, entry 1).
Since the commercially available (+)-fenchone has 98% enan-
tiomeric purity, BIFOXSi(OH)2 can be further purified. rac-
BIFOXSi(OH)2 crystallizes as a dimer from toluene
(Figure 14). BIFOXSi(OH)2 (9) crystallizes as a tetramer from
n-hexane (Figure 15), where six OH groups build a network of
hydrogen bonds. Thus the polar core is shielded against the sol-
vent (Figure 15). For silanediols 2a and 2b (Figure 1) dimeric
structures are reported as well [41-44]. In these, hydrogen bond
lengths of 1.86 Å to 2.01 Å (H···O) and 2.65–2.80 Å (O–H···O)
are observed. Bond angles vary from 157.3° to 174.3° for the
hydrogen bonds between the silanediols [41-44]. In the dimeric
and tetrameric structure of BIFOXSi(OH)2 (9, Figure 14 and
Figure 15) those distances are 1.82(4) Å to 2.02(4) Å (H···O)
and 2.66(4) Å to 2.79(5) Å (O–H···O) with angles between
152,4(6)° and 172,0(7)° (Table 5). These distances indicate me-
dium strong hydrogen bonds [74].
Figure 13: X-ray crystal structure of BIFOXSiCl(OH) (8). H atoms on
the chiral backbone are omitted for clarity issues and the ellipsoids are
shown with 65% probability.
177

Beilstein J. Org. Chem. 2019, 15, 167–186.
Chlorosilanol 8 binds one acetone with a bonding length of
2.16(0) Å (H3···O4) and 2.89(4) Å (O3–H···O4) (Table 5,
Figure 17), which is the longest hydrogen bond for
BIFOXSiCl(OH) (8) and BIFOXSi(OH)2 (9). In dimeric struc-
tures of silanediol 9 (Figure 14) the hydroxy group O4H is a
hydrogen bond donor to O3. The hydrogen atom of the O–H
group (O3H) is pointing outwards and can form a hydrogen
bond to an additional molecule. For silanediols 2a and 2b Franz
et al. observed hydrogen bond distances of 1.88 Å (H···O) and
2.68 Å (O–H···O) on average to guest molecules [41-44].
BIFOXSi(OH)2 (9, Figure 16) binds an acetone in a similar
manner (O4’–H···O4–H···O6=C(CH3)2) with distances of
1.88(3) Å (H4···O6) and 2.62(1) Å (O4–H···O6) as well as
2.05(2) Å (H4···O4’) and 2.73(1) Å (O4–H···O4’) between the
hydroxy groups. The second acetone is bonded with one
hydroxy group of each of the BIFOXSi(OH)2 (9) with longer
distances of 2.03(0) Å (H···O) and 2.80(3) Å (O–H···O)
(Table 5). Similarly to the previously reported silanediol deriva-
tives 2a and 2b [43], an increase of acidity of one outward
facing OH group is achieved by intermolecular hydrogen bonds
[43].
Figure 14: X-ray crystal structure ofrac-BIFOXSi(OH)2 (9) forming
dimers. H atoms on the chiral backbone are omitted for clarity issues
and the ellipsoids are shown with 65% probability. For bond lengths
and angles see Table 5.
X-ray structures of BIFOXSi(OH)2 (9, Figure 16) and Chloride binding
BIFOXSiCl(OH) (8, Figure 17) with co-crystallized acetone in- The X-ray crystal structures of chlorosilanol 8 (Figure 17) and
dicate the bonding behavior of the silanediols to carbonyl silanediol 9 (Figure 16) with co-crystallized acetone indicate the
acceptors.
ability of binding ions or molecules via hydrogen bonds. To in-
Figure 15: X-ray crystal structure of BIFOXSi(OH)2 (9) forming a tetramer. H atoms on the chiral backbone are omitted for clarity issues and the ellip-
soids are shown with 65% probability. For bond lengths and angles see Table 5.
178

Beilstein J. Org. Chem. 2019, 15, 167–186.
Table 5: Bond lengths and angles of hydrogen bonds in X-ray crystal structures of BIFOXSiCl(OH) (8) and BIFOXSi(OH)2 (9).
D–H···A
D (D···A)a [Å]
2.76(1)
D (H···A)b [Å]
1.92(0)
(D-H···A) [°]
170.0(5)
BIFOXSi(OH)2 (9)
(Figure 14)
O4H–O3
BIFOXSi(OH)2 (9)
(Figure 15)
O4H–O3’
O4’H–O4’’
O4’’H–O4
O3H–O3’’
O3’’H–O4’’’
O4’’’H–O3
2.76(2)
2.73(5)
2.66(4)
2.68(3)
2.79(9)
2.74(7)
1.98(0)
1.95(0)
1.82(4)
1.85(8)
2.02(1)
2.02(4)
163.7(4)
172.0(7)
165.5(0)
168.9(8)
152.4(6)
165.9(3)
BIFOXSi(OH)2 (9)
(Figure 16)
O3H–O5
O4H–O4’
O4H–O6
2.80(3)
2.73(1)
2.62(1)
2.03(0)
2.05(2)
1.88(3)
161.1(8)
176.2(8)
146.3(6)
BIFOXSiCl(OH) (8)
O3H–O4
2.89(4)
2.16(0)
167.1(8)
(Figure 17)
aDistance for hydrogen bond donor (D) to hydrogen bond acceptor (A). bDistance for hydrogen (H) to hydrogen bond acceptor (A).
vestigate this ability, UV–vis titration experiments with tetra- Counter ion catalyses
butylammonium chloride (TBA-Cl) are carried out, with silane- The N-acyl Mannich reaction of isochinolin (16), which is acti-
diol 1 as a reference (Table 6) [47,75]. For BIFOXSi(OH)2 (9, vated with 2,2,2-trichloroethoxycarbonyl chloride (17, TrocCl)
Figure 14, Figure 15) a binding constant of 5274.9 M−1 (13%) to carbamate 10, and different silyl ketene acetals 11a–d
for chloride is determined, which is in the same order as di(1-
naphthyl)silanediol (1, Figure 1) with 4688.0 M−1 (5%,
Table 6). The binding constant of chlorosilanol 8 (Figure 13)
for chloride is 451.1 M−1 (4%). Thus chlorosilanol 8 and silane-
diol 9 are feasible for anion binding of chloride.
Figure 16: X-ray crystal structure of BIFOXSi(OH)2 (9) forming a
dimeric structure with two bridged acetone molecules. H atoms on the
chiral backbone are omitted for clarity issues. The acetone on the
upper side is disordered by 50%. Ellipsoids are shown with 65% prob-
ability. For bond lengths and angles see Table 5.
Figure 17: X-ray crystal structure of BIFOXSiCl(OH) (8), binding an
acetone molecule. H atoms on the chiral backbone are omitted for
clarity issues and the ellipsoids are shown with 65% probability. For
bond lengths and angles see Table 5.
179

Beilstein J. Org. Chem. 2019, 15, 167–186.
In DCM the highest yield is isolated, but that is due to a fast
background reaction [45]. With toluene as solvent, no back-
ground reaction is observed (Table 9, entry 9). To stabilize and
improve the ion pair, polar solvents are tested as diethyl ether
and dimethylformamide gave no conversion and starting materi-
al is obtained (Table 7, entries 4 and 5), acetonitrile and ace-
tone increase the yield (Table 7, entries 6 and 7), but without
any enantiomeric excess. In toluene, BIFOXSi(OH)2 (9), forms
43% yield at −80 °C and 5% ee (Table 7, entry 8). At higher
temperature, 12 is isolated with 52% yield and 12% ee (−60 °C,
Table 6: Chloride binding constants (K [M−1], error (%)) to
BIFOXSiCl(OH) (8), BIFOXSi(OH)2 (9) and di(1-naphthyl)silanediol (1)
in HCCl3 at 22 °C [75].
8
9
1
binding constanta 451.1 (4%) 5274.9 (13%) 4688.0 (5%)
aCalculated for 1:1 binding mode between chloride and hydrogen bond
donor [75].
yielding product 12 (Scheme 6) [45,47], is studied. Mattson et Table 7, entry 9). Further aromatic solvents are tested (Table 7,
al. proposed a mechanism where the chloride ion is abstracted entries 10–13), but without any improvement in yield or ee.
from 10 and binds via hydrogen bonding to the catalyst
(Scheme 6) [45,47]. This leads to an ion pair [cat•Cl]− and
Table 7: N-acyl Mannich reaction of 10 and 11c catalyzed by silane-
[isoquinolinium cation]+ (Scheme 6). The nucleophilic silyl
ketene acetal reacts with the [isoquinolinium cation]+ and forms
the C–C bond, yielding product 12 (Scheme 6).
diol 9 yielding product 12 with different solvents (Scheme 6)a.
entry solvent
T [°C]
yield [%]b ee [%]c
1
n-hexane
DCM
−60
−60
−30
−60
0
–
2
87
33
0
0
3
1.2-DCE
diethyl ether
0
4
–
5
dimethylformamide −40
0
–
6
acetonitrile
acetone
−40
−80
−80
–60
rt
35
10
43
52
10
<1
40
0
1
7
0
8
toluene
5
9
toluene
12
1
10
11
12
13
benzene
m-xylene
nitrobenzene
pyridine
−60
rt
12
0
−30
–
aReactions carried out with 20 mol % 9, 0.1 mmol 16, 0.11 mmol 17
and 0.15 mmol 11c in 4 mL solvent; bisolated yields; cchiral
HPLC OD-H, n-hexane/iPrOH 90:10, 1 mL/min, 220 nm, 25 °C, (−)-12
correlates to (S)-12 [45,76].
Variation of the catalyst loading suggests a ratio of 10 mol % of
BIFOXSi(OH)2 (9, Table 8, entries 1–4) to be optimal. An
increase of temperature results in decreasing yields and ee
(Table 8, entries 5–8). The highest ee is found with 20 mol %
catalyst (12% ee, 52% yield, Table 7, entry 9).
Scheme 6: Hydrogen-bond-catalyzed N-acyl Mannich reaction of in
situ-generated 10 with different silyl ketene acetals 11 a–d and
BIFOXSi(OH)2 (9) yielding C–C coupling product 12 (Tables 6–8);
(TMS: trimethylsilane. TES: triethylsilane. TIPS: triisopropylsilane.
TBDMS: tert-butyldimethylsilane).
BIFOXSi(OH)2 (9) performs better than BIFOXSiCl(OH) (8)
which is in accordance with the determined binding constant for
chloride (Table 6, Table 9). With BIFOXSiCl(OH) (8) a yield
up to 60% is isolated (Table 9, entry 3), but as racemate.
The reactivity and stability of such an ion pair depend on the BIFOXSi(OH)2 (9) catalyses the reaction with good yields up to
employed solvent. For this reaction and BIFOXSi(OH)2 (9) as 73% and an ee value of 12% (Table 9, entry 7). For 11a, b and
catalyst, several solvents are tested (Table 7). In a nonpolar sol- d and silanediol 9 as catalyst, an enantiomeric inversion is ob-
vent like n-hexane, no catalytic activity is observed (Table 7, served (Table 9, entries 5, 6 and 8).
entry 1). In halogenated solvents as dichloromethane (DCM)
and 1,2-dichloroethane (1,2-DCE) the reaction takes place but The substrate scope is broadened with 1-chloroisochroman (18)
without any enantiomeric excess (ee) (Table 7, entries 2 and 3). as alternative substrate (Table 10). The reaction mechanism is
180

Beilstein J. Org. Chem. 2019, 15, 167–186.
Table 8: Different catalyst loadings of BIFOXSi(OH)2 (9) and different
temperatures in the N-acyl Mannich reaction of 10 and 11c yielding
product 12 (Scheme 6)a.
Table 10: Hydrogen-bond-catalyzed addition of silyl ketene acetals
11a–d with 1-chloroisochroman (18) to product 19 with chlorosilanol 8
and silanediol 9 in different solventsa (Scheme 7).
entry cat loading [mol %]
T [°C] yield [%]b ee [%]c
entry cat. solvent
SiR3
yield [%]b ee [%]c
1
2
3
4
5
6
7
8
20
10
5
−80
−80
−80
−80
−60
−40
0
43
52
12
2
5
7
0
2
5
7
1
0
1
9
9
9
9
9
9
9
9
8
8
8
8
–
–
toluene
MTBE
THF
11a TMS
11a TMS
11a TMS
0
–
–
–
–
1
3
5
3
0
2
5
3
–
–
2
0
3
0
1
4
diethyl ether 11a TMS
0
10
10
10
10
37
18
9
5
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
11a TMS
11b TES
11c TIPS
11d TBDMS
11a TMS
11b TES
11c TIPS
85
37
12
8
6
7
rt
20
8
9
54
46
16
aReactions carried out with 0.1 mmol 16, 0.11 mmol 17 and 0.15 mmol
11c in 4 mL toluene; bisolated yields, cchiral HPLC OD-H, n-hexane/
iPrOH 90:10, 1 mL/min, 220 nm, 25 °C, (−)-12 correlates to (S)-12
[45,76].
10
11
12
13
14
11d TBDMS 12
11a TMS
11c TIPS
58
5
aReactions carried out with 0.15 mmol 18, 0.22 mmol 11a–d and
20 mol % cat in 1.2 mL solvent at −60 °C; bisolated yields; cchiral
HPLC OD-H, n-hexane/iPrOH 100:0, 1.0 mL/min, 210 nm, 25 °C,
(−)-18 correlates to (S)-18 [77].
Table 9: Performance of catalyst 8 and 9 in the N-acyl Mannich reac-
tion with 10 and different silyl ketene acetals 11a–d and yielding in 12
(Scheme 6)a.
entry catalyst
SiR3
yield [%]b
ee [%]c
analogue to the N-acyl Mannich reaction (Scheme 6 vs
Scheme 7). The catalyst abstracts and binds the chloride anion
and forms an ion pair [cat•Cl]− and oxocarbenium ion [18]+.
Silyl ketene acetal 11 reacts with this ion pair complex to prod-
uct 19 [77,78]. Only with DCM as solvent, product 19 of the
reaction has been isolated (Table 10). Silanediol 9 and silyl
ketene acetal 11a provide the highest yield (85%, Table 10,
entry 5). The substitution pattern on the silyl ketene has a direct
influence on the yield.
1
2
3
4
5
6
7
8
9
8
8
8
8
9
9
9
9
–
11a TMS
11b TES
11c TIPS
56
42
60
3 S-12
4 S-12
4 S-12
2 S-12
6 R-12
2 R-12
12 S-12
2 R-12
–
11d TBDMS 46
11a TMS
11b TES
11c TIPS
73
67
52
11d TBDMS 72
11c TIPS
0
aReactions carried out with 0.1 mmol 16, 0.11 mmol 17, 0.15 mmol
11a–d and 20 mol % cat in 4 mL toluene at −60 °C; bisolated yields;
cchiral HPLC OD-H, n-hexane/iPrOH 90:10, 1 mL/min, 220 nm, 25 °C,
(−)-12 correlates to (S)-12 [45,76].
The highest yield is reached with TMS substitution (silanediol
9, 85% yield, Table 10, entry 5; chlorosilanol 8, 54% yield,
Table 10, entry 9). The yield decreases as the substituents
Scheme 7: Hydrogen-bond-catalyzed nucleophilic substitution of 18 with BIFOXSi(OH)2 (9) and nucleophile silyl ketene acetals 11. 18 and 9 form an
activated electrophile ion pair complex which yields C–C coupling product 19 (Table 10).
181

Beilstein J. Org. Chem. 2019, 15, 167–186.
become larger (Table 10, entries 6–8, 10 and 11). This trend can
also be seen in the uncatalyzed reaction (Table 10, entries 13,
14). Only for 11c and silandiol 9 a considerable ee with 5% is
determined (Table 10, entries 7 and 11). Chlorosilanol 8 does
not show catalytic activity for the reaction of 18 with 11a, as
the background reaction is slightly faster (54% vs 58%,
Table 10, entries 9 and 13). With increasing of the steric
demand of the nucleophilic silyl group, the background reac-
tion slows down and chlorosilanol 8 has a positive influence on
the yields and the enantiomeric excess.
In a third reaction, the 1,4 addition of silyl keten acetals 11 to
chromone 20 is investigated (Table 11, Scheme 8). Chromone
20 is first transformed to the oxonium ion pair 21. Catalyst
BIFOXSi(OH)2 (9) binds the triflate anion via hydrogen bond-
ing and leaves the pyrylium derivative 21 for the nucleophilic
attack of silyl keten acetals 11 to form product 22 (Scheme 8).
With BIFOXSi(OH)2 (9) an increase of yield (71% yield,
4% ee, Table 11, entry 2) compared to the not catalyzed reac-
tion (48%, Table 11, entry 10) is achieved. BIFOXSiCl(OH) (8)
has no activation ability, but little effect on the ee (46% yield,
1% ee, Table 11, entry 6). Here, the sterically demanding silyl
keten acetals increase yields. With BIFOXSi(OH)2 (9), the
Scheme 8: Nucleophilic substitution of 20 with BIFOXSi(OH)2 (9) and
nucleophile silyl ketene acetals 11, 20 and 9 form an activated electro-
phile ion pair complex which yields C–C coupling product 22
(Table 11).
bulkiest acetal 11d yields 98% and the smallest 11a yields 60% BIFOXSi(OH)2 (9), which results in a lower yield and ee
of product 22 (Table 11, entries 1–4). This tendency is the same (Table 11, entry 9).
for BIFOXSiCl(OH) (8, Table 11, entries 5–8), with exception
of acetal 11a, which yields 55% of product 22. Mattson et al. Conclusion
used 2,6-di-tert-butyl-4-methylpyridine as additive [48]. It is Enantiopure fenchole-based silanediol BIFOXSi(OH)2 (9,
added at the beginning to the reaction, so it should support the Figure 1) and chlorosilanol BIFOXSiCl(OH) (8, Figure 1) are
formation of the ion pair 21. As organic base it binds also to efficiently accessible from BIFOL (5) via enforced hydrolysis
of dichlorosilane 7, i.e., H2O/THF reflux, 19 h (Scheme 3,
Figure 2).
Table 11: Hydrogen-bond-catalyzed addition of silyl ketene acetals
11a–d with chromone 20 to product 22 with chlorosilanol 8 and silane-
diol 9 in toluenea (Scheme 8).
DFT computations reveal two different hydrolysis mechanisms
and explain the unusual low reactivity of BIFOXSiCl2 (7) and
entry catalyst
SiR3
yield [%]b ee [%]c
BIFOXSiCl(OH) (8, Table 3) with sterically demanding endo
fenchone groups. For BIFOXSiCl(OH) (8) two isomers (8eq vs
8ax) are found computationally. Chlorosilanol 8ax, with the
axial Si–OH alignment, is the thermodynamically more stable
isomer (ΔEr = 2.7 kcal mol−1, Table 3), in accordance with
X-ray crystal structure analyses of 8 (Figure 13). The first
hydrolysis has a higher activation barrier than the second step,
and thus appears to be rate-determining.
1
9
9
9
9
8
8
8
8
9
–
11d TBDMS
11c TIPS
11b TES
98
71
69
60
70
46
35
55
50
48
1
4
1
0
0
1
1
1
2
–
2
3
4
11a TMS
11d TBDMS
11c TIPS
11b TES
5
6
7
8
11a TMS
11c TIPS
11c TIPS
9d
10e
In the X-ray crystal structures of BIFOXSiCl(OH) (8,
Figure 13) and BIFOXSi(OH)2 (9, Figures 14–16), intermolecu-
lar hydrogen bonds are apparent. The lengths of these hydrogen
bonds vary from 1.88(3) to 2.16(2) Å (Table 5). The longest
bond appears between BIFOXSiCl(OH) (8) and acetone
(Figure 17). This suggests that BIFOXSiCl(OH) (8) is the
aReactions carried out with 0.15 mmol 20, 0.22 mmol 11a–d and
20 mol % cat in 4 mL toluene at −80°C; bisolated yields; cchiral HPLC
AD-H, n-hexane/iPrOH 98:2, 1 mL/min, 254 nm, 25 °C, (+)-22 corre-
lates to (S)-22 [48]; dwith 20 mol % 2.6-di-tert-butyl-4-methylpyridine
as additive for step 1 (Scheme 8); ewithout catalyst.
182

Beilstein J. Org. Chem. 2019, 15, 167–186.
weaker hydrogen bond donor, compared to BIFOXSi(OH)2 (9). purification with silica gel flash column chromatography
This is additionally supported by UV–vis titrations of chloride (100% n-hexane, Rf: 0.58) BIFOXSiCl2 (7) was obtained as a
with BIFOXSiCl(OH) (8, 451.1 (4%) M−1) and BIFOXSi(OH)2 white solid (2.5 g, 4.6 mmol, 92%); mp 219.4 °C;
(9, 5274.9 (13%) M−1, Table 6).
[α]43620 = −54.90 (c 0.46, CHCl3); 1H NMR (300 MHz, CDCl3,
25 °C, TMS) δ 7.61 (dd, J = 8.1, 1.1 Hz, 2H), 7.26–7.19 (m,
Both new hydrogen bond catalysts can be used for the C–C cou- 2H), 7.14–7.06 (m, 2H), 6.97 (dd, J = 7.7, 1.6 Hz, 2H),
pling in the N-acyl Mannich reaction with activated isochinolin 2.46–2.32 (m, 4H), 1.72–1.60 (m, 4H), 1.56 (s, 6H), 1.46–1.35
10, 1-chloroisochroman (18) and chromone 21 with different (m, 4H), 1.25 (td, J = 5.2 Hz, 2H), 0.64 (s, 6H), 0.49 (s, 6H);
silyl ketene acetals. Due to more efficient bifunctional Si(OH)2- 13C NMR (75 MHz, CDCl3, 25 °C, TMS) δ 143.20, 141.37,
hydrogen bonding, silandiol 9 tops chlorosilanol 8, also on cata- 136.14, 128.83, 125.06, 124.63, 94.59, 55.33, 50.19, 48.39,
lytic application.
44.06, 35.91, 28.89, 23.47, 20.80, 20.74; 29Si NMR (60 MHz,
CDCl3, 25 °C, TMS) δ −21.92.
Computational Details
In this work computations were performed using GAUSSIAN Synthesis of BIFOXSiCl(OH) (8): In a dried Schlenk flask
09 [79]. Geometry optimizations and frequency computations BIFOXSiCl2 (7, 1 g, 1.8 mmol, 1 equiv) was solved in THF
were performed at the B3LYP-D3BJ/6-31G(d) level of theory. (10 mL). Then triethylamine (0.52 mL, 3.6 mmol, 2 equiv) and
Zero-point energies were scaled by 0.96 [80]. Single point ener- H2O (0.032 mL, 1.8 mmol, 1 equiv) was added. The reaction
gies were performed at the M06-2X-D3/6-311++G(d,p) level of mixture was stirred for 20 h at 20 °C and concentrated in vacuo.
theory using the PCM method.
The residue was purified by silica gel flash column chromatog-
raphy (n-hexane/ethyl acetate: 9:0.5, Rf: 0.43) which resulted in
BIFOXSiCl(OH) (8, 642.6 mg, 1.2 mmol, 67%) as a white solid
Experimental
General considerations: All reactions were carried out under and BIFOXSi(OH)2 (9, 90.6 mg. 0.1 mmol. 6%) as a white
an argon atmosphere by using Schlenk techniques, unless other- solid; mp 105.7–112.5 °C; [α]58920 = −3.24 (c 0.658, CHCl3);
wise stated. Solvents used in chemical conversions were dried 1H NMR (300 MHz, CDCl3, 25 °C, TMS) δ 7.73 (d, J = 8.0 Hz,
by standard methods and distilled under argon prior to use 1H), 7.61 (dd, J = 7.6, 1.7 Hz, 1H), 7.35–7.17 (m, 4H), 7.03 (t,
unless otherwise specified. NMR spectra were recorded on a J = 7.3 Hz, 1H), 6.72 (dd, J = 7.8, 1.5 Hz, 1H), 2.66–2.48 (m,
Bruker Avance II 300 instrument. UV–vis spectra were re- 2H), 2.40 (s, 1H), 2.31 (d, J = 10.5 Hz, 1H), 1.72 (s, 3H), 1.61
corded by using a Perkin Elmer Lambda35 spectrometer. The (s, 5H), 1.52 (s, 3H), 1.51–1.20 (m, 6H), 0.90 (s, 3H), 0.82 (s,
samples were placed in quartz cells of 1 cm path length. NMR 3H), 0.45 (s, 3H), 0.08 (s, 3H); 13C NMR (75 MHz, CDCl3, 25
spectra, UV–vis spectra, crystal data and the coordinates of °C, TMS) δ 145.10, 144.39, 142.08, 140.14, 137.33, 133.86,
computed stationary points/transition states, as well as experi- 129.25, 129.05, 128.23, 125.63, 125.25, 124.60, 123.70, 92.83,
mental details can be found in Supporting Information File 1. 92.25, 56.38, 54.22, 50.96, 49.57, 49.31, 46.78, 43.87, 43.78,
CCDC-1833170 (BIFOXSiCl2 (7)), CCDC-1833171 35.80, 35.02, 29.45, 28.36, 23.86, 23.42, 22.28, 21.49, 20.63,
(BIFOXSiCl(OH) (8)), CCDC-1833172 (BIFOXSi(OH)2 (9, 19.33, 19.18; 29Si NMR (60 MHz, CDCl3, 25 °C, TMS) δ
dimer)), CCDC-1833173 (BIFOXSi(OH)2 (9, tetramer)), −21.93; MS (HRMS ESI) m/z: [M + Na]+ calcd for
CCDC-1833174 (BIFOXSiCl(OH) 8·acetone) and CCDC- C32H41O3ClNaSi, 559.2405; found, 559.2404 (−0.1 ppm).
1833175 (BIFOXSi(OH)2 9·acetone) contain the supplemen-
tary crystallographic data for this paper. These data can be ob- Synthesis BIFOXSi(OH)2 (9): In a dried Schlenk flask
tained free of charge from The Cambridge Crystallographic BIFOXSiCl2 (7, 1 g, 1.8 mmol, 1 equiv) was solved in THF
Data Centre via http://www.ccdc.cam.ac.uk/data_request/cif. (25 mL) and H2O (25 mL). The solution was heated to reflux
and stirred overnight. Then the solution was concentrated in
Synthesis of BIFOXSiCl2 (7): In a dried Schlenk flask BIFOL vacuo and purified by silica gel flash column chromatography
(5, 2.3 g, 5 mmol. 1 equiv) was solved in THF (25 mL) in an (n-hexane/ethyl acetate 9:1, Rf: 0.26). BIFOXSi(OH)2 (9) was
inert gas atmosphere. After cooling to 0 °C, n-BuLi (4 mL, obtained as white solid (0.78 g, 1.5 mmol, 84%); mp 199.4 °C;
10 mmol, 2 equiv, 2.5 M in n-hexane) was slowly added. The [α]58920 = 24.02 (c 0.769, CHCl3); 1H NMR (300 MHz, CDCl3,
solution was stirred for 30 min und was allowed to warm up to 25 °C, TMS) δ 7.60 (d, J = 8.0 Hz, 2H), 7.20 (td, J = 7.8, 1.7
20 °C. After cooling to 0 °C again tetrachlorosilane (2.86 mL, Hz, 2H), 7.07 (td, J = 7.5, 1.1 Hz, 2H), 6.95 (dd, J = 7.7, 1.5
25 mmol, 5 equiv) was added dropwise. The reaction mixture Hz, 2H). 2.48–2.19 (m, 4H), 2.03 (d, J = 2.5 Hz, 2H), 1.70–1.57
was warmed to 20 °C and stirred overnight. Aqueous work-up (m, 4H), 1.49 (s, 6H), 1.43–1.30 (m, 4H), 1.18 (td, J = 12.5,
with saturated NH4Cl followed by extracting with Et2O (three 4.8 Hz, 2H), 0.59 (s, 6H), 0.45 (s, 6H); 13C NMR (75 MHz,
times) and concentrated in vacuo results in crude product. After CDCl3, 25 °C, TMS) δ 144.28, 141.97, 135.16, 128.80, 124.70,
183

Beilstein J. Org. Chem. 2019, 15, 167–186.
124.17, 90.24, 55.04, 50.08, 48.11, 43.98, 35.33, 29.01, 23.65, dried toluene under inert gas atmosphere. TIPSOTf (29.5 μL,
20.85, 19.76; MS (HRMS ESI) m/z: [M + Na]+ calcd for 0.11 mmol, 1.1 equiv) was added and heated to 60 °C for 1 h.
C32H42O4NaSi, 541.2744; found, 541.2742 (−0.4 ppm); After this, the reaction mixture was cooled to −80 °C, catalyst
29Si NMR (60 MHz, CDCl3, 25 °C, TMS) δ −21.92.
(0.02 mmol, 0.2 equiv) and silyl ketene acetal 11 (0.14 mmol,
1.25 equiv), solved in 2 mL dried toluene, were added. The re-
General procedure for the hydrolysis studies of dichlorosi- sulting reaction mixture was stirred for 4 h. The reaction was
lanes 7, 13 and 14: Dichlorosilane (0.09 mmol) was solved in quenched by adding 3 M HCl (0.2 mL), concentrated in vacuo
THF (2.5 mL) or THF/H2O (1.25 mL/1.25 mL). For THF/H2O/ and purified by silica gel flash column chromatography
KOH conditions, KOH (0.9 mmol, 50.5 mg, 10 equiv) was (n-hexane/ethyl acetate 9:1). The enantiomeric excess is deter-
added. The reaction mixture was heated and stirred as stated. mined by chiral HPLC analysis (see Supporting Information
After the reaction time the mixture was extracted two times File 1).
with diethyl ether (2 mL) and concentrated in vacuo. The
residue was solved in THF (5 mL). A sample (0.5 mL) was
Supporting Information
transferred to a GC vial and n-tetradecane solution (0.01 M in
THF, 0.5 mL) was added as standard for GC analysis.
Supporting Information File 1
Copies of all NMR spectra, HPLC graphs, GC graphs of
General procedure for the N-acyl Mannich reaction of iso-
quinolin 16 with silyl ketene acetals 11 to product 12: In a
heat dried Schlenk tube isoquinolin (16, 11 μL, 0.1 mmol,
1 equiv) was solved in solvent (4 mL) and cooled to 0 °C under
inert gas atmosphere. To this solution 2,2,2-trichlorethoxycar-
bonyl chloride (15 μL, 0.11 mmol, 1.1 equiv) was added. The
cooling was removed. The solution warmed to 20 °C and stirred
for 30 min. After this the solution was cooled to reaction tem-
perature. The catalyst was added and stirred for 10 minutes.
Then silyl ketene acetall 11 (0.15 mmol, 1.5 equiv) was added
and the reaction mixture stirred for 6 h. The reaction was
quenched by adding NaOMe (0.2 mL, 0.5 M in MeOH), filtered
through silica gel with ethyl acetate as eluent and concentrated
in vacuo. After further purification by silica gel flash column
chromatography (n-hexane/ethyl acetate 95:5) product 12 was
obtained. The enantiomeric excess is determined by chiral
HPLC analysis (see Supporting Information File 1).
the kinetic study.
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-15-17-S1.pdf]
Acknowledgements
We thank the Fonds der Chemischen Industrie, the Deutsche
Forschungsgemeinschaft (DFG GO-930-13), Bayer AG, BASF
AG, Wacker AG, Evonic AG, Raschig GmbH, Symrise GmbH,
Solvay GmbH, the OMG group, and INEOS-Köln for support.
We also thank the computing center of the University of
Cologne (RRZK) for providing CPU time on the DFG-funded
supercomputer CHEOPS, as well as for support. Special thanks
go to Niklas Kolks and Matthias Spilles for their contributions
during their practical courses.
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