Lithium-titanium exchange of tertiary α-sulfonyl carbanions: Synthesis, structure, dynamics and reactivity of bis(1-sulfonylalkyl) titaniums

Article abstract of DOI:10.1002/ejoc.201402896

Lithium-titanium exchange of tertiary α-sulfonyl carbanions with ClTi(OiPr)₃ and Cl₂Ti(OiPr)₂ in diethyl ether gave bis(1-sulfonylalkyl) titaniums and not the corresponding (1-sulfon-ylalkyl) titaniums. X-ray crystal structure analysis of di(iso-propoxy) bis[1-(phenylsulfonyl) cyclobutyl]titanium and di-(isopropoxy) bis[1-(phenylsulfonyl) isopropyl]titanium showed asymmetric distorted octahedral complexes, having hexaco-ordinate Ti atoms, two C-Ti bonds, four Ti-O bonds, and two four-membered Ti-O-S-C_α rings. According to ¹H NMR spectroscopy bis(1-sulfonylcycloalkyl) titaniums are non-flux-ional at room temperature. This suggests that chiral bis(1-sulfonylalkyl) titaniums should be configurationally stable. The bis(1-sulfonylalkyl) titaniums are stable at room temperature towards β-H elimination. They selectively add to benzaldehyde in the presence of acetophenone but do not react with methyl iodide. The reaction of tertiary acyclic α-sulfonyl carbanions with ClTi(OiPr)₃ in tetrahydrofuran (THF) gives different titanium derivatives with unspecified structures, which not only selectively react with benzaldehyde in the presence of acetophenone but are also alkylated by methyl iodide.

Full text of DOI:10.1002/ejoc.201402896

FULL PAPER
DOI: 10.1002/ejoc.201402896
Lithium–Titanium Exchange of Tertiary α-Sulfonyl Carbanions: Synthesis,
Structure, Dynamics and Reactivity of Bis(1-sulfonylalkyl)titaniums
Thomas Heß,[a,b] Gerhard Raabe,[a] and Hans-Joachim Gais*[a]
Keywords: Alkylation / Carbanions / Lithium / Titanium / Chemoselectivity / Structure elucidation
Lithium–titanium exchange of tertiary α-sulfonyl carbanions
with ClTi(OiPr)3 and Cl2Ti(OiPr)2 in diethyl ether gave bis(1-
sulfonylalkyl)titaniums and not the corresponding (1-sulfon-
ylalkyl)titaniums. X-ray crystal structure analysis of di(iso-
propoxy)bis[1-(phenylsulfonyl)cyclobutyl]titanium and di-
(isopropoxy)bis[1-(phenylsulfonyl)isopropyl]titanium showed
sulfonylalkyl)titaniums should be configurationally stable.
The bis(1-sulfonylalkyl)titaniums are stable at room tempera-
ture towards β-H elimination. They selectively add to benzal-
dehyde in the presence of acetophenone but do not react
with methyl iodide. The reaction of tertiary acyclic α-sulfonyl
carbanions with ClTi(OiPr)3 in tetrahydrofuran (THF) gives
asymmetric distorted octahedral complexes, having hexaco- different titanium derivatives with unspecified structures,
ordinate Ti atoms, two C–Ti bonds, four Ti–O bonds, and two
four-membered Ti–O–S–Cα rings. According to 1H NMR
spectroscopy bis(1-sulfonylcycloalkyl)titaniums are non-flux-
ional at room temperature. This suggests that chiral bis(1-
which not only selectively react with benzaldehyde in the
presence of acetophenone but are also alkylated by methyl
iodide.
sess a higher configurational stability and chemoselectivity
than 3 because of the Cα–Ti bond. Lithium α-sulfonyl carb-
anions are important intermediates in organic synthesis,[13]
and the availability of the chiral titanium derivatives 4 could
significantly add to their synthetic utility. In contrast to 1
and 2, knowledge about the Li–Ti exchange of 3 and precise
information about the structure and reactivity of (1-sulfon-
ylalkyl)titaniums is scarce.[3,14–17] For example, titanation of
the primary carbanion 3 (R1 = R2 = H, R3 = Ph) with
ClTi(OiPr)3 gave, according to reactivity studies[14] and 13C
NMR spectroscopy,[3,15] a Cα–Ti bonded titanium deriva-
tive, the precise structure of which was, however, not estab-
lished. X-ray crystal structure analysis and NMR spec-
troscopy had shown that the reaction of similar primary
Introduction
Lithium–titanium exchange of stabilised carbanions is a
valuable technique that can be used to gain selectivity in
reactions with electrophiles.[1] Some time ago, we and others
studied the Li–Ti exchange of dilithium α-sulfonyl dicarb-
anions 1[2–5] and lithium α-sulfonimidoyl carbanions 2[6–10]
(Figure 1). Titanation of 1 and 2 yields Cα–Ti bonded tita-
nium complexes, which possess synthetically valuable reac-
tivities and exhibit interesting fluxional behaviour. In a con-
tinuation of these studies, we became interested in the Li–
Ti exchange of tertiary α-sulfonyl carbanions 3 (R1, R2 =
alkyl, aryl). Chiral carbanions 3, carrying two different
alkyl groups or an alkyl and an aryl group at the Cα atom
and a tert-butyl or trifluoromethyl group at the S atom,
are accessible in enantiopure form through stereoselective
deprotonation of the corresponding chiral sulfones.[11,12]
Reactions of 3 with electrophiles are highly stereoselective.
However, carbanions 3 are configurationally stable only at
low temperatures. At elevated temperatures, they undergo
fast racemisation through rotation around the Cα–S bond
and Cα inversion. This precludes, for example, isolation of
3 in non-racemic form and their utilisation in reactions with
electrophiles at elevated temperatures. The corresponding
central chiral (sulfonylalkyl)titaniums 4 are expected to pos-
[a] Institute of Organic Chemistry, RWTH Aachen University,
Landoltweg 1, 52074 Aachen, Germany
E-mail: gais@rwth-aachen.de
http://www.oc-rwth-aachen.de/akgais/akgais_d.html
[b] Present address: Jaspertstrasse 5 H, 60435 Frankfurt, Germany
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402896.
Figure 1. Lithium α-sulfonyl and α-sulfonimidoyl carbanions and
titanium derivatives.
7134
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 7134–7147

Lithium–Titanium Exchange of Bis(1-sulfonylalkyl)titaniums
carbanion 3 (R1 = R2 = H, R3 = Tol), with Cl2TiCp2, fur- of the corresponding titanium derivatives by 1H NMR
nishes the corresponding Cα–Ti bonded (1-sulfonylalkyl)- spectroscopy. Finally, the S-phenyl carbanions were selected
titanium.[17]
A
13C NMR spectroscopic investigation of the to study the influence of a sterically less demanding group
Li–Ti exchange of the secondary carbanion 3 (R1 = H, R2 at the S atom upon the Li–Ti exchange and to gain infor-
= SiMe3, R3 = Ph) with ClTi(OiPr)3 provided evidence for mation about the scope and limitations of the process. All
C-titanation. In contrast, a similar study of the Li–Ti ex- acyclic carbanions carried alkyl groups of different sizes at
change of the tertiary carbanion 3 (R1 = Et, R2 = SiMe3, the anionic C atom to determine their influence upon the
R3 = Ph), revealed the absence of a C-titanation and Li–Ti exchange. The lithium carbanions 3a–h and 5a–c
pointed to O-titanation.[3,18] The only explicit information were synthesised from the corresponding sulfones 8a–h and
about the Li–Ti exchange of a tertiary α-sulfonyl carbanion 7a–c upon treatment with nBuLi in tetrahydrofuran (THF)
concerns the cyclopropylsulfonyl anion 5a. Titanation of 5a and diethyl ether.[11,20–23]
with ClTi(OiPr)3 afforded the bis(1-sulfonylcyclopropyl)-
Titanation of the cyclobutyl anion 5b with 1.1 equiv.
titanium 6a and not, as expected, the corresponding (1-sulf- ClTi(OiPr)3 in diethyl ether at –50 °C to room temperature
onylcyclopropyl)titanium derivative.[15] The structure of 6a gave bis(1-sulfonylcyclobutyl)titanium 6b (Scheme 2), which
was secured by X-ray crystal structure analysis and by was isolated through crystallisation from n-hexane in 47%
NMR spectroscopy.
yield. Similar treatment of the cyclopentyl anion 5c with
The reactivity of (1-sulfonylalkyl)titaniums has been less ClTi(OiPr)3 in diethyl ether afforded bis(1-sulfonylcy-
explored than the Li–Ti exchange of 3. The titanium species clopentyl)titanium 6c, which was isolated in 59% yield
derived from the primary carbanion 3 (R1 = R2 = H, R3 = through crystallisation from n-hexane. Bis(1-sulfonylcy-
Ph), was found to selectively react with aldehydes in the clopropyl)titanium 6a was prepared from 5a and
presence of ketones,[14] and 6a was observed to be inert ClTi(OiPr)3 in diethyl ether, as described previously, in 60%
towards methyl iodide.[15]
yield.[3,15] Titanation of 5b and 5c with 0.7 equiv.
Given the paucity of information about (1-sulfonylalkyl)- Cl2Ti(OiPr)2 in diethyl ether and crystallisation also fur-
titaniums, we chose to first study the Li–Ti exchange of nished the corresponding bis(1-sulfonylcycloalkyl)titaniums
racemic and achiral tertiary α-sulfonyl carbanions 3 and the 6b and 6c each in 66% yield.
chemistry of their titanium derivatives.
In this paper we describe the synthesis, structure, dynam-
ics and reactivity of bis(1-sulfonylalkyl)titaniums.[19]
Results and Discussion
Synthesis of Bis(1-sulfonylalkyl)titaniums in Diethyl Ether
Three different groups of tertiary α-sulfonyl carbanions
were selected for the investigation of the Li–Ti exchange,
the cyclic S-phenyl carbanions 5a–c, the acyclic S-phenyl
carbanions 3a–e, and the acyclic S-tert-butyl carbanions 3f–
h (Scheme 1). The S-tert-butyl-substituted carbanions were
picked because of the envisioned synthesis of chiral, non-
racemic (1-sulfonylalkyl)titaniums of type 4, carrying a tert-
butyl group at the S atom. The cyclic carbanions were cho-
sen because of an investigation of the fluxional behaviour
Scheme 2. Titanation of lithium α-sulfonyl carbanions with chloro-
titanium reagents.
Titanation of the dimethyl-substituted carbanion 3a and
the diethyl-substituted carbanion 3b, each with 1.1 equiv.
ClTi(OiPr)3 in diethyl ether at –50 °C to room temperature,
provided, after crystallisation from diethyl ether, the corre-
sponding bis(1-sulfonylalkyl)titaniums 9a and 9b in 53 and
50% yield, respectively.
According to 1H NMR spectroscopic analysis of the
crude reaction mixtures, the carbanions 3a, 3b and 5a–c
Scheme 1. Secondary sulfones and tertiary α-sulfonyl carbanions.
were quantitatively converted upon treatment with
Eur. J. Org. Chem. 2014, 7134–7147
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7135

T. Heß, G. Raabe, H.-J. Gais
FULL PAPER
ClTi(OiPr)3 in diethyl ether into 1:1 mixtures of the corre-
sponding bis(1-sulfonylalkyl)titaniums and Ti(OiPr)4. For-
mation of further (1-sulfonylalkyl)titaniums was not ob-
served. In all cases, lithium chloride precipitated from the
ethereal solutions of Ti(OiPr)4 and the titanium derivatives.
The mode of combination of the carbanions 3a, 3b and
5a–c with the titanium reagents had no influence upon the
formation of the corresponding bis(1-sulfonylalkyl)titani-
ums and Ti(OiPr)4. Crystallisation gave the pure titanium
derivatives in medium to good yields. A quantitative isola-
tion of the titanium derivatives by crystallisation was not
attempted because the mixtures with Ti(OiPr)4 could be
used in reactions with electrophiles (see below). Addition
of water to 6a–c, 9a and 9b caused rapid hydrolysis with
formation of the corresponding sulfones. The bis(1-sulfon-
ylalkyl)titaniums 6a–c, 9a and 9b are stable at room tem-
perature in benzene, THF, and n-hexane solutions and in
the crystal, for a prolonged period of time, provided water
and oxygen are excluded.
Scheme 3. Li–Ti exchange of lithium α-sulfonimidoyl carbanions.
Structure and Dynamics of Bis(1-sulfonylalkyl)titaniums
X-ray crystal structure analyses of 6b and 9a provided
proof for their structures as bis(1-sulfonylalkyl)titaniums,
showing Ti–C distances of 2.174–2.251 Å and Ti–OiPr dis-
tances of 1.745–1.789 Å (Figures 2 and 3, Tables 1 and
2).[29]
Generally, alkyltitaniums with β-H atoms can undergo
β-hydride elimination.[1b,24,25] Interestingly, a β-H elimi-
nation of 6a–c, 9a and 9b with formation of the correspond-
ing α,β-unsaturated sulfones was not observed in the above
solvents at room temperature or during crystallisation from
n-hexane at elevated temperatures. Whereas the kinetic sta-
bility of 6a and 6b is perhaps not surprising because of the
small rings both contain, that of 6c and, in particular, of
9a and 9b, which carry four and six β-H atoms, respectively,
is noteworthy. A direct comparison with the kinetic stability
of R2Ti(OiPr)2 (R = cC3H5, cC4H7, cC5H9, CHMe2,
CHEt2) is not possible, because isolation and structural
characterisation of the parent dialkyltitaniums have not
been described.[1b,24,26] It has been postulated that the syn-
thesis of the Kulinkovich reagent from Ti(OiPr)4 and
iPrMgBr involves the formation of (iPr)2Ti(OiPr)2 as inter-
mediate,[27] which apparently suffers β-H elimination al-
ready at low temperatures.[28]
The reactions of carbanions 3c–h with ClTi(OiPr)3 in di-
ethyl ether also quantitatively furnished, according to nega-
tive test reactions with MeI (see below), the corresponding
bis(1-sulfonylalkyl)titaniums 9c–h, which were, however,
not isolated. Considering the use of racemic carbanions, 9c,
9d, 9e and 9h were perhaps mixtures of the d,l- and meso-
configured complexes.
Figure 2. Structure of bis(1-sulfonylcyclobutyl)titanium 6b in the
crystal.
The synthesis of bis(1-sulfonylalkyl)titaniums 6b, 6c and
9a–h shows that the C-titanion of 5a is no exemption. The
titanation of tertiary α-sulfonyl carbanions in diethyl ether
generally affords the corresponding bis(1-sulfonyalkyl)tita-
niums, irrespective of the size of the alkyl groups at the
anionic C atom, the substituent at the S atom, and the ring
size in case of the cyclic carbanions.
It seems interesting to compare the Li–Ti exchange of
the α-sulfonyl carbanions 3 with that of α-sulfonimidoyl
carbanions 2 (Scheme 3). Whereas the reaction of the allylic
carbanions 2a with ClTi(OiPr)3 in diethyl ether (and THF)
also afforded bis(1-sulfonimidoylalkenyl)titaniums 10,[6]
that of the alkyl-substituted carbanions 2b–d gave the corre-
sponding (1-sulfonimidoylalkyl)titaniums 11b–d.[7]
Figure 3. Structure of bis(1-sulfonylisopropyl)titanium 9a in the
crystal.
7136
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 7134–7147

Lithium–Titanium Exchange of Bis(1-sulfonylalkyl)titaniums
Table 1. Selected bond lengths [Å] of 6a,[15] 6b and 9a.
Table 3. Selected 13C NMR spectroscopic data of lithium α-sulfonyl
carbanions 3a, 3b and 5a[a] and bis(1-sulfonylalkyl)titaniums 6a–c,
9a and 9b.[b]
Cα–Ti
Ti–OiPr
Ti-O
Cα–S
6a
6b
9a
2.181(3)
2.174(4)
2.205(3)
2.223(3)
2.234(6)
2.251(6)
1.771(3)
1.745(2)
1.789(3)
1.751(2)
1.768(5)
1.763(4)
2.315(3)
2.243(2)
2.242(2)
2.278(2)
2.204(4)
2.271(4)
1.725(4)
1.719(4)
1.733(3)
1.737(3)
1.748(6)
1.742(7)
δ (13Cα) [ppm]
δ (13Cα) [ppm]
δ [ppm]
5a
5b
5c
3a
3b
28.5
n.d.[c]
n.d.[c]
42.5
6a
6b
6c
9a
9b
52.4
69.5
76.7
64.5
75.8
23.9
n.d.[c]
n.d.[c]
22.0
54.3
21.5
[a] In [D8]THF. [b] In [D6]benzene. [c] n.d.: not determined.
Table 2. Selected bond and dihedral angles [°] of 6a,[15] 6b and 9a.
1
The H NMR spectra of 6a–c, 9a and 9b in [D6]benzene
C–Ti–C
O–Ti-O
Ti–Cα–S Cα–S–O(Ti) O-S-Cα–Ti
and [D8]THF at room temperature showed only half the
number of signals expected for asymmetric structures of the
type found in the crystal. This means that the titanium de-
rivatives in solution either undergo rapid enantiomeris-
ation, leading to an exchange of the diastereotopic groups
at the Cα atoms and of the diastereotopic isopropoxy
groups, or adopt an achiral structure with a tetrahedral tet-
racoordinated Ti atom. Enantiomerisation can occur via an
achiral tetracoordinated intermediate I, having no bonds
between the sulfonyl O atoms and the Ti atom (Scheme 4),
or by a twisting mechanism without rupturing any of the
Ti–O and Ti–C bonds.[6,31] It is interesting to note that 10a
shows a dynamic phenomenon, which leads to intramolecu-
lar exchange of the diastereotopic groups at the Ti atom.[6]
6a 139.8(1)
6b 141.5(1)
9a 143.4(2)
102.6(1)
103.7(1)
103.0(2)
95.8(1)
92.1(1)
90.7(2)
99.8(1)
101.5(1)
100.8(2)
–83.8(1)
–2.5(1)
5.5(4)
In the crystal, the Ti atoms of 6b and 5a are hexacoordi-
nate and have distorted octahedral coordination geometries,
because of an additional coordination by two O atoms of
the sulfonyl groups. Evidence for the two O–Ti–Cα–S che-
late rings is provided by the O–Ti distances, the Cα–Ti–O–
S dihedral angles, the conformations around the Cα–S
bonds, and the widening of the Cα–Ti–Cα bond angles. The
coordination of the sulfonyl O atoms to the Ti atom makes
the S atoms of 6b and 9a stereogenic, having opposite con-
figurations, and both complexes are asymmetric. Bis(1-sulf-
onylcyclopropyl)titanium 6a adopts a similar structure in
the crystal.[15] It would have been interesting to compare
the crystal structures of 6a, 6b and 9a with those of the
parent dialkyldialkoxytitaniums; however, crystal structures
of dialkyldialkoxytitaniums carrying secondary alkyl
groups at the Ti atom are not available.[30]
It is interesting to note that bis(1-sulfonimidoylpropen-
yl)titanium 10a adopts a similar structure in the crystal
(Figure 4) as bis(1-sulfonylalkyl)titaniums 6a, 6b and 9a.[6]
Whereas 10a has the cis,cis,cis-configuration, 6a, 6b and 9a
have the cis,cis,trans-configuration.
Scheme 4. Exchange of diastereotopic groups R and X of the octa-
hedral bis(1-sulfonylalkyl)titaniums 6a–c, 9a and 9b.
Fluxional Behaviour of Bis(1-sulfonylalkyl)titaniums
Crucial to the envisioned synthesis of chiral, non-racemic
bis(1-sulfonylalkyl)titaniums of type 9 will be the configura-
tional stability of the Cα atom. Therefore, bis(1-sulfonylcy-
cloalkyl)titaniums 6a–c were investigated by 1H NMR spec-
troscopy to establish whether they are fluxional, resulting
in a topomerisation of the titanyl group. The tris(isoprop-
oxy)(1-sulfonimidoylalkyl)titaniums 11a and 11b were
found to be non-fluxional at room temperature by 1H
NMR spectroscopic analysis.[7] Topomerisation of the tit-
anyl group of 6a–c should proceed via the intermediate for-
mation of the O-titanated carbanions IIa–c, IIIa–c and
Figure 4. Structure of bis(1-sulfonimidoylpropenyl)titanium 10a.
The C-titanation of α-sulfonyl carbanions 3 causes a IVa–c, including (1) a migration of the titanyl group to an
downfield shift of the signal of the Cα atom in the 13C O atom under cleavage of the Cα–Ti bond, (2) inversion of
NMR spectra of the titanium derivatives (Table 3).[3,15] This the Cα atom, (3) rotation around the Cα–S bond, (4) mi-
effect can be used as a probe for the C-titanation of α-sulf- gration of the titanyl group to the Cα atom with formation
onyl carbanions in case of an in situ synthesis.
of the Cα–Ti bond, and (5) ring inversion in the cases of 6b
Eur. J. Org. Chem. 2014, 7134–7147
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7137

T. Heß, G. Raabe, H.-J. Gais
FULL PAPER
and 6c (not shown). The topomerisation causes an ex- even at low temperatures.[15] To see whether the lack of a
change of environments of the syn and anti H atoms. The reaction of 6a is typical for titanium derivatives of this type,
1H NMR spectra of 6a–c in [D6]benzene exhibited at room bis(1-sulfonylalkyl)titaniums 9a–h were studied. Treatment
temperature different sharp signals for the H atoms in syn of the bis(1-sulfonylalkyl)titaniums, which were admixed
1
and anti positions to the titanyl group. In addition, the H with Ti(OiPr)4, with methyl iodide in diethyl ether at –35 °C
NMR spectra of 6a in [D8]toluene at room temperature and to room temperature did not afford the corresponding
at 80 °C showed no differences. Thus, 6a–c are non-flux- methylated sulfones. Quenching of the reaction mixtures
ional and a topomerisation of the titanyl group either does with CF3CO2D gave the corresponding deuterated sulfones
not take place or is slow at these temperatures.
D-8a–h (82% D to 98% D) in 91–97% yield (Scheme 6).
In principle, each step of the topomerisation of 6a–c
could be rate determining (Scheme 5). There is evidence,
however, suggesting that cleavage of the Cα–Ti bond should
1
be the rate-determining step. The H NMR spectra of the
lithium sulfonyl carbanions 5a–c in [D8]THF, which are ex-
pected to form a C–Li contact ion pair (5a)[32] and O–Li
bonded contact ion pairs (5b, 5c),[23] show only single sig-
nals for the respective syn and anti H atoms at room tem-
perature. This indicates that Cα inversion and Cα–S bond
rotation, which lead to an exchange of environments of the
H atoms, are fast. Variable-temperature 1H NMR spec-
troscopy of 5a in [D8]THF had given an estimated barrier
of ΔG϶ = 11.6Ϯ0.3 kcalmol–1 for the exchange.[3]
247
Scheme 6. Attempted methylation of bis(1-sulfonylalkyl)titaniums.
For comparison, the tertiary carbanions 3a–h were
treated with methyl iodide under similar conditions, which
afforded the corresponding methylated sulfones 12a–h in
79–97% yield (Scheme 7).
Scheme 7. Methylation of lithium α-sulfonyl carbanions.
Scheme 5. Topomerisation of the titanyl group of 6a–c.
Reaction with Benzaldehyde and Acetophenone
The lack of a fluxional behaviour of 6a–c also excludes
the possibility of the titanium derivatives undergoing a re-
versible β-titanium hydride elimination as observed in the
case of the tris(diethylamino) analogue of 11c.[7]
In summary, the above results strongly suggest that chiral
bis(1-sulfonylalkyl)titaniums of type 9 should have configu-
rationally stable Cα atoms, at least at room temperature.
The reactivity of bis(1-sulfonylalkyl)titaniums 9 towards
aldehydes was then investigated. Treatment of a mixture of
9b and Ti(OiPr)4, which was prepared from carbanion 3b
and ClTi(OiPr)3 in diethyl ether, first with methyl iodide
and then with benzaldehyde gave β-hydroxy sulfone 13b in
91% yield (Scheme 8). Formation of the methylated sulfone
12b was not detected. Treatment of a mixture of 8f and
Ti(OiPr)4 with a 1:1 mixture of benzaldehyde and acetophe-
none only provided β-hydroxy sulfone 13f, according to GC
analysis. Formation of the β-hydroxy sulfone 14 could not
be detected. Interestingly, both sulfonylalkyl groups of 9b
Reactivity of Bis(1-sulfonylalkyl)titaniums
Reaction with Methyl Iodide
Bis(1-sulfonylcyclopropyl)titanium 6a did not react with and 9f were utilised in the reaction with the aldehyde. The
methyl iodide at room temperature, whereas the corre- Cα–Ti bonded titanium derivative of 3 (R1 = R2 = H, R3 =
sponding sulfonyl carbanion 5a was rapidly methylated Ph) shows a similar aldehyde-ketone selectivity.[14]
7138
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 7134–7147

Lithium–Titanium Exchange of Bis(1-sulfonylalkyl)titaniums
large difference in reactivity between 3 and 9 towards
methyl iodide was used as a chemical probe for the forma-
tion of the latter. Whereas carbanions 3 already react at
–78 °C with methyl iodide, titanium derivatives 9 are inert
even at room temperature. Carbanions 3b and 3g were
treated with ClTi(OiPr)3 in diethyl ether at –78 °C. After
the mixtures were kept for 3 h at low temperatures, methyl
iodide was added at the same temperature. The reactions
were quenched after 1 h with CF3CO2D at –78 °C. This se-
quence of steps gave the corresponding deuterated sulfones
D-8b (95% D) and D-8k (95% D) in 91 and 97% yield,
respectively (Scheme 10). Formation of the methylated sulf-
ones 12b and 12g was not observed. These results show that
formation of 9b and 9g from the corresponding carbanions
3b and 3g in diethyl ether already occurred at –78 °C. This
observation is of significance for the envisioned synthesis of
chiral, non-racemic derivatives of 9, because of the limited
configurational stability of 3.
Scheme 8. Reaction of bis(1-sulfonylalkyl)titaniums with carbonyl
compounds.
Reaction of α-sulfonyl carbanions 3a–c, 3f and 3g with
benzaldehyde under similar conditions afforded the corre-
sponding β-hydroxy sulfones 13a–c, 13f and 13g in 82–88%
yield (Scheme 9). The reaction of carbanion 3f with a 1:1
mixture of benzaldehyde and acetophenone was, as ex-
pected,[11] unselective and gave, according to GC–MS
analysis, a mixture of β-hydroxy sulfones 13f and 14 in a
ratio of 55:45.
Scheme 10. Li–Ti exchange of α-sulfonyl carbanions at low tem-
peratures.
Lithium–Titanium Exchange in Tetrahydrofuran
Titanation of the tertiary α-sulfonyl carbanions with
ClTi(OiPr)3 in THF was also investigated to establish
whether (1-sulfonylalkyl)titaniums instead of bis(1-sulfon-
ylalkyl)titaniums are obtained. Carbanions 3b and 3g were
treated with 1.1 equiv. ClTi(OiPr)3 in THF at –78 °C and
then the mixtures were warmed to room temperature. Pre-
cipitation of lithium chloride, in contrast to the reactions in
diethyl ether, did not occur. Subsequently, methyl iodide
was added at –78 °C to the mixtures, which were sub-
sequently warmed to room temperature. Surprisingly, the
two-step sequences afforded the corresponding methyl sulf-
ones 12b and 12g in 96 and 91% yield, respectively
(Scheme 11). Formation of 12b and 12g occurred already at
low temperatures.
Scheme 9. Reaction of lithium α-sulfonyl carbanions with carbonyl
compounds.
The bis(1-sulfonylalkyl)titaniums showed a lower reactiv-
ity towards benzaldehyde than the corresponding lithium
carbanions.
Scheme 11. Titanation of α-sulfonyl carbanions in THF and reac-
tivity of the titanium derivatives towards methyl iodide.
Estimation of the Rate of the Lithium–Titanium Exchange
in Diethyl Ether
A similar treatment of carbanions 3a–c, 3f and 3g first
It was of interest to obtain information about the rates with ClTi(OiPr)3 in THF and then with benzaldehyde, fur-
of titanation of 3 and formation of 9 in diethyl ether. The nished the corresponding β-hydroxy sulfones 13a–c, 13f and
Eur. J. Org. Chem. 2014, 7134–7147
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7139

T. Heß, G. Raabe, H.-J. Gais
FULL PAPER
13g in 60–89% yield. The β-hydroxy sulfone 13c was ob- which suffer disproportionation and furnish the bis(1-sulf-
tained as a 1:1 mixture of the diastereomers. onylalkyl)titaniums 9(6) and Ti(OiPr)4. In THF the solubil-
The results obtained in the experiments with methyl iod- ity of lithium chloride precludes a shift of the equilibrium
ide implied that in THF either a C-titanation of the α-sulf- towards 4A and thus the ate complexes are the dominating
onyl carbanions 3b and 3g had not occurred or titanium species.
derivatives other than 9b and 9g had been formed. To dis-
tinguish between these possibilities, a competition experi-
ment with benzaldehyde/acetophenone was conducted. Tit-
anation of 3f with ClTi(OiPr)3 in THF under similar condi-
tions followed by the addition of a 1:1 mixture of benzalde-
hyde and acetophenone only afforded β-hydroxy sulfone
13f, according to GC–MS analysis (Scheme 12). Formation
of 14 was not detected. These results clearly show that the
reactions of 3b, 3g and 3f, and most likely also those of 3a
and 3c, with ClTi(OiPr)3 in THF had not given the corre-
sponding bis(1-sulfonylalkyl)titaniums. Instead, titanium
derivatives of different structures had been formed that
show a similar selectivity for benzaldehyde as bis(1-sulfon-
ylalkyl)titaniums, but, in contrast to the latter, are also reac-
tive towards methyl iodide.
Scheme 13. Proposed course of the titanation of tertiary α-sulfonyl
carbanions.
A key feature of Scheme 13 is the proposed Schlenk-type
equilibrium of (1-sulfonylalkyl)titaniums 4A shown in
Equation (1).
(1)
Whereas the disproportionation of heteroatom-substi-
tuted titanium(IV) derivatives is well documented,[33]
a
Schlenk equilibrium of alkyl(aryl)titaniums has, to our
knowledge, not been described. It had been postulated,
however, that protonolysis of (PhCH2)4Ti with one equiva-
lent of EtOH affords (PhCH2)3Ti(OEt), which suffers dis-
proportionation, giving a mixture of (PhCH2)2Ti(OEt)2 and
(PhCH2)4Ti.[26b,34,35] Disproportionation of 4A could occur
within a dimer through a stepwise transfer first of an isop-
ropoxy group and then of a sulfonylalkyl group.
Formation of bis(1-sulfonylalkyl)titaniums 6 from carb-
anions 5 upon titanation with Cl2Ti(OiPr)2 in diethyl ether
has to follow a somewhat different course because of the
application of only 0.7 equiv. of the titanium reagent. Reac-
tion of the carbanions with the titanium reagent presum-
ably gave the ate complexes 15B together with unreacted
5. Driven by the precipitation of lithium chloride, the ate
complexes were perhaps converted into chloro(1-sulfon-
ylalkyl)titaniums 4B, which reacted with carbanions 5 at
the Ti atom and afforded 6.
Scheme 12. Titanation of α-sulfonyl carbanions in THF and reac-
tivity of the titanium derivatives derived thereof towards carbonyl
compounds.
The Li–Ti exchange of 3 and 5 gave two unexpected re-
sults. First, titanation of the carbanions in diethyl ether af-
fords bis(1-sulfonylalkyl)titaniums instead of (1-sulfon-
ylalkyl)titaniums. Second, titanation in THF furnished dif-
ferent titanium derivatives. According to the trapping ex-
periments with methyl iodide (cf. Scheme 10), titanation of
the carbanions and formation of the bis(1-sulfonylalkyl)-
titaniums in diethyl ether are relatively fast processes at low
temperatures. Carbanions 3(5) are expected to react with
ClTi(OiPr)3 in both solvents under C-titanation and forma-
tion of the ate complexes 15A (Scheme 13). The ate com-
plexes are perhaps in equilibrium with the corresponding
(1-sulfonylalkyl)titaniums 4A and lithium chloride. Given
Conclusions
The Li–Ti exchange of tertiary alkyl-substituted α-sulf-
the low solubility of lithium chloride in diethyl ether, equi- onyl carbanions with chlorotitanium reagents takes place at
librium is shifted towards the 1-(sulfonylalkyl)titaniums 4A, the anionic C atom and yields bis(1-sulfonylalkyl)titaniums
7140
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 7134–7147

Lithium–Titanium Exchange of Bis(1-sulfonylalkyl)titaniums
bons with one or three attached protons, as determined from the
APT pulse sequence. Assignments in the 1H NMR spectra were
made by GMQCOSY, GNOE, HETCOR experiments and those
in the 13C NMR spectra were made by DEPT experiments. Solu-
tions of titanium derivatives in [D8]THF and [D6]benzene for
NMR spectroscopy were sealed in tubes. IR spectra were recorded
in diethyl ether as solvent. The bis(1-sulfonylalkyl)titaniums
adopt distorted octahedral structures in the crystal, because
of additional coordination of sulfonyl O atoms to the Ti
atom. The mechanism of the formation of the bis(1-sulfon-
ylalkyl)titaniums is has not yet been elucidated. The topom-
erisation of the titanyl group of bis(1-sulfonylalkyl)titani-
ums, which has to involve cleavage of the Cα–Ti bond, is
either slow or nonexistent at room temperature. This indi-
cates that chiral bis(1-sulfonylalkyl)titaniums should be
with a Perkin–Elmer PE 1759 FT instrument. Only peaks of ν Ն
˜
800 cm–1 are listed, vs. = very strong, s = strong, m = medium, w
= weak. Low-resolutions mass spectra were recorded with a Varian
MAT 212 S instrument using electron impact ionisation (EI,
configurationally stable at room temperature. The bis(1- 70 eV). Only peaks of m/z Ն 80 and an intensity of Ն 10%, except
decisive ones, are listed. Elemental analyses were performed by the
Institute of Organic Chemistry (RWTH Aachen University) micro
analytical laboratory with a Perkin–Elmer CHN-analyzer 240C
and a Heraeus CHN-Rapid analyzer. Melting points were deter-
mined with a SMP 20 Büchi apparatus and are uncorrected.
sulfonylalkyl)titaniums are inert towards methyl iodide and
react selectively with benzaldehyde in the presence of aceto-
phenone, whereby both sulfonylalkyl residues are transfer-
red to the aldehyde. The reaction of the dialkyl-substituted
α-sulfonyl carbanions with chlorotitanium reagents in THF
takes a different course. Titanium derivatives of undefined Reaction of Lithium α-Sulfonyl Carbanions 3 with Methyl Iodide.
General Procedure (GP1): To a solution of sulfone 8 (2.20 mmol)
in diethyl ether (10 mL) was added at –78 °C, nBuLi (1.60 m in n-
hexane, 1.62 mL, 2.59 mmol). The yellow mixture was stirred for
15 min at room temperature, then cooled to –35 °C and treated
dropwise with MeI (4.10 mmol). The mixture was stirred for 30 min
at room temperature, then cooled to 0 °C and treated with
CF3CO2D (2.00 m in THF, 3.40 mL, 6.80 mmol). The mixture was
treated with H2O (20 mL) and 2 n aqueous HCl (5 mL) and ex-
tracted with diethyl ether (3ϫ 40 mL). The combined organic
phases were washed with saturated aqueous Na2S2O3 and H2O
(40 mL). The organic phase was dried (MgSO4) and concentrated
in vacuo. Purification by chromatography (n-hexane/EtOAc, 1:1)
gave methylated sulfone 12.
structure are formed, which are methylated by methyl iod-
ide but react selectively with benzaldehyde in the presence
of acetophenone.
Experimental Section
General Comments and Materials: All reactions were carried out in
anhydrous solvents under argon in oven-dried glassware by using
Schlenk, cannula and syringe techniques. ClTi(OiPr)3 was obtained
from commercial sources and distilled under argon before use.
Cl2Ti(OiPr)2 was obtained as colourless crystals from Ti(OiPr)4
and TiCl4 in n-hexane.[3,36] Diethyl ether (denoted as ether) and
tetrahydrofuran (THF) were filtered through alumina and distilled
from potassium/benzophenone under argon. n-Hexane was distilled
from potassium/benzophenone under argon. Methyl iodide was
distilled from CaH2 under argon. [D8]THF and [D6]benzene were
distilled from potassium in a micro solvent still under argon. Benz-
aldehyde and acetophenone were distilled from CaH2. nBuLi was
standardised by titration with diphenylacetic acid.[37] All other rea-
gents were obtained from commercial sources and used without
further purification. Sulfones 8a–c and 8f–h were prepared through
oxidation of the corresponding sulfanes, which were obtained from
the corresponding thiols and alkyl halides by following standard
procedures. Sulfones 8d and 8e were synthesised through methyl-
ation of the corresponding parent sulfones, which were obtained
starting from the corresponding thiols and alkyl halides via the
corresponding sulfanes by following standard procedures. Analyti-
cal thin-layer chromatography (TLC) was performed on E. Merck
pre-coated TLC plates (silica gel 60 F254, layer thickness 0.2 mm).
Flash chromatography (denoted as chromatography) was per-
formed with E. Merck silica gel 60 (0.063–0.200 mm). Gas
chromatography was done with a Chrompack CP-9000 instrument
by using a DB 5 Carlo Erba CP-Sil-8 column: length 30 m, dia-
Treatment of Bis(1-sulfonylalkyl)titaniums 9 with Methyl Iodide. Ge-
neral Procedure (GP2): To a solution of sulfone 8 (2.20 mmol) in
diethyl ether (10 mL) was added at –78 °C, nBuLi (1.60 m in n-
hexane, 1.62 mL, 2.59 mmol). The yellow mixture was stirred for
15 min at room temperature, then cooled to –78 °C and treated
dropwise with ClTi(OiPr)3 (688 mg, 2.64 mmol). The orange mix-
ture was stirred for 3 h at room temperature, then cooled to –35 °C
and treated with MeI (594 mg, 4.18 mmol). The mixture was stirred
for 30 min at room temperature, then CF3CO2D (2.00 m in THF,
3.40 mL, 6.80 mmol) was added at 0 °C. The mixture was stirred
for 30 min at room temperature, treated with H2O (20 mL) and 2 n
aqueous HCl (5 mL) and extracted with diethyl ether (3ϫ 40 mL).
The combined organic phases were washed with saturated aqueous
Na2S2O3 and H2O (40 mL). The organic phase was dried (MgSO4)
and concentrated in vacuo. Purification by chromatography (n-hex-
ane/EtOAc, 1:1) gave deuterated sulfone D-8.
Reaction of Putative Titanium Derivatives 15A with Methyl Iodide.
General Procedure (GP3): To a solution of sulfone 8 (2.20 mmol)
in THF (10 mL) was added at –78 °C, nBuLi (1.60 m in n-hexane,
1.62 mL, 2.59 mmol). The yellow mixture was stirred for 15 min at
room temperature, then cooled to –78 °C and treated dropwise with
ClTi(OiPr)3 (688 mg, 2.64 mmol). The orange mixture was then
stirred for 3 h at room temperature, cooled to –78 °C and treated
1
meter 0.32 mm, film thickness 0.25 μm. H and 13C NMR spectra
were recorded with Varian VXR 300 (300 MHz, 75 MHz), Varian
Gemini 300 (300 MHz, 75 MHz) or Varian Unity 500 (500 MHz, with MeI (594 mg, 4.18 mmol). The mixture was stirred for 30 min
125 MHz) instruments. Chemical shifts are reported relative to
SiMe4 (δ = 0.00 ppm), CHCl3 (δ = 7.24 ppm, 77.1 ppm) and [D6]-
benzene (δ = 7.16 ppm, 128.0 ppm) as internal standards. Splitting
patterns in the 1H NMR spectra are designated as s, singlet; d,
doublet; dd, double doublet; t, triplet; q, quartet; quin, quintet;
sept, septet; m, multiplet; br, broad; app, apparent, and combina-
tions thereof. Peaks in the 13C NMR spectra are denoted as “u”
for carbons with zero or two attached protons and as “d” for car-
at room temperature, then cooled to 0 °C and treated with
CF3CO2D (2.00 m in THF, 3.40 mL, 6.80 mmol). The mixture was
stirred for 30 min at room temperature, treated with H2O (20 mL)
and 2 n aqueous HCl (5 mL) and extracted with diethyl ether (3ϫ
40 mL). The combined organic phases were washed with saturated
aqueous Na2S2O3 and H2O (40 mL). The organic phase was dried
(MgSO4) and concentrated in vacuo. Purification by chromatog-
raphy (n-hexane/EtOAc, 1:1) gave methylated sulfone 12.
Eur. J. Org. Chem. 2014, 7134–7147
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7141

T. Heß, G. Raabe, H.-J. Gais
FULL PAPER
Reaction of Lithium α-Sulfonyl Carbanions 3 with Benzaldehyde. ClTi(OiPr)3 (1.290 g, 4.95 mmol) in diethyl ether (15 mL). The mix-
General Procedure (GP4): To a solution of sulfone 8 (2.20 mmol) ture was then warmed to room temperature, whereby LiCl precipi-
in THF (20 mL) was added at –78 °C, nBuLi (1.60 m in n-hexane, tated after 10 min. The orange mixture was stirred for 1.5 h at room
1.62 mL, 2.59 mmol). The yellow mixture was stirred for 15 min at temperature, then filtered under argon through a fritted glass cov-
room temperature, then cooled to –78 °C and treated dropwise with
PhCHO (466 mg, 4.39 mmol). The mixture was stirred for 15 min
at room temperature, then cooled to 0 °C and treated with 2 n
aqueous HCl (25 mL) and extracted with diethyl ether (3ϫ 70 mL).
The combined organic phases were washed with saturated aqueous
NaHCO3 and H2O (40 mL). The organic phase was dried (MgSO4)
and concentrated in vacuo. A layer of n-hexane (3 mL) was placed
on the viscous oil and the mixture was stored at 2 °C. Crystallisa-
tion was complete after 24 h. The liquid phase was removed by
using a syringe, and the solid alcohol 13 was washed with cold n-
hexane (1 mL) and dried in vacuo.
ered with dry kieselguhr. Concentration in vacuo gave a yellow so-
lid, which was dissolved in n-hexane (75 mL) at 50 °C. Cooling the
mixture to 2 °C for 12 h produced yellow crystals. The mother
liquor was removed by using a syringe and the crystals were washed
with a small amount of cold n-hexane. Drying in vacuo gave bis(1-
sulfonylcycloalkyl)alkyltitanium 6b (655 mg, 57%) as yellow crys-
tals. 1H NMR (300 MHz, C6D6): δ = 1.43 (d, J = 6.3 Hz, 12 H,
iPr), 1.70 (m, 2 H, CH2), 2.15 (m, 2 H, CH2), 2.48 (m, 4 H, CH2),
2.80 (m, 4 H, CH2), 5.09 (sept, J = 6.1 Hz, 2 H, iPr), 7.04 (m, 6
H, Ph), 8.24 (m, 4 H, Ph) ppm. 13C NMR (75 MHz, C6D6): δ =
18.2 (u, CH2), 26.9 (d, iPr), 32.9 (u, CH2), 69.5 (u, CTi), 80.7 (d,
iPr), 129.6 (d, Ph), 129.3 (d, Ph), 133.3 (d, Ph), 139.5 (u, Ph) ppm.
C26H36O6S2Ti (556.56): calcd. C 56.11, H 6.52; found C 55.78, H
6.58.
Reaction of the Putative Titanium Derivatives 15A with Benzalde-
hyde. General Procedure (GP5): To a solution of sulfone 8
(2.20 mmol) in THF (20 mL) was added at –78 °C, nBuLi (1.60 m
in n-hexane, 1.62 mL, 2.59 mmol). The yellow mixture was stirred
for 15 min at room temperature, then cooled to –78 °C and treated
dropwise with ClTi(OiPr)3 (688 mg, 2.64 mmol). The orange mix-
ture was stirred for 3 h at room temperature, cooled to –78 °C and
treated with PhCHO (466 mg, 4.39 mmol). The mixture was stirred
for 1 h at room temperature, then treated with 2 n aqueous HCl
(25 mL) and extracted with diethyl ether (3ϫ 40 mL). Drying
(MgSO4) and concentration of the combined organic phases in
vacuo gave alcohol 13.
Synthesis with Cl2Ti(OiPr)2: To a solution of sulfone 7b (1.070 g,
5.44 mmol) in diethyl ether (30 mL) was added at –78 °C, nBuLi
(1.50 m in n-hexane, 4.00 mL, 6.00 mmol). The yellow solution was
then added by using a cannula to a solution of Cl2Ti(OiPr)2
(910 mg, 3.84 mmol) in diethyl ether (20 mL) at –78 °C whereby,
after 30 min, LiCl precipitated. After the suspension was stirred for
3 h at room temperature, it was filtered under argon through a
fritted glass covered with dry kieselguhr. Concentration of the fil-
trate in vacuo gave a brown sticky oil, which was dissolved in n-
hexane (60 mL) at 60 °C. The solution was concentrated in vacuo
to half of its original volume and kept for 3 h at 2 °C. Filtration
and drying in vacuo gave 6b (999 mg, 66%) as yellow crystals.
Bis[1-(phenylsulfonyl)cyclopropyl-C,O]bis(2-propanolato)titanium
(6a): To a solution of sulfone 7a (1.110 g, 6.09 mmol) in diethyl
ether (20 mL) was added at –78 °C, nBuLi (1.52 m in n-hexane,
4.41 mL, 6.70 mmol). After the colourless suspension of the lithium
carbanion 5a was stirred for 15 min at room temperature, it was
cooled to –50 °C and added dropwise by using a cannula at –50 °C
to a solution of ClTi(OiPr)3 (1.910 g, 7.33 mmol) in diethyl ether
(15 mL). The mixture was then warmed to room temperature,
whereby the suspension became a clear solution from which, after
10 min, LiCl precipitated. The suspension was stirred for 1 h at
Bis[1-(phenylsulfonyl)cyclopentyl-C,O]bis(2-propanolato)titanium
(6c): To a solution of nBuLi (1.52 m in n-hexane, 4.43 mL,
6.73 mmol) in diethyl ether (10 mL) was added at –78 °C a solution
of sulfone 7c (1.290 g, 6.13 mmol) in diethyl ether (30 mL) by using
a cannula. The mixture was stirred at room temperature for 15 min
then the solution of carbanion 5c was cooled to –50 °C and added
by using a cannula at –50 °C to a solution of ClTi(OiPr)3 (1.920 g,
room temperature, then filtered under argon through a fritted glass 7.36 mmol) in diethyl ether (20 mL). The mixture was warmed to
covered with dry kieselguhr. Concentration in vacuo gave a yellow
oil, which was dissolved in n-hexane (25 mL) at 60 °C. Cooling the
mixture to 2 °C for 3 h produced colourless crystals. The mother
liquor was removed by using a syringe and the crystals were washed
with a small amount of cold n-hexane. Drying in vacuo gave bis(1-
sulfonylcycloalkyl)titanium 6a (965 mg, 60%) as colourless crystals.
1H NMR (300 MHz, [D6]benzene): δ = 1.24 (d, J = 6.04 Hz, 12 H,
room temperature, whereby LiCl precipitated after 10 min. The yel-
low mixture was stirred for 2 h at room temperature, then filtered
under argon through a fritted glass covered with dry kieselguhr.
Concentration in vacuo gave a yellow oil, which was dissolved in
n-hexane (25 mL) at 60 °C. Cooling the mixture to 2 °C for 12 h
produced colourless crystals. The mother liquor was removed by
using a syringe and the crystals were washed with a small amount
iPr), 1.26 (m, 4 H, CH2), 1.58 (m, 4 H, CH2), 4.86 (sept, J = of cold n-hexane. Drying in vacuo gave bis(1-sulfonylcycloalkyl)-
6.04 Hz, 2 H, iPr), 6.98 (m, 6 H, Ph), 8.25 (m, 4 H, Ph) ppm. 13C
NMR (75 MHz, [D6]benzene): δ = 16.9 (u, CH2), 26.1 (d, iPr), 52.3
(u, CTi), 80.4 (d, iPr), 128.6 (d, Ph), 128.7 (d, Ph), 132.7 (d, Ph),
140.4 (u, Ph) ppm. 1H NMR (300 MHz, [D8]toluene): δ = 1.13 (m,
titanium 6c (1.057 g, 59 %) as colourless crystals. 1H NMR
(300 MHz, [D6]benzene): δ = 1.29 (m, 4 H, CH2), 1.35 (d, J =
6.04 Hz, 12 H, iPr), 1.50 (m, 4 H, CH2), 2.43 (m, 4 H, CH2), 2.55
(m, 4 H, CH2), 4.99 (sept, J = 6.04 Hz, 2 H, iPr), 7.00 (m, 6 H,
4 H, CH2), 1.19 (d, J = 6.04 Hz, 12 H, iPr), 1.46 (m, 4 H, CH2), Ph), 8.20 (m, 4 H, Ph) ppm. 13C NMR (75 MHz, [D6]benzene): δ
4.79 (sept, J = 6.04 Hz, 2 H, iPr), 7.00 (m, 2 H, Ph), 7.08 (m, 4 H, = 26.3 (d, iPr), 27.0 (u, CH2), 35.2 (u, CH2), 76.7 (u, CTi), 79.5 (d,
Ph), 8.08 (m, 4 H, Ph) ppm. 13C NMR (75 MHz, [D8]toluene): δ = iPr), 129.0 (d, Ph), 129.2 (d, Ph), 132.6 (d, Ph), 140.3 (u, Ph) ppm.
16.8 (u, CH2), 26.1 (d, iPr), 52.3 (u, CTi), 80.3 (d, iPr), 128.5 (d,
Synthesis with Cl2Ti(OiPr)2: To a solution of sulfone 7c (1.619 g,
7.70 mmol) in diethyl ether (30 mL) was added at –78 °C, nBuLi
(1.50 m in n-hexane, 5.80 mL, 8.70 mmol). The solution of 5c was
Ph), 128.6 (d, Ph), 132.6 (d, Ph), 140.5 (u, Ph) ppm. C24H36O6S2Ti
(528.50): calcd. C 54.54, H 6.10; found C 54.26, H 6.16.
Bis[1-(phenylsulfonyl)cyclobutyl-C,O]bis(2-propanolato)titanium stirred at room temperature for 15 min, then cooled to –78 °C and
(6b): To a solution of sulfone 7b (810 mg, 4.13 mmol) in diethyl
ether (25 mL) was added at –78 °C, nBuLi (1.59 m in n-hexane,
2.84 mL, 4.54 mmol). The yellow suspension of the lithium carban-
ion 5b was stirred at room temperature for 15 min, cooled to –50 °C
and then added by using a cannula at –50 °C to a solution
added by using a cannula at –78 °C to a solution of Cl2Ti(OiPr)2
(1.322 g, 5.58 mmol) in diethyl ether (20 mL). After 10 min, LiCl
started to precipitate. The orange mixture was stirred for 3 h at
room temperature, then filtered under argon through a fritted glass
covered with dry kieselguhr. Concentration of the mixture in vacuo
7142
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 7134–7147

Lithium–Titanium Exchange of Bis(1-sulfonylalkyl)titaniums
gave a orange sticky oil, which was dissolved at 60 °C in n-hexane
(60 mL). The warm solution was filtered under argon through a
fritted glass covered with dry kieselguhr and concentrated in vacuo
to half of its volume. Cooling the mixture to 2 °C for 12 h produced
yellow crystals. The mother liquor was removed by using a syringe
and the crystals were washed with a small amount of cold n-hexane.
Drying in vacuo gave 6c (1.485 g, 66%) as yellow crystals.
n-hexane (1:3), as colourless crystals, m.p. 83 °C. 1H NMR
(300 MHz, CDCl3): δ = 1.35 (s, 9 H, tBu), 7.56 (m, 2 H, Ph), 7.66
(m, 1 H, Ph), 7.88 (m, 2 H, Ph) ppm. 13C NMR (75 MHz, CDCl3):
δ = 23.6 (d, tBu), 59.8 (u, tBu), 128.7 (d, Ph), 130.5 (d, Ph), 133.5
(d, Ph), 135.4 (u, Ph) ppm. IR (KBr): ν = 3435 (m), 3062 (m), 3029
˜
(m), 2978 (s), 2937 (s), 2873 (m), 2208 (m), 2017 (m), 1931 (m),
1838 (m), 1718 (m), 1625 (m), 1584 (m), 1478 (s), 1452 (s), 1398
(m), 1366 (m), 1284 (vs), 1205 (s), 1135 (vs), 1078 (vs), 1022 (s),
997 (m), 942 (m), 804 (s) cm–1. MS (EI, 70 eV): m/z (%) = 198 (2)
[M+], 143 (5), 78 (7), 77 (6), 58 (5), 57 (100), 56 (5), 51 (5).
C10H14O2S (198.28): calcd. C 60.57, H 7.12; found C 60.30, H 7.14.
Bis[1-(phenylsulfonyl)isopropyl-C,O]bis(2-propanolato)titanium (9a):
To a solution of sulfone 8a (1.210 g, 6.57 mmol) in diethyl ether
(20 mL) was added at –78 °C, nBuLi (1.52 m in n-hexane, 4.76 mL,
7.23 mmol). The yellow suspension of the lithium carbanion 3a was
stirred at room temperature for 15 min, cooled to –50 °C and then
added by using a cannula at –50 °C to a solution ClTi(OiPr)3
(2.053 g, 7.88 mmol) in diethyl ether (15 mL). The mixture was then
warmed to room temperature, whereby LiCl precipitated after
10 min. The orange mixture was stirred for 1 h at room tempera-
ture, then filtered under argon through a fritted glass covered with
dry kieselguhr. Concentration in vacuo gave a yellow solid, which
was dissolved in n-hexane (25 mL) at 60 °C. Cooling the mixture
to 2 °C for 72 h produced yellow crystals. The mother liquor was
removed by using a syringe and the crystals were washed with a
small amount of cold n-hexane. Drying in vacuo gave bis(1-sulfon-
ylalkyl)titanium 9a (927 mg, 53 %) as yellow crystals. 1H NMR
(300 MHz, [D6]benzene): δ = 1.34 (d, J = 6.05 Hz, 12 H, iPr), 1.68
(s, 12 H, Me), 4.94 (sept, J = 6.05 Hz, 2 H, iPr), 6.95–7.07 (m, 6
H, Ph), 8.08 (m, 4 H, Ph) ppm. 13C NMR (75 MHz, [D6]benzene):
δ = 23.9 (d, Me), 26.1 (d, iPr), 64.5 (u, CTi), 79.8 (u, iPr), 128.6
(d, Ph), 128.8 (d, Ph), 132.5 (d, Ph), 139.9 (u, Ph) ppm.
Treatment of sulfone 8a (486 mg, 2.64 mmol) with nBuLi (1.50 m
in n-hexane, 1.91 mL, 2.86 mmol), ClTi(OiPr)3 (745 mg,
2.86 mmol), MeI (260 μL, 4.10 mmol) and CH3CO2D (420 μL,
6.80 mmol) in ether as described in GP2 gave sulfone D-8a
(466 mg, 96%) (88% D) as colourless crystals.
[(3-Methylpentane-3-yl)sulfonyl]benzene (12b): Treatment of sulfone
8b (467 mg, 2.20 mmol) with nBuLi (1.50 m in n-hexane, 1.76 mL,
2.64 mmol) and MeI (260 μL, 4.10 mmol) in THF as described in
GP1 gave sulfone 12b (393 mg, 79%) as a yellow oil. 1H NMR
(300 MHz, CDCl3): δ = 1.01 (t, J = 7.40 Hz, 6 H, CH3CH2), 1.21
(s, 3 H, Me), 1.66 (app. sext, J = 7.39 Hz, 2 H, CH3CH2), 1.88
(app. sext, J = 7.38 Hz, 2 H, CH3CH2), 7.55 (m, 2 H, Ph), 7.64 (m,
1 H, Ph), 7.87 (m, 2 H, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ
= 8.5 (d, CH3CH2), 19.4 (d, Me), 25.6 (u, CH3CH2), 66.1 (u, CS),
128.7 (d, Ph), 130.3 (d, Ph), 133.4 (d, Ph), 136.5 (u, Ph) ppm. IR
(KBr): ν = 3539 (w), 3335 (w), 3066 (m), 2973 (s), 2942 (s), 2884
˜
(s), 2345 (w), 1754 (w), 1725 (w), 1585 (m), 1460 (vs), 1447 (vs),
1386 (s), 1337 (m), 1286 (vs), 1206 (m), 1163 (vs), 1128 (vs), 1079
(vs), 1012 (m), 1000 (m), 933 (w), 875 (m) cm–1. MS (EI, 70 eV):
m/z (%) = 226 (0.1) [M+], 143 (4), 86 (6), 85 (100), 84 (5), 77 (6), 69
(7.14), 57 (17), 55 (5), 51 (4). C12H18O2S (226.34): calcd. C 63.68, H
8.02; found C 63.57, H 8.04.
Bis[3-(phenylsulfonyl)pentyl-C,O]bis(2-propanolato)titanium (9b): To
a solution of nBuLi (1.50 m in n-hexane, 5.16 mL, 7.74 mmol) in
diethyl ether (10 mL) was added at –78 °C a solution of sulfone 8b
(1.500 g, 7.06 mmol) in diethyl ether (20 mL) by using a cannula.
The mixture was stirred at room temperature for 15 min, then the
solution of carbanion 3b was cooled to –50 °C and added by using
a cannula at –50 °C to a solution of ClTi(OiPr)3 (2.210 g,
8.48 mmol) in diethyl ether (15 mL). The mixture was warmed to
room temperature, whereby LiCl precipitated after 10 min. The yel-
low mixture was stirred for 4 h at room temperature, then filtered
under argon through a fritted glass covered with dry kieselguhr.
The mixture was concentrated to half of its volume and cooled to
2 °C for 12 h, which produced yellow crystals. The mother liquor
was removed by using a syringe and the crystals were washed with
a small amount of cold n-hexane. Drying in vacuo gave bis(1-sulf-
Treatment of sulfone 8b (467 mg, 2.20 mmol) with nBuLi (1.50 m
in n-hexane, 1.76 mL, 2.64 mmol), ClTi(OiPr)3 (745 mg,
2.86 mmol), MeI (260 μL, 4.10 mmol) and CH3CO2D (420 μL,
6.80 mmol) in ether as described in GP2 gave sulfone D-8b
(439 mg, 94%) (90% D).
Treatment of sulfone 8b (467 mg, 2.20 mmol) with nBuLi (1.50 m
in n-hexane, 1.76 mL, 2.64 mmol), ClTi(OiPr)3 (687 mg,
2.64 mmol) and MeI (260 μL, 4.10 mmol) in THF as described in
GP3 gave sulfone 12b (478 mg, 96%) as a yellow oil.
1
onylalkyl)titanium 9b (1.039 g, 50%) as yellow crystals. H NMR
(tert-Pentylsulfonyl)benzene (12c): Treatment of sulfone 8c (436 mg,
2.20 mmol) with nBuLi (1.50 m in n-hexane, 1.76 mL, 2.64 mmol)
and MeI (260 μL, 4.10 mmol) in THF as described in GP1 gave
sulfone 12c (411 mg, 88%) as a pale-yellow oil. Rf = 0.64 (EtOAc/
n-hexane, 1:1). 1H NMR (300 MHz, CDCl3): δ = 0.95 (t, J =
7.56 Hz, 3 H, CH3CH2), 1.28 (s, 6 H, Me), 1.75 (q, J = 7.41 Hz, 2
H, CH3CH2), 7.55 (m, 2 H, Ph), 7.65 (m, 1 H, Ph), 7.88 (m, 2 H,
Ph) ppm. 13C NMR (75 MHz, CDCl3): δ = 8.2 (d, CH3CH2), 12.0
(d, Me), 27.8 (u, CH3CH2), 63.3 (u, CMe2), 128.7 (d, Ph), 130. 6
(300 MHz, [D6]benzene): δ = 1.05 (br. s, 12 H, CH3CH2), 1.38 (d,
J = 6.05 Hz, 12 H, iPr), 1.80–2.40 (br. s, 8 H, CH3CH2), 5.02 (sept,
J = 6.05 Hz, 2 H, iPr), 6.95–7.07 (m, 6 H, Ph), 8.16 (m, 4 H,
Ph) ppm. 13C NMR (75 MHz, [D6]benzene): δ = 12.2 (d, CH3CH2),
21.1 (u, CH3CH2), 26.6 (d, iPr), 75.8 (u, CTi), 80.5 (d, iPr), 129.4
1
(d, Ph), 129.6 (d, Ph), 132.9 (d, Ph), 141.5 (u, Ph) ppm. H NMR
(300 MHz, [D8]THF): δ = 0.95 (tr, J = 7.42 Hz, 12 H, CH3CH2),
1.40 (d, J = 6.04 Hz, 12 H, iPr), 1.92–1.94 (br. s, 8 H, CH3CH2),
5.01 (sept, J = 6.04 Hz, 2 H, iPr), 7.53–7.60 (m, 6 H, Ph), 7.97–
8.01 (m, 4 H, Ph) ppm. 13C NMR (75 MHz, [D8]THF): δ = 11.7
(d, CH3CH2), 21.0 (u, CH3CH2), 26.3 (d, iPr), 75.5 (u, CTi), 80.5
(d, iPr), 129.5 (d, Ph), 129.6 (d, Ph), 133.3 (d, Ph), 141.4 (u,
Ph) ppm. C28H44O6S2Ti (588.64): calcd. C 57.13, H 7.53; found C
57.9, H 7.55.
(d, Ph), 133.5 (u, Ph) ppm. IR (KBr): ν = 3386 (w), 3065 (m), 2975
˜
(s), 2941 (s), 2882 (m), 2370 (w), 2346 (w), 1795 (w), 1724 (w), 1585
(m), 1463 (vs), 1447 (vs), 1391 (s), 1366 (m), 1296 (vs), 1287 (vs),
1169 (s), 1130 (vs), 1078 (vs), 1060 (m), 1024 (m), 999 (m), 923 (w),
875 (m), 806 (m) cm–1. MS (EI, 70 eV): m/z (%) = 212 (0.3) [M+],
143 (9), 85 (9), 77 (7), 71 (100), 70 (8), 55 (13), 51 (6). C11H16O2S
(212.31): calcd. C 62.23, H 7.60; found C 62.11, H 7.71.
(tert-Butylsulfonyl)benzene (12a): Treatment of sulfone 8a (486 mg,
2.64 mmol) with nBuLi (1.50 m in n-hexane, 1.91 mL, 2.86 mmol) Treatment of sulfone 8c (436 mg, 2.20 mmol) with nBuLi (1.50 m
and MeI (260 μL, 4.10 mmol) in THF as described in GP1 gave
sulfone 12a (439 mg, 84%) after crystallisation from diethyl ether/
in n-hexane, 1.76 mL, 2.64 mmol), ClTi(OiPr)3 (745 mg,
2.86 mmol), MeI (260 μL, 4.10 mmol) and CH3CO2D (420 μL,
Eur. J. Org. Chem. 2014, 7134–7147
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7143

T. Heß, G. Raabe, H.-J. Gais
FULL PAPER
6.80 mmol) in ether as described in GP2 gave sulfone D-8c (409 mg,
94%) (67% D).
Treatment of sulfone 8f (361 mg, 2.20 mmol) with nBuLi (1.50 m in
n-hexane, 1.76 mL, 2.64 mmol), ClTi(OiPr)3 (745 mg, 2.86 mmol),
MeI (260 μL, 4.10 mmol) and CH3CO2D (420 μL, 6.80 mmol) in
ether as described in GP2 gave sulfone D-8f (350 mg, 97%) (82%
D).
[(2,3-Dimethylbutan-2-yl)sulfonyl]benzene (12d): Treatment of sulf-
one 8d (467 mg, 2.20 mmol) with nBuLi (1.50 m in n-hexane,
1.76 mL, 2.64 mmol) and MeI (260 μL, 4.10 mmol) in THF as de-
scribed in GP1 gave sulfone 12d (473 mg, 95%) after crystallisation
from diethyl ether/n-hexane (1:3), as colourless crystals, m.p. 78 °C.
1H NMR (300 MHz, CDCl3): δ = 1.08 (d, J = 6.87 Hz, 6 H, iPr),
1.24 (s, 6 H, Me), 2.22 (sept, J = 6.86 Hz, 1 H, iPr), 7.55 (m, 2 H,
Ph), 7.64 (m, 1 H, Ph), 7.87 (m, 2 H, Ph) ppm. 13C NMR (75 MHz,
CDCl3): δ = 18.9 (d, iPr), 19.4 (d, Me), 31.5 (d, iPr), 66.45 (u, CS),
128.7 (d, Ph), 130.3 (d, Ph), 133.4 (d, Ph), 136.8 (u, Ph) ppm. IR
(3-tert-Butylsulfonyl)-3-methylpentane (12g): Treatment of sulfone
8g (423 mg, 2.20 mmol) with nBuLi (1.50 m in n-hexane, 1.76 mL,
2.64 mmol) and MeI (260 μL, 4.10 mmol) in THF as described in
GP1 gave sulfone 12g (400 mg, 88%) after crystallisation from di-
ethyl ether/n-hexane (1:3) as pale-yellow crystals, m.p. 54 °C. 1H
NMR (300 MHz, CDCl3): δ = 1.02 (t, J = 7.39 Hz, 6 H, CH3CH2),
1.43 (s, 3 H, Me), 1.50 (s, 9 H, tBu), 1.85 (app. sext, J = 7.39 Hz,
2 H, CH3CH2), 2.05 (app. sext, J = 7.38 Hz, 2 H, CH3CH2) ppm.
13C NMR (75 MHz, CDCl3): δ = 8.6 (d, CH3CH2), 21.0 (d, Me),
26.1 (d, tBu), 27.5 (u, CH3CH2), 66.0 (u, tBu), 72.2 (u, CS) ppm.
(KBr): ν = 3078 (m), 2996 (s), 2965 (s), 2941 (s), 2877 (s), 2196 (w),
˜
2014 (w), 1914 (w), 1827 (w), 1786 (w), 1706 (w), 1621 (w), 1583
(m), 1465 (vs), 1450 (vs), 1386 (s), 1371 (m), 1318 (s), 1288 (vs),
1218 (s), 1176 (s), 1150 (vs), 1124 (vs), 1074 (vs), 1025 (s), 997 (s),
936 (m), 883 (m) cm–1. MS (EI, 70 eV): m/z (%) = 226 (10) [M+],
143 (27), 86 (12), 85 (100), 84 (42), 77 (46), 69 (23), 57 (30), 55
(15), 51 (43). C12H18O2S (226.34): calcd. C 63.68, H 8.02; found C
63.26, H 8.01.
IR (KBr): ν = 3485 (w), 2974 (vs), 2942 (s), 2882 (s), 1468 (s), 1385
˜
(s), 1368 (s), 1337 (s), 1275 (vs), 1186 (s), 1148 (s), 1112 (vs), 1094
(vs), 1070 (s), 1017 (m), 946 (w), 804 (m) cm–1. MS (EI, 70 eV): m/z
(%) = 207 (0.008) [M+], 85 (17), 71 (8), 69 (5), 58 (5), 57 (100), 56
(22), 55 (11). C10H22O2S (206.35): calcd. C 58.21, H 10.75; found
C 58.38, H 10.40.
Treatment of sulfone 8d (467 mg, 2.20 mmol) with nBuLi (1.50 m
in n-hexane, 1.76 mL, 2.64 mmol), ClTi(OiPr)3 (745 mg,
2.86 mmol), MeI (260 μL, 4.10 mmol) and CH3CO2D (420 μL,
6.80 mmol) in ether as described in GP2 gave sulfone D-8d
(434 mg, 93%) (88% D).
Treatment of sulfone 8g (423 mg, 2.20 mmol) with nBuLi (1.50 m
in n-hexane, 1.76 mL, 2.64 mmol), ClTi(OiPr)3 (745 mg,
2.86 mmol), MeI (260 μL, 4.10 mmol) and CH3CO2D (420 μL,
6.80 mmol) in ether as described in GP2 gave sulfone D-8g
(392 mg, 88%) (86% D).
(2,4-Dimethylpentan-2-yl)sulfonylbenzene (12e): Treatment of sulf-
one 8e (498 mg, 2.20 mmol) with nBuLi (1.50 m in n-hexane,
1.73 mL, 2.60 mmol) and MeI (260 μL, 4.10 mmol) in THF as de-
scribed in GP1 gave sulfone 12e (513 mg, 97%) after crystallisation
from diethyl ether/n-hexane (1:3) as colourless crystals, m.p. 60 °C.
1H NMR (300 MHz, CDCl3): δ = 0.96 (d, J = 6.60 Hz, 6 H, iPr),
1.34 (s, 6 H, Me), 1.66 (d, J = 5.50 Hz, 2 H, CH2), 1.75 (m, J =
6.59 Hz, 1 H, iPr), 7.55 (m, 2 H, Ph), 7.65 (m, 1 H, Ph), 7.87 (m,
2 H, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.0 (d, iPr), 24.3
(d, iPr), 25.1 (d, Me), 42.7 (u, CH2), 63.9 (u, CS), 128.7 (d, Ph),
Treatment of sulfone 8g (423 mg, 2.20 mmol) with nBuLi (1.50 m
in n-hexane, 1.76 mL, 2.64 mmol), ClTi(OiPr)3 (687 mg,
2.64 mmol) and MeI (260 μL, 4.10 mmol) in THF as described in
GP3 gave sulfone 12g (413 mg, 91%) after crystallisation from di-
ethyl ether/n-hexane (1:3) as colourless crystals.
(2-tert-Butylsulfonyl)-2-methylbutane (12h): Treatment of sulfone 8h
(392 mg, 2.20 mmol) with nBuLi (1.50 m in n-hexane, 1.76 mL,
2.64 mmol) and MeI (260 μL, 4.10 mmol) in THF as described in
GP1 gave sulfone 12h (376 mg, 89%) after crystallisation from di-
ethyl ether/n-hexane (1:3) as colourless crystals, m.p. 64 °C. 1H
NMR (300 MHz, CDCl3): δ = 1.00 (t, J = 7.39 Hz, 3 H, CH3CH2),
1.45 (s, 6 H, Me), 1.51 (s, 9 H, tBu), 1.96 (q, J = 7.38 Hz, 2 H,
CH3CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 8.4 (d, CH3CH2),
22.1 (d, Me), 26.2 (d, tBu), 29.9 (u, CH3CH2), 65.3 (u, CS), 69.1
130.7 (d, Ph), 133.5 (d, Ph), 135.5 (u, Ph) ppm. IR (KBr): ν = 3426
˜
(w), 3063 (w), 2969 (vs), 2935 (s), 2869 (s), 2199 (w), 1583 (m),
1467 (s), 1448 (s), 1388 (s), 1369 (m), 1353 (m), 1297 (vs), 1162
(vs), 1129 (vs), 1074 (vs), 1023 (s), 998 (m), 982 (m), 941 (m), 866
(w), 805 (m) cm–1. MS (EI, 70 eV): m/z (%) = 241 (0.5) [M+], 99
(42), 83 (7), 78 (6), 77 (13), 57 (100), 55 (9), 51 (10). C13H20O2S
(240.36): calcd. C 64.96, H 8.39; found C 64.93, H 8.33.
(u, CS) ppm. IR (KBr): ν = 3905 (w), 3855 (w), 3843 (w), 3752 (w),
˜
3736 (w), 3690 (w), 3677 (w), 3657 (w), 3630 (m), 3414 (m), 2977
(vs), 2946 (s), 2886 (s), 2374 (w), 2346 (m), 2176 (w), 1720 (m),
1687 (m), 1656 (m), 1638 (m), 1562 (m), 1474 (vs), 1391 (s), 1368
(s), 1308 (s), 1267 (vs), 1185 (s), 1156 (s), 1089 (vs), 1040 (s), 1018
(s), 967 (w), 938 (m), 923 (w), 800 (s) cm–1. MS (EI, 70 eV): m/z
(%) = 193 (0.2) [M+], 72 (6), 71 (100), 70 (14), 57 (70), 56 (8), 55
(11).
Treatment of sulfone 8e (498 mg, 2.20 mmol) with nBuLi (1.50 m
in n-hexane, 1.73 mL, 2.60 mmol), ClTi(OiPr)3 (745 mg,
2.86 mmol), MeI (260 μL, 4.10 mmol) and CH3CO2D (420 μL,
6.80 mmol) in ether as described in GP2 gave sulfone D-8e (468 mg,
94%) (86% D).
(2-tert-Butylsulfonyl)-2-methylpropane (12f): Treatment of sulfone
8f (361 mg, 2.20 mmol) with nBuLi (1.50 m in n-hexane, 1.76 mL,
2.64 mmol) and MeI (260 μL, 4.10 mmol) in THF as described in
GP1 gave sulfone 12e (329 mg, 84%) after crystallisation from di-
ethyl ether/n-hexane (1:3) as colourless crystals, m.p. 127 °C. 1H
NMR (300 MHz, CDCl3): δ = 1.51 (s, 18 H, tBu) ppm. 13C NMR
(75 MHz, CDCl3): δ = 26.1 (d, tBu), 64.7 (u, tBu) ppm. IR (KBr):
Treatment of sulfone 8h (392 mg, 2.20 mmol) with nBuLi (1.50 m
in n-hexane, 1.76 mL, 2.64 mmol), ClTi(OiPr)3 (745 mg,
2.86 mmol), MeI (260 μL, 4.10 mmol) and CH3CO2D (420 μL,
6.80 mmol) in ether as described in GP2 gave sulfone D-8h
(358 mg, 91%) (99% D).
(؎)-2-Methyl-1-phenyl-2-(phenylsulfonyl)propan-1-ol (13a). From 3a
and PhCHO: Treatment of sulfone 8a (750 mg, 4.07 mmol) with
nBuLi (1.50 m in n-hexane, 2.98 mL, 4.48 mmol) and PhCHO
(860 mg, 8.10 mmol) in THF as described in GP4 gave alcohol 13a
(976 mg, 84%) as colourless crystals.
ν = 3904 (w), 3855 (w), 3839 (w), 3736 (w), 3690 (w), 3677 (w),
˜
3650 (w), 3630 (w), 3422 (m), 2989 (s), 2976 (s), 2939 (s), 2374 (w),
2346 (w), 2161 (w), 1687 (m), 1655 (m), 1561 (m), 1476 (vs), 1456
(s), 1394 (s), 1376 (s), 1364 (s), 1270 (vs), 1179 (s), 1088 (vs), 1013
(s), 965 (m), 946 (m), 934 (m) cm–1. MS (EI, 70 eV): m/z (%) = 71 From Putative 15Aa and PhCHO in THF: Treatment of sulfone
(11), 58 (4), 57 (100), 56 (12), 55 (8). C8H18O2S (178.29): calcd. C
53.89, H 10.18; found C 53.79, H 10.25.
8a (750 mg, 4.07 mmol) with nBuLi (1.50 m in n-hexane, 2.98 mL,
4.48 mmol), ClTi(OiPr)3 (1.27 g, 4.88 mmol) and PhCHO (860 mg,
7144
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 7134–7147

Lithium–Titanium Exchange of Bis(1-sulfonylalkyl)titaniums
8.10 mmol) in THF as described in GP5 gave alcohol 13a (1.005 g,
85%) as pale-yellow crystals, m.p. 174–176 °C, Rf = 0.53 (EtOAc/
From Putative 15Ac and PhCHO: Treatment of sulfone 8c (750 mg,
3.78 mmol) with nBuLi (1.50 m in n-hexane, 2.80 mL, 4.20 mmol),
n-hexane, 1:1). 1H NMR (300 MHz, CDCl3): δ = 0.94 (s, 3 H, Me), ClTi(OiPr)3 (1.183 g, 4.54 mmol) and PhCHO (864 mg, 8.14 mmol)
1.41 (s, 3 H, Me), 4.24 (s, 1 H, OH), 5.19 (s, 1 H, CHO), 7.30–7.96
(m, 10 H, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ = 13.9 (d, Me),
21.6 (d, Me), 66.7 (u, CS), 74.7 (d, CO), 128.00 (d, Ph), 128.03 (d,
Ph), 129.0 (d, Ph), 130.5 (d, Ph), 128.3 (d, Ph), 134.2 (d, Ph), 134.9
in THF as described in GP5 gave a mixture of diastereomeric
alcohols 13c (862 mg, 75%) as colourless crystals, m.p. 130 °C, Rf
= 0.62 (EtOAc/n-hexane, 1:1). 1H NMR (300 MHz, CDCl3): δ =
0.52 (dd, J = 7.4 Hz, 3 HA, CH3CH2), 0.98 (dd, J = 7.6 Hz, 3 HB,
(d, Ph), 137.9 (u, Ph) ppm. IR (KBr): ν = 3905 (w), 3547 (vs), 3087 CH3CH2), 1.05 (s, 3 HA, Me), 1.35 (dq, J = 7.5, 15.1 Hz, 1 HA,
˜
(m), 3052 (m), 3029 (m), 3000 (m), 2969 (m), 2937 (m), 2196 (w), CH3CH2), 1.46 (s, 3 HB, Me), 1.49 (dq, J = 7.5, 15.1 Hz, 1 HA,
1967 (w), 1914 (w), 1831 (w), 1601 (m), 1581 (m), 1494 (m), 1450
(s), 1386 (s), 1368 (m), 1338 (m), 1284 (vs), 1189 (s), 1148 (vs), 1122
CH3CH2), 1.95 (dq, J = 7.6, 15.4 Hz, 1 HB, CH3CH2), 2.29 (dq, J
= 7.6, 15.4 Hz, 1 HB, CH3CH2), 4.27 (d, J = 1.4 Hz, 1 HA, OH),
(vs), 1074 (vs), 1048 (vs), 1027 (s), 1002 (s), 948 (m), 921 (s), 851 4.30 (d, J = 1.7 Hz, 1 HB, OH), 4.97 (d, J = 1.7 Hz, 1 HB, CHO),
(m) cm–1. MS (EI, 70 eV): m/z (%) = 290 (7) [M+], 184 (100), 149
(71), 132 (17), 79 (35), 77 (62), 57 (52). C16H18O3S (290.38): calcd.
C 66.18, H 6.25; found C 65.85, H 6.26.
5.12 (d, J = 1.4 Hz, 1 HA, CHO), 7.30–7.96 (m, 10 HA, 10 HB,
Ph) ppm. 13C NMR (75 MHz, CDCl3): δ = 8.2 (d, CH3CH2A), 9.3
(d, CH3CH2B), 11.1 (d, MeA), 18.6 (d, MeB), 20.6 (u, CH3CH2A),
26.2 (u, CH3CH2B), 69.5 (u, CSA), 70. 6 (u, CSB), 74.9 (d, COA),
(؎)-2-Ethyl-1-phenyl-2-(phenylsulfonyl)butan-1-ol (13b). From 3b
and PhCHO in THF: Treatment of sulfone 8b (750 mg, 3.53 mmol)
with nBuLi (1.50 m in n-hexane, 2.60 mL, 3.90 mmol) and PhCHO
(750 mg, 7.07 mmol) in THF as described in GP4 gave alcohol 13b
(921 mg, 82%) as colourless crystals.
76.0 (d, CO ), 127.9–138.6 (16 signals, Ph) ppm. IR (KBr): ν =
˜
B
3461 (vs), 3064 (m), 3028 (m), 3001 (m), 2979 (m), 2943 (m), 2202
(w), 957 (w), 1892 (w), 1583 (w), 1494 (m), 1451 (vs), 1391 (m),
1346 (m), 1285 (vs), 1195 (m), 1151 (vs), 1132 (vs), 1074 (vs), 1060
(vs), 1041 (s), 1026 (s), 907 (w), 859 (w), 809 (w) cm–1. MS (EI,
70 eV): m/z (%) = 304 (16) [M+], 198 (100), 183 (92), 163 (76), 105
(43), 143 (48) (33), 79, 77 (81), 57 (39). C17H20O3S (304.40): calcd.
C 67.08, H 6.62; found C 66.84, H 6.53.
From Putative 15Ab and PhCHO in THF: Treatment of sulfone
8b (750 mg, 3.53 mmol) with nBuLi (1.50 m in n-hexane, 2.60 mL,
3.90 mmol), ClTi(OiPr)3 (1.100 g, 4.22 mmol) and PhCHO
(750 mg, 7.07 mmol) in THF as described in GP5 gave alcohol 13b
(899 mg, 80%) as colourless crystals.
(؎)-2-(tert-Butylsulfonyl)-2-methyl-1-phenylpropan-1-ol (13f). From
3f and PhCHO: Treatment of sulfone 8f (750 mg, 4.57 mmol) with
nBuLi (1.50 m in n-hexane, 3.40 mL, 5.10 mmol) and PhCHO
(970 mg, 9.14 mmol) in THF as described in GP4 gave alcohol 13f
(1.087 g, 88%) as colourless crystals.
From 9b and PhCHO in Ether in the Presence of MeI: To a solution
of sulfone 8b (750 mg, 3.53 mmol) in diethyl ether (20 mL) was
added at –78 °C, nBuLi (1.50 m in n-hexane, 2.60 mL, 3.98 mmol).
The yellow mixture was stirred for 15 min at room temperature,
then cooled to –78 °C and treated dropwise with ClTi(OiPr)3
(1.100 g, 4.22 mmol). The orange mixture was stirred for 3 h at
room temperature, cooled to –78 °C and treated with MeI (424 μL,
6.70 mmol). After the mixture was stirred for 30 min at room tem-
perature, it was cooled to –78 °C and treated with PhCHO (116 mg,
10.9 mmol). The mixture was then stirred for 1 d at room tempera-
ture, treated with 2 n aqueous HCl (25 mL) and extracted with di-
ethyl ether (3ϫ 40 mL). Drying (MgSO4) and concentration of the
combined organic phases gave alcohol 13b (1.023 g, 91 %) as
colourless crystals, m.p. 114 °C, Rf = 0.63 (EtOAc/n-hexane, 1:1).
1H NMR (300 MHz, CDCl3): δ = 0.62 (dd, J = 7.4 Hz, 3 H,
CH3CH2), 1.16 (dd, J = 7.6 Hz, 3 H, CH3CH2), 1.53 (dq, J = 7.4,
14.8 Hz, 1 H, CH3CH2), 1.76 (dq, J = 7.4, 14.8 Hz, 1 H, CH3CH2),
2.00 (dq, J = 7.6, 15.4 Hz, 1 H, CH3CH2), 2.25 (dq, J = 7.6,
15.1 Hz, 1 H, CH3CH2), 4.23 (s, 1 H, OH), 4.97 (s, 1 H, CHO),
7.28–7.95 (m, 10 H, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ = 8.4
(d, CH3CH2), 9.4 (d, CH3CH2), 19.3 (u, CH3CH2), 23.9 (u,
CH3CH2), 73.9 (u, CS), 76.1 (d, CO), 128.1 (d), 128.3 (d), 128.9
(d), 130.1 (d, Ph), 128.3 (d), 133.8 (d, Ph), 137.3 (u), 138.9 (u,
From Putative 15Af and PhCHO in THF: Treatment of sulfone 8f
(750 mg, 4.57 mmol) with nBuLi (1.50 m in n-hexane, 3.40 mL,
5.10 mmol), ClTi(OiPr)3 (1.430 g, 5.48 mmol) and PhCHO
(970 mg, 9.13 mmol) in THF as described in GP5 gave alcohol 13f
(865 mg, 70%) as colourless crystals, m.p. 112–114 °C; Rf = 0.58
1
(EtOAc/n-hexane, 1:1). H NMR (300 MHz, CDCl3): δ = 1.18 (s,
3 H, Me), 1.54 (s, 3 H, Me), 1.60 (s, 9 H, tBu), 4.2–4.4 (br. s, 1 H,
OH), 5.41 (s, 1 H, CHO), 7.28–7.40 (m, 5 H, Ph) ppm. 13C NMR
(75 MHz, CDCl3): δ = 16.3 (d, Me), 22.9 (d, Me), 26.0 (d, tBu),
67.3 (u, tBu), 72.6 (u, CS), 75.7 (d, CO), 128.0 (d, Ph), 128.2 (d,
Ph), 128.3 (d, Ph), 138.0 (u, Ph) ppm. IR (KBr): ν = 3415 (vs),
˜
3086 (w), 3060 (m), 3032 (m), 2997 (m), 2937 (m), 2882 (m), 2161
(w), 1957 (w), 1889 (w), 1719 (w), 1602 (m), 1489 (s), 1470 (m),
1452 (s), 1397 (m), 1377 (m), 1365 (s), 1296 (s), 1259 (vs), 1190 (s),
1146 (m), 1131 (s), 1080 (vs), 1062 (vs), 1028 (m), 1004 (s), 962 (m),
946 (m), 919 (w), 854 (m), 801 (w) cm–1. MS (EI, 70 eV): m/z (%)
= 270 (15) [M+], 164 (40), 149 (100), 132 (30), 108 (60), 91 (48), 79
(27), 57 (98). C14H22O3S (270.39): calcd. C 62.19, H 8.20; found C
62.10, H 8.20.
Ph) ppm. IR (KBr): ν = 3493 (vs), 3070 (m), 3031 (w), 2991 (m), (؎)-2-(tert-Butylsulfonyl)-2-ethyl-1-phenylbutan-1-ol (13g). From 3g
˜
2945 (m), 2923 (m), 2884 (m), 2183 (w), 1627 (m), 1583 (m), 1494 and PhCHO: Treatment of sulfone 8g (750 mg, 3.90 mmol) with
(m), 1451 (s), 1386 (m), 1344 (m), 1279 (vs), 1179 (m), 1150 (s), nBuLi (1.50 m in n-hexane, 2.90 mL, 4.35 mmol) and PhCHO
1133 (s), 1110 (s), 1092 (m), 1073 (s), 1056 (s), 1027 (m), 999 (m), (830 mg, 7.82 mmol) in THF as described in GP4 gave alcohol 13g
974 (w), 925 (m), 816 (m) cm–1. MS (EI, 70 eV): m/z (%) = 318 (6) (1.013 g, 87%) as colourless crystals.
[M+], 212 (96), 197 (100), 177 (58), 143 (52), 107 (40), 91 (40), 77
From Putative 15Ag and PhCHO in THF: Treatment of sulfone
(62), 57 (91). C18H22O3S (318.43): calcd. C 67.89, H 6.96; found C
8g (750 mg, 3.90 mmol) with nBuLi (1.50 m in n-hexane, 2.90 mL,
67.70, H 6.88.
4.35 mmol), ClTi(OiPr)3 (1.220 g, 4.68 mmol) and PhCHO
(؎)-2-Methyl-1-phenyl-2-(phenylsulfonyl)butan-1-ol (13c). From 3c (830 mg, 7.82 mmol) in THF as described in GP5 gave alcohol 13g
and PhCHO: Treatment of sulfone 8c (750 mg, 3.78 mmol) with (698 g, 60 %) as colourless crystals, m.p. 117–118 °C; Rf = 0.62
nBuLi (1.50 m in n-hexane, 2.80 mL, 4.20 mmol) and PhCHO
(800 mg, 7.53 mmol) in THF as described in GP4 gave a mixture
of diastereomeric alcohols 13c (990 mg, 86%) in a ratio of 1:1 as
colourless crystals.
(EtOAc/n-hexane, 1:1). 1H NMR (300 MHz, CDCl3): δ = 0.52 (dd,
J = 7.4 Hz, 3 H, CH3CH2), 1.15 (dd, J = 7.4 Hz, 3 H, CH3CH2),
1.61 (s, 9 H, tBu), 1.74 (dq, J = 7.4, 14.8 Hz, 1 H, CH3CH2), 2.01
(dq, J = 7.5, 15.1 Hz, 1 H, CH3CH2), 2.14 (dq, J = 7.5, 14.8 Hz, 1
Eur. J. Org. Chem. 2014, 7134–7147
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7145

T. Heß, G. Raabe, H.-J. Gais
FULL PAPER
H, CH3CH2), 2.31 (dq, J = 7.6, 15.4 Hz, 1 H, CH3CH2), 4.41 (s, 1
H, OH), 5.33 (s, 1 H, CHO), 7.33 (m, 2 H, Ph), 7.35 (m, 1 H, Ph),
7.43 (m, 2 H, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ = 8.8 (d,
CH3CH2), 9.9 (d, CH3CH2), 20.4 (u, CH3CH2), 24.9 (u, CH3CH2),
26.1 (d, tBu), 69.1 (u, CS), 76.5 (d, CO), 81.2 (u, tBu), 128.2 (d,
Acknowledgments
The authors thank the Volkswagen Foundation for financial sup-
port and Dr. Jan Runsink for NMR measurements.
Ph), 128.4 (d, Ph), 128.4 (d, Ph), 139.2 (u, Ph) ppm. IR (KBr): ν =
˜
3475 (vs), 2980 (s), 2946 (m), 2373 (w), 2345 (w), 2150 (w), 1655
(m), 1498 (m), 1482 (m), 1459 (s), 1408 (m), 1385 (m), 1372 (m),
1363 (m), 1338 (m), 1322 (m), 1267 (vs), 1243 (s), 1201 (s), 1175
(m), 1156 (m), 1117 (m), 1092 (s), 1077 (vs), 1046 (m), 1016 (m),
982 (w), 966 (w), 931 (m), 879 (w), 813 (m) cm–1. MS (EI, 70 eV):
m/z (%) = 298 (6) [M+], 192 (28), 177 (100), 136 (44), 119 (54), 107
(40), 91 (40), 77 (17), 57 (62). C16H26O3S (298.44): calcd. C 64.39,
H 8.78; found C 64.26, H 8.85.
[1] a) B. Weidmann, D. Seebach, Angew. Chem. Int. Ed. Engl.
1983, 22, 31–45; Angew. Chem. 1983, 95, 12–26; b) M. T. Reetz,
Organotitanium Reagents in Organic Synthesis Springer-Verlag,
Berlin, 1986; c) D. Hoppe, in: Methoden Org. Chem. (Houben-
Weyl) (Eds.: G. Helmchen, R. W. Hoffmann, J. Mulzer, E.
Schaumann), Thieme, Stuttgart, Germany, 1996, vol. E21, vol.
3, p. 1551–1583; d) M. Reggelin, C. Zur, Synthesis 2000, 1–
64; e) M. T. Reetz in, Organometallics in Synthesis (Ed.: M.
Schlosser), Wiley-VCH, Weinheim, Germany, 2002, p. 817–923;
f) H.-J. Gais, in: Asymmetric Synthesis with Chemical and Bio-
logical Methodes (Eds.: D. Enders, K.-E. Jäger), Wiley-VCH,
Weinheim, Germany, 2007, p. 75–115.
[2] J. Vollhardt, H.-J. Gais, K. L. Lukas, Angew. Chem. Int. Ed.
Engl. 1985, 24, 696–697; Angew. Chem. 1985, 97, 695–697.
[3] J. Vollhardt, Ph. D. Thesis, TU Darmstadt, Germany, 1990.
[4] H.-J. Gais, J. Vollhardt, H. Günther, D. Moskau, H. J. Lindner,
S. Braun, J. Am. Chem. Soc. 1988, 110, 978–980.
[5] J. F. K. Müller, M. Neuburger, H.-P. Weber, J. Am. Chem. Soc.
1999, 121, 12212–12213.
[6] 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.
[7] a) H.-J. Gais, P. R. Bruns, G. Raabe, R. Hainz, M. Schleusner,
J. Runsink, G. S. Babu, J. Am. Chem. Soc. 2005, 127, 6617–
6631; b) P. R. Bruns, Ph. D. Thesis, RWTH Aachen, Germany,
2003.
Reaction of Lithium α-Sulfonyl Carbanion 3f with Benzaldehyde and
Acetophenone: (؎)-2-(tert-Butylsulfonyl)-2-methyl-1-phenylpropan-
1-ol (13f) and (؎)-3-(tert-Butylsulfonyl)-3-methyl-2-phenylbutan-2-
ol (14): To a solution of sulfone 8f (820 mg, 5.00 mmol) in diethyl
ether (20 mL) was added at –78 °C, nBuLi (1.38 m in n-hexane,
3.99 mL, 5.50 mmol). The solution of 3f was stirred for 15 min at
room temperature, cooled to –78 °C then added by using a cannula
to a solution of PhCHO (530 mg, 5.00 mmol) and PhCOMe
(600 mg, 5.00 mmol) in diethyl ether (20 mL) at –78 °C. After the
mixture was warmed to room temperature within 4 h, it was stirred
for 12 h. Then 2 n aqueous HCl was added and the mixture was
extracted with diethyl ether (4ϫ 25 mL). GC–MS analysis [Rt =
3.55 (PhCHO), 6.11 (PhCOMe), 13.49 (13f), 17.78 (14) min] re-
vealed the formation of 13f and 14 in a ratio of 55:45.
Treatment of Bis(1-sulfonylalkyl)titanium 9f with Benzaldehyde and
Acetophenone: (؎)-2-(tert-Butylsulfonyl)-2-methyl-1-phenylpropan-
1-ol (13f): To a solution of sulfone 8f (820 mg, 5.00 mmol) in di-
ethyl ether (20 mL) was added at –78 °C, nBuLi (1.38 m in n-hex-
ane, 3.99 mL, 5.50 mmol). The solution of 3f was then stirred for
15 min at room temperature, cooled to –78 °C and ClTi(OiPr)3
(1.560 g, 5.99 mmol) was added. The mixture was stirred at room
temperature for 3 h then cooled to –78 °C and added by using a
cannula to a solution of PhCHO (530 mg, 5.00 mmol) and
PhCOMe (600 mg, 5.00 mmol) in diethyl ether (20 mL) at –78 °C.
The mixture was warmed to room temperature over 4 h, stirred for
12 h, then 2 n aqueous HCl was added and the mixture was ex-
tracted with diethyl ether (4ϫ 25 mL). GC analysis [Rt = 13.49
(13f) min] only showed the formation of 13f.
[8] a) M. Lejkowski, P. Banerjee, S. Schüller, A. Münch, J. Run-
sink, C. Vermeeren, H.-J. Gais, Chem. Eur. J. 2012, 18, 3529–
3548; b) M. Lejkowski, P. Banerjee, G. Raabe, J. Runsink, H.-
J. Gais, Eur. J. Org. Chem. 2014, 529–553.
[9] a) M. Reggelin, H. Weinberger, Angew. Chem. Int. Ed. Engl.
1994, 33, 444–446; Angew. Chem. 1994, 106, 489–491; b) M.
Reggelin, H. Weinberger, M. Gerlach, R. Welcker, J. Am.
Chem. Soc. 1996, 118, 4765–4777; c) M. Reggelin, B. Junker,
T. Heinrich, S. Slavik, P. Bühle, J. Am. Chem. Soc. 2006, 128,
4023–4034.
[10] According to ab initio calculations, sulfones (E. D. Glendening,
A. L. Shrout, J. Phys. Chem. A 2005, 109, 4966–4972) and sulf-
oximines (P. S. Kumar, P. V. Bharatam, Tetrahedron 2005, 61,
5633–5639) have ylide-like S–O and S–N single bonds with
negative charged O and N atoms and double positive charged
S atoms. For convenience, however, both groups are depicted
in all structural formulas of this work with S=O and S=N
double bonds.
[11] R. Scholz, G. Hellmann, S. Rohs, D. Özdemir, G. Raabe, C.
Vermeeren, H.-J. Gais, Eur. J. Org. Chem. 2010, 4588–4616.
[12] G. Hellmann, A. Hack, E. Thiemermann, O. Luche, G. Raabe,
H.-J. Gais, Chem. Eur. J. 2013, 19, 3869–3897.
[13] a) N. S. Simpkins, Sulfones in Organic Synthesis (Eds.: J. E. Bal-
dwin, P. D. Magnus), Pergamon Press, Oxford, UK, 1993; b)
C. Najera, J. M. Sansano, Recent Research Developments in Or-
ganic Chemistry (Ed.: S. G. Pandalai), Transworld Research
Network, Trivandrum, India, USA, 1998, vol. 2, 637–683; c)
H.-J. Gais, in: Organosulfur Chemistry in Asymmetric Synthesis
(Eds.: T. Toru, C. Bolm), Wiley-VCH, Weinheim, Germany,
2008, p. 375–398; d) A. El-Awa, M. N. Noshi, X. Mol-
lat du Jourdin, P. L. Fuchs, Chem. Rev. 2009, 109, 2315–2349;
e) B. Zajc, R. Kumar, Synthesis 2010, 1822–1836; f) F. Marti-
nelli, A. Palmieri, M. Petrini, Phosphorus Sulfur Silicon Relat.
Elem. 2011, 186, 1032–1045.
Treatment of the Putative Titanium Derivative 15Af with Benzalde-
hyde and Acetophenone: (؎)-2-(tert-Butylsulfonyl)-2-methyl-1-phen-
ylpropan-1-ol (13f): To a solution of sulfone 8f (820 mg, 5.00 mmol)
in THF (20 mL) was added at –78 °C, nBuLi (1.38 m in n-hexane,
3.99 mL, 5.50 mmol). The solution of 3f was then stirred for 15 min
at room temperature, cooled to –78 °C and ClTi(OiPr)3 (1.560 g,
5.99 mmol) was added. The mixture was stirred at room tempera-
ture for 3 h then cooled to –78 °C and added by using a cannula to
a solution of PhCHO (530 mg, 5.00 mmol) and PhCOMe (600 mg,
5.00 mmol) in diethyl ether (20 mL) at –78 °C. The mixture was
warmed to room temperature over 4 h, stirred for 12 h, then 2 n
aqueous HCl was added and the mixture was extracted with diethyl
ether (4ϫ 25 mL). GC analysis [Rt = 13.49 (13f) min] only revealed
the formation of 13f.
Supporting Information (see footnote on the first page of this arti-
cle): Analytical and spectroscopic data of sulfones 8a–h and copies
[14] a) M. T. Reetz, J. Westermann, R. Steinbach, B. Wenderoth,
R. Peter, R. Ostarek, S. Maus, Chem. Ber. 1985, 118, 1421–
1440; b) M. T. Reetz, S. Afr. J. Chem. 1989, 42, 49–56.
1
of the H and 13C NMR spectra of 6a–c, 7a–c, 8a–h, 12a–h, 13a–
c, 13f and 13g.
7146
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 7134–7147

Lithium–Titanium Exchange of Bis(1-sulfonylalkyl)titaniums
[15] H.-J. Gais, J. Vollhardt, H. J. Lindner, H. Paulus, Angew. Chem.
Int. Ed. Engl. 1988, 27, 1540–1542; Angew. Chem. 1988, 100,
1598–1600.
[16] U. Gerlach, T. Haubenreich, S. Hünig, Y. Keita, Chem. Ber.
1993, 126, 1205–1215.
[17] P. G. Cozzi, C. Floriani, A. Chiesi-Villa, C. Rizzoli, Organome-
tallics 1995, 14, 1756–1760.
[18] For the O-titanation of Ag[CH(SO2CF3)2] with ClTi(OiPr)3,
see: A. R. Siedle, J. C. Huffman, Inorg. Chem. 1990, 29, 3131–
3134.
[19] All chiral α-sulfonyl carbanions and chiral sulfones used in this
work are racemic.
[20] H.-J. Gais, J. Vollhardt, G. Hellmann, H. Paulus, H. J. Lindner,
Tetrahedron Lett. 1988, 29, 1259–1262.
[21] H.-J. Gais, J. Müller, J. Vollhardt, H. J. Lindner, J. Am. Chem.
Soc. 1991, 113, 4002–4003.
[22] M. Linnert, C. Bruhn, C. Wagner, D. Steinborn, J. Organomet.
Chem. 2006, 691, 2358–2367.
[28]
[29]
[30]
However, a report described putative (iPr)2Ti(OiPr)2 as being
stable in the temperature range of –78 to 25 °C, see: J. J. Eisch,
A. A. Adeosun, J. N. Gitua, Eur. J. Org. Chem. 2003, 4721–
4727.
CCDC-1007114 (for 6b) and -1007113 (for 9a) contain the sup-
plementary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.ac.uk/data_request/cif.
A search in the Cambridge Structural Database (CSD) gave
[Ti(OC6H3Ph2-2,6)2{CH(Ph)CH2CH2CH(Ph)}] (NIVKAE) as
the only structurally related compound, see: M. G. Thorn, J. E.
Hill, S. A. Waratuke, E. S. Johnson, P. E. Fanwick, I. P.
Rothwell, J. Am. Chem. Soc. 1997, 119, 8630–8641.
[31]
[32]
N. Serpone, D. G. Bickley, Prog. Inorg. Chem. 1972, 17, 391–
566.
W. Hollstein, K. Harms, M. Marsch, G. Boche, Angew. Chem.
Int. Ed. Engl. 1988, 27, 846–847; Angew. Chem. 1988, 100, 868–
869.
[23] R. Scholz, G. Hellmann, S. Rohs, G. Raabe, J. Runsink, D.
Özdemir, O. Luche, T. Heß, A. W. Giesen, J. Atodiresei, Eur. J.
Org. Chem. 2010, 4559–4587.
[33] a) E. C. Alyea, A. Malek, P. H. Merrell, Transition Met. Chem.
1979, 4, 172–178; b) L. T. Armistead, P. S. White, M. R. Gagné,
Organometallics 1998, 17, 216–220; c) K. Osakada, T. Hosoda,
T. Yamamoto, Bull. Chem. Soc. Jpn. 2000, 73, 923–930; d) S.
Lim, B. Choi, Y. Min, D. Kim, I. Yoon, S. S. Lee, I. Lee, J.
Organomet. Chem. 2004, 689, 224–237.
[24] T. Takahashi, Y. Liu, Sci. Synth. 2004, 7, 597–628.
[25] However, the propensity of alkyltitaniums for β-H elimination
can vary significantly. For example, whereas RTi(OiPr)3 (R =
iPr, tBu) are unstable in solution,[14a] (cC6H11)Ti(OiPr)3 (Q. Li,
H.-M. Gau, Chirality 2011, 23, 929–939) and tBuTi-
(OC6H3iPr2-2,6)3 (H. Nöth, M. Schmidt, Organometallics
1995, 14, 4601–4610) are stable crystalline compounds at room
temperature.
[26] For the isolation and spectroscopic characterization of
(cC6H11)2Ti(OR)2 (R = Me, Et, cC6H11), see: a) J.-B. Weber, J.
Porret, A. Jacot-Guillarmod, Helv. Chim. Acta 1978, 61, 2949–
2955; b) E. M. Meyer, A. Jacot-Guillarmod, Helv. Chim. Acta
1983, 66, 898–901.
[34] U. Zucchini, E. Albizzati, U. Giannini, J. Organomet. Chem.
1971, 26, 357–372.
[35] Protonolyis of (PhCH2)4Ti with equimolar amounts of
(PhCH2)2NOH gave a mixture of (PhCH2)2Ti[ON(CH2Ph)2]2
and (PhCH2)4Ti, see: M. K. Mahannthappa, A. P. Cole, R. M.
Waymouth, Organometallics 2004, 23, 1405–1410.
[36] J. S. Jennings, W. Wardlaw, W. J. R. Way, J. Chem. Soc. 1936,
637–640.
[37] W. G. Kofron, L. M. Baclawski, J. Org. Chem. 1976, 41, 1879–
[27] a) O. G. Kulinkovich, A. de Meijere, Chem. Rev. 2000, 100,
2789–2834; b) F. Sato, H. Urabe, S. Okamoto, Chem. Rec.
2000, 100, 2835–2886; c) J. K. Cha, O. G. Kulinkovich, Org.
React. 2012, 77, 1–159.
1880.
Received: July 9, 2014
Published Online: October 1, 2014
Eur. J. Org. Chem. 2014, 7134–7147
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7147