Functionalized organolithium compounds of DTBB-catalyzed sulfur-lithium exchange

Article abstract of DOI:10.1055/s-1999-3426

The successive reaction of β- or γ-hydroxy or amino phenyl thioethers (1,4) with butyllithium and an excess of lithium powder in the presence of a catalytic amount of DTBB in THF at - 78°C leads to the formation of the corresponding β- or γ-functionalized organolithium compounds 2 or 5, respectively, which by treatment with different electrophiles [D₂O, t- BuCHO, PhCHO, Me₂CO, (CH₂)₄CO, (CH₂)₅CO] at temperatures ranging between - 78°C and room temperature yields, after hydrolysis with water, the expected functionalized alcohols or amines 3 or 6, respectively, in a completely regioselective manner.

Full text of DOI:10.1055/s-1999-3426

FEATURE ARTICLE
503
Functionalized Organolithium Compounds by DTBB-Catalyzed
SulfurÐLithium Exchange
Francisco Foubelo, Ana GutiŽrrez, Miguel Yus*
Departamento de Qu’mica Org‡nica, Facultad de Ciencias, Universidad de Alicante, Apdo. 99, E-03080 Alicante, Spain
Fax +34(96)5903549; E-mail: yus@ua.es
Received 10 October 1998
examples of functionalized organolithium compounds
(mainly having the lithium atom at a benzylic position)
have been described by sulfur/lithium exchange using a
lithiumÐarene reagent in the lithiation step.19 In this article
Abstract: The successive reaction of b- or g-hydroxy or amino
phenyl thioethers (1, 4) with butyllithium and an excess of lithium
powder in the presence of a catalytic amount of DTBB in THF at Ð
78¡C leads to the formation of the corresponding b- or g-function-
alized organolithium compounds 2 or 5, respectively, which by we describe the application of an arene-catalyzed lithia-
treatment with different electrophiles [D2O, t-BuCHO, PhCHO,
Me2CO, (CH2)4CO, (CH2)5CO] at temperatures ranging between Ð
78¡C and room temperature yields, after hydrolysis with water, the
g-functionalized organolithium intermediates by a sulfur/
expected functionalized alcohols or amines 3 or 6, respectively, in
a completely regioselective manner.
tion, a methodology developed in our laboratory in the last
few years,11,12 to the general preparation of b- and
lithium exchange.20,21
Key words: lithiation, arene-catalysis, functionalization, organo-
lithium
Functionalized organolithium compounds (I)1 are inter-
esting intermediates in synthetic organic chemistry be-
cause they are able to transfer their functionality to
electrophilic reagents, thus in only one reaction step poly-
functionalized molecules (II) can be directly prepared.
The stability of these intermediates depends strongly on
the separation between the functional group and the car-
The reaction of different b-hydroxy or b-phenylamino
phenyl thioethers 1aÐf with butyllithium (1:1 molar ratio)
bonÐlithium bond: b- or g-functionalized derivatives (I, n
= 2, 3) are especially unstable undergoing b- or g-elimi-
nation, respectively, even at very low temperatures giving
alkenes2 and cyclopropanes,3 respectively, as the reaction
products. One way to decrease the ability of the heteroat-
om X to act as a leaving group is to transform this neutral
group into a negative one locating a negative charge on it,
so intermediates of type III are far more stable than I as
they are able to survive at low temperatures. These sp3-hy-
bridized b-functionalized organolithium compounds (III,
m = 2), also called d2 reagents,4 have been prepared by (a)
mercuryÐlithium exchange from the corresponding
hydroxy or amino mercurials;5 (b) chlorineÐlithium ex-
change from b-chloro alcohols6 or amines7 using a lithium
arene;8 (c) reductive opening of oxiranes9 or aziridines10
using the last lithiation mixture8 or an excess of lithium
and a catalytic amount of an arene,11 naphthalene and 4,4'-
di-tert-butylbiphenyl (DTBB) being the most commonly
used;12 and (d) to the best of our knowledge, only one ex-
ample has been described in the literature6f,g of using a
tinÐlithium transmetallation reaction. Concerning sp3-hy-
bridized g-functionalized organolithium compounds (III,
m = 3), also called d3 reagents,4 they have been prepared
following the former routes (b),13 (c) (from the corre-
in THF at Ð78¡C for 10 min followed by treatment with a
dark green suspension of an excess of lithium powder (ca.
1:14 molar ratio) and a catalytic amount of DTBB (1:0.1
molar ratio; 5 mol%) in THF at the same temperature for
1Ð3 h (see experimental part; after this time the dark green
colour appeared again) gave a solution of the correspond-
ing dilithiated intermediate 2aÐf, which by reaction with
different electrophiles [D2O, t-BuCHO, PhCHO, Me2CO,
(CH2)4CO, (CH2)5CO] at temperatures ranging between
Ð78¡C and room temperature afforded, after hydrolysis
with water, the expected functionalized alcohols or
amines 3aaÐfe (Scheme 1 and Table 1). In all cases a vari-
able amount (<20%) of the corresponding ÒreducedÓ
products (3 with E = H) was detected in the reaction mix-
sponding four-membered saturated heterocycles),14 and (a) i. BuLi, THF, Ð78¡C, 2 min., ii. Li, DTBB cat. (5 mol %), THF,
Ð78¡C, 1Ð5 h (see experimental); (b) i. E+ = D2O, t-BuCHO,
PhCHO, Me2CO, Et2CO, (CH2)4CO, (CH2)5CO, Ð78¡C → r.t.,
overnight, ii. H2O
(d),15 as well as by addition of an alkyllithium to allylic
derivatives,16 and in some very special cases by direct
deprotonation.17,18 To the best of our knowledge, very few
Scheme 1
Synthesis 1999, No. 3, 503Ð514 ISSN 0039-7881 © Thieme Stuttgart á New York

504
F. Foubelo et al.
FEATURE ARTICLE
ture, which could be easily separated by column chroma- an aliphatic amine. These dianionic species are not acces-
tography, except when deuterium oxide was used as sible by any route mentioned above, so even reacting with
electrophile (Table 1, entries 1, 6, 12 and 17); the forma- electrophiles in poor yields (Table 1, entries 21Ð23) their
tion of these byproducts is due to the partial decomposi- preparation results in an intrinsic novelty.
tion of very reactive intermediates of type 2 by abstracting
Starting materials 1 were prepared following classical
methodologies. Thus, hydroxy thioethers 1aÐc were ob-
tained by reaction of the corresponding epoxides with
potassium thiophenolate. Successive reaction of 1-bromo-
2-chloroethane with potassium thiophenolate and aniline
or isopropylamine yielded aminated thioethers 1d or 1f,
respectively. Finally, compound 1e was prepared by treat-
a proton from the reaction medium.10b
Concerning the stereochemical stability of intermediates
of type 2, we prepared the starting material 1c as the pure
trans-diastereoisomer and submitted it to the reaction
shown in Scheme 1. After isolation different ratios of a
trans/cis diastereoisomeric mixture were obtained (1.3Ð
5:1; Table 1, entries 10 and 11), so we conclude that inter-
ment of benzylidene aniline with lithiomethyl phenyl
mediates 2 are configurationally unstable.
thioether. In all cases the final hydrolysis with water af-
From the results shown in Table 1 it can be seen that this forded the corresponding products 1aÐf.
methodology allows us to prepare for the first time b-
functionalized organolithium compounds 2f derived from
In the second part of this study we report on the applica-
tion of the methodology shown in Scheme 1 to the prepa-
Biographical Sketches
Francisco Foubelo was 1991) at Princeton Universi- current research interests in-
born in Carre–a-Cabrales ty, he joined the research clude the preparation of new
(Asturias) in 1961, and re- group of Professot Miguel chiral polyfunctionalized
ceived his BSc (1984), MSc Yus at the University of anionic synthons and the de-
(1986) and PhD (1989) de- Alicante where he became velopment of new method-
grees in chemistry from the Associate Professor in ologies
for
preparing
University of Oviedo. After 1995. He has published organolithium compounds.
a postdoctoral stay (1989Ð more than 40 papers. His
Ana GutiŽrrez was born in her BSc and MSc degrees in Miguel Yus on the prepara-
Alicante in 1972. She stud- 1995. Currently she is carry- tion of functionalized orga-
ied chemistry at the Univer- ing out her PhD studies nolithium compounds from
sity of Alicante and earned within the research group of phenyl thioethers.
Miguel Yus was born in In 1988, he moved to a chair Spain, Switzerland and
Zaragoza in 1947. He re- in organic chemistry at the United States. He is co-au-
ceived BSc (1969), MSc University of Alicante thor of more than 200 pa-
(1971) and PhD (1973) de- where he is currently head pers mainly in the field of
grees from the University of of the Organic Chemistry development of new meth-
Zaragoza. After spending Department. Professor Yus odologies involving organo-
two years as a postdoc in the has been a visiting professor metallic intermediates. His
Max Planck Institut fŸr at different institutions such current research interest is
Kohlenforschung in MŸl- as ETH-ZŸrich and the uni- focused on the preparation
heim a. d. Ruhr, he returned versities of Oxford, Har- of very reactive functional-
to the University of Oviedo vard, Uppsala, Marseille ized organolithium com-
where he became Associate and Tucson. He is a member pounds and their use in
Professor in 1977, being or fellow of the chemical synthetic organic chemistry.
promoted to full professor in societies of Argentina.
1987 at the same university. England, Germany, Japan,
Synthesis 1999, No. 3, 503Ð514 ISSN 0039-7881 © Thieme Stuttgart · New York

FEATURE ARTICLE Functionalized Organolithium Compounds by DTBB-Catalyzed SulfurÐLithium Exchange
Table 2 Compounds 6 Prepared
505
Table 1 Compounds 3 Prepared
R1
R2
E
Yield
(%)a
Entry Product
Electro-
phile
Y
R
E
Yield
(%)a
Entry Prod- Electro-
uct phile
Y
(90)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
6ab
6ac
6ad
6ae
6bc
6be
t-BuCHO
PhCHO
Me2CO
(CH2)5CO O
PhCHO
(CH2)5CO O
O
O
O
Me t-BuCHOH 55b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
3aa D2O
3ab t-BuCHO O
3ac PhCHO
3ad Me2CO
O
Ph
Ph
Ph
Ph
H
H
H
H
H
H
H
H
H
D
64c
t-BuCHOH 21 (47)c
Me PhCHOH
Me Me2COH
O
O
PhCHOH
Me2COH
48 (69)d
62 (93)
33(73)
Me (CH2)5COH 53
O
Ph PhCHOH
33(68)d
3ae (CH2)5CO O
3ba D2O
3bb t-BuCHO O
3bd Me2CO
3be (CH2)5CO O
3cd Me2CO
3ce (CH2)5CO O
3da D2O
3db t-BuCHO PhN
3dc PhCHO PhN
3dd Me2CO
3de (CH2)5CO PhN
3ea D2O
3eb t-BuCHO PhN Ph
3ec PhCHO PhN Ph
3ee (CH2)5CO PhN Ph
3fc PhCHO i-PrN H
Ph
(CH2)5COH 32 (42)
65 (88)b
t-BuCHOH 49 (59)e
Me2COH 50
(CH2)5COH 24 (32)
Me2COH
21f
(CH2)5COH 20 (40)g
43 (99)b
t-BuCHOH 21 (32)
Ph (CH2)5COH 53
O
n-C6H13
n-C6H13
n-C6H13
n-C6H13
Ð(CH2)4Ð
Ð(CH2)4Ð
H
H
H
H
H
D
(S)-6bd
(S,S/R)-6bc PhCHO
Me2CO
O
O
i-PrN
Ph Me2COH
Ph PhCHOH
43
60c
16
O
6cc
6ce
6cf
6cg
6db
6dc
6dd
6de
PhCHO
(CH2)5CO i-PrN
Et2CO i-PrN
(CH2)4CO i-PrN
t-BuCHO NH
PhCHO
Me2CO
H
H
H
H
PhCHOH
(CH2)5COH 30
Et2COH 11
(CH2)4COH 18
O
PhN
H
H
H
H
H
H
H
H
H
H
H
H
D
Me t-BuCHOH 28(36)c
NH
NH
Me PhCHOH
Me Me2COH
23(24)c
52
PhCHOH
Me2COH
61
39 (94)
PhN
(CH2)5CO NH
Me (CH2)5COH 34
(CH2)5COH 25 (38)
99b
t-BuCHOH (78)h
PhN Ph
D
a Yield of isolated product (>95% from GC and 300 MHz 1H NMR)
after column chromatography (silica gel, hexane/ethyl acetate) and
recrystallization based on the starting materials 7; in parenthesis
isolated crude yield (purity >90% from 300 MHz 1H NMR).
b 1:0.7 Diastereoisomeric ratio (from 75 MHz 13C NMR).
c 1:1 Diastereoisomeric ratio (from 75 MHz 13C NMR).
PhCHOH
(CH2)5COH 28
PhCHOH
Me2COH
(CH2)5COH 10 (10)
52 (61)h
10 (14)
17
3fd Me2CO
3fe (CH2)5CO i-PrN H
i-PrN H
d 1:1.5Ð2.2 Diastereoisomeric ratio (from 75 MHz 13C NMR).
a Yield of isolated pure product (> 95% from GC and 300 MHz 1H
NMR) after column chromatography (silica gel, hexane/ethyl ace-
tate) and recrystallization based on the starting materials 1; in paren-
thesis isolated crude yield (purity > 90% from 300 MHz 1H NMR).
b > 90% deuterium incorporation measured by mass spectrometry.
c 1.7:1 Diastereoisomeric ratio (from 75 MHz 13C NMR).
d 1.2:1 Diastereoisomeric ratio (from 75 MHz 13C NMR).
e 1.3:1 Diastereoisomeric ratio (from 75 MHz 13C NMR).
f 5:1 trans:cis ratio (from 75 MHz 13C NMR).
nitrogen has no substitution (5d), i.e., a primary amine de-
rivative, and from this, although with modest yields, func-
tionalized primary amines 6dbÐde could be directly
prepared (Table 2, entries 13Ð16).
g 1.3:1 trans:cis ratio (from 75 MHz 13C NMR).
In this case, and in order to study the possibility of prepar-
ing enantiomerically pure compounds, we prepared the
chiral derivative (S)-4b and reacted it under the reaction
conditions shown in Scheme 2; when acetone was used as
electrophile enantiomerically pure product (S)-6bd was
isolated (Table 2, entry 7). However, using a prochiral
electrophile such as benzaldehyde, a ca. 1:1 diastereomer-
ic mixture was obtained. This result, which has been al-
ready observed in other cases,6c,9e,14h shows that the
asymmetric induction is practically nonexistent; an expla-
nation for this behaviour can be found by considering the
high reactivity of intermediates of type 5.
h 1:1 Diastereoisomeric ratio (from 75 MHz 13C NMR).
ration of g-functionalized organolithium compounds of
type III with m = 3. Thus, when γ−oxygenated or γ-ami-
nated thioethers 4aÐd were submitted to the same protocol
as for starting materials 1, and using different electro-
philes [D2O, t-BuCHO, PhCHO, Me2CO, (CH2)4CO,
(CH2)5CO], the expected products 6abÐde were isolated
after hydrolysis, dianionic intermediates 5aÐd being pre-
sumably involved in the reaction (Scheme 2 and Table 2).
One important remark has to be noted concerning the re-
sults shown in Scheme 2. Not only aliphatic amine deriv-
atives (5c) can be prepared for the first time (which are
also not accessible by other methodologies) but also we
were able to generate an intermediate in which the anionic
Concerning starting materials 4, oxygenated derivatives
4a,b [or (S)-4b] were prepared by treatment of the corre-
sponding epoxides with lithiomethyl phenyl thioether and
final hydrolysis. Compound 4c was prepared following
the same procedure as for 1f but using 1-bromo-3-chloro-
propane instead of 1-bromo-2-chloroethane. Finally
Michael-type addition of thiophenol to methyl vinyl
ketone followed by reductive amination (H4NOAc/
NaBH3CN) afforded compound 4d, after hydrolysis.
In conclusion, we have shown in this paper that the
DTBB-catalyzed lithiation of oxygen- or nitrogen-con-
taining phenyl thioethers is an adequate methodology to
(a) and (b) as shown in Scheme 1
Scheme 2
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506
F. Foubelo et al.
FEATURE ARTICLE
MS (EI): m/z (%) = 238 (M+, 12), 124 (100), 110 (26), 109 (17), 91
(14), 78 (13), 69 (24), 65 (11), 55 (52), 51 (11), 45 (34), 44 (43), 43
(44).
1H NMR (300 MHz, CDCl3): d = 0.87 (t, J = 6.7 Hz, CH3, 3H),
1.24Ð1.58 [m, CH3(CH2)5, 10H], 2.50 br s, OH, 1H), 2.84 (dd, J =
8.5 Hz, 13.7, CHHSPh, 1H), 3.14 (dd, J = 3.5, 13.7 Hz, CHHSPh,
1H), 3.60Ð3.70 (m, CHOH, 1H), 7.14Ð7.40 (m, ArH, 5H).
13C NMR (75 MHz, CDCl3): d = 14.01 (CH3), 22.52, 25.56, 29.19,
31.68, 36.08 [(CH3CH2)5],42.13 (CH2S), 69.33 (CHOH), 126.47,
128.98, 129.92, 135.35 (ArC).
IR (film): n = 3683Ð3131 (OH) cm–1.
prepare b- and g-functionalized organolithium intermedi-
ates, which are rather stable at low temperature and react
with different electrophiles (mainly carbonyl compounds)
to give functionalized alcohols or amines. In some cases
(aliphatic amine derivatives) the mentioned derivatives
are only accesible by the way described in this paper. Fi-
nally, the results of this methodology compare well with
other methodologies used : as an example, either the re-
ductive opening of styrene oxide or the lithiation of its
chlorohydrin (2-chloro-2-phenylethanol) afford the ben-
zylic derivative 2'a. However, the successive thiopheno-
late opening of the same epoxide followed by DTBB-
catalyzed lithiation afforded the corresponding regioiso-
mer 2a (Table 1, entry 1).
HRMS: calcd for C14H22OS: 238.1391; found: 238.1382.
trans-2-Phenylsulfanylcyclohexanol (1c)
Pale yellow oil, Rf 0.38 (hexane/EtOAc: 5/1).
MS (EI): m/z (%) = 208 (M+, 23), 110 (100), 98 (14), 81 (29), 79
(11), 55 (16), 45 (14), 43 (11).
1H NMR (300 MHz, CDCl3): d = 1.18Ð1.39 (m, CH2CH2, 4H),
1.64Ð1.72 (m, CH2CHS, 2H), 2.03Ð2.14 (m, CH2CHOH, 2H), 2.79
(td, J = 4.0 Hz, 10.1, CHSPh, 1H), 3.13 (br s, OH, 1H), 3.34 (td, J
= 4.4 Hz, 10.1, CHOH, 1H), 7.26Ð7.32, 7.45Ð7.48 (2m, ArH, 5H).
13C NMR (75 MHz, CDCl3): d = 24.1, 25.9, 32.5, 33.7 [(CH2)4],
56.2 (CHS), 71.9 (CHOH), 127.5, 128.7, 132.6, 133.5 (ArC).
Melting points are uncorrected. IR were recorded on a Nicolet 510
P-FT and only the structurally most important peaks are listed.
NMR spectra were determined on a Bruker AC-300 using TMS as
internal standard; coupling constants (J) are given in Hz. Optical ro-
tations were measured on a Jasco DIP-1000 polarimeter. Low reso-
lution electron impact (EI) mass spectra were obtained at 70 eV on
a Shimadzu QP-5000. HRMS (EI) were recorded on VG-Micro-
mass ZAB-ZF, Kratos MS 80 RFA, and Finnigan MAT 95 S. Mi-
croanalysis were performed by the Microanalyses Service of the
University of Alicante and the University of Zaragoza. All reagents
were commercially available and of the best grade. Reaction sol-
vents were dried and distilled under N2 using standard procedures.
Analytical TLC was performed on Schleicher & Schuell F1400/LS
silica gel plates andthe spots visualized with UV light at 254 nm.
GLC analysis were performed on a HP 5890.
IR (neat): n = 3657Ð3118 (OH) cm–1.
HRMS: calcd for C14H22OS: 208.0922; found: 208.0916.
2-Chloroethyl Phenyl Thioether22
Thiophenol (1.65 g, 1.54 mL, 15 mmol) was added dropwise to
KOH (1.00 g, 18 mmol) in MeOH (40 mL) at r.t. After 10 min, 1-
bromo-2-chloroethane (2.14 g, 1.24 mL, 15 mmol) was added drop-
wise and stirring was continued for 1 h at the same temperature.
Then, the solvent was removed on a rotary evaporator and the resi-
due was hydrolyzed with H2O (25 mL) and extracted with EtOAc
(3 × 25 mL). The organic layer was dried (Na2SO4) and evaporated
(15 mmHg) to give a residue which was purified by column chro-
matography (silica gel, hexane) to give the title compound as a pale
yellow oil, Rf 0.35 (hexane).
MS (EI): m/z (%) = 172 (M+, 19), 123 (68), 110 (13), 109 (18), 77
(14), 69 (16), 66 (11), 65 (34), 63 (10), 51 (27), 50 (12), 45 (100).
1H NMR (300 MHz, CDCl3): d = 3.17Ð3.24 (m, CH2SPh, 2H),
3.57Ð3.63 (m, ClCH2, 2H), 7.23Ð7.40 (m, ArH, 5H).
Preparation of Compounds 1aÐc; General Procedure
Thiophenol (1.10 g, 1.02 mL, 10 mmol) was added dropwise to
KOH (0.68g, 12 mmol) in MeOH (30 mL) at r.t. After 10 min, the
corresponding epoxide (10 mmol) was added dropwise. The mix-
ture was heated at 50¡C for 2 h. After that, the solvent was removed
on a rotary evaporator and the residue was hydrolyzed with H2O
(20 mL) and extracted with EtOAc (3 × 25 mL). The organic layer
was dried (Na2SO4) and evaporated (15 mmHg) to give a residue,
which was purified by column chromatography (silica gel, hexane/
EtOAc) to give title compounds 1aÐc.
13C NMR (75 MHz, CDCl3): d = 36.1 (CH2S), 42.2 (CH2Cl), 127.0,
129.15, 130.4, 134.2 (ArC).
IR (neat): n = 3075Ð3060, 3020 (ArH) cm–1.
1-Phenyl-2-phenylsulfanylethanol (1a)
Pale yellow oil, Rf 0.33 (hexane/EtOAc: 5/1).
N-Phenyl-2-phenylsulfanylethylamine (1d)
To 2-chloroethyl phenyl thioether (1.73 g, 10 mmol) in MeOH
(30 mL) was added NaHCO3 (2.52 g, 30 mmol) and aniline (0.93 g,
0.91 mL, 10 mmol). The mixture was heated at 50¡C for 2 h. After
that, the solvent was removed on a rotary evaporator and the residue
was hydrolyzed with H2O (25 mL) and extracted with EtOAc
(3 × 25 mL). The organic layer was dried (Na2SO4) and evaporated
(15 mmHg) to give a residue, which was purified by column chro-
matography (silica gel, hexane/EtOAc) to give the title compound
as a white solid, mp 39¡C, Rf 0.29 (hexane/EtOAc: 20/1).
MS (EI): m/z (%) = 230 (M+, 7), 212 (11), 124 (100), 107 (29), 91
(15), 79 (45), 78 (17), 77 (41), 65 (10), 51 (32), 45 (37).
1H NMR (300 MHz, CDCl3): d = 2.99 (br s, OH, 1H), 3.07 (dd, J =
9.5 Hz, 13.7, CHH, 1H), 3.28 (dd, J = 3.7 Hz, 13.7, CHH, 1H), 4.68
(dd, J = 3.7 Hz, 9.5, CHOH, 1H), 7.20Ð7.40 (m, ArH, 10H).
13C NMR (75 MHz, CDCl3): d = 43.78 (CH2), 71.61 (CHOH),
125.77, 126.62, 127.87, 128.44, 129.02, 130.02, 134.91, 142.10
(ArC).
MS (EI): m/z (%) = 229 (M+, 10), 124 (26), 106 (100), 77 (25), 65
(12), 51 (16), 45 (12).
IR (neat): n = 3600Ð3100 (OH) cm–1.
1H NMR (300 MHz, CDCl3): d = 3.13 (t, J = 6.4 Hz, CH2SPh, 2H),
3.35 (t, J = 6.4 Hz, PhNHCH2, 2H), 4.01 (br s, NH, 1H), 6.55Ð6.74,
7.13Ð7.40 (2m, ArH, 10H).
HRMS: calcd for C14H14OS: 230.0765; found: 230.0768.
1-Phenylsulfanyloctan-2-ol (1b)
Pale yellow oil, Rf 0.51 (hexane/EtOAc: 5/1).
Synthesis 1999, No. 3, 503Ð514 ISSN 0039-7881 © Thieme Stuttgart · New York

FEATURE ARTICLE Functionalized Organolithium Compounds by DTBB-Catalyzed SulfurÐLithium Exchange
507
13C NMR (75 MHz, CDCl3): d = 33.7 (CH2S), 42.55 (CH2NH),
oxide or (S)-styrene oxide] was added dropwise. The system was al-
113.0, 117.75, 126.6, 129.0, 129.3, 130.2, 135.1, 147.45 (ArC).
lowed to reach r.t. after 3 h and was hydrolyzed with H2O (30 mL)
and extracted with EtOAc (3 × 25 mL). The organic layer was dried
(Na2SO4) and evaporated (15 mmHg) to give a residue, which was
purified by column chromatography (silica gel, hexane/EtOAc) to
give the title compounds.
IR (neat): n = 3400 (NH) cm–1.
HRMS: calcd for C14H15NS: 229.0925; found: 229.0926.
1-Phenyl-N-phenyl-2-phenylsulfanylethylamine (1e)
4-Phenylsulfanylbutan-2-ol (4a):23
Pale yellow oil, Rf 0.33 (hexane/EtOAc: 3/1).
MS (EI): m/z (%) = 182 (M+, 6), 110 (25), 77 (11), 72 (42), 66 (11),
65 (18), 57 (47), 55 (22), 51 (17), 45 (68), 43 (100).
1H NMR (300 MHz, CDCl3): d = 1.20 (d, J = 6.4 Hz, CH3, 3H),
1.71Ð1.80 (m, PhSCH2CH2, OH, 3H), 2.95Ð3.11 (m, PhSCH2, 2H),
3.96 (sextet, J = 6.1 Hz, CHOH, 1H), 7.14Ð7.36 (m, ArH, 5H).
13C NMR (75 MHz, CDCl3): d = 23.5 (CH3), 30.1 (CH2CH2S), 38.1
(CH2S), 66.9 (CHOH), 125.9, 128.9, 129.1, 136.3 (ArC).
To a cooled (0¡C) solution of thioanisole (1.24 g, 1.17 mL,
10 mmol) and tetramethylethylenediamine (1.16 g, 1.51 mL,
10 mmol) in THF was added a 1.6 M BuLi hexane solution
(6.89 mL, 11 mmol) under Ar and stirring was continued at the
same temperature for 1 h. After that, the mixture was cooled to
Ð78¡C and a THF solution (2 mL) of N-benzylideneaniline (1.81 g,
10 mmol) was added via syringe. The system was allowed to reach
r.t. after 3 h and was hydrolyzed with H2O (30 mL) and extracted
with EtOAc (3 × 25 mL). The organic layer was dried (Na2SO4)
and evaporated (15 mmHg) to give a residue, which was purified by
column chromatography (silica gel, hexane/EtOAc) to give the title
compound as a white solid mp 56Ð57¡C; Rf 0.18 (hexane/EtOAc:
20/1).
MS (EI): m/z (%) = 213 (M+ Ð PhNH, 2), 212 (16), 183 (14), 182
(100), 104 (28), 93 (20), 78 (13), 77 (54), 66 (15), 65 (16), 51 (32),
45 (13), 44 (20).
1H NMR (300 MHz, CDCl3): d = 3.14 (dd, J = 9.16, 13.43 Hz,
CHH, 1H), 3.36 (dd, J = 4.27, 13.43 Hz,CHH, 1H), 4.39 (dd, J =
4.58, 9.15 Hz, CH, 1H), 4.51 (br s, NH, 1H), 6.44Ð6.68, 7.02Ð7.38
(2m, ArH, 15H).
IR (neat): n = 3715Ð3110 (OH) cm–1.
1-Phenyl-3-phenylsulfanylpropanol (4b)
White solid, mp 44¡C, Rf 0.39 (hexane/EtOAc: 3/1).
MS (EI): m/z (%) = 244 (M+, 5), 135 (11), 134 (44), 133 (66), 124
(18), 117 (34), 115 (16), 110 (30), 109 (28), 107 (18), 105 (42), 91
(29), 79 (78), 78 (29), 77 (100), 69 (17), 66 (19), 65 (43), 59 (10),
57 (22), 56 (16), 55 (27), 52 (12), 51 (64), 50 (20), 45 (62), 44 (40),
43 (48), 41 (25).
1H NMR (300 MHz, CDCl3): d = 1.93Ð2.15 (m, CHOHCH2, 2H),
2.21 (br s, OH, 1H), 2.98 (t, J = 7.0 Hz, PhSCH2, 2H), 4.83 (dd, J =
4.9 Hz, 7.9, CHOH, 1H), 7.15Ð7.35 (m, ArH, 10H).
13C NMR (75 MHz, CDCl3): d = 29.9 (CH2S), 38.0 (CH2CH2S),
72.0 (CHOH), 125.7, 125.9, 127.7, 128.5, 128.9, 129.1, 136.1,
143.9 (ArC).
IR (CHCl3): n = 3725Ð3120 (OH) cm–1.
13C NMR (75 MHz, CDCl3) d = 34.7 (CH2), 57.2 (CH), 113.8,
117.8, 126.3, 126.9, 127.55, 128.8, 129.0, 129.1, 130.6, 135.0,
142.4, 147.1 (ArC).
IR (CHCl3) n = 3400 (NH) cm–1.
Anal. calcd for C20H19NS: C, 78.66; H, 6.28; N, 4.59; S, 10.48;
found: C, 78.23; H, 6.34; N, 4.57; S, 10.73.
Anal. calcd for C15H16OS: C, 73.74; H, 6.61; S, 13.10; found: C,
73.53; H, 7.01; S, 12.84.
N-Isopropyl-2-phenylsulfanylethylamine (1f)
A solution of 2-chloroethyl phenyl thioether (1.73 g, 10 mmol) in
isopropylamine (8 mL) was heated at 50¡C in a sealed tube for 20 h.
After that, the solvent was removed on a rotary evaporator and the
residue was hydrolyzed with H2O (25 mL) and extracted with
EtOAc (3 × 25 mL). The organic layer was extracted with 1 M HCl
(2 × 20 mL) and this acidic aqueous layer was basified with NaOH
and extracted again with EtOAc (3 × 25 mL). This new organic lay-
er was dried (Na2SO4) and evaporated (15 mmHg) to give a residue
which was the title compound (>90% pure) as a yellow oil, Rf 0.41
(hexane/EtOAc: 1/1).
(S)-1-Phenyl-3-phenylsulfanylpropanol [(S)-4b]
White solid, mp 61¡C, Rf 0.42 (hexane/EtOAc: 3/1).
MS (EI): m/z (%) = 244 (M+, 5), 135 (11), 134 (44), 133 (66), 124
(18), 117 (34), 115 (16), 110(30), 109 (28), 107 (18), 105 (42), 91
(29), 79 (78), 78 (29), 77 (100), 69 (17), 66 (19), 65 (43), 59 (10),
57 (22), 56 (16), 55 (27), 52 (12), 51 (64), 50 (20), 45 (62), 44 (40),
43 (48), 41 (25).
1H NMR (300 MHz, CDCl3): d = 1.93Ð2.15 (m, CHOHCH2, 2H),
2.21 (br s, OH, 1H), 2.98 (t, J = 7.0 Hz, PhSCH2, 2H), 4.83 (dd, J =
4.9 Hz, 7.9, CHOH, 1H), 7.15Ð7.35 (m, ArH, 10H).
13C NMR (75 MHz, CDCl3): d = 29.9 (CH2S), 38.0 (CH2CH2S),
73.0 (CHOH), 125.7, 125.9, 127.7, 128.5, 128.9, 129.1, 136.1,
143.9 (ArC).
IR (neat): n = 3720Ð3120 (OH) cm–1.
MS (EI): m/z (%) = 195 (M+, 1), 124 (21), 72 (100), 44 (11), 43 (17),
42 (14).
1H NMR (300 MHz, CDCl3): d = 1.05 [2d, J = 6.4 Hz, (CH3)2CH,
6H], 2.14 (br s, NH, 1H), 2.76Ð2.85 (m, CHNHCH2CH2, 3H), 3.05Ð
3.10 (m, CH2NH, 2H), 7.16Ð7.38 (m, ArH, 5H).
13C NMR (75 MHz, CDCl3): d = 22.8 [(CH3)2CH], 34.2 (CH2SPh),
45.6 [(CH3)2CH], 48.25 (CH2NH), 126.2, 128.9, 129.6, 135.6
(ArC).
Anal. calcd for C15H16OS: C, 73.74; H, 6.61; S, 13.10; found: C,
73.88; H, 6.27; S, 12.90.
IR (neat): n = 3300 (NH) cm–1.
3-Chloropropyl Phenyl Thioether24
HRMS: calcd for C11H17NS: 195.1082; found: 195.1050.
Thiophenol (1.65 g, 1.54 mL, 15 mmol) was added dropwise to
KOH (1.00 g, 18 mmol) in MeOH (40 mL) at r.t. After 10 min, 1-
bromo-3-chloropropane (2.35 g, 1.48 mL, 15 mmol) was added
dropwise and stirring was continued for 1 h at the same temperature.
Then, the solvent was removed on a rotary evaporator and the resi-
due was hydrolyzed with H2O (30 mL) and extracted with EtOAc
(3 × 25 mL). The organic layer was dried (Na2SO4) and evaporated
(15 mmHg) to give a residue, which was purified by column chro-
Preparation of Compounds 4a,b. General Procedure
To a cooled (0¡C) solution of thioanisole (1.24 g, 1.17 mL,
10 mmol) and tetramethylethylenediamine (1.16 g, 1.51 mL,
10 mmol) in THF was added a 1.6 M BuLi hexane solution
(6.87 mL, 11 mmol) under Ar and stirring was continued at the
same temperature for 1 h. After that, the mixture was cooled down
to Ð78¡C and the corresponding epoxide [propylene oxide, styrene
Synthesis 1999, No. 3, 503Ð514 ISSN 0039-7881 © Thieme Stuttgart á New York

508
F. Foubelo et al.
FEATURE ARTICLE
matography (silica gel, hexane) to give title compound, pale yellow
oil, Rf 0.32 (hexane).
MS (EI): m/z (%) = 186 (M+, 17), 122 (51), 110 (51), 109 (14), 77
pounds 1aÐe and 4aÐb, 2 h in the case of compound 4c, 3 h in the
case of compound 1f and 5 h in the case of compound 4d. Then, the
corresponding electrophile (1.1 mmol, 0.5 mL in the case of deute-
rium oxide) was added at Ð78¡C and the temperature was allowed
to rise to 20¡C overnight. The resulting mixture was hydrolyzed
with H2O (15 mL) and extracted with EtOAc (3 × 20 mL). The or-
ganic layer was dried (Na2SO4) and evaporated (15 mmHg) to give
a residue, which was purified by column chromatography (silica
gel, hexane/EtOAc) and/or recrystallized to yield pure products 3
and 6. Yields are included in Tables 1 and 2. Physical, spectroscop-
ical and analytical data as well as literature references for known
compounds follow.
(18), 69 (15), 66 (20), 65 (34), 51 (37), 50 (12), 45 (100), 41 (35).
1H NMR (300 MHz, CDCl3): d = 2.05 (q, J = 6.7 Hz, CH2CH2CH2,
2H), 3.05 (t, J = 7.0 Hz, CH2S, 2H), 3.64 (t, J = 6.1 Hz, ClCH2, 2H),
7.17Ð7.36 (m, ArH, 5H).
13C NMR (75 MHz, CDCl3): d = 30.7, 31.6 (CH2CH2S), 43.3
(CH2Cl), 126.2, 128.9, 129.5, 135.6 (ArC).
IR (neat): n = 3075, 3060, 3020, 3000 (ArH) cm–1.
N-Isopropyl-3-phenylsulfanylpropylamine (4c)
2-Deuterio-1-phenylethanol (3aa)26
Colorless liquid, Rf 0.31 (hexane/EtOAc: 5/1).
Compound 4c was prepared following the same reaction conditions
as that for compound 1f, using in this case 3-chloropropyl phenyl
thioether instead of 2-chloroethyl phenyl thioether resulting in a
pale yellow liquid, Rf 0.11 (EtOAc).
MS (EI): m/z (%) =124 (M, 18), 107 (64), 105 (18), 104 (11), 79
(100), 78 (31), 77 (57), 53 (21), 52 (17), 51 (46), 50 (19), 44 (58).
1H NMR (300 MHz, CDCl3): d = 1.44Ð1.49 (m, CH2D, 2H), 2.04
(br s, OH, 1H), 4.86 (t, J = 6.4 Hz, CHOH, 1H), 7.23Ð7.37 (m, ArH,
5H).
13C NMR (75 MHz, CDCl3): d = 24.8 (t, J = 19.5 Hz, CH2D), 70.3
(CHOH), 125.3, 127.4, 128.4, 145.8 (ArC).
MS (EI): m/z (%) = 209 (M+, 10), 84 (14), 72 (100), 58 (41), 56 (21),
45 (12), 44 (12), 43 (34), 42 (25).
1H NMR (300 MHz, CDCl3): d = 1.04 [d, J = 6.1 Hz, (CH3)2CH,
6H], 1.23 (br s, NH, 1H), 1.82 (q, J = 7.2 Hz, CH2CH2CH2, 2H),
2.71 (t, J = 6.7 Hz, CH2SPh, 2H), 2.69Ð2.79 [m, (CH3)2CH, 1H],
2.98 (t, J = 7.17, NHCH2, 2H), 7.16Ð7.19, 7.24Ð7.35 (2m, ArH,
5H).
13C NMR (75 MHz, CDCl3): d = 22.9 [(CH3)2CH], 29.8 (CH2SPh),
31.6 (CH2CH2NH), 46.15 (CH2NH), 48.6 [(CH3)2CH], 125.8,
128.8, 129.04, 136.5 (ArC).
IR (neat): n = 3745Ð3110 (OH) cm–1.
HRMS calcd for C8H9DO: 123.0794; found: 123.0794.
syn-4,4-Dimethyl-1-phenylpentane-1,3-diol [syn-3ab]27
White solid mp 99¡C, Rf 0.15 (hexane/EtOAc: 5/1).
MS (EI): m/z (%) = 208 (M+, 2), 190 (12), 134 (16), 133 (62), 120
(13), 107 (66), 105 (71), 104 (28), 103 (12), 92 (15), 84 (41), 79
(54), 78 (24), 77 (51), 71 (21), 69 (55), 57 (100), 55 (15), 51 (25),
43 (47).
IR (neat): n = 3380 (NH) cm–1.
HRMS: calcd for C14H19NS: 209.1238; found: 209.1236.
4-Phenylsulfanyl-2-butanamine (4d)25
1H NMR (300 MHz, CDCl3): d = 0.85 [s, (CH3)3C, 9H], 1.76 (ddd,
J = 3.4, 10.5, 14.4 Hz, CHH, 1H), 1.88 (ddd, J = 2.4, 7.6, 14.4 Hz,
CHH, 1H), 3.21 (br s, OH, 2H), 3.49 [dd, J = 2.4, 10.5 Hz,
(CH3)3CCHOH, 1H], 5.04 (dd, J = 3.4, 7.6 Hz, PhCHOH, 1H),
7.25Ð7.38 (m, ArH, 5H).
13C NMR (75 MHz, CDCl3): d = 25.5 [(CH3)3C], 34.6 [(CH3)3C],
39.35 (CCHOHCH2), 71.7 (PhCHOH), 76.1 (CCHOH), 125.5,
127.1, 128.4, 144.8 (ArC).
Sodium cyanoborohydride (0.50 g, 8 mmol) was added to
4-phenylsulfanylbutan-2-one (1.44 g, 8 mmol, easily prepared from
thiophenol and methyl vinyl ketone)23 in MeOH (30 mL), 4• mo-
lecular sieves (1.30 g) and ammonium acetate (6.16 g, 80 mmol) at
r.t. under Ar. The mixture was stirred for 48 h at the same tempera-
ture and after that it was filtered, the solvent removed on a rotary
evaporator and the residue diluted with H2O (5 mL), basified with
15% NaOH and extracted with EtOAc (3 × 25 mL). The organic
layer was extracted with 1 M HCl (2 × 20 mL) and this acidic aque-
ous layer was basified with NaOH and extracted again with EtOAc
(3 × 25 mL). This new organic layer was dried (Na2SO4) and evap-
orated (15 mmHg) to give a residue, containing the title compound
(>90% pure) as a yellow liquid, Rf 0.41 (EtOAc).
IR (CHCl3): n = 3600Ð3150 (OH) cm–1.
anti-4,4-Dimethyl-1-phenylpentane-1,3-diol [anti-3ab]27
White solid mp 93¡C, Rf 0.16 (hexane/EtOAc: 5/1).
MS (EI): m/z (%) = 182 (M+, 4), 44 (100).
MS (EI): m/z (%) = 208 (M+, 2), 133 (52), 107 (55), 105 (66), 104
(28), 103 (12), 92 (16), 84 (40), 79 (51), 78 (22), 77 (48), 71 (19),
69 (50), 57 (100), 55 (13), 51 (24), 43 (41).
1H NMR (300 MHz, CDCl3): d = 0.89 [s, (CH3)3C, 9H], 1.71Ð1.85
(m, CH2, 2H), 3.58 [dd, J = 2.4 Hz, 9.8, (CH3)3CCHOH, 1H], 3.73
(br s, OH, 2H), 4.89 (dd, J = 3.36, 9.46, PhCHOH, 1H), 7.26Ð7.39
(m, ArH, 5H).
13C NMR (75 MHz, CDCl3): δ = 25.5 [(CH3)3C], 34.9 [(CH3)3C],
39.9 (CCHOHCH2), 75.75 (PhCHOH), 80.85 (CCHOH), 125.7,
127.5, 128.5, 144.7 (ArC).
1H NMR (300 MHz, CDCl3): d = 1.08 (d, J = 6.7 Hz, CH3, 3H), 1.19
(br s, NH2, 2H), 1.41Ð1.73 (m, NHCHCH2, 2H), 2.90Ð3.08 (m,
CH2SPh, CHNH2, 3H), 7.13Ð7.35 (m, ArH, 5H).
13C NMR (75 MHz, CDCl3): d = 24.0 (CH3), 30.6 (CH2S), 39.05
(CH2CH), 46.0 (CHNH), 125.75, 128.8, 128.9, 136.6 (ArC).
IR (CHCl3) n = 3300 (NH) cm–1.
Lithiation of Functionalized Phenyl Thioethers 1 and 4 and Re-
action with Electrophiles. Preparation of Compounds 3 and 6;
General Procedure
IR (CHCl3): ν = 3600Ð3150 (OH) cm–1.
A 1.6 M BuLi hexane solution (0.69 mL, 1.1 mmol) was added at
Ð78¡C to a functionalized phenyl thioether (1 or 2, 1.0 mmol) THF
solution (2 mL) under Ar at Ð78¡C. After 10 min at this tempera-
ture, the corresponding alcoholate (compounds 1) or amide (com-
pounds 4) solution was added via syringe to a cooled (Ð78¡C) blue
suspension of lithium powder (0.10 g, 14.0 mmol) and a catalytic
amount of DTBB (0.03 g, 0.11 mmol) in THF under Ar. The mix-
ture was stirred at the same temperature for 1.5 h in the case of com-
1,3-Diphenylpropane-1,3-diol (3ac) (diastereoisomeric mixture)28
White solid mp 123¡C, Rf 0.18 (hexane/EtOAc: 3/1).
MS (EI): m/z (%) = 211 (M++1ÐH2O, 5), 108 (12), 107 (23), 105
(55), 104 (100), 103 (13), 79 (49), 78 (23), 77 (54), 51 (28).
1H NMR (300 MHz, CDCl3): δ = 2.11 (t, J = 5.8 Hz, CH2, 2H), 3.28
(br s, OH, 2H), 4.89Ð4.96 (m, CHOHCH2CHOH, 2H), 7.23Ð7.33
(m, ArH, 10H).
Synthesis 1999, No. 3, 503Ð514 ISSN 0039-7881 © Thieme Stuttgart · New York

FEATURE ARTICLE Functionalized Organolithium Compounds by DTBB-Catalyzed SulfurÐLithium Exchange
509
13C NMR (75 MHz, CDCl3): δ = 46.4, 47.5 (CH2), 71.6, 74.9
MS (EI): m/z (%) = 170 (M+ Ð H2O, 1), 95 (21), 85 (30), 82 (16), 81
(CHOH), 125.3, 125.65, 127.4, 127.6, 128.4, 128.4, 144.1 (ArC).
IR (CHCl3): ν = 3650Ð3090 (OH) cm–1.
(25), 79 (12), 71 (61), 69 (17), 68 (42), 67 (46), 55 (32), 53 (15), 43
(100), 42 (10).
1H NMR (300 MHz, CDCl3): δ = 0.88 (t, J = 6.7 Hz, CH3, 3H),
1.24Ð1.67 [m, (CH3)2COH, CH3(CH2)5, CH2COH, 18H], 3.69 (br s,
CHOH, COH, 2H), 3.98 (m, CHOH, 1H).
3-Methyl-1-phenylbutane-1,3-diol (3ad)29
Colorless oil, Rf 0.47 (hexane/EtOAc: 3/1).
13C NMR (75 MHz, CDCl3): δ = 14.0 (CH3CH2), 22.5, 25.35, 27.6,
29.3 [CH3(CH2)4], 31.8, 31.9 [(CH3)2COH], 38.3 (CHOHCH2),
47.6 [CH2COH(CH3)2], 69.7 (CHOH), 71.6 [COH(CH3)2].
MS (EI): m/z (%) = 162 (M+ Ð H2O, 28), 147 (25), 107 (100), 105
(33), 104 (52), 103 (11), 79 (58), 78 (24), 77 (51), 71 (21), 59 (51),
56 (85), 51 (30), 43 (91).
IR (neat): ν = 3660Ð3070 (OH) cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.21 (s, CH3COHCH3, 3H), 1.37
(s, CH3COHCH3, 3H), 1.62 (d, J = 14.7 Hz, CHH, 1H), 1.91 (dd, J
= 11.3 Hz, 14.7, CHH, 1H), 3.85 (br s, OH, 2H), 5.00 (d, J = 11.3
Hz, CHOH, 1H), 7.21Ð7.32 (m, ArH, 5H).
1-(2-Hydroxyoctyl)cyclohexanol (3be)31,
Colorless oil, Rf 0.32 (hexane/EtOAc: 5/1).
13C NMR (75 MHz, CDCl3): δ = 27.4, 31.6 [(CH3)2COH], 50.2
(CH2), 71.5 (CH3COHCH3), 72.1 (PhCOH), 125.6, 127.3, 128.3,
144.7 (ArC).
MS (EI): m/z (%) = 210 (M+ Ð H2O, 1), 192 (22), 135 (17), 125 (19),
121 (18), 112 (16), 108 (12), 107 (21), 97 (11), 95 (14), 93 (49), 91
(15), 83 (48), 80 (14), 79 (100), 77 (13), 67 (58), 53 (13), 43 (13).
IR (CHCl3): ν = 3700Ð3100 (OH) cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.85Ð0.89 (m, CH3, 3H), 1.06Ð
1.77 [m, CH3(CH2)5, CHOHCH2COH, COH(CH2)5, 22H], 3.66 (br
s, OH, 2H), 3.95Ð4.00 (m, CHOH, 1H).
1-(2-Hydroxy-2-phenylethyl)cyclohexanol (3ae)
13C NMR (75 MHz, CDCl3): δ = 14.0, 14.05 (CH3), 22.05, 22.2,
22.5, 22.6, 25.4, 25.8, 29.3, 29.3, 31.7, 31.8, 35.7, 38.3, 38.4, 40.2
[(CH2)5], 46.2 (CHOHCH2COH), 68.7 (CHOH), 72.5 (COH).
White solid mp 100¡C, Rf 0.25 (hexane/EtOAc: 3/1).
MS (EI): m/z (%) = 202 (M+ Ð H2O, 10), 120 (12), 107 (39), 104
(100), 96 (40), 81 (49), 79 (40), 77 (39), 71 (10), 69 (13), 68 (10),
67 (17), 55 (54), 54 (12), 51 (22), 43 (27), 42 (27).
IR (neat): ν = 3725Ð3040 (OH) cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.30Ð1.80 (m, 6 CH2, 12H), 3.31
(br s, OH, 2H), 5.01 (dd, J = 4.4 Hz, 9.0, CHOH, 1H), 7.23Ð7.33 (m,
ArH, 5H).
2-(1-Hydroxy-1-methylethyl)cyclohexanol (3cd)
(diastereoisomeric mixture)31
Colorless oil, Rf 0.41 (hexane/EtOAc: 3/1).
MS (EI): m/z (%) = 143 (M+ Ð CH3, 5), 101 (100), 83 (20), 69 (18),
13C NMR (75 MHz, CDCl3): δ = 22.3, 25.7, 35.6, 40.0 (CH2), 71.3
(CH2COHCH2), 72.5 (PhCHOH), 125.6, 127.2, 128.3, 144.9 (ArC).
59 (19), 58 (17), 57 (29), 56 (19), 55 (60), 45 (92), 43 (71).
1H NMR (300 MHz, CDCl3): δ = 0.80Ð2.05 [m, (CH3)2CO, (CH2)5,
16H], 3.68 (br s, OH, 2H), 4.17Ð4.24 (m, CHOH, 1H).
IR (CHCl3): ν = 3700Ð3100 (OH) cm–1.
HRMS: calcd for C14H20O2ÐH2O: 202.1358; found: 202.1358.
13C NMR (75 MHz, CDCl3): δ = 23.6 (CH3COHCH3), 24.8, 25.9,
27.5 [(CH2)3], 29.9 (CH3COHCH3), 36.0 (CHOHCH2), 53.8
(CHCHOH), 73.3 (CHOH), 75.1 (COH).
1-Deuteriooctan-2-ol (3ba)30
Colorless liquid, Rf 0.26 (hexane/EtOAc: 10/1).
MS (EI): m/z (%) = 202 (M+ Ð CH3, 1), 55 (22), 46 (100), 45 (14),
44 (12), 43 (19).
IR (neat): ν = 3750Ð3025 (OH) cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.86Ð0.91 (m, CH3, 3H), 1.06Ð
1.52 [s, (CH2)5CHOHCH2D, 12H], 1.52 (br s, OH, 1H), 3.74Ð3.81
(m, CHOH, 1H).
13C NMR (75 MHz, CDCl3): δ = 14.1 (CH3), 22.6 (CH3CH2), 23.3
(t, J = 19.2 Hz, CH2D), 25.7,29.3, 31.8, 39.35 [(CH2)4], 68.1
(CHOH).
1-(2-Hydroxycyclohexyl)cyclohexanol (3ce)
(diastereoisomeric mixture)
White solid mp 67¡C, Rf 0.22 (hexane/EtOAc: 5/1).
MS (EI): m/z (%) = 180 (M+ Ð H2O, 11), 162 (49), 147 (12), 137
(50), 134 (13); 133 (47), 124 (11), 120 (21), 119 (35), 115 (11), 109
(27), 106 (10), 105 (31), 95 (27), 94 (57), 93 (30), 92 (21), 91 (78),
81 (66), 80 (42), 79 (100), 78 (23), 77 (48), 67 (47), 66 (15), 65 (21),
55 (83), 53 (45), 52 (12), 51 (28), 44 (15), 43 (33).
IR (neat): ν = 3675Ð3105 (OH) cm–1.
2,2-Dimethylundecane-3,5-diol (3bb)
(diastereoisomeric mixture)31
Colorless oil, Rf 0.30 (hexane/EtOAc: 5/1).
MS (EI): m/z (%) = 159 (M+ Ð t-Bu, 5),123 (12), 113 (15), 97 (21),
95 (23), 87 (15), 84 (15), 81 (44), 71 (16), 70 (16), 69 (46), 67 (28),
57 (61), 56 (22), 55 (86), 45 (22), 44 (17), 43 (100), 42 (20).
1H NMR (300 MHz, CDCl3): δ = 0.85Ð2.06 [m, (CH2)4CH, (CH2)5,
19H], 3.72 (td, J = 10.1, 4.3 Hz, CHOH, 1H), 7.28 (br s, OH, 2H).
13C NMR (75 MHz, CDCl3): δ = 21.05, 21.3, 24.8, 25.9, 26.1, 26.8,
30.3, 36.2, 36.3 (CH2), 54.3 (CH), 72.4 (CHOH), 75.8 (COH).
IR (CHCl3): ν = 3690Ð3025 (OH) cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.90 [s, (CH3)3C, CH3CH2, 12H],
1.4Ð1.67 [m, (CH2)5CHOHCH2, 12H], 2.64 (br s, OH, 2H), 3.46Ð
3.61 [m, (CH3)3CCHOH, 1H], 3.91Ð3.98 (m, CH2CHOHCH2, 1H).
HRMS: calcd for C12H22O2ÐH2O: 180.1514; found: 180.1514.
2-Deuterio-N-phenylethylamine (3da)26
Colorless oil, Rf 0.52 (hexane/EtOAc: 5/1).
MS (EI): m/z (%) = 122 (M+, 30), 106 (100), 79 (17), 77 (30), 65
(10), 53 (12), 51 (24).
1H NMR (300 MHz, CDCl3): δ = 1.10Ð1.25 (m, CH2D, 2H), 3.13 (t,
J = 7.0 Hz, PhNHCH2, 2H), 3.38 (br s, NH, 1H), 6.57Ð6.71, 7.14Ð
7.21 (2m, ArH, 5H).
13C NMR (75 MHz, CDCl3) δ = 14.0 (CH3), 22.6 (CH2), 25.3, 25.5,
25.6 [(CH3)3C], 25.95, 29.3, 31.8 (CH2), 34.6, 34.8 [(CH3)3C], 36.9,
37.0, 37.1, 38.3 (CH2), 69.7, 73.4 (CH2CHOHCH2), 75.9, 81.2
(CCHOH).
IR (neat) ν = 3715Ð3055 (OH) cm–1.
2-Methyldecane-2,4-diol (3bd)32
Colorless oil, Rf 0.25 (hexane/EtOAc: 5/1).
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13C NMR (75 MHz, CDCl3): δ = 14.55 (t, J = 7.0 Hz, CH2D), 38.3
(CH2NH), 112.7, 117.1, 129.2, 148.4 (ArC).
IR (neat): ν = 3400 (NH) cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.50 (d, J = 6.7 Hz, CH2D, 2H),
1.47Ð2.00 (br s, NH, 1H), 4.48 (t, J = 6.7 Hz, CH, 1H), 6.49Ð6.67,
7.05Ð7.38 (2m, ArH, 10H).
13C NMR (75 MHz, CDCl3): δ = 24.3 (t, J = 19.6 Hz, CH2D), 53.4
(CH), 113.2, 117.2, 125.8, 126.8, 128.61, 129.8, 145.2, 147.3
(ArC).
4,4-Dimethyl-1-phenylaminopentan-3-ol (3db)33
White solid mp 67¡C, Rf 0.48 (hexane/EtOAc: 2/1).
IR (neat): ν = 3410 (NH) cm–1.
MS (EI): m/z (%) = 207 (M+, 10), 106 (100), 93 (14), 77 (19), 57
(11), 51 (10).
syn-4,4-Dimethyl-1-phenyl-1-phenylaminopentan-3-ol (syn-3eb):
White solid mp 148¡C, Rf 0.36 (hexane/EtOAc: 5/1).
MS (EI): m/z (%) = 283 (M+, 5), 183 (16), 182 (100), 104 (23), 93
(26), 78 (12), 77 (43), 66 (10), 57 (23), 51 (18), 44 (43).
1H NMR (300 MHz, CDCl3): δ = 0.91 [s, (CH3)3C, 9H], 1.52Ð1.63
(m, CHHCHOH, 1H), 1.79Ð1.88 (m, CHHCHOH, 1H), 2.95 (br s,
OH, NH, 2H), 3.30 (t, J = 6.4 Hz, PhNHCH2, 2H), 3.38 (d, J =
10.7 Hz, CHOH, 1H), 6.63Ð6.74, 7.14Ð7.20 (2m, ArH, 5H).
13C NMR (75 MHz, CDCl3): δ = 25.5 [(CH3)3C], 30.6 (CH2CHOH),
34.9 [(CH3)3C], 43.0 (CH2NH), 79.4 (CHOH), 113.3, 117.7, 129.2,
148.3 (ArC).
1H NMR (300 MHz, CDCl3): δ = 0.88 [s, (CH3)3C, 9H], 1.57 (br s,
OH, NH, 2H), 1.71Ð1.96 (m, CH2, 2H), 3.40 d(d, J = 1.9 Hz, 9.8,
CHOH, 1H), 4.46 (dd, J = 5.2 Hz, 8.8, CHNH, 1H), 6.42Ð6.69,
7.05Ð7.51 (2m, ArH, 10H).
13C NMR (75 MHz, CDCl3): δ = 25.3 [(CH3)3C], 34.95 [(CH3)3C],
39.85 (CH2), 59.2 (CHNH), 79.6 (CHOH), 114.2, 117.75, 126.1,
128.6, 128.9, 144.1, 147.2 (ArC).
IR (CHCl3): ν = 3770Ð3125 (OH), 3290 (NH) cm–1.
1-Phenyl-3-phenylaminopropanol (3dc)10b
White solid mp 44¡C, Rf 0.36 (hexane/EtOAc: 2/1).
IR (CHCl3): ν = 3710Ð3140 (OH), 3395 (NH) cm–1.
MS (EI): m/z (%) = 227 (M+, 22), 209 (23), 133 (12), 130 (15), 107
(14), 106 (100), 105 (70), 104 (54), 103 (15), 94 (20), 93 (26), 91
(15), 79 (21), 78 (26), 77 (75), 65 (14), 52 (15), 51 (47), 50 (15).
Anal. calcd for C19H25NO: C, 80.51; H, 8.90; N, 4.94; found: C,
80.01; H, 8.93; N, 4.81.
1H NMR (300 MHz, CDCl3): δ = 2.01Ð2.06 (m, CH2CHOH, 2H),
3.25 (t, J = 6.4 Hz, PhNHCH2, 2H), 3.10Ð3.70 (br s, OH, NH, 2H),
4.85 (t, J = 5.2 Hz, CH, 1H), 6.59Ð6.75, 7.14Ð7.35 (2m, ArH,10H).
anti-4,4-Dimethyl-1-phenyl-1-phenylaminopentan-3-ol (anti-3eb):
Colorless oil, Rf 0.38 (hexane/EtOAc: 5/1).
13C NMR (75 MHz, CDCl3): δ = 38.1 (CH2CHOH), 41.6 (CH2NH),
73.6 (CHOH), 113.2, 117.7, 125.7, 127.6, 129.2, 144.3, 148.2
(ArC).
MS (EI): m/z (%) = 183 (15), 182 (100), 104 (26), 93 (30), 78 (10),
77 (47), 57 (22), 51 (16), 44 (38).
1H NMR (300 MHz, CDCl3): δ = 0.86 [s, (CH3)3C, 9H], 1.60 (br s,
OH, NH, 2H), 1.79Ð1.93 (m, CH2, 2H), 3.44 d(d, J = 2.7 Hz, 8.8,
CHOH, 1H), 4.72 (dd, J = 4.3 Hz, 7.3, CHNH, 1H), 6.42Ð6.69,
7.05Ð7.57 (2m, ArH, 10H).
IR (CHCl3): ν = 3735Ð3130 (OH), 3395 (NH) cm–1.
2-Methyl-4-phenylaminobutan-2-ol (3dd)10b
13C NMR (75 MHz, CDCl3): δ = 25.5 [(CH3)3C], 34.8 [(CH3)3C],
40.1 (CH2), 55.2 (CHNH), 76.3 (CHOH), 113.2, 117.05, 126.25,
126.8, 128.6, 132.0, 143.85, 148.2 (ArC).
White solid mp 60¡C, Rf 0.18 (hexane/EtOAc: 3/1).
MS (EI): m/z (%) = 179 (M+, 11), 146 (13), 106 (100), 105 (33), 104
(29), 93 (16), 77 (56), 65 (11), 56 (14), 51 (36), 50 (15).
IR (CHCl3): ν = 3650Ð3100 (OH), 3360 (NH) cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.26 [s, (CH3)2C, 6H], 1.77 (t, J =
6.7 Hz, CH2CHOH, 2H), 3.12 (br s, OH, NH, 2H), 3.25 (t, J =
6.7 Hz, PhNHCH2, 2H), 6.62Ð6.74, 7.14Ð7.20 (2m, ArH, 5H).
HRMS: calcd for C19H25NO: 283.1936; found: 283.1931.
13C NMR (75 MHz, CDCl3): δ = 29.5 [(CH3)2COH], 40.4 (CH2NH),
41.7 (CH2COH), 70.9 (COH), 113.2, 117.6, 129.1, 148.3 (ArC).
1,3-Diphenyl-3-phenylaminopropanol (3ec)
(diastereoisomeric mixture)5b
Colorless oil, Rf 0.39 (hexane/EtOAc: 5/1).
IR (CHCl3): ν = 3670Ð3100 (OH), 3275 (NH) cm–1.
MS (EI): m/z (%) = 303 (M+, 1), 285 (15), 206 (13), 194 (12), 182
(33), 181 (55), 180 (59), 105 (17), 104 (53), 103 (22), 93 (16), 79
(10), 78 (39), 77 (100), 76 (11), 76 (11), 63 (11), 52 (14), 51 (64),
50 (20), 44 (43).
1H NMR (300 MHz, CDCl3): δ = 2.00Ð2.29 (m, CH2, 2H), 3.38Ð
3.60 (br s, OH, NH, 2H), 4.50Ð4.58 (m, CHNH, 1H), 4.75Ð4.79 (m,
CHOH, 1H), 6.47Ð6.67, 7.03Ð7.38 (2m, ArH, 15H).
13C NMR (75 MHz, CDCl3): δ = 46.7, 47.4 (CH2), 55.3, 57.9
(CHNH), 71.7, 73.6 (CHOH), 113.6, 114.2, 117.4, 117.9, 125.7,
125.7, 126.2, 126.3, 126.9, 126.9, 127.1, 127.5, 127.6, 127.7, 128.5,
128.5, 128.5, 128.6, 128.7, 128.7, 129.0, 143.4, 143.7, 144.3, 144.5,
147.2, 147.2 (ArC).
1-(2-Phenylaminoethyl)cyclohexanol (3de)10b
White solid mp 120¡C, Rf 0.32 (hexane/EtOAc: 3/1).
MS (EI): m/z (%) = 219 (M+, 5), 106 (100), 105 (14), 104 (13), 81
(12), 79 (12), 77 (31), 67 (13), 55 (11), 51 (18).
1H NMR (300 MHz, CDCl3): δ = 1.25Ð1.63 [m, (CH2)5, 10H], 1.79
(t, J = 6.7 Hz, CH2COH, 2H), 2.55Ð3.50 (br s, OH, NH, 2H), 3.28
(t, J = 6.7 Hz, CH2NH, 2H), 6.62Ð6.74, 7.15Ð7.25 (2m, ArH, 5H).
13C NMR (75 MHz, CDCl3): δ = 22.2, 25.7, 37.7 [(CH2)5], 39.5
(NHCH2CH2), 55.4 (NHCH2) 71.8 (COH); 113.2, 117.6, 129.2,
148.4 (ArC).
IR (CHCl3): ν = 3600Ð2990 (OH), 3270 (NH) cm–1.
IR (neat): ν = 3600Ð3100 (OH), 3300 (NH) cm–1.
2-Deuterio-1-phenyl-N-phenylethylamine (3ea)26
Colorless oil, Rf 0.46 (hexane/EtOAc: 10/1).
MS (EI): m/z (%) = 198 (M+, 36), 183 (15), 182 (100), 121 (17), 107
(22), 106 (79), 105 (27), 104(32), 99 (11), 94 (21), 93 (60), 90 (12),
80 (23), 79 (23), 78 (36), 77 (78), 57 (20), 52 (11), 51 (53), 50 (14),
43 (41), 42 (10).
1-(2-Phenyl-2-phenylaminoethyl)cyclohexanol (3ee)
Colorless oil, Rf 0.21 (hexane/EtOAc: 10/1).
MS (EI): m/z (%) = 295 (M+, 1), 183 (15), 182 (100), 181 (33), 180
(39); 104 (25), 93 (12), 81 (15), 79 (15), 78 (14), 77 (70), 67 (13),
55 (13), 51 (33).
Synthesis 1999, No. 3, 503Ð514 ISSN 0039-7881 © Thieme Stuttgart · New York

FEATURE ARTICLE Functionalized Organolithium Compounds by DTBB-Catalyzed SulfurÐLithium Exchange
511
1H NMR (300 MHz, CDCl3): δ = 0.86Ð2.03 [m, CHCH2COH,
(CH2)5, 12H], 3.80 (br s, OH, NH, 2H), 4.57 (dd, J = 4.9 Hz, 9.2,
CHNH, 1H), 6.52Ð6.68, 7.02Ð7.42 (2m, ArH, 10H).
13C NMR (75 MHz, CDCl3): δ = 23.3, 23.9 (CH3CH), 25.7, 25.7
[(CH3)3C], 27.0, 28.4, 35.0, 35.0 [(CH2)2], 36.5, 37.2 [(CH3)3C],
67.5, 68.5 (CH3CHOH), 80.0, 80.4 (CCHOH).
13C NMR (75 MHz, CDCl3): δ = 22.1, 22.3, 25.7, 31.4, 35.8
[(CH2)5], 40.0 (CHNHCH2), 55.4 (CHNH), 72.1 (COH); 114.3,
117.8, 125.9, 126.8, 128.65, 128.95, 144.8, 147.3 (ArC).
IR (CHCl3): ν = 3715Ð3010 (OH) cm–1.
Anal. calcd for C9H20O2: C, 67.44; H, 12.59; found: C, 67.27; H,
12.61.
IR (neat): ν = 3550Ð3110 (OH), 3370 (NH) cm–1.
1-Phenylpentane-1,4-diol (6ac) (diastereoisomeric mixture)34
Colorless oil, Rf 0.32 (hexane/EtOAc: 1/2).
HRMS: calcd for C20H25NO: 295.1936; found: 295.1931.
3-Isopropylamino-1-phenylpropanol (3fc)
Colorless oil, Rf 0.32 (EtOAc).
MS (EI): m/z (%) = 180 (M+, 1), 120 (33), 117 (13), 107 (79), 106
(79), 105 (27), 91 (15), 79 (100), 78 (21), 77 (66), 71 (14), 57 (10),
56 (55), 55 (14), 51 (28), 45 (32), 43 (51), 41 (36).
1H NMR (300 MHz, CDCl3): δ = 1.14, 1.15 (2d, J = 6.1 Hz, CH3,
3H), 1.25Ð1.57 (m, CH2CHH, 3H), 1.78Ð1.84 (m, CH2CHH, 1H),
3.12 (br s, OH, 2H), 3.74Ð3.84 (m, CHOHCH3, 1H), 4.61Ð4.70 (m,
CHOHPh, 1H), 7.22Ð7.33 (m, ArH, 5H).
13C NMR (75 MHz, CDCl3): δ = 23.3, 23.6 (CH3), 34.9, 35.0, 35.9,
36.1 (CH2CH2), 67.6, 68.15 (CHOHCH3), 74.1, 74.6 (CHOHPh),
125.7, 125.8, 127.3, 127.3, 128.3, 144.7, 144.8 (ArC).
MS (EI): m/z (%) = 193 (M+, 3), 117 (15), 105 (17), 104 (19), 91
(18), 79 (12), 78 (15), 77 (33),72 (41), 71 (12), 58 (13), 57 (15), 56
(83), 51 (28), 50 (11), 44 (100), 43 (51), 42 (30).
1H NMR (300 MHz, CDCl3): δ = 1.16 (d, J = 6.1 Hz, CH3, 3H), 1.16
(d, J = 6.7 Hz, CH3, 3H), 1.7Ð1.91, 1.92Ð2.03 (2m, CHOHCH2,
2H), 2.89Ð2.99 (m, CHNHCH2, 3H), 4.91 (dd, J = 3.1 Hz, 8.5,
CHOH, 1H), 6.28 (br s, OH, NH, 2H), 7.20Ð7.37 (m, ArH, 5H).
13C NMR (75 MHz, CDCl3): δ = 20.9, 21.0 [(CH3)2CH], 36.2
(CH2CH2NH), 43.9 (CH2NH), 49.1 (CHNH), 73.45 (CHOH),
125.4, 126.9, 128.15, 144.6 (ArC).
IR (neat): ν = 3620Ð3800 (OH) cm–1.
2-Methylhexane-2,5-diol (6ad)35
Colorless oil, Rf 0.22 (hexane/EtOAc: 1/1).
MS (EI): m/z (%) = 105 (M+ Ð 27, 1), 59 (32), 45 (12), 43 (100), 41
IR (neat): ν = 3550Ð3100 (OH, NH) cm–1.
HRMS: calcd for C12H19NO: 193.1467; found: 193.1455.
(13).
4-Isopropylamino-2-methylbutan-2-ol (3fd)
Brown oil, Rf 0.20 (EtOAc).
1H NMR (300 MHz, CDCl3): δ = 1.20 (d, J = 6.1 Hz, CHOHCH3,
3H), 1.23 [s, (CH3)2C, 6H], 1.57 (t, J = 1.22, COHCH2, 2H), 1.52Ð
1.64 (m, CHOHCH2, 2H), 2.70 (br s, OH, 2H), 3.75Ð3.84
(m,CHOH, 1H).
13C NMR (75 MHz, CDCl3): δ = 23.6 (CH3CHOH), 29.0, 29.75
[(CH3)2COH], 33.7 (CHOHCH2), 39.8 (COHCH2), 68.3 (CHOH),
70.6 (COH).
MS (EI): m/z (%) = 145 (M+, 1), 130 (22), 112 (19), 73 (14), 72
(100), 70 (14), 59 (19), 58 (29), 56 (100), 55 (11), 45 (16), 44 (94),
43 (68), 42 (27).
1H NMR (300 MHz, CDCl3): δ = 1.07 [d, J = 6.1 Hz, (CH3)2CH,
6H], 1.22 [s, (CH3)2COH, 6H], 1.59 (t, J = 6.1 Hz, CH2COH, 2H),
2.73Ð2.82 (m, CHNH, 1H), 2.89 (t, J = 5.8 Hz, CH2NH, 2H), 3.55
(br s, OH, NH, 2H).
IR (neat): ν = 3730Ð3030 (OH) cm–1.
13C NMR (75 MHz, CDCl3): δ = 22.6 [(CH3)2CH], 29.6
[(CH3)2COH], 40.65 (CH2COH), 43.3 (CH2NH), 48.7 (CHNH),
70.8 (COH).
1-(3-Hydroxybutyl)cyclohexanol (6ae)31
Colorless oil, Rf 0.46 (EtOAc).
MS (EI): m/z (%) = 154 (M+ Ð H2O, 1), 99 (38), 98 (13), 81 (43), 79
(10), 71 (11), 69 (15), 67 (14), 58 (18), 57 (22), 56 (16), 55 (100),
45 (16), 44 (13), 43 (66), 42 (22), 41 (50).
IR (neat): ν = 3750Ð3020 (OH), 3275 (NH) cm–1.
HRMS: cald for C8H19NO: 145.1467; found: 145.1467.
1H NMR (300 MHz, CDCl3): δ = 1.20 (d, J = 6.1 Hz, CH3, 3H),
1.25Ð1.56 [m, CHOH(CH2)2, (CH2)5, 14H], 2.66 (br s, OH, 2H),
3.76Ð3.80 (m, CHOH, 1H).
13C NMR (75 MHz, CDCl3): δ = 22.2, 22.3 (CH2), 23.5 [(CH3)3C],
25.8, 32.8, 37.1, 37.9 (CH2), 68.35 (CHOH), 71.1 (COH).
1-(2-Isopropylaminoethyl)cyclohexanol (3fe)31
Colorless oil, Rf 0.24 (MeOH).
MS (EI): m/z (%) = 152 (M+ Ð 33, 1), 72 (36), 56 (10), 44 (100), 43
(25), 42 (12), 41 (19).
1H NMR (300 MHz, CDCl3): δ = 1.29 [d, J = 6.7 Hz, (CH3)2CH,
6H], 1.20Ð1.70 [m, (CH2)5, 10H], 1.85 (t, J = 6.3 Hz, CH2COH,
2H), 3.04 (t, J = 6.3 Hz, CH2NH, 2H), 3.08Ð3.14 (m, CHNH, 1H),
6.82 (br s, OH, NH, 2H).
13C NMR (75 MHz, CDCl3): δ = 19.85 (CH2), 21.9 [(CH3)2CH],
25.8, 36.8, 37.4 (CH2), 40.9 (CH2NH), 49.3 (CHNH), 71.0 (COH).
IR (neat): ν = 3750Ð3035 (OH) cm–1.
1,4-Diphenylbutane-1,4-diol (6bc) (diastereoisomeric mixture)36
White solid mp 88Ð94¡C, Rf 0.34 (hexane/EtOAc: 1/1).
MS (EI): m/z (%) = 224 (M+ Ð H2O, 1), 120 (10), 118 (23), 117 (25),
105 (20), 104 (17), 91 (16), 79 (23), 78 (13), 77 (45), 71 (12), 57
(64), 56 (45), 55 (15), 51 (28), 50 (10), 44 (88), 43 (100), 42 (50),
41 (84).
1H NMR (300 MHz, CDCl3): δ = 1.73Ð1.89 (m, CH2CH2, 4H), 3.04
(br s, OH, 2H), 4.59Ð4.65 [m, CHOH, 2H], 7.19Ð7.32 (m, ArH,
10H).
13C NMR (75 MHz, CDCl3): δ = 35.0, 35.9 (CH2), 74.0, 74.4
(CHOH), 125.7, 127.35, 128.3, 144.5 (ArC).
IR (CHCl3): ν = 3735Ð3115 (OH) cm–1.
IR (neat): ν = 3690Ð3100 (OH), 3370 (NH) cm–1.
6,6-Dimethylheptane-2,5-diol (6ab) (diastereoisomeric mixture):
White solid mp 70¡C, Rf 0.31 (hexane/EtOAc: 1/1).
MS (EI): m/z (%) = 130 (M+ Ð 30, 1), 85 (69), 71 (12), 70 (13), 67
(31), 58 (11), 57 (69), 56 (21), 55 (19), 45 (25), 44 (17), 43 (100),
42 (10), 41 (78).
1H NMR (300 MHz, CDCl3): δ = 0.90 [s, (CH3)3C, 9H], 1.20 (d, J
= 6.3 Hz, CHCH3, 3H), 1.25Ð1.38 (m, CH2CHH, 1H), 1.49Ð1.74
(m, CH2CHH, 3H), 2.75 (br s, OH, 2H), 3.17Ð3.22 (m, CCHOH,
2H), 3.77Ð3.81, 3.86Ð3.91 (2m, CH3CHOH, 1H).
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FEATURE ARTICLE
1-(3-Hydroxy-3-phenylpropyl)cyclohexanol (6be)
1-(3-Isopropylaminopropyl)cyclohexanol (6ce)31
White solid mp 83Ð85¡C, Rf 0.34 (hexane/EtOAc: 1/1).
Colorless oil, Rf 0.21 (EtOAc),
MS (EI): m/z (%) = 216 (M+ Ð H2O, 3), 120 (15), 118 (12), 117 (14),
107 (14), 105 (16), 104 (11),91 (25), 82 (10), 81 (40), 79 (39), 78
(14), 77 (39), 69 (12), 67 (24), 65 (11), 57 (26), 56 (18), 55 (100),
53 (16), 51 (22), 44 (71), 43 (66), 42 (30), 41 (80).
1H NMR (300 MHz, CDCl3): δ = 1.22Ð1.61 [m, CH2COH, (CH2)5,
12H], 1.73Ð1.91 (m, CHOHCH2, 2H), 2.82 (br s, OH, 2H), 4.64 (dd,
J = 4.9 Hz, 7.9, CHOH, 1H), 7.17Ð7.33 (m, ArH, 5H).
13C NMR (75 MHz, CDCl3): δ = 22.1, 22.2, 25.7, 35.6, 37.1, 37.8
(CH2), 71.1 (COH), 74.7 (CHOH), 125.8, 127.2, 128.3, 144.95
(ArC).
MS (EI): m/z (%) = 182 (M+ Ð H2O, 2), 86 (10), 85 (20), 81 (16), 72
(100), 70 (15), 67 (11), 58 (20), 56 (13), 55 (12), 44 (24), 43 (20),
42 (13).
1H NMR (300 MHz, CDCl3): δ = 1.09 [d, J = 6.4 Hz, (CH3)2CH, 6H],
1.10Ð1.97 [m, (CH2)5, NHCH2(CH2)2, 14H], 2.63Ð2.67 (m, NHCH2,
2H), 2.76Ð2.85 [m, (CH3)2CH, 1H], 3.64 (br s, NH, OH, 2H).
13C NMR (75 MHz, CDCl3): δ = 22.3 (CH2), 22.35 [(CH3)2CH],
23.4, 26.0, 37.4, 37.85 (CH2), 47.4 (CH2NH), 48.6 (CHNH), 69.6
(COH).
IR (neat): ν = 3450Ð3100 (OH), 3355 (NH) cm–1.
IR (CHCl3): ν = 3675Ð3084 (OH) cm–1.
3-Ethyl-6-isopropylaminohexan-3-ol (6cf)31
Colorless oil, Rf 0.16 (MeOH).
Anal. calcd for C15H22O2: C, 76.87; H, 9.47; found: C, 77.10; H,
9.54.
MS (EI): m/z (%) = 172 (M+ Ð CH3, 1), 104 (15), 99 (22), 91 (13),
72 (100), 70 (11), 69 (22), 58 (19), 57 (42), 56 (10), 55 (17), 44 (40),
43 (48).
1H NMR (300 MHz, CDCl3): δ = 0.85 [t, J = 7.3 Hz,
(CH3CH2)2COH, 6H], 1.07 [d, J = 6.1 Hz, (CH3)2CH, 6H], 1.45 (q,
J = 7.3 Hz, CH3CH2COH, 2H), 1.47 (q, J = 7.6 Hz, CH3CH2COH,
2H), 1.41Ð1.55 [m, COH(CH2)2, 4H], 1.54 (br s, NH, OH, 2H),
2.61Ð2.65 (m, NHCH2, 2H), 2.71Ð2.85 [m, (CH3)2CH, 1H].
(1S,4R/S)-1,4-Diphenylbutane-1,4-diol [(S)-6bc]
(diastereoisomeric mixture)36
White solid mp 90Ð96¡C, Rf 0.38 (hexane/EtOAc: 1/1), [α]D25 Ð1.75
(c = 1.03, CH2Cl2).
MS (EI): m/z (%) = 224 (M+ Ð H2O, 3), 120 (28), 118 (62), 117 (68),
115 (18), 107 (21), 105 (38), 104 (46), 91 (38), 89 (10), 79 (60), 78
(30), 77 (100), 65 (18), 63 (15), 57 (10), 52 (14), 51 (60), 50 (18),
44 (63), 43 (24), 41 (20).
1H NMR (300 MHz, CDCl3): δ = 1.74Ð1.87 [m, (CH2)2, 4H], 2.91
(br s, OH, 2H), 4.60Ð4.68 [m, CHOH, 2H], 7.21Ð7.30 (m, ArH,
10H).
13C NMR (75 MHz, CDCl3): δ = 8.1 [(CH3CH2)2COH], 22.6
[(CH3)2CH], 24.2, 31.0, 37.7 (CH2), 47.7 (CH2NH), 48.7 (CHNH),
72.85 (COH).
IR (neat): ν = 3745Ð3050 (OH, NH) cm–1.
13C NMR (75 MHz, CDCl3): δ = 35.0, 35.9 (CH2), 74.1, 74.5
(CHOH), 125.8, 127.35, 127.4, 128.3, 144.5, 144.6 (ArC).
1-(3-Isopropylaminopropyl)cyclopentanol (6cg)
IR (CHCl3): ν = 3735Ð3110 (OH) cm–1.
White solid mp 52¡C, Rf 0.29 (MeOH).
MS (EI): m/z (%) = 186 (M++1, 1), 152 (10), 72 (10), 70 (12), 67
(18), 58 (17), 56 (11), 55 (11), 44 (26), 43 (34), 42 (15).
1H NMR (300 MHz, CDCl3): δ = 1.08 [d, J = 6.4 Hz, (CH3)2CH,
6H], 1.50Ð1.98 [m, (CH2)4, (CH2)2CH2N, 12H], 2.63Ð2.70 (m,
NHCH2, 2H), 2.76Ð2.84 [m, (CH3)2CH, 1H], 3.40 (br s, NH, OH,
2H).
13C NMR (75 MHz, CDCl3): δ = 22.5 (CH2), 24.0 [(CH3)2CH], 26.0,
39.7, 40.0 (CH2), 47.4 (CH2NH), 48.7 (CHNH), 80.40 (COH).
(S)-4-Methyl-1-phenylpentane-1,4-diol [(S)-6bd]37
White solid mp 87Ð89¡C, Rf 0.23 (hexane/EtOAc: 1/1), [α]D25
+34.48 (c = 1.01, CH2Cl2).
MS (EI): m/z (%) = 176 (M+ Ð H2O, 2), 120 (17), 117 (11), 107 (27),
79 (32), 77 (27), 70 (54), 59 (41), 55 (37), 51 (12), 43 (100), 42 (16),
41 (14).
1H NMR (300 MHz, CDCl3): δ = 1.16, 1.17 [2s, (CH3)2C, 6H],
1.40Ð1.50 (m, CHOHCHH, 1H), 1.56Ð1.67 (m, CHOHCHH, 1H),
1.71Ð1.89 (m, COHCH2, 2H), 3.54 (br s, OH, 2H), 4.61 (dd, J =
4.9 Hz, 7.9, CHOH, 1H), 7.23Ð7.32 (m, ArH, 5H).
13C NMR (75 MHz, CDCl3): δ = 28.9, 29.6 [(CH3)2COH], 33.85,
39.7 [(CH2)2], 70.5 (COH), 74.5 (CHOH), 125.8, 127.2, 128.3,
144.85 (ArC).
IR (CHCl3): ν = 3300Ð3100 (OH), 3255 (NH) cm–1.
HRMS: calcd for C11H23NOÐH2OÐCH3: 152.1439; found:
152.1439.
6-Amino-2,2-dimethylheptan-3-ol (6db)
(diastereoisomeric mixture)
Colorless oil, Rf 0.29 (MeOH).
IR (CHCl3): ν = 3675Ð3085 (OH) cm–1.
MS (EI): m/z (%) = 159 (M+, 1), 85 (18), 57 (19), 56 (11), 44 (100),
Anal. calcd for C12H18O2: C, 74.18; H, 9.34; found: C, 74.34; H, 9.53.
43 (26), 42 (12), 41 (26).
4-Isopropylamino-1-phenylbutanol (6cc)
Colorless liquid, Rf 0.17 (EtOAc).
MS (EI): m/z (%) = 207 (M+, 7), 174 (34), 131 (43), 91 (20), 77 (17),
72 (100), 58 (22), 56 (15), 44 (41), 43 (25), 42 (15).
1H NMR (300 MHz, CDCl3): δ = 0.90 [s, (CH3)3C, 9H], 1.10, 1.14
2(d, J = 6.4 Hz, CHCH3, 3H), 1.25Ð1.77 70 (m, CH2CH2, 4H), 2.87
(br s, OH, NH2, 3H), 3.11Ð3.13 (m, CHNH2, 1H), 3.15 (d, J = 1.5
Hz, CHOH, 1H), 3.16 (d, J = 1.2 Hz, CHOH, 1H).
1H NMR (300 MHz, CDCl3): δ = 1.12 [d, J = 6.4 Hz, (CH3)2CH,
6H], 1.50Ð1.95 [m, NHCH2(CH2)2, 4H], 2.53Ð2.61 [m, (CH3)2CH,
1H], 2.73Ð2.85 (m, NHCH2, 2H), 3.76 (br s, NH, OH, 2H), 4.66 (dd,
J = 3.1 Hz, 8.2, CHOH, 1H), 7.21Ð7.38 (m, ArH, 5H).
13C NMR (75 MHz, CDCl3): δ = 22.3 [(CH3)2CH], 22.5
(CH2CH2NH), 27.5 (CH2CHOH), 46.9 (CH2NH), 48.7 (CHNH),
73.4 (CHOH), 125.7, 126.6, 128.05, 145.8 (ArC).
13C NMR (75 MHz, CDCl3): δ = 23.3 (CH3CH), 25.8, 25.9
[(CH3)2CH], 27.4, 29.9(CH2CH2CHNH2), 34.8, 34.9 (CH2CHNH2),
36.6, 37.8 [(CH3)2CH], 46.1, 48.1 (CHNH2), 79.4, 80.0 (COH).
IR (neat): ν = 3600Ð3050 (OH), 3350, 3285 (NH2) cm–1.
HRMS: calcd for C9H21NO: 159.1623; found: 159.1617.
4-Amino-1-phenylpentan-1-ol (6dc) (diastereoisomeric
mixture)
IR (neat): ν = 3370Ð3120 (OH), 3380 (NH) cm–1.
Colorless oil, Rf 0.25 (hexane/EtOAc: 3/1).
HRMS: calcd for C12H19NS: 207.1623; found: 207.1619.
Synthesis 1999, No. 3, 503Ð514 ISSN 0039-7881 © Thieme Stuttgart · New York

FEATURE ARTICLE Functionalized Organolithium Compounds by DTBB-Catalyzed SulfurÐLithium Exchange
513
MS (EI): m/z (%) = 179 (M+, 1), 57 (10), 44 (100).
(6) (a) Barluenga, J.; Fl—rez, J.; Yus, M. J. Chem. Soc., Chem.
Commun. 1982, 1153.
(b) Barluenga, J.; Fl—rez, J.; Yus, M. J. Chem. Soc., Perkin
Trans. 1 1983, 3019.
(c) N‡jera, C.; Yus, M.; Seebach, D. Helv. Chim. Acta 1984,
67, 289.
1H NMR (300 MHz, CDCl3): δ = 1.05, 1.08 (2d, J = 6.4 Hz, CH3,
3H), 1.18Ð1.53 (m, CH2CHNH2, 2H), 1.72Ð1.88 (m, CH2CHOH,
2H), 2.83Ð2.93 (m, CHNH2, 1H), 3.04 (br s, OH, NH2, 3H), 4.58Ð
4.67 (m, CHOH, 1H), 7.21Ð7.36 (m, ArH, 5H).
13C NMR (75 MHz, CDCl3): δ = 23.8, 25.05 (CH3), 35.2, 35.9,
36.55, 37.6 (CH2CH2), 46.5, 47.4 (CHNH2), 73.3, 74.0 (CHOH),
125.7, 125.7, 126.75, 126.8, 128.1, 145.5, 145.6 (ArC).
(d) Barluenga, J.; Fern‡ndez-Sim—n, J. L.; Concell—n, J. M.;
Yus, M. J. Chem. Soc., Chem. Commun. 1987, 915.
(e) Wittmann, V.; Kessler, H. Angew. Chem. 1993, 105, 1138;
Angew. Chem. Int. Ed. Engl. 1993, 32, 1091.
(f) Frey, O.; Hoffmann, M.; Wittmann, V.; Kessler, H.; Uhl-
mann, P.; Vasella, A. Helv. Chim. Acta 1994, 77, 2060.
(g) Frey, O.; Hoffmann, M.; Kessler, H. Angew. Chem. 1995,
107, 2194; Angew. Chem., Int. Ed. Engl. 1995, 34, 2026.
(7) Barluenga, J.; Foubelo, F.; Fa–an‡s, F. J.; Yus, M. Tetrahe-
dron Lett. 1988, 29, 2859.
IR (neat): ν = 3700Ð3000 (OH), 3350, 3280 (NH2) cm–1.
HRMS: calcd for C11H17NO: 179.1310; found: 179.1314.
5-Amino-2-methylhexan-2-ol (6dd)38
Colorless oil, Rf 0.33 (MeOH).
MS (EI): m/z (%) = 202 (M+ Ð H2O, 1), 44 (100), 43 (36).
1H NMR (300 MHz, CDCl3): δ = 1.12 (d, J = 6.4 Hz, CH3, 3H), 1.21
[s, (CH3)2COH, 6H], 1.22Ð1.70 [m, (CH2)2, 4H], 2.54 (br s, OH,
NH2, 3H), 2.87Ð2.96 (m, CHNH2, 1H).
13C NMR (75 MHz, CDCl3): δ = 24.7 (CH3CH), 22.2, 29.8
[(CH3)2COH], 34.1 (CH2CHNH2), 40.7 (CH2COH), 47.5 (CHNH2),
69.6 (COH).
Barluenga, J.; Foubelo, F.; Fa–an‡s, F. J.; Yus, M. Tetrahe-
dron 1989, 45, 2183.
Barluenga, J.; Montserrat, J. M.; Fl—rez, J. Tetrahedron Lett.
1992, 33, 6183.
Barluenga, J.; Montserrat, J. M.; Fl—rez, J. J. Org. Chem.
1993, 58, 5976.
Foubelo, F.; Yus, M. Tetrahedron Lett. 1994, 35, 4831.
Hoffmann, M.; Kessler, H. Tetrahedron Lett. 1994, 35, 6067.
Foubelo, F.; Yus, M. Tetrahedron: Asymmetry 1996, 7, 2911.
Hoffmann, M.; Burkhart, F.; Hessler, G.; Kessler, H. Helv.
Chim. Acta 1996, 79, 1519.
IR (neat): ν = 3685Ð3040 (OH, NH) cm–1.
1-(3-Aminobutyl)cyclohexanol (6de)31
Colorless oil, Rf 0.36 (MeOH).
MS (EI): m/z (%) = 153 (M+ Ð H2O, 1), 57 (19), 55 (17), 44 (100),
43 (16), 42 (11), 41 (16).
(8) For a review, see: Holy, N. L. Chem. Rev. 1974, 74, 243.
(9) (a) Bartmann, E. Angew. Chem. 1986, 98, 629; Angew. Chem.,
Int. Ed. Engl. 1986, 25, 653.
1H NMR (300 MHz, CDCl3): δ = 1.11 (d, J = 6.4 Hz, CH3, 3H),
1.12Ð1.70 [m, (CH2)2CH, (CH2)5,14H], 2.31 (br s, OH, NH2, 3H),
2.87Ð2.92 (m, CHNH2, 1H).
13C NMR (75 MHz, CDCl3): δ = 22.3, 22.35 (CH2), 24.8 (CH3),
25.9, 32.7, 37.45, 38.0, 41.9 (CH2), 47.6 (CHNH2), 70.1 (COH).
(b) Cohen, T.; Jeong, I.-H.; Mudryk, B.; Bhupathy, M.; Awad,
M. A. J. Org. Chem. 1990, 55, 1528.
(c) Conrow, R. E. Tetrahedron Lett. 1993, 34, 5553.
(d) Bachki, A.; Foubelo, F.; Yus, M. Tetrahedron: Asymmetry
1995, 6, 1907.
(e) Bachki, A.; Foubelo, F.; Yus, M. Tetrahedron: Asymmetry
1996, 7, 2997.
IR (neat): ν = 3690Ð3075 (OH), 3400, 3370 (NH2) cm–1.
(10) (a) Almena, J.; Foubelo, F.; Yus, M. Tetrahedron Lett. 1993,
34, 1649.
Acknowledgement
(b) Almena, J.; Foubelo, F.; Yus, M. J. Org. Chem. 1994, 59,
3210.
We are grateful to the Direcci—n General de Investigaci—n Cient’-
Þca y TŽcnica (DGICYT) of the Spanish Ministerio de Educaci—n
y Cultura for Þnantial support (no. PB94-1514).
(11) For the first account on this reaction, see: Yus, M.; Ram—n, D.
J. J. Chem. Soc., Chem. Commun. 1991, 398.
For a polymer supported catalyst version, see: G—mez, C.;
Ruiz, S.; Yus, M. Tetrahedron Lett. 1998, 39, 1397.
(12) For a review, see: Yus, M. Chem. Soc. Rev. 1996, 155.
(13) Eaton, P. E.; Cooper, G. I.; Johnson, R. C.; Mueller, R. H.
J. Org. Chem. 1972, 37, 1947.
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(d) Barluenga, J.; Villama–a, J.; Fa–an‡s, F. J.; Yus, M.
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(e) Barluenga, J.; Fa–an‡s, F. J.; Villama–a, J.; Yus, M.
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Synthesis 1999, No. 3, 503Ð514 ISSN 0039-7881 © Thieme Stuttgart á New York

514
F. Foubelo et al.
FEATURE ARTICLE
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(15) Meyer, N.; Seebach, D. Chem. Ber. 1980, 113, 1290.
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105, 629; Angew. Chem., Int. Ed. Engl. 1993, 32, 582.
(16) (a) Felkin, H.; Swierczewsk, G.; TambutŽ, A. Tetrahedron
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(c) Kato, T.; Marumoto, S.; Sato, T.; Kuwajima, I. Synlett
1990, 671.
(d) Kammermeier, B. O. T.; Klumpp, G. W.; Kolthof, K.; Vos,
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(e) Klein, S.; Marek, I.; Normant, J.-F. J. Org. Chem. 1994,
59, 2925.
(27) Zakharkin, L. I.; Savina, L. A. Zh. Obshch. Khim. 1967, 37,
2565; Chem. Abstr. 1968, 68, 104629g.
(f) Klein, S.; Marek, I.; Poisson, J. F., Normant, J. -F. J. Am.
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(g) MŸck-Lichtenfeld, C.; Ahlbrecht, H. Tetrahedron 1996,
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(17) Carlson, R. M. Tetrahedron Lett. 1978, 111.
Klumpp, G. W.; Kool, M.; Schakel, M.; Schmitz, R. F.; Bout-
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(30) Hudrlik, P. F.; Holmes, P. E.; Hudrlik, A. M. Tetrahedron
Lett. 1988, 29, 6395.
(31) For this product, it was not possible to obtain the correspond-
ing HRMS due to the absence of the M+ signal.
(32) Esafov, V. I.; Marek, E. M.; Kotlyarova, S. I.; Malyarenko, A.
V.; Korzun, N. V. Izv. Vyssh. Ucheb. Zaved., Khim. Khim.Tek-
hnol 1970, 13, 1144; Chem. Abstr. 1970, 73, 130579p.
(33) Tilak, B. D.; Gogte, V. N.; Ravindranathan, T. Indian J.
Chem. 1969, 7, 24; Chem. Abstr. 1969, 71, 49745b.
(34) Schmitt, A.; Reissig, H.-U. Chem. Ber. 1995, 128, 871.
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H. E. J. Org. Chem. 1963, 28, 144.
Carpita, A.; Bonaccorsi, F.; Rossi, R. Tetrahedron Lett. 1984,
25, 5193.
(18) Lithium homoenolates have been not considered here as γ-
functionalized organolithium compounds (the same case for
normal lithium enolates and β-functionalized organolithium
reagents) because of the different hybridization or oxidation
grade at the functional group.
(36) Chong, J. M.; Clarke, I. S.; Koch, I.; Olbach, P. C.; Taylor, N.
J. Tetrahedron: Asymmetry 1995, 6, 409.
(19) Screttas, C. G.; Micha-Screttas, M. J. Org. Chem. 1978, 43,
1064.
(37) Jakovac, I. J.; Jones, J. B. J. Org. Chem. 1979, 44, 2165.
(38) Asensio, G.; Gonz‡lez-Nœ–ez, M. E.; Bernardini, C. B.; Mel-
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Synthesis 1999, No. 3, 503Ð514 ISSN 0039-7881 © Thieme Stuttgart · New York