Nucleophilic (phenylsulfinyl)difluoromethylation of carbonyl compounds with difluoromethyl phenyl sulfoxide

Article abstract of DOI:10.1016/j.jfluchem.2007.05.003

We have successfully achieved nucleophilic (phenylsulfinyl)difluoromethylation of both enolizable and non-enolizable aldehydes and ketones by using difluoromethyl phenyl sulfone (1) as the fluoroalkylating agent. Although the chemical yields of the reactions are good to excellent, the observed diastereoselectivity is poor (dr = 1:1.04-2.03). The present synthetic methodology provides a convenient alternative for the preparation of α-(phenylsulfinyl)difluoromethylated carbinols that were previously synthesized via a two-step procedure.

Full text of DOI:10.1016/j.jfluchem.2007.05.003

Journal of Fluorine Chemistry 128 (2007) 1241–1247
www.elsevier.com/locate/fluor
Nucleophilic (phenylsulfinyl)difluoromethylation of carbonyl
compounds with difluoromethyl phenyl sulfoxide
b
Lingui Zhu a, Ya Li a, Chuanfa Ni a, Jinbo Hu a, , Petr Beier ,
*
b
b,**
Ying Wang b, G.K. Surya Prakash
, George A. Olah
a Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Road, Shanghai 200032, China
b Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California, Los Angeles, CA 90089-1661, USA
Received 31 March 2007; received in revised form 6 May 2007; accepted 7 May 2007
Available online 22 May 2007
Dedicated to Professor Kenji Uneyama with friendship and admiration on the occasion of his receipt of 2007 ACS Award for Creative Work in Fluorine Chemistry.
Abstract
We have successfully achieved nucleophilic (phenylsulfinyl)difluoromethylation of both enolizable and non-enolizable aldehydes and ketones
by using difluoromethyl phenyl sulfone (1) as the fluoroalkylating agent. Although the chemical yields of the reactions are good to excellent, the
observed diastereoselectivity is poor (dr = 1:1.04–2.03). The present synthetic methodology provides a convenient alternative for the preparation
of a-(phenylsulfinyl)difluoromethylated carbinols that were previously synthesized via a two-step procedure.
# 2007 Elsevier B.V. All rights reserved.
Keywords: (Phenylsulfinyl)difluoromethylation; Difluoromethyl sulfoxide; Nucleophilic addition
1. Introduction
interested in the chemistry of phenylsulfonyl-substituted fluor-
inated carbanions that are generated from fluorinated sulfones
[10–11]. However, the chemistry on the phenylsulfinyl-
substituted fluorinated carbanions has been rarely explored [12].
Recently, Pohmakotr et al. [13] reported a two-step
preparation of (phenylsulfinyl)difluoromethylated carbinols 5,
which can be converted to the corresponding gem-difluoroalk-
enes 6 by pyrolysis (see Scheme 1, eq (1)). We envisioned that it
would be more convenient if compounds 5 can be prepared from
Nucleophilic fluoroalkylation with fluorinated carbanions
(RFÀ, the fluorine substitution is commonly on the carbanion
center) is one of the most important methods to introduce fluor-
inated moieties into organic molecules [1–8]. Although there is a
recent argument that ‘‘fluorine is more effective than the heavier
halogens’’ in a-stabilization of carbanions [9], most primary and
secondary fluorinated carbanions are well recognized as
kinetically unstable species [1]. The lifetimes, reactivity and
synthetic utility of fluorinated carbanions are effected by many
factors, and as a result, the chemistry of fluorinated carbanions is
much different from their non-fluorinated counterparts [1,2]. a-
Functionalization of the fluorinated carbanions with softening
group(s) (such as phenylsulfonyl group) is a useful approach to
alleviate the ‘‘negative fluorine effect’’ and enhance the nucleo-
philicity of the RFÀ species [10a]. In this context, we have been
À
one-step (phenylsulfinyl)difluoromethylation with PhSOCF2
anion (generated from PhSOCF2H (1) and a base; see Scheme 1,
eq. (2)). Furthermore, during a recent symposium [14] a question
was raised regarding the diastereoselectivity issue of the reaction
between carbonyl compounds 3 and 1 (as shown in Scheme 1, eq.
(2)). Intrigued by these factors, we studied the nucleophilic
(phenylsulfinyl)difluoromethylation of carbonyl compounds
with difluoromethyl phenyl sulfoxide (PhSOCF2H, 1).
2. Results and discussion
* Corresponding author. Tel.: +86 21 54925174; fax: +86 21 64166128.
** Corresponding author.
Difluoromethyl phenyl sulfoxide (1) (in a racemic form) was
prepared in 88% isolated yield by simple oxidation of
E-mail addresses: jinbohu@mail.sioc.ac.cn (J. Hu), gprakash@usc.edu
(G.K. Surya Prakash).
0022-1139/$ – see front matter # 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2007.05.003

1242
L. Zhu et al. / Journal of Fluorine Chemistry 128 (2007) 1241–1247
Scheme 1.
reaction mixture was usually stirred at À30 8C for 30 min after
the addition was complete. The products 5 were obtained after
simple work-up and purification with silica gel column
chromatography. The results are summarized in Table 2. Both
enolizable and non-enolizable aldehydes and ketones 3 can be
readily (phenylsulfinyl)difluoromethylated to give correspond-
ing carbinol products 5 in 77–99% yields. The reaction yield for
enolizable aldehyde (Table 2, entry 6) was somewhat lower
than those for enolizable ketones (entries 7 and 12), which is
similar to our previous report of (phenylsulfonyl)difluoro-
methylation with PhSO2CF2H [11c]. All these results indicaÀte
Scheme 2.
difluoromethyl phenyl sulfide 7 [15] with m-chloroperbenzoic
acid (Scheme 2). With compound 1 in hand, we quickly
scanned the reaction conditions between 1 and 2-naphthalde-
hyde. As shown in Table 1, when lithium hexamethyldisilazide
(LiHMDS) was applied as a base, the product yields were only
19–76% (entries 1–3). The best yield (93%) of 5a was obtained
when potassium tert-butoxide was used as a base and DMF was
used as a solvent (entry 4).
that the (phenylsulfinyl)difluoromethyl anion (PhSOCF2
,
generated in situ from 1 and t-BuOK) has good nucleophilicity
towards carbonyl compounds. However, as shown in Table 2,
the diastereoselectivities of the reactions were generally poor
(dr = 1:1.04–2.03), which were determined by 19F NMR on the
product mixtures (for an example, see Fig. 1). This low
diastereoselectivity is similar to the known reactions of non-
fluorinated a-sulfinyl carbanions with carbonyl compounds,
which also resulted in low diastereoselectivity [16].
Encouraged by the above result, we examined the scope of
the nucleophilic (phenylsulfinyl)difluoromethylation. The
typical reaction procedure is as follows: into the mixture of
difluoromethyl phenyl sulfoxide 2 (1 mmol), carbonyl com-
pounds 3 (2 mmol) and DMF (5 mL) at À30 8C, was added
dropwise t-BuOK (2 mmol, dissolved in 1 mL of DMF). The
To demonstrate other synthetic application of difluoromethyl
phenyl sulfoxide 1, we also subjected 1 in the one-pot synthesis
of anti-2,2-difluoro-1,3-diol (8) (Scheme 3). Compounds 1 (1
Table 1
Survey of reaction conditions
Entrya
3a (equiv)
Base
Solvent
Temperature
Time (h)
Yield of 5a (%)b
Recovery of 1 (%)c
1
2
3
4
1.05
2.0
LiHMDS (1.1 equiv)
LiHMDS (2.2 equiv)
LiHMDS (2.0 equiv)
t-BuOK (2.0 equiv)
THF
À78 8C to rt
À78 8C to rt
À30 8C to rt
À30 8C
12
12
12
0.5
19
36
76
93
53
43
20
0
THF/HMPAc
DMF/HMPAc
DMF
2.0
2.0
a
Typical procedure: into a mixture of 1, 3a and solvent, base (dissolved in THF or DMF) was added at À30 8C or À78 8C.
b
c
Isolated yield based on compound 1 used.
Solvent ratio = 10:1 (v/v).

L. Zhu et al. / Journal of Fluorine Chemistry 128 (2007) 1241–1247
1243
Table 2
Nucleophilic (phenylsulfinyl)difluoromethylation of carbonyl compounds with PhSOCF2H (1)
Entrya
Carbonyl compounds 3 Product 5
Yield (%)b
drc
1
93
48:52
2
82
43:57
3
4
80
82
33:67
47:53
5
82
42:58
6
77
49:51
7
8
94
99
33:67
44:56
9
92
95
46:54
48:52
10
11
94
–
12
96
–
a
Typical procedure: A mixture of 1 (1 mmol), 3 (2 mmol), t-BuOK (2 mmol) and DMF (6 mL) was stirred at À30 8C for 30 min, followed by usual work-up and purification.
Isolated yields of 5 based on reagent 1 used.
Diasteromeric ratios were determined by 19F NMR spectroscopy.
b
c

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L. Zhu et al. / Journal of Fluorine Chemistry 128 (2007) 1241–1247
Scheme 3.
Fig. 1. 19F NMR of the product 5c (as a diastereomeric mixture with dr (A/B) = 33:67).
equiv), 3c (3 equiv) and t-BuOK (4 equiv) were mixed under N2
atmosphereatÀ50 8C, andthemixturewasstirredatÀ50 8Ctort
overnight to give product 8 in 68% yield (not optimized) with
94:6 dr (anti/syn). The mechanism of this transformation is
expected to be similar to those proposed by us [11f] and Liu et al.
[17] (but with different difluoromethylene dianion synthons).
recorded on a high-resolution mass spectrometer in the EI or
MALDI mode.
4.1. Preparation of difluoromethyl phenyl sulfoxide 1
To a solution of PhSCHF2 (6.367 g, 39.7 mmol) in CH2Cl2
(80 mL) was added m-CPBA (85%, 8.473 g, 41.734 mmol) at
0 8C and then the reaction mixture was stirred overnight at
room temperature. After filtration, the filtrate was washed with
cold 1 M sodium hydroxide solution, dried over Na2SO4. The
solvent was removed under vacuum and the crude product was
purified by flash column chromatography (petroleum ether/
ethyl acetate = 12:1) to give the sulfoxide 1 [11e,18] as a
colorless oily liquid (6.132 g, 88% yield). 1H NMR (300 MHz,
3. Conclusions
In conclusion, we have successfully achieved nucleophilic
(phenylsulfinyl)- difluoromethylation of both enolizable and
non-enolizable aldehydes and ketones by the use of difluor-
omethyl phenyl sulfone (1) as the fluoroalkylating agent.
Although the chemical yields of the reactions are good to
excellent, the observed diastereoselectivity is poor (dr = 1:1.04–
2.03). The present synthetic methodology provides a convenient
alternative for the preparation of a-(phenylsulfinyl)difluoro-
methylated carbinols that were previously synthesized via a
two-step procedure [13].
CDCl3): d 7.76–7.58 (m, 5H), 6.05 (t, JH–F = 55.4 Hz, 1H). 19
F
NMR (282 MHz, CDCl3): d À119.7 (dd, JF–F = 8.6 Hz, JH–
F = 55.5 Hz, 2F).
4.2. Typical experimental procedure for nucleophilic
(phenylsulfinyl)difluoromethylation of carbonyl compounds
with 1
4. Experimental
Unless otherwise mentioned, solvents and reagents were
purchased from commercial sources and used as received.
DMF was freshly distilled over calcium hydride and stored
under nitrogen atmosphere. Difluoromethyl phenyl sulfide
was prepared from PhSH and CHClF2 using a modified
procedure as described in [15]. 1H NMR spectra were
recorded on Bruker 300 or Mercury 300 spectrometers with
Me4Si as internal standard. 19F NMR spectra were recorded
on Bruker 300 or Mercury 300 spectrometers with CFCl3 as
external standard. 13C NMR spectra were recorded on Avance
500 or DPX-400 spectrometers. Mass spectra were obtained
on a HP5989A spectrometer. High-resolution mass data were
The reaction was carried out in a Schlenk flask under a
nitrogen atmosphere. To a solution of difluoromethyl phenyl
sulfoxide 1 (176 mg, 1 mmol) and 2-naphthal- dehyde 3a
(312 mg, 2 mmol) in DMF (5 mL) at À30 8C, was added a
solution of t-BuOK (224 mg, 2 mmol) in anhydrous DMF
(1 mL). The reaction mixture was kept at À30 8C for 30 min.
The reaction mixture was poured into water (10 mL) and
extracted with Et2O (4 Â 15 mL). The combined ether phase
was washed with a saturated aqueous solution of NH4Cl.
After drying over Na2SO4, the ether solvent was removed
under vacuum. The crude product was further purified by
flash column chromatography (petroleum ether/ethyl acetate

L. Zhu et al. / Journal of Fluorine Chemistry 128 (2007) 1241–1247
1245
6/1, then 3/1) to afford product 5a (pale yellow solid) as a
mixture of two diastereomers (dr = 48:52), yield: 308 mg,
93% yield.
1083, 1036, 976, 751, 727, 698, 689 cmÀ1. HRMS (EI, m/z)
calculated for C14H12O2F2S(M+): 282.0526; found: 282.0530.
4.2.4. 1-(Benzo[1,3]dioxol-5-yl)-2,2-difluoro-2-
(phenylsulfinyl)ethanol (5d)
4.2.1. 2,2-Difluoro-1-(naphthalen-2-yl)-2-
(phenylsulfinyl)ethanol (5a)
Pale yellow solid; m.p.: 105–108 8C; 82% yield. A mixture of
two diastereomers (47:53). 1H NMR (300 MHz, CDCl3): d 7.75–
7.54 (m, 5H), 7.02–6.77 (m, 3H), 5.98 (s, 0.53 Â 2H), 5.96 (s,
0.47 Â 2H), 5.35–5.26 (m, 1H), 4.22 (d, J = 4.5 Hz, 0.47H), 3.57
(d, J = 4.5 Hz, 0.53H). 19F NMR (282 MHz, CDCl3): d À109.4
(dd, J = 9.9, 218.8 Hz, 0.53F) and À119.6 (dd, J = 14.7, 218.3
Hz, 0.53F); À109.9 (d, J = 224.5 Hz, 0.47F) and À117.2 (dd,
J = 21.9, 225.2 Hz, 0.47F). IR (KBr): 3262, 1504, 1490, 1446,
1250, 1110, 1036, 982, 921, 788, 762, 749, 686 cmÀ1. MS (EI, m/
z, %): 326 (M+, 2), 126 (100). HRMS (EI, m/z): calculated for
C15H12O2F2S(M+): 326.0424; found: 326.0424.
Pale yellow solid; m.p.: 109–111 8C; 93% yield. A mixture
of two diastereomers (48:52). H NMR (300 MHz, CDCl3): d
1
8.00–7.48 (m, 12H), 5.66–5.52 (m, 1H), 4.73(d, JH–H = 5.4 Hz,
0.48H), 3.89 (d, JH–H = 3.6 Hz, 0.52H). 19F NMR (282 MHz,
CDCl3): d À109.1 (dd, J = 10.4, 218.6 Hz, 0.48 F) and À116.4
(dd, J = 22.9, 224.4 Hz, 0.48F); À110.0 (d, J = 226.2 Hz,
0.52F) and À118.9 (dd, J = 15.1, 218.4 Hz, 0.52F). IR (KBr):
3294, 1602, 1510, 1445, 1271, 1194, 1111, 1085, 1040, 987,
973, 794, 747, 687 cmÀ1. MS (EI, m/z, %): 332(M+, 2),
126(100). HRMS (EI, m/z) calculated for C18H14O2F2S(M+):
332.0683; found: 332.0676.
4.2.5. 1-(2,5-Dimethoxyphenyl)-2,2-difluoro-2-
(phenylsulfinyl)ethanol (5e)
4.2.2. 1-(4-Bromophenyl)-2,2-difluoro-2-
(phenylsulfinyl)ethanol (5b)
Pale yellow solid; m.p.: 123–127 8C; 82% yield. A mixture of
two diastereomers (42:58). 1H NMR (300 MHz, CDCl3): d 7.81–
7.55 (m, 5H), 7.00 (m, 3H), 5.73–5.40 (m, 1H), 4.46(s, 0.42H),
4.45(d, J = 6.3 Hz, 0.58H)3.84 (s, 3 Â 0.58H), 3.76 (s, 3H), 3.74
(s, 3 Â 0.42H). 19F NMR (282 MHz, CDCl3): d À109.6 (dd, J =
8.2, 219.1 Hz, 0.58F) and À119.8 (dd, J = 17.8, 216.2 Hz,
0.58F); À111.8 (d, J = 221.0 Hz, 0.42F) and À117.7 (dd, J =
24.3, 223.3 Hz, 0.42F). IR (KBr): 3287, 1504, 1467, 1446, 1430,
1280, 1220, 1160, 1116, 1085, 1068, 1045, 1022, 983, 815, 755,
703, 693 cmÀ1. MS(EI, m/z, %):342(M+, 15), 216 (100). HRMS
(EI, m/z): 342.0743, calculated for C16H16O4F2S: 342.0737.
White solid; m.p.: 130–132 8C; 82% yield. A mixture of two
diastereomers (43:57). H NMR (300 MHz, CDCl3): d 7.71–
1
7.33 (m, 9H), 5.45–5.33 (m, 1H), 5.13 (d, J = 4.2 Hz, 0.43H),
4.11 (d, J = 3.3 Hz, 0.57H). 19F NMR (282 MHz, CDCl3): d
À109.3 (dd, J = 8.8 Hz, 219.9 Hz, 0.57F) and À120.0(dd,
J = 15.1, 219.5 Hz, 0.57F); À111.0 (d, J = 222.5 Hz, 0.43F)
and À117.6 (dd, J = 22.9, 225.3 Hz, 0.43F). IR (KBr): 3287,
1591, 1489, 1475, 1446, 1399, 1203, 1194, 1122, 1108, 1083,
1041, 975, 773,767, 749, 689 cmÀ1. MS (EI, m/z, %):
362([M + 1]+, 1), 126(100). HRMS (EI, m/z): calculated for
C14H11O2F2SBr(M+): 359.9624; found: 359.9631.
4.2.6. 1,1-Difluoro-4-phenyl-1-(phenylsulfinyl)butan-2-ol
(5f)
4.2.3. 2,2-Difluoro-1-phenyl-2-(phenylsulfinyl)ethanol (5c)
White solid; m.p.: 103–107 8C; 80% yield. A mixture of two
diastereomers (33:67). 1H NMR (300 MHz, CDCl3): d 7.74–7.36
(m, 10H), 5.47–5.32 (m, 1H), 4.48 (d, J = 5.4 Hz, 0.43H), 4.11
(d, J = 3.3 Hz, 0.57H). 19F NMR (282 MHz, CDCl3): d À108.9
(dd, J = 9.2, 219.3 Hz, 0.33F) and À116.6 (dd, J = 21.7,
224.8 Hz, 0.33F); À110.0 (d, J = 224.8 Hz, 0.67F) and
À119.1(dd, J = 14.8, 219.3 Hz, 0.67F). MS (EI, m/z, %) 282
(M+, 1), 126 (100). IR (KBr): 3296, 1494, 1446, 1203, 1109,
Yellow solid; m.p.: 95–99 8C; 77% yield. A mixture of two
diastereomers (49:51). H NMR (300 MHz, CDCl3): d 7.74–
1
7.53 (m, 5H), 7.32–7.16 (m, 5H), 4.75 (d, J = 6.6 Hz, 0.49H),
4.38–4.10 (m, 1H), 3.65 (d, J = 6.3 Hz, 0.51H), 3.00–2.67 (m,
2H), 2.13–1.89 (m, 2H). 19F NMR (282 MHz, CDCl3): d
À109.1 (dd, J = 5.9, 219.6 Hz, 0.51F) and À119.7 (dd,
J = 14.0, 220.9 Hz, 0.51F); À114.0 (d, J = 221.9 Hz, 0.49F)
and À118.9 (dd, J = 22.9, 221.9 Hz, 0.49F). IR (KBr): 3326,

1246
L. Zhu et al. / Journal of Fluorine Chemistry 128 (2007) 1241–1247
2952, 1603, 1497, 1455, 1446, 1205, 1100, 1085, 1031, 1021,
1007, 996, 945, 931, 751, 700, 689 cmÀ1. MS (EI, m/z, %): 311
(M+, 1), 126 (100). HRMS (EI, m/z): calculated for
C16H16O4F2S: 310.0839(M+); found: 310.0830.
À106.2 (d, J = 219.4 Hz, 0.54F) and À119.1 (d, J = 218.7 Hz,
0.54F). IR(KBr): 3308, 2920, 1610, 1511, 1475, 1446, 1409,
1396, 1372, 1232, 1220, 1185, 1161, 1118, 1046, 1021, 966,
820, 806, 763, 745, 698, 687 cmÀ1. MS (EI, m/z, %): 310 (M+,
1), 126 (100). HRMS (EI, m/z): calculated for
C16H16O2F2S(M+): 310.0839; found: 310.0838.
4.2.7. 1,1-Difluoro-2-phenyl-1-(phenylsulfinyl)propan-2-ol
(5g)
4.2.10. 1,1-Difluoro-2-(4-methoxyphenyl)-1-
(phenylsulfinyl)propan-2-ol (5j)
Pale yellow solid; m.p.: 114–117 8C; 94% yield. A mixture
of two diastereomers (33:67). H NMR (300 MHz, CDCl3): d
1
7.71–7.32 (m, 10H), 4.80 (s, 0.67H), 4.38 (s, 0.33H), 2.08 (s,
0.33 Â 3H), 1.75 (s, 0.67 Â 3H). 19F NMR (282 MHz, CDCl3):
d À104.7 (d, J = 220.8 Hz, 0.33F) and À116.5 (d, J = 221.3 Hz,
0.33F); À106.1 (d, J = 221.3 Hz, 0.67F) and À119.0 (d,
J = 219.9 Hz, 0.67F). IR (KBr): 3294, 3063, 1494, 1477, 1447,
1397, 1371, 1236, 1121, 1085, 1074, 1046, 968, 937, 747, 699,
687, 670 cmÀ1. MS (EI, m/z, %): 297 ([M + 1]+, 1), 126 (100).
HRMS (EI, m/z): calculated for C15H14O2F2S(M+): 296.0683;
found: 296.0674.
Sticky oil; 95% yield. A mixture of two diastereomers
1
(48:52). H NMR (300 MHz, CDCl3): d 7.70–7.49 (m, 7H),
6.99 (d, J = 9.0 Hz, 1H), 6.87 (d, J = 8.7Hz, 1H), 4.80 (s,
0.52H), 4.33 (s, 0.48H), 3.85 (s, 0.52 Â 3H), 3.79 (s,
0.48 Â 3H), 2.04 (s, 0.48 Â 3H), 1.72 (s, 0.52 Â 3H). 19F
NMR (282 MHz, CDCl3): d À104.9 (d, J = 218.8 Hz, 0.48F)
and À116.9 (d, J = 221.0 Hz, 0.48F); À106.0 (d, J = 218.5 Hz,
0.52F) and À118.9 (d, J = 217.1 Hz, 0.52F). IR (KBr): 3371,
3002, 2839, 1611, 1584, 1513, 1446, 1377, 1303, 1253, 1181,
1034, 967, 922, 836, 810, 750, 689 cmÀ1. MS (EI, m/z, %) 326
(M+, 0.1), 126 (100). HRMS (EI, m/z): calculated for
C16H16O3F2S(M+): 326.0788; found: 326.0779.
4.2.8. 2-(4-Chlorophenyl)-1,1-difluoro-1-
(phenylsulfinyl)propan-2-ol (5h)
4.2.11. 2,2-difluoro-1,1-diphenyl-2-(phenylsulfinyl)ethanol
(5k)[13]
White solid; m.p.: 122–124 8C; 99% yield. A mixture of two
diastereomers (44:56). H NMR (300 MHz, CDCl3): d 7.69–
1
7.29 (m, 9H), 4.89 (s, 0.56H), 4.54 (s, 0.44H), 2.04 (s,
0.44 Â 3H), 1.73 (s, 0.56 Â 3H). 19F NMR (282 MHz, CDCl3):
d À104.7 (d, J = 223.3 Hz, 0.44F) and À116.4 (d, J = 221.0 Hz,
0.44F); À105.8 (d, J = 220.2 Hz, 0.56F) and À118.9 (d,
J = 220.2 Hz, 0.56F). IR (KBr): 3422, 3325, 1595, 1492, 1446,
1405, 1375, 1217, 1194, 1165, 1133, 1122, 1106, 1092, 1083,
1045, 1012, 779, 746, 726, 686 cmÀ1. MS (EI, m/z, %): 330
(M+, 0.2), 126 (100). HRMS (EI, m/z): calculated for
C15H13O2F2SCl(M+): 330.0293; found: 330.0281.
1
White solid; 94% yield. H NMR (300 MHz, CDCl3): d
7.84–7.26 (m, 15H), 5.20 (s, 1H). 19F NMR (282 MHz, CDCl3):
d À98.6 (d, JF–F = 219.4 Hz, 1F), À112.5 (d, JF–F = 219.4 Hz,
1F). The data are consistent with the previous report [13].
4.2.12. 1,1-Difluoro-2-methyl-1-(phenylsulfinyl)propan-2-
ol (5l)
4.2.9. 1,1-Difluoro-1-(phenylsulfinyl)-2-p-tolylpropan-2-ol
(5i)
White solid; m.p.:75–77 8C; 96% yield. 1H NMR
(300 MHz, CDCl3): d 7.76–7.55 (m, 5H), 3.66 (s, 1H), 1.63
(s, 3H), 1.46 (s, 3H). 19F NMR (282 MHz, CDCl3): d À107.7 (d,
White solid; m.p.: 108–110 8C; 92% yield. A mixture of two
diastereomers (46:54). H NMR (300 MHz, CDCl3): d 7.70–
7.15 (m, 9H), 4.76 (s, 0.54H), 4.26 (s, 0.44H), 2.41 (s,
0.54 Â 3), 2.33 (s, 0.46 Â 3), 2.05 (s, 0.46 Â 3), 1.72 (s,
0.54 Â 3). 19F NMR (282 MHz, CDCl3): d À104.0 (d,
J = 219.2 Hz, 0.46F) and À116.7 (d, J = 218.9 Hz, 0.46F);
J
F-F = 218.8 Hz, 1F), À120.1 (d, JF-F = 219.9 Hz, 1F). IR
1
(KBr): 3370, 2995, 2949, 1583, 1471, 1448, 1368, 1310, 1257,
1210, 1122,,1095, 1084, 1055, 1011, 987, 952, 827, 748,
690 cmÀ1. MS (EI, m/z, %): 235 (M+, 11), 126 (100). HRMS
(EI, m/z): calculated for C10H12O2F2S(M+): 234.0526; found:
234.0532.

L. Zhu et al. / Journal of Fluorine Chemistry 128 (2007) 1241–1247
1247
[11] (a) G.K.S. Prakash, J. Hu, Y. Wang, G.A. Olah, J. Fluorine Chem. 126
(2005) 529–534;
Acknowledgements
(b) G.K.S. Prakash, Y. Wang, J. Hu, G.A. Olah, J. Fluorine Chem. 126
(2005) 1361–1367;
We gratefully acknowledge the National Natural Science
Foundation of China (20502029), Shanghai Rising-Star
Program (06QA14063), and the Chinese Academy of Sciences
(Hundreds-Talent Program) for financial support. Partial
support of the work at USC was provided by NICAS/NIH
program project grant (GKSP).
(c) G.K.S. Prakash, J. Hu, Y. Wang, G.A. Olah, Eur. J. Org. Chem. (2005)
2218–2223;
(d) G.K.S. Prakash, J. Hu, Y. Wang, G.A. Olah, Angew. Chem. Int. Ed. 43
(2004) 5203–5206;
(e) G.K.S. Prakash, J. Hu, Y. Wang, G.A. Olah, Org. Lett. 6 (2004) 4315–
4317;
(f) G.K.S. Prakash, J. Hu, T. Mathew, G.A. Olah, Angew. Chem. Int. Ed.
42 (2003) 5216–5219;
References
(g) G.K.S. Prakash, J. Hu, G.A. Olah, Org. Lett. 5 (2003) 3253–3256;
(h) G.K.S. Prakash, J. Hu, G.A. Olah, J. Org. Chem. 68 (2003) 4457–
4463.
[1] W.B. Farnham, Chem. Rev. 96 (1996) 1633–1640, and the references
cited therein.
[12] (a) V. Reutrakul, V. Rukachaisirikul, Tetrahedron Lett. 24 (1983) 725–
728;
[2] R.D. Chambers, Fluorine in Organic Chemistry, Blackwell, Oxford, 2004.
[3] K. Uneyama, Organofluorine Chemistry, Blackwell, New Delhi, 2006.
[4] P. Kirsch, Modern Fluoroorganic Chemistry, Wiley-VCH, Weinheim, 2004.
[5] T. Hiyama, Organofluorine Compounds: Chemistry and Applications,
Springer, New York, 2000.
(b) V. Reutrakul, T. Kruahong, M. Pohmaktor, Tetrahedron Lett. 35
(1994) 4851–4852.
[13] M. Pohmakotr, K. Boonkitpattarakul, W. Ieawsuwan, S. Jarussophon,
N. Duangdee, P. Tuchinda, V. Reutrakul, Tetrahedron 62 (2006) 5973–
5985.
[6] G.K.S. Prakash, A. Yudin, Chem. Rev. 97 (1997) 757–786.
[7] G.K.S. Prakash, M. Mandal, J. Fluorine Chem. 112 (2001) 123–131.
[8] G.K.S. Prakash, J. Hu, New Nucleophilic Fluoroalkylation Chemistry, in
Fluorine-Containing Synthons (V.A. Soloshonok, Ed.), ACS Symposium
Series 911, American Chemical Society, 2005.
[14] The Japan–Korea–China Joint Seminar on Fluorine Chemistry, Kyoto,
Japan, January 25–26, 2007.
[15] K.I. Petko, L.M. Yagupol’skii, Russ. J. Org. Chem. 40 (2004) 601–602.
[16] See reviews on a-sulfinyl carbanion chemistry:
(a) G. Hanquet, F. Colobert, S. Lanners, G. Solladie, ARKIVOC Vii
(2003) 328–401;
[9] F.M. Bickelhaupt, H.L. Hermann, G. Boche, Angew. Chem. Int. Ed. 45
(2006) 823–826.
[10] (a) C. Ni, Y. Li, J. Hu, J. Org. Chem. 71 (2006) 6829–6833;
(b) C. Ni, J. Liu, L. Zhang, J. Hu, Angew. Chem. Int. Ed. 46 (2007) 786–
789;
(b) M.C. Carrenno, Chem. Rev. 95 (1995) 1717–1760;
(c) A.J. Walker, Tetrahedron Asymm. 3 (1992) 961–998;
(d) S. Patai, Z. Rappoport, C.J.M. Stirling (Eds.), The Chemistry of
Sulfones and Sulfoxides, Wiley, Chichester, UK, 1988.
[17] J.-L. Li, J.-T. Liu, Tetrahedron 63 (2007) 898–903.
[18] (a) J. Chiba, T. Sugihara, C. Kaneko, Chem. Lett. 24 (1995) 581–582;
(b) A. Toyota, Y. Ono, J. Chiba, T. Sugihara, C. Kaneko, Chem. Pharm.
Bull. 44 (1996) 703–708.
(c) Y. Li, C. Ni, J. Liu, L. Zhang, J. Zheng, L. Zhu, J. Hu, Org. Lett. 8
(2006) 1693–1696;
(d) J. Liu, C. Ni, Y. Li, L. Zhang, G. Wang, J. Hu, Tetrahedron Lett. 47
(2006) 6753–6756;
(e) Y. Li, J. Hu, Angew. Chem. Int. Ed. 44 (2005) 5882–5886;
(f) C. Ni, J. Hu, Tetrahedron Lett. 46 (2005) 8273–8277.