Regioselective synthesis of 6-[chloro(difluoro)methyl]salicylates by [3+3] cyclocondensations of 1,3-bis(trimethylsilyloxy)buta-1,3-dienes with 1-chloro-1,1-difluoro-4-(trimethylsilyloxy)pent-3-en-2-one

Article abstract of DOI:10.1002/hlca.201100494

The TiCl₄-mediated [3+3] cyclocondensation of various 1,3-bis(trimethylsilyloxy)buta-1,3-dienes with 1-chloro-1,1-difluoro-4- (trimethylsilyloxy)pent-3-en-2-one provides a regioselective access to novel 6-(chlorodifluoromethyl)salicylates (=6-(chlorodifluoromethyl)-2- hydroxybenzoates) with very good regioselectivity. For selected products, it was demonstrated that the CF₂Cl group can be transformed to CF ₂H and CF₂(Allyl) by free-radical reactions.

Full text of DOI:10.1002/hlca.201100494

Helvetica Chimica Acta – Vol. 95 (2012)
1037
Regioselective Synthesis of 6-[Chloro(difluoro)methyl]salicylates by [3 þ 3]
Cyclocondensations of 1,3-Bis(trimethylsilyloxy)buta-1,3-dienes with
1-Chloro-1,1-difluoro-4-(trimethylsilyloxy)pent-3-en-2-one
by Silke Erflea)b), Sebastian Reimanna)b), Alina Bunescua)b), Zharylkasyn A. Abilovc),
Anke Spannenbergb), and Peter Langer*a)b)
a) Institut fꢀr Chemie, Universitꢁt Rostock, Albert Einstein Strasse 3a, D-18059 Rostock
b) Leibniz-Institut fꢀr Katalyse an der Universitꢁt Rostock e.V., Albert Einstein Strasse 29a,
D-18059 Rostock
c) Al-Farabi Kazakh National University, Al-Farabi ave. 71, 050040 Almaty, Kazakhstan
The TiCl4-mediated [3 þ 3] cyclocondensation of various 1,3-bis(trimethylsilyloxy)buta-1,3-dienes
with 1-chloro-1,1-difluoro-4-(trimethylsilyloxy)pent-3-en-2-one provides a regioselective access to novel
6-(chlorodifluoromethyl)salicylates (¼6-(chlorodifluoromethyl)-2-hydroxybenzoates) with very good
regioselectivity. For selected products, it was demonstrated that the CF2Cl group can be transformed to
CF2H and CF2(Allyl) by free-radical reactions.
Introduction. – [Chloro(difluoro)methyl]-substituted arenes are of considerable
interest in medicinal chemistry, for example, as tyrosine kinase inhibitors [1][2]. They
have been prepared by reaction of arenes with bis[chloro(difluoro)acetyl] peroxide [3],
by UV-mediated reaction of difluoromethyl arenes with Cl2 [4], by reaction of
(ethylsulfanyl)difluoromethyl arenes with BrF3 [5], and by fluorination of trichloro-
methyl arenes (using Olahꢂs reagent or KF in ionic liquids) [6]. All these methods rely
on the fluorination or chlorination of suitable benzene derivatives. Despite their utility,
they have severe drawbacks with regard to their preparative scope. In addition, some
halogenation reagents are toxic and/or very expensive. In addition, the starting
materials, i.e., functionalized benzene derivatives, are not readily available. An
alternative way for the synthesis of halogenated arenes relies on a ꢃbuilding blockꢂ
approach. Chan and Brownbridge were the first to report [7] a convenient synthesis of
functionalized salicylates by TiCl4-mediated [3 þ 3] cyclization [8] of 1,3-bis(trime-
thylsilyloxy)buta-1,3-dienes [9] with 3-alkoxy- and 3-(silyloxy)-alk-2-en-1-ones. We
have reported the application of this methodology to the synthesis of CF3-substituted
arenes [10]. Here, we report a new synthesis of 6-[chloro(difluoro)methyl]salicylates
(¼6-[chloro(difluoro)methyl]-2-hydroxybenzoates) by regioselective [3 þ 3] cyclo-
condensation of various 1,3-bis(trimethylsilyloxy)buta-1,3-dienes with alkyl- and aryl-
substituted 1-chloro-1,1-difluoro-4-(trimethylsilyloxy)pent-3-en-2-ones. The novel
products reported in this work are formed with very good regioselectivity, and they
are not readily available by other methods.
Results and Discussion. – 1-Chloro-1,1-difluoro-4-(trimethylsilyloxy)pent-3-en-2-
one (1) was prepared by silylation of known 1-chloro-1,1-difluoro-4-hydroxypent-3-en-
ꢄ 2012 Verlag Helvetica Chimica Acta AG, Zꢀrich

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Helvetica Chimica Acta – Vol. 95 (2012)
2-one (Scheme 1). The latter was obtained from the NaH-mediated reaction of acetone
with methyl 2-chloro-2,2-difluoroacetate. 1,3-Bis(trimethylsilyloxy)buta-1,3-dienes
2a – 2y were prepared in two steps from the corresponding b-keto esters [7][11][12].
Scheme 1. Synthesis of 1
The TiCl4-mediated reaction of 1 with 4-methoxy-1,3-bis(trimethylsilyloxy)buta-
1,3-diene (2a) afforded 6-[chloro(difluoro)methyl]-4-methylsalicylate (3a) in 59%
yield (Scheme 2). The formation of 3a can be explained, in analogy to the synthesis of
the corresponding CF3-substituted analogs [10], by the mechanism depicted in
Scheme 2: the reaction of 1 with TiCl4 affords allylic cation A. The reaction of the
latter with the terminal C-atom of 2a gives intermediate B. The latter undergoes a
cyclization via intermediate C to afford D, which is finally transformed to the product
by aromatization (before or during the aqueous workup).
Scheme 2. Mechanism Proposed for the Formation of 3a
The TiCl4-mediated reaction of 1 with 1,3-bis(trimethylsilyloxy)buta-1,3-dienes
2a – 2y afforded the 6-(chlorodifluoromethyl)-4-methylsalicylates 3a – 3y in 34 – 81%

Helvetica Chimica Acta – Vol. 95 (2012)
Table 1. Synthesis of 3a – 3y
1039
Pruduct
R1
R2
Yield [%]a)
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
H
H
H
H
Me
Me2CH
Me2CHCH2
Me2CHCH2CH2
59
41
45
57
62
81
47
52
54
51
42
59
42
56
55
55
59
34
62
41
61
65
35
66
62
H
Me(CH2)6CH2
Me
Et
Et
Pr
Me
Me
Et
Me
Me
Et
Me
Et
Et
CH2¼CH ꢀ CH2
Me2CH
Me2CHCH2CH2
Me(CH2)3CH2
Me(CH2)4CH2
Me(CH2)5CH2
Me(CH2)6CH2
Me(CH2)7CH2
Me(CH2)8CH2
Me(CH2)10CH2
Me(CH2)14CH2
Ph(CH2)2
Et
Me
Me
Et
Me
Me
Me
Me
Me
Me
Me
3s
3t
3u
3v
3w
3x
3y
4-FꢀC6H4ꢀCH2
Cl
Cl(CH2)3
Cl(CH2)4
a) Yields of isolated products.
yield (Table 1). The yields of most of the products are in the range of 41 – 66%. The
yields drop for sterically hindered dienes (i.e., 2k) and, in case of the Cl-substituted
diene 2w. The purity of each individual diene also plays an important role. In some
reactions, the formation of a small amount of b-keto ester from the hydrolysis of the
diene was observed. Its chromatographic separation from the product was difficult in
some cases. Therefore, practical problems during the chromatographic purification also
influenced the yields. During the optimization, the stoichiometry and the concentration
played an important role (Table 2). The best yield was obtained when 1, 2a, and TiCl4
were used in a stoichiometry of 1:2 :1 with a concentration of 1 of 0.2m.
All reactions proceeded with very good regioselectivity. The CF2Cl group is located
ortho to the ester group. This type of regioselectivity was previously observed for
cyclizations of related CF3-substituted silyl enol ethers [10a]. The structures of various

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Helvetica Chimica Acta – Vol. 95 (2012)
Table 2. Optimization of the Synthesis of 3a
n(1) [mmol]
n(2a) [mmol]
n(TiCl4) [mmol]
CH2Cl2 [ml]
Yield of 3a [%]a)
1
1
1
1
2
2
2
1
1
1
1
1
1
2
5
30
29
59
34
10
a) Yields of isolated product.
Fig. 1. NOESY (H $ H) Correlations for the corroboration of the structure of 3
Fig. 2. ORTEP Plot of 3a (50% probability level)
products were established by NOESY experiments (Fig. 1). The structure of 3a was
independently confirmed by X-ray crystal-structure analysis (Fig. 2)1).
Conclusions. – In conclusion, we reported a convenient and regioselective synthesis
of 6-[chloro(difluoro)methyl]-4-methylsalicylates by TiCl4-mediated [3 þ 3] cyclo-
condensation of 1,3-bis(trimethylsilyloxy)buta-1,3-dienes with 1-chloro-1,1-difluoro-4-
(trimethylsilyloxy)pent-3-en-2-one.
1
)
CCDC-865454 contains all crystallographic details of this publication and is available free of charge
at www.ccdc.cam.ac.uk/conts/retrieving.html or can be ordered from the following address:
Cambridge Crystallographic Data Centre, 12 Union Road, GB-Cambridge CB21EZ; Fax:
(þ44)1223-336-033; or deposit@ccdc.cam.ac.uk.

Helvetica Chimica Acta – Vol. 95 (2012)
1041
Experimental Part
General. CH2Cl2 (anh. 99.8%) was purchased directly from ACROS and used without further
purification. TiCl4 was purchased from Aldrich. All cyclization reactions were carried out in Schlenk
tubes under Ar using dried solvents. Column chromatography (CC): 60 A silica gel (SiO2, 60 – 200 mesh).
Anal. TLC: 0.20 mm 60 A SiO2 plates. M.p.: Microheating table HMK 67/1825 Kuestner (Bꢀchi
apparatus); uncorrected. IR Spectra: FT-IR spectrometer; ˜n in cmꢀ1 1H-NMR Spectra: at 300 and
.
400 MHz resp.; in CDCl3. 13C-NMR Spectra: at 75 and 100 MHz, resp.; in CDCl3; d in ppm with the
solvent as internal standard (CHCl3, 7.26 and 77.0 ppm, resp.); J in Hz. MS: electron ionization (EI,
70 eV), chemical ionization (CI, isobutane), or electrospray ionization (ESI); in m/z. Crystallographic
data were collected on a STEO IPDS 2 diffractometer with MoKa radiation (l ¼ 0.71073 ꢅ). The
structure was solved by direct methods using SHELXS-97 and refined against F2 on all data by full-
matrix least-squares with SHELXL-97. All non-H-atoms were refined anisotropically, and the H-atoms
(except H3b) were refined in the model at geometrically calculated positions and refined using a riding
model.
General Procedure for the Synthesis of 1-Chloro-1,1-difluoro-4-hydroxypent-3-en-2-one. The syn-
thesis of the title compound has been reported in [13]. To a soln. of NaH (1.1 equiv.) in Et2O (2.0 ml/
mmol reactant) was added acetone (1.0 equiv.) at 08. The soln. was stirred at 08 for 10 min, before methyl
2-chloro-2,2-difluoroacetate (1.0 equiv.) was added. The temp. was allowed to rise to 208 over 14 h. To the
soln. was added HCl (10%), and the mixture was extracted with Et2O. The org. layers were dried
(Na2SO4) and filtered, and the filtrate was concentrated in vacuo. The residue was purified by
chromatography (heptane/AcOEt) to give the product.
1,3-Bis(trimethylsilyloxy)buta-1,3-dienes 2a – 2y were prepared according to the literature from the
corresponding b-keto esters in two steps [7][11][12]. Silyl enol ethers 1 were also prepared in analogy to
reported procedures [7].
Procedure for the Synthesis of 3a – 3y. To 1 (1.0 equiv.) and 2 (1.0 equiv.) in CH2Cl2 (2.0 ml/1 mmol of
1) was added TiCl4 (1.0 equiv.) at ꢀ 788. The soln. was slowly allowed to warm to 208 with stirring. To the
soln. was added HCl (10%), and the org. and the aq. layers were separated. The latter was extracted with
CH2Cl2. The combined org. layers were dried (Na2SO4) and filtered, and the filtrate was concentrated in
vacuo. The residue was purified by CC (SiO2, heptane/AcOEt 30 :1).
Methyl 2-[Chloro(difluoro)methyl]-6-hydroxy-4-methylbenzoate (3a). 4-(Trimethylsilyloxy)-1-
chloro-1,1-difluoropent-3-en-2-one (1; 0.242 g, 1.0 mmol), 1-methoxy-1,3-bis(trimethylsilyloxy)buta-1,3-
diene (2a; 0.521 g, 2.0 mmol), and TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml) gave 3a (0.148 g, 59%).
Slight yellow solid. M.p. 41 – 428. Rf (hexane/CH2Cl2 3 :2) 0.50. IR (ATR): 3389w, 2960w, 2866w, 2740w,
1
1710m, 1619m, 1435m, 1386w, 1326m, 1300s, 1273s, 1119s, 1090s, 956s, 830s, 806s. H-NMR (300 MHz):
2.37 (s, Me); 3.96 (s, MeO); 6.97 (s, HꢀC(5)); 7.08 (s, HꢀC(3)); 10.31 (s, OH). 13C-NMR (75 MHz): 21.7
(Me); 52.5 (MeO); 108.3 (t, J(C,F) ¼ 1.9, C(1)); 119.2 (t, J(C,F) ¼ 8.8, C(5)); 125.1 (t, J(C,F) ¼ 286.4,
CF2Cl); 135.9 (t, J(C,F) ¼ 25.8, C(6)); 144.8; 161.1 (C); 169.6 (COO). 19F-NMR (282 MHz): ꢀ 44.8
(CF2Cl). GC/MS (EI, 70 eV): 252 (11), 250 (Mþ, 33), 220 (35), 219 (22), 218 (100), 215 (10), 195 (17),
180 (10), 155 (80), 127 (11). HR-MS (EI, 70 eV): 250.020617 (C10H9ClF2Oþ3 ; calc. 250.02028).
1-Methylethyl 2-[Chloro(difluoro)methyl]-6-hydroxy-4-methylbenzoate (3b). Compound 1 (0.242 g,
1.0 mmol), 1-(1-methylethoxy)-1,3-bis(trimethylsilyloxy)buta-1,3-diene (2b; 0.577 g, 2.0 mmol), and TiCl4
(0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml), yielded 3b (0.108 g, 41%). White solid. M.p. 47 – 488. Rf (hexane/
CH2Cl2 3 :2) 0.67. IR (ATR): 3184w, 3063w, 2986w, 2936w, 2884w, 1665m, 1619m, 1580w, 1495w, 1453m,
1
1374m, 1274m, 1217m, 1148m, 1094s, 954s, 855s, 805s, 792s. H-NMR (300 MHz): 1.40 (s, Me); 1.42 (s,
Me), 2.36 (s, Me); 5.26 – 5.41 (m, 2 CH); 6.95 (s, CH); 7.06 (d, 4J ¼ 1.5, HꢀC(5)); 10.56 (s, OH). 13C-NMR
(100 MHz): 21.4, 21.6 (Me); 71.0 (CH); 108.9 (C(1)); 119.1 (t, J(C,F) ¼ 8.8, C(5)); 121.3 (C(3)); 125.1 (t,
J(C,F) ¼ 290.0, CF2Cl); 135.8 (t, J(C,F) ¼ 25.6, C(6)); 144.5; 161.2 (C); 168.8 (COO). 19F-NMR
(282 MHz): ꢀ 43.9 (CF2Cl). GC/MS (EI, 70 eV): 278 (Mþ, 11), 236 (13), 220 (34), 219 (22), 218 (100),
155 (37). Anal. calc. for C12H13ClF2O3 (278.68): C 51.72, H 4.70; found: C 51.68, H 4.76.
2-Methylpropyl 2-[Chloro(difluoro)methyl]-6-hydroxy-4-methylbenzoate (3c). Compound 1
(0.242 g, 1.0 mmol), 1-(2-methylpropoxy)-1,3-bis(trimethylsilyloxy)buta-1,3-diene (2c; 0.605 g, 2.0 mmol)
and TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml) furnished 3c (0.132 g, 45%). Colorless liquid. Rf (hexane/

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Helvetica Chimica Acta – Vol. 95 (2012)
CH2Cl2 3 :2) 0.63. IR (ATR): 3057w, 2963w, 2877w, 1667m, 1619m, 1577w, 1469m, 1399m, 1324m, 1269s,
959s, 816m, 795s, 706m. 1H-NMR (400 MHz): 1.00, 1.01 (s, Me); 2.07 – 2.20 (m, CH); 2.36 (s, Me); 4.16 (d,
3J ¼ 6.7, HꢀC(3)); 6.96 (br. s, HꢀC(5)); 7.08 (d, 4J ¼ 1.5, CH); 10.37 (s, OH). 13C-NMR (100 MHz): 19.2;
21.6 (Me); 27.4 (CH); 72.9 (CH2O); 108.7 (t, J(C,F) ¼ 1.6, C(1)); 119.1 (t, J(C,F) ¼ 8.6, C(5)); 121.3
(C(3)); 125.2 (t, J(C,F) ¼ 290.1, CF2Cl); 135.7 (t, J(C,F) ¼ 25.7, C(6)); 144.5; 161.1 (C); 169.5 (COO).
19F-NMR (282 MHz): ꢀ 44.4 (CF2Cl). GC/MS (EI, 70 eV): 292 (Mþ, 10), 236 (10), 220 (35), 219 (22),
218 (100), 155 (28). Anal. calc. for C13H15ClF2O3 (292.71): C 53.34, H 5.17; found: C 53.30, H 5.20.
3-Methylbutyl 2-[Chloro(difluoro)methyl]-6-hydroxy-4-methylbenzoate (3d). Compound 1 (0.242 g,
1.0 mmol), 1-(3-methylbutoxy)-1,3-bis(trimethylsilyloxy)buta-1,3-diene (2d; 0.633 g, 2.0 mmol), and
TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml) gave 3d (0.174 g, 57%). White solid. M.p. 30 – 318. Rf
(hexane/CH2Cl2 3 :2) 0.40. IR (ATR): 3057w, 2956m, 2925w, 2872w, 2840w, 1660s, 1620m, 1581m,
1496w, 1452m, 1324s, 1099s, 956s, 944s, 795s, 702s. 1H-NMR (300 MHz): 0.94 (s, Me); 0.96 (s, Me); 1.65 –
3
4
4
1.87 (m, (CH2)CH); 2.37 (s, Me); 4.40 (t, J ¼ 6.9, CH2O); 6.96 (d, J ¼ 0.6, CH); 7.07 (d, J ¼ 1.3, CH);
10.44 (s, OH). 13C-NMR (75 MHz): 21.6; 22.3 (Me); 24.8 (CH); 36.7 (CH2); 65.2 (CH2O); 108.2 (t,
J(C,F) ¼ 1.9, C(1)); 119.1 (t, J(C,F) ¼ 8.7, C(5)); 125.1 (t, J(C,F) ¼ 289.1, CF2Cl); 135.8 (t, J(C,F) ¼ 25.8,
C(6)); 144.6; 161.1 (C); 169.4 (COO). 19F-NMR (282 MHz): ꢀ 44.4 (CF2Cl). GC/MS (EI, 70 eV): 306
(Mþ, 12), 220 (34), 219 (22), 218 (100), 155 (27), 71 (13), 70 (21), 43 (17). Anal. calc. for C14H17ClF2O3
(306.73): C 54.82, H 5.59; found: C 54.82, H 5.61.
Octyl 2-[Chloro(difluoro)methyl]-6-hydroxy-4-methylbenzoate (3e). Compound 1 (0.242 g,
1.0 mmol), 1-(octyloxy)-1,3-bis(trimethylsilyloxy)buta-1,3-diene (2e; 0.717 g, 2.0 mmol), and TiCl4
(0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml) gave 3e (0.215 g, 62%). Colorless oil. Rf (hexane/CH2Cl2 3 :2)
0.47. IR (ATR): 2956m, 2926m, 2856m, 1668m, 1665m, 1620m, 1577w, 1456 m, 1395m, 1327m, 1270s,
1146m, 1099m, 962s, 797s. 1H-NMR (300 MHz): 0.88 (t, 3J ¼ 6.8, Me); 1.28 – 1.43 (m, Me(CH2)5); 2.36 (s,
Me); 1.75 – 1.84 (m, CH2); 2.37 (s, Me); 4.36 (t, 3J ¼ 6.8, CH2); 6.96 (s, CH); 7.07 (d, 4J ¼ 1.6, CH); 10.45 (s,
OH). 13C-NMR (75 MHz): 14.1; 21.7 (Me); 22.6, 25.8, 28.1, 29.1, 29.1, 31.7, 66.7 (CH2); 19.8 (Me); 62.4
(CH2); 108.5 (t, J(C,F) ¼ 1.9, C(1)); 119.1 (t, J(C,F) ¼ 8.7, C(5)); 125.1 (t, J(C,F) ¼ 289.1, CF2Cl); 135.8 (t,
J(C,F) ¼ 25.7, C(6)); 144.6; 161.2.0 (C); 169.4 (COO). 19F-NMR (282 MHz): ꢀ 44.4 (CF2Cl). GC/MS
(EI, 70 eV): 348 (Mþ, 10), 236 (12), 220 (33), 219 (20), 218 (100), 155 (20). Anal. calc. for C17H23ClF2O3
(348.81): C 58.54, H 6.65; found: C 58.74, H 6.57.
Methyl 6-[Chloro(difluoro)methyl]-2-hydroxy-3,4-dimethylbenzoate (3f). Compound 1 (0.242 g,
1.0 mmol), 1-methoxy-1,3-bis(trimethylsilyloxy)penta-1,3-diene (2f; 0.549 g, 2.0 mmol), and TiCl4 (0.1 ml,
1.0 mmol) in CH2Cl2 (5 ml) yielded (3f) (0.216 g, 81%). Slight yellow oil. Rf (heptane/AcOEt 3 :2) 0.72.
IR (ATR): 3349w, 3043w, 3014w, 2986w, 2960w, 2929w, 2861w, 1703s, 1608m, 1570w, 1492w, 1435m, 1283s,
1236s, 1196m, 1119s, 998s, 969s, 859s, 807s, 795s, 711m. 1H-NMR (300 MHz): 2.21 (s, Me); 2.33 (s, Me);
3.96 (s, MeO); 7.08 (s, HꢀC(5)); 10.61 (s, OH). 13C-NMR (75 MHz): 12.0; 20.6 (Me); 52.5 (MeO); 107.9
(t, J(C,F) ¼ 2.3, C(1)); 119.3 (t, J(C,F) ¼ 8.3, C(5)); 125.4 (t, J(C,F) ¼ 288.0, CF2Cl); 132.7 (t, J(C,F) ¼
25.5, C(6)); 129.3; 142.7; 159.1 (C); 170.3 (COO). 19F-NMR (282 MHz): ꢀ 44.4 (CF2Cl). GC/MS (EI,
70 eV): 264 (Mþ, 37), 234 (17), 233 (19), 232 (48), 214 (34), 213 (17), 212 (100), 209 (19), 196 (52), 169
(22), 141 (10). Anal. calc. for C11H11ClF2O3 (264.04): C 49.92, H 4.19; found: C 49.96, H 4.23.
Methyl 6-[Chloro(difluoro)methyl]-3-ethyl-2-hydroxy-4-methylbenzoate (3g). Compound 1; 0.242 g,
1.0 mmol), 1-methoxy-1,3-bis(trimethylsilyloxy)hexa-1,3-diene (2g; 0.577 g, 2.0 mmol), and TiCl4 (0.1 ml,
1.0 mmol) in CH2Cl2 (5.0 ml) afforded 3g (0.130 g, 47%). Colorless oil. Rf (hexane/CH2Cl2 3 :2) 0.63. IR
(ATR): 3139w, 3060w, 3040w, 3008w, 2979w, 2957w, 2880w, 2853w, 1668s, 1438s, 1333m, 1286s, 1232m,
1148s, 1102s, 978m, 962m, 950m, 865s, 804s, 766s, 657s. 1H-NMR (400 MHz): 1.27 (t, 3J ¼ 7.6, Me); 2.36 (s,
Me); 2.72 (q, 3J ¼ 7.2, CH2); 3.96 (s, MeO); 7.07 (s, HꢀC(5)); 10.54 (s, OH). 13C-NMR (100 MHz): 12.7
(Me); 19.8 (Me); 19.8 (CH2); 52.4 (MeO); 108.2 (t, J(C,F) ¼ 2.0, C(1)); 119.6 (t, J(C,F) ¼ 9.0, C(5));
125.4 (t, J(C,F) ¼ 288.0, CF2Cl); 132.8 (t, J(C,F) ¼ 25.0, C(6)); 143.0; 159.0 (C); 170.3 (COO). 19F-NMR
(282 MHz): ꢀ 44.4 (CF2Cl). GC/MS (EI, 70 eV): 278 (Mþ, 45), 248 (20), 247 (20), 246 (55), 228 (16),
226 (44), 223 (14), 211 (15), 210 (100), 182 (23), 160 (11). Anal. calc. for C12H13ClF2O3 (278.68): C 51.72,
H 4.70; found: C 51.76, H 4.90.
Ethyl 6-[Chloro(difluoro)methyl]-3-ethyl-2-hydroxy-4-methylbenzoate (3h). Compound 1 (0.242 g,
1.0 mmol), 1-ethoxy-1,3-bis(trimethylsilyloxy)hexa-1,3-diene (2h; 0.605 g, 2.0 mmol), and TiCl4 (0.1 ml,
1.0 mmol) in CH2Cl2 (5 ml) gave 3h (0.146 g, 52%). Colorless oil. Rf (hexane/CH2Cl2 3 :2) 0.69. IR

Helvetica Chimica Acta – Vol. 95 (2012)
1043
(ATR): 2978w, 2936w, 2907w, 2876w, 1665m, 1607w, 1573w, 1457w, 1391m, 1373m, 1279s, 1147s, 1104s,
958s, 804s. 1H-NMR (300 MHz): 1.12 (t, 3J ¼ 7.5, Me); 1.43 (t, 3J ¼ 7.2, Me); 2.36 (s, Me); 2.72 (q, 3J ¼ 7.5,
CH2); 4.44 (q, 3J ¼ 7.2, CH2); 7.06 (s, HꢀC(5)); 10.67 (s, OH). 13C-NMR (75 MHz): 12.6; 13.6 (Me); 19.7
(CH2); 19.8 (Me); 62.4 (CH2); 108.3 (t, J(C,F) ¼ 1.9, C(1)); 119.6 (t, J(C,F) ¼ 8.8, C(5)); 125.4 (t,
J(C,F) ¼ 289.7, CF2Cl); 132.7 (t, J(C,F) ¼ 25.7, C(6)), 134.9; 141.8; 159.0 (C); 169.9 (COO). 19F-NMR
(282 MHz): ꢀ 43.8 (CF2Cl). GC/MS (EI, 70 eV): 294 (12), 292 (Mþ,37), 248 (20), 247 (19), 246 (53), 228
(15), 226 (41), 211 (13), 210 (100), 209 (16), 189 (10), 182 (18). Anal. calc. for C13H15ClF2O3 (292.71): C
53.34, H 5.17; found: C 53.33, H 5.09.
Methyl 6-[Chloro(difluoro)methyl]-2-hydroxy-4-methyl-3-propylbenzoate (3i). Compound 1
(0.242 g, 1.0 mmol), 1-methoxy-1,3-bis(trimethylsilyloxy)hepta-1,3-diene (2i; 0.605 g, 2.0 mmol), and
TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml) afforded 3i (0.154 g, 54%). White solid. Rf (hexane/CH2Cl2
3 :2) 0.58. IR (ATR): 3006w, 2960w, 2873w, 1672m, 1607w, 1572w, 1438m, 1391m, 1329m, 1273s, 1145s,
1107s, 977s, 960s, 856s, 801s. 1H-NMR (300 MHz): 0.99 (t, 3J ¼ 7.3, Me); 1.48 – 1.60 (m, MeCH2); 2.35 (s,
Me); 2.66 (t, 3J ¼ 7.9, ArCH2); 3.95 (s, MeO); 7.06 (s, HꢀC(5)); 10.55 (s, OH). 13C-NMR (75 MHz): 14.4;
20.0 (Me); 21.7; 28.5 (CH2); 52.4 (MeO); 108.7 (t, J(C,F) ¼ 1.9, C(1)); 119.6 (t, J(C,F) ¼ 8.8, C(5)); 125.4
(t, J(C,F) ¼ 289.6, CF2Cl); 132.7 (t, J(C,F) ¼ 25.7, C(6)); 133.6, 142.3, 159.1 (C); 170.3 (COO). 19F-NMR
(282 MHz): ꢀ 44.3 (CF2Cl). GC/MS (EI, 70 eV): 294 (23), 293 (10), 292 (Mþ,69), 263 (10), 262 (26), 261
(27), 260 (72), 257 (15), 247 (25), 246 (10), 245 (85), 243 (32), 240 (25), 237 (19), 233 (19), 232 (24), 231
(51), 225 (30), 224 (100), 214 (21), 213 (10), 212 (61), 197 (15), 196 (57), 193 (18), 177 (11), 175 (19), 174
(13), 140 (16). Anal. calc. for C13H15ClF2O3 (292.71): C 53.34, H 5.17; found: C 53.50, H 5.30.
Methyl 6-[Chloro(difluoro)methyl]-2-hydroxy-4-methyl-3-(prop-2-en-1-yl)benzoate (3j). Com-
pound 1 (0.242 g, 1.0 mmol), 1-methoxy-1,3-bis(trimethylsilyloxy)hepta-1,3,6-triene (2j; 0.601 g,
2.0 mmol), and TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml) gave 3j (0.148 g, 51%). Colorless oil. Rf
(hexane/CH2Cl2 3 :2) 0.60. IR (ATR): 3080w, 3008w, 2980w, 2955w, 2930w, 2854w, 1672m, 1638w, 1608w,
1572w, 1438m, 1331m, 1273s, 1144s, 1108s, 967s, 801s. 1H-NMR (300 MHz): 2.35 (s, Me); 3.47 (dt, 3J ¼ 6.0,
CH2); 3.96 (s, MeO); 4.92 – 5.04 (m, CH2CH); 5.83 – 5.96 (m, CH); 7.09 (s, HꢀC(5)); 10.59 (s, OH).
13C-NMR (75 MHz): 19.9 (Me); 30.5 (CH2); 52.5 (MeO); 108.3 (t, J(C,F) ¼ 1.9, C(1)); 115.4 (CH2); 119.6
(t, J(C,F) ¼ 8.7, C(5)); 125.2 (t, J(C,F) ¼ 289.7, CF2Cl); 130.4 (C(3)); 133.4 (t, J(C,F) ¼ 25.8, C(6)); 134.2
(CH); 143.1; 158.9 (C); 170.2 (OꢀCO). 19F-NMR (282 MHz): ꢀ 44.5 (CF2Cl). GC/MS (EI, 70 eV): 292
(19), 290 (Mþ, 56), 261 (10), 260 (24), 259 (33), 258 (65), 255 (27), 254 (10), 245 (33), 244 (12), 243
(100), 239 (15), 238 (17), 235 (18), 230 (17), 224 (10), 223 (69), 222 (16), 220 (15), 219 (29), 217 (11), 215
(35), 211 (10), 210 (11), 205 (15), 195 (30), 194 (25), 180 (10), 175 (25), 151 (18), 147 (13), 146 (17), 145
(10), 133 (10), 127 (13), 115 (22). Anal. calc. for C13H13ClF2O3 (290.69): C 53.71, H 4.51; found: C 53.60,
H 4.55.
Ethyl 6-[Chloro(difluoro)methyl]-2-hydroxy-4-methyl-3-(1-methylethyl)benzoate (3k). Compound
1 (0.242 g, 1.0 mmol), 1-ethoxy-1,3-bis(trimethylsilyloxy)-5-methylhexa-1,3-diene (2k; 0.633 g, 2.0 mmol),
and TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml) provided 3k (0.128 g, 42%). Colorless liquid. Rf (hexane/
CH2Cl2 3 :2) 0.67. IR (ATR): 2915s, 2848s, 1667w, 1606w, 1468m, 1375w, 1316w, 1265w, 718m. 1H-NMR
(300 MHz): 1.34 (s, Me); 1.36 (s, Me); 1.42 (t, 3J ¼ 7.2, Me); 2.37 (s, Me); 4.43 (q, 3J ¼ 7.1, CH2); 7.03 (s,
HꢀC(5)); 10.59 (s, OH). 13C-NMR (75 MHz): 13.6; 19.6; 21.2; 24.1 (Me); 28.7 (CH); 62.4 (CH2O); 109.1
(t, J(C,F) ¼ 1.6, C(1)); 120.05 (t, J(C,F) ¼ 8.6, C(5)); 125.4 (t, J(C,F) ¼ 289.6, CF2Cl); 132.7 (t, J(C,F) ¼
25.7, C(6)); 137.7; 141.4; 159.9 (C); 169.9 (COO). 19F-NMR (282 MHz): ꢀ 43.8 (CF2Cl). GC/MS (EI,
70 eV): 308 (13), 306 (Mþ, 38), 262 (17), 261 (19), 260 (48), 247 (13), 245 (44), 243 (18), 240 (23), 225
(27), 224 (100), 223 (18), 212 (22), 197 (13), 196 (26), 133 (13). Anal. calc. for C14H17ClF2O3 (306.73): C
54.82, H 5.59; found: C 54.83, H 5.59.
Methyl 6-[Chloro(difluoro)methyl]-2-hydroxy-4-methyl-3-(3-methylbutyl)benzoate (3l). Compound
1
(0.242 g, 1.0 mmol), 1-methoxy-1,3-bis(trimethylsilyloxy)-7-methylocta-1,3-diene (2l; 0.661 g,
2.0 mmol), and TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml) afforded 3l (0.189 g, 59%). Colorless oil. Rf
(hexane/CH2Cl2 3 :2) 0.78. IR (ATR): 2955w, 2870w, 1673m, 1607w, 1572w, 1438m, 1384m, 1269s, 1145s,
1
1109s, 972 s, 802s. H-NMR (300 MHz): 0.96 (s, Me); 0.98 (s, Me); 1.31 – 1.38 (m, CH2); 1.60 – 1.73 (m,
CH); 2.35 (s, Me); 2.64 – 2.69 (m, ArCH2); 3.96 (s, MeO); 7.06 (s, HꢀC(5)); 10.53 (s, OH). 13C-NMR
(75 MHz): 19.9; 22.4 (Me); 24.5 (CH2); 28.6 (CH); 37.4 (CH2); 52.4 (MeO); 108.1 (t, J(C,F) ¼ 1.9, C(1));
119.6 (t, J(C,F) ¼ 8.7, C(5)); 125.4 (t, J(C,F) ¼ 289.6, CF2Cl); 132.7 (t, J(C,F) ¼ 25.7, C(6)); 134.1, 142.1,

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Helvetica Chimica Acta – Vol. 95 (2012)
159.0 (C); 170.3 (COO). 19F-NMR (282 MHz): ꢀ 44.3 (CF2Cl). GC/MS (EI, 70 eV): 322 (13), 320 (Mþ,
37), 289 (11), 288 (11), 285 (11), 273 (19), 234 (34), 233 (24), 232 (100), 231 (31), 214 (32), 213 (11), 212
(95), 208 (14), 197 (10), 196 (34), 193 (15). Anal. calc. for C15H19ClF2O3 (320.76): C 56.17, H 5.97; found:
C 56.12, H 5.83.
Ethyl 6-[Chloro(difluoro)methyl]-2-hydroxy-4-methyl-3-pentylbenzoate (3m). Compound
1
(0.242 g, 1.0 mmol), 1-ethoxy-1,3-bis(trimethylsilyloxy)nona-1,3-diene (2m; 0.680 g, 2.0 mmol), and TiCl4
(0.1 ml, 1.0 mmol) in CH2Cl2 (5.0 ml) furnished 3m (0.137 g, 42%). Colorless oil. Rf (hexane/CH2Cl2 3 :2)
0.19. IR (ATR): 2958w, 2929w, 2872w, 2860w, 1666m, 1374m, 1324m, 1278s, 1148s, 1109s, 987s, 961m,
912 m, 865m, 822m, 802s, 725w. 1H-NMR (400 MHz): 0.92 (t, 3J ¼ 7.2, Me); 1.35 – 1.54 (m, 9 H, Me,
Me(CH2)4); 2.35 (s, Me); 2.69 (t, 3J ¼ 5.6, CH2); 4.44 (q, 3J ¼ 7.2, CH2); 7.06 (s, HꢀC(5)); 10.66 (s, OH).
13C-NMR (75 MHz): 13.6, 14.0, 20.0 (Me); 22.7, 26.6, 28.1, 32.1 (CH2); 62.4 (CH2O); 108.3 (t, J ¼ 2.0,
C(1)); 119.6 (t, J(C,F) ¼ 8.0, C(5)); 125.5 (t, J(C,F) ¼ 288.0, CF2Cl); 132.7 (t, J(C,F) ¼ 26.0, C(6)); 133.9;
142.0; 159.2 (C); 170.0 (COO). 19F-NMR (282 MHz): ꢀ 43.8 (CF2Cl). GC/MS (EI, 70 eV): 335 (Mþ, 4),
334 (23), 275 (33), 274 (15), 273 (100), 271 (12), 251 (10), 234 (10), 233 (11), 232 (30), 231 (22), 214 (17),
212 (48), 196 (19). Anal. calc. for C16H21ClF2O3 (334.79): C 57.40, H 6.32; found: C 57.40, H 6.42.
Ethyl 6-[Chloro(difluoro)methyl]-3-hexyl-2-hydroxy-4-methylbenzoate (3n). Compound 1 (0.242 g,
1.0 mmol), 1-ethoxy-1,3-bis(trimethylsilyloxy)deca-1,3-diene (2n; 0.717 g, 2.0 mmol), and TiCl4 (0.1 ml,
1.0 mmol) in CH2Cl2 (5 ml) gave 3n (0.186 g, 56%). Colorless liquid. Rf (hexane/CH2Cl2 3 :2) 0.76. IR
(ATR): 2957w, 2927m, 2858w, 1666m, 1607w, 1465m, 1392m, 1373m, 1273s, 1148s, 1110s, 990s, 802s.
1H-NMR (300 MHz): 0.87 (t, 3J ¼ 6.9, Me); 1.24 – 1.38 (m, Me(CH2)4), Me); 2.31 (s, Me), 2.62 (t, 3J ¼ 7.3,
ArCH2); 4.28 (q, 3J ¼ 7.1, CH2); 7.06 (s, HꢀC(5)); 9.30 (s, OH). 13C-NMR (75 MHz): 3.7; 13.8; 19.2 (Me);
21.9; 25.9; 28.0; 28.9; 30.9 (CH2); 61.2 (CH2O); 117.8 (t, J(C,F) ¼ 2.5, C(1)); 118.0 (t, J(C,F) ¼ 6.1, C(5));
125.5 (t, J(C,F) ¼ 289.7, CF2Cl); 129.1 (t, J(C,F) ¼ 25.5, C(6)); 133.7, 139.1, 151.9 (C), 165.9 (COO). 19F-
NMR (282 MHz): ꢀ 45.0 (CF2Cl). GC/MS (EI, 70 eV): 348 (Mþ, 26), 303 (10), 289 (33), 288 (15), 287
(100), 285 (11), 266 (13), 265 (10), 234 (12), 233 (12), 232 (37), 231 (22), 214 (18), 212 (52), 196 (21).
Anal. calc. for C17H23ClF2O3 (348.81): C 58.54, H 6.65; found: C 58.26, H 6.58.
Ethyl 6-[Chloro(difluoro)methyl]-3-heptyl-2-hydroxy-4-methylbenzoate (3o). Compound 1 (0.242 g,
1.0 mmol), 1-ethoxy-1,3-bis(trimethylsilyloxy)undeca-1,3-diene (2o; 0.744 g, 2.0 mmol), and TiCl4 (0.1 ml,
1.0 mmol) in CH2Cl2 (5.0 ml) afforded 3o (0.199 g, 55%). Slightly yellow oil. Rf (hexane/CH2Cl2 3 :2)
0.77. IR (ATR): 2957w, 2926w, 2857w, 1667m, 1608w, 1374m, 1270s, 1232m, 1148s, 1111s, 975m, 803m.
1H-NMR (300 MHz): 0.92 (t, 3J ¼ 7.3, Me); 1.21 – 1.5 (m, 13 H, Me, Me(CH2)6); 2.35 (s, Me); 2.67 (t, 3J ¼
3
8.1, CH2); 4.44 (q, J ¼ 7.2, CH2); 7.06 (s, HꢀC(5)); 10.68 (s, OH). 13C-NMR (75 MHz): 13.6, 14.1, 20.0
(Me); 22.7, 26.7, 28.5, 29.2, 30.0, 31.9 (CH2); 62.4 (CH2O); 108.3 (C(1)); 119.6 (t, J(C,F) ¼ 8.3, C(5));
125.4 (t, J(C,F) ¼ 288.0, CF2Cl); 132.7 (t, J(C,F) ¼ 26.1, C(6)); 133.9; 142.0; 159.2 (C); 170.0 (COO). 19F-
NMR (282 MHz): ꢀ 43.8 (CF2Cl). GC/MS (EI, 70 eV): 363 (Mþ, 5), 362 (22), 303 (34), 302 (17), 301
(100), 299 (11), 280 (15), 279 (10), 234 (12), 233 (12), 232 (37), 214 (17), 212 (50), 196 (19). Anal. calc.
for C18H25ClF2O3 (362.84): C 59.58, H 6.94; found: C 59.71, H 6.69.
Methyl 6-[Chloro(difluoro)methyl]-2-hydroxy-4-methyl-3-octylbenzoate (3p). Compound 1 (0.242 g,
1.0 mmol), 1-methoxy-1,3-bis(trimethylsilyloxy)dodeca-1,3-diene (2p; 0.745 g, 2.0 mmol), and TiCl4
(0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml) gave 3p (0.200 g, 55%). Colorless liquid. Rf (hexane/CH2Cl2 3 :2)
0.60. IR (ATR): 2951w, 2920m, 2869w, 2850m, 1663s, 1608w, 1576w, 1472w, 1461w, 1438m, 1338s, 1294s,
1278s, 1099s, 975s, 960s, 805s. 1H-NMR (300 MHz): 0.88 (t, 3J ¼ 6.7, Me); 1.28 – 1.52 (m, 12 H, Me(CH2)6);
2.35 (s, Me); 2.67 (t, 3J ¼ 7.7, ArCH2); 3.95 (s, MeO); 7.06 (s, HꢀC(5)); 10.54 (s, OH). 13C-NMR
(75 MHz): 14.1, 20.0 (Me); 22.7, 26.7, 28.4, 29.3, 29.5, 30.0, 31.9 (CH2); 52.4 (MeO); 108.0 (t, J(C,F) ¼ 1.9,
C(1)); 119.6 (t, J(C,F) ¼ 8.7, C(5)); 125.4 (t, J(C,F) ¼ 289.6, CF2Cl); 132.7 (t, J(C,F) ¼ 25.8, C(6)); 133.9;
142.2; 159.1 (C); 170.3 (COO). 19F-NMR (282 MHz): ꢀ 44.3 (CF2Cl). GC/MS (EI, 70 eV): 362 (Mþ,
22), 317 (34), 316 (17), 315 (100), 294 (15), 234 (12), 233 (13), 232 (36), 231 (24), 214 (17), 212 (51), 196
(20), 193 (12). Anal. calc. for C18H25ClF2O3 (362.84): C 59.58, H 6.94; found: C 59.57, H 6.94.
Methyl 6-[Chloro(difluoro)methyl]-2-hydroxy-4-methyl-3-nonylbenzoate (3q). Compound 1
(0.242 g, 1.0 mmol), 1-methoxy-1,3-bis(trimethylsilyloxy)trideca-1,3-diene (2q; 0.773 g, 2.0 mmol), and
TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml) yielded 3q (0.221 g, 59%). White solid. M.p. 36 – 378. Rf
(hexane/CH2Cl2 3 :2) 0.79. IR (ATR): 2950w, 2920m, 2868w, 2849m, 1663s, 1608w, 1577w, 1472m, 1461m,
1438m, 1338s, 1099s, 977s, 966s, 804s. 1H-NMR (300 MHz): 0.88 (t, 3J ¼ 6.7, Me); 1.27 – 1.52 (m,

Helvetica Chimica Acta – Vol. 95 (2012)
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Me(CH2)7); 2.35 (s, Me); 2.67 (t, 3J ¼ 7.4, ArCH2); 3.95 (s, MeO); 7.06 (s, HꢀC(5)); 10.54 (s, OH).
13C-NMR (75 MHz): 14.1, 20.0 (Me); 22.7, 26.7, 28.4, 29.3, 29.5, 29.6, 30.0, 31.9 (CH2); 52.4 (MeO); 108.0
(t, J(C,F) ¼ 1.9, C(1)); 119.6 (t, J(C,F) ¼ 8.9, C(5)); 125.4 (t, J(C,F) ¼ 289.6, CF2Cl); 132.7 (t, J(C,F) ¼
25.8, C(6)); 133.9; 142.2; 159.1 (C); 170.3 (COO). 19F-NMR (282 MHz): ꢀ 44.3 (CF2Cl). GC/MS (EI,
70 eV): 376 (Mþ, 22), 331 (34), 330 (18), 329 (100), 308 (14), 234 (12), 233 (12), 232 (37), 231 (23), 214
(17), 212 (49), 196 (19), 193 (11). Anal. calc. for C19H27ClF2O3 (376.87): C 60.55, H 7.22; found: C 60.50,
H 7.18.
Ethyl 6-[Chloro(difluoro)methyl]-3-decyl-2-hydroxy-4-methylbenzoate (3r). Compound 1 (0.242 g,
1.0 mmol), 1-ethoxy-1,3-bis(trimethylsilyloxy)tetradeca-1,3-diene (2r; 0.829 g, 2.0 mmol), and TiCl4
(0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml) provided 3r (0.138 g, 34%). Colorless liquid. Rf (hexane/CH2Cl2
3 :2) 0.61. IR (ATR): 2956w, 2924m, 2854m, 1666m, 1607w, 1465w, 1392m, 1373m, 1271s, 1148s, 1112s,
990s, 802s, 721m. 1H-NMR (300 MHz): 0.88 (t, 3J ¼ 6.7, Me); 1.26 – 1.53 (m, Me(CH2)8); 1.42 (t, 3J ¼ 7.1,
Me); 2.34 (s, Me); 2.67 (t, 3J ¼ 7.7, ArCH2); 4.43 (q, 3J ¼ 7.1, CH2); 7.05 (s, HꢀC(5)); 10.67 (s, OH).
13C-NMR (75 MHz): 13.6, 14.1, 20.0 (Me); 22.7, 26.6, 28.4, 29.3, 29.5, 29.6, 29.6, 30.0, 31.9 (CH2); 62.3
(CH2O); 108.2 (t, J(C,F) ¼ 1.9, C(1)); 119.5 (t, J(C,F) ¼ 8.7, C(5)); 125.4 (t, J(C,F) ¼ 289.7, CF2Cl); 132.6
(t, J(C,F) ¼ 25.7, C(6)); 133.8; 142.0; 159.1 (C); 169.9 (COO). 19F-NMR (282 MHz): ꢀ 43.7 (CF2Cl).
GC/MS (EI, 70 eV): 404 (Mþ, 18), 345 (33), 344 (20), 343 (100), 341 (10), 322 (14), 234 (12), 233 (11),
232 (37), 231 (21), 214 (17), 213 (10), 212 (47), 196 (18). Anal. calc. for C21H31ClF2O3 (404.92): C 62.29,
H 7.72; found: C 62.30, H 7.62.
Methyl 6-[Chloro(difluoro)methyl]-3-dodecyl-2-hydroxy-4-methylbenzoate (3s). Compound 1
(0.242 g, 1.0 mmol), 1-methoxy-1,3-bis(trimethylsilyloxy)hexadeca-1,3-diene (2s; 0.856 g, 2.0 mmol),
and TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml) gave 3s (0.259 g, 62%). White solid. M.p. 52 – 538. Rf
(hexane/CH2Cl2 3 :2) 0.70. IR (ATR): 2958w, 2915m, 2847m, 1663m, 1608w, 1472m, 1462m, 1438 m,
1
3
1338s, 1101s, 974s, 805s. H-NMR (300 MHz): 0.88 (t, J ¼ 6.7, Me); 1.26 – 1.49 (m, Me(CH2)10); 2.35 (s,
Me); 2.67 (t, 3J ¼ 7.8, ArCH2); 3.95 (s, MeO); 7.06 (s, HꢀC(5)); 10.54 (s, OH). 13C-NMR (75 MHz): 14.1
(Me); 20.0, 22.7, 26.6, 28.4, 29.3, 29.5, 29.6, 29.6, 29.7, 30.0, 31.9 (CH2); 52.4 (MeO); 108.0 (t, J(C,F) ¼ 1.9,
C(1)); 119.6 (t, J(C,F) ¼ 8.7, C(5)); 125.4 (t, J(C,F) ¼ 289.6, CF2Cl); 132.7 (t, J(C,F) ¼ 25.7, C(6)); 133.9,
142.2, 159.1 (C), 170.3 (COO). 19F-NMR (282 MHz): ꢀ 44.3 (CF2Cl). GC/MS (EI, 70 eV): 418 (Mþ,
19), 373 (35), 372 (24), 371 (100), 350 (10), 234 (14), 233 (14), 232 (35), 231 (25), 214 (19), 212 (50), 196
(17), 193 (12), 43 (10). Anal. calc. for C22H33ClF2O3 (418.95): C 63.07, H 7.94; found: C 63.22, H 7.88.
Methyl 6-[Chloro(difluoro)methyl]-3-hexadecyl-2-hydroxy-4-methylbenzoate (3t). Compound 1
(0.242 g, 1.0 mmol), 1-methoxy-1,3-bis(trimethylsilyloxy)icosa-1,3-diene (2t; 0.969 g, 2.0 mmol), and
TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml) afforded 3t (0.196 g, 41%). White solid. M.p. 67 – 688. Rf
(hexane/CH2Cl2 3 :2) 0.66. IR (ATR): 2983w, 2959w, 2915s, 2847s, 1663s, 1608w, 1472m, 1462m, 1438m,
1338s, 1286s, 1101s, 974s, 805s. 1H-NMR (300 MHz): 0.88 (t, 3J ¼ 6.7, Me); 1.25 – 1.51 (m, 28 H,
Me(CH2)14); 2.35 (s, Me); 2.67 (t, 3J ¼ 7.7, ArCH2); 3.95 (s, MeO); 7.06 (s, HꢀC(5)); 10.54 (s, OH).
13C-NMR (100 MHz): 14.1; 20.0 (Me); 22.7, 26.6, 28.4, 29.3, 29.5, 29.6, 29.7, 29.7, 30.0, 31.9 (CH2); 52.4
(MeO); 108.0 (C(1)); 119.6 (t, J(C,F) ¼ 8.7, C(5)); 125.4 (t, J(C,F) ¼ 289.6, CF2Cl); 132.7 (t, J(C,F) ¼ 25.7,
C(6)); 133.9; 142.1; 159.1 (C); 170.3 (COO). 19F-NMR (282 MHz): ꢀ 44.3 (CF2Cl). GC/MS (EI, 70 eV):
475 (Mþ, 6), 474 (26), 442 (14), 429 (30), 428 (22), 427 (100), 234 (15), 233 (13), 232 (54), 231 (21), 214
(16), 212 (57), 196 (15), 147 (13), 69 (12), 57 (15), 55 (14), 44 (12), 43 (15), 41 (12). Anal. calc. for
C26H41ClF2O3 (475.05): C 65.74, H 8.70; found: C 65.58, H 8.69.
Methyl 6-[Chloro(difluoro)methyl]-2-hydroxy-4-methyl-3-(2-phenylethyl)benzoate (3u). Com-
pound 1 (0.242 g, 1.0 mmol), 1-methoxy-1,3-bis(trimethylsilyloxy)-6-phenylhexa-1,3-diene (2u; 0.729 g,
2.0 mmol), and TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml) yielded 3u (0.215 g, 61%). White solid. M.p.
56 – 578. Rf (hexane/CH2Cl2 3 :2) 0.56. IR (ATR): 3431m, 3086w, 3065w, 3030w, 2987w, 2952w, 2871w,
1689s, 1603m, 1570w, 1495w, 1452m, 1312s, 1106s, 1006s, 970s, 805s, 743s, 704s. 1H-NMR (300 MHz): 2.22
3
3
(s, Me); 2.81 (t, J ¼ 4.6, CH2); 2.96 (t, J ¼ 4.6, CH2); 3.97 (s, MeO); 7.05 (s, HꢀC(5)); 7.17 – 7.35 (m, 5
arom. H); 10.68 (s, OH). 13C-NMR (75 MHz): 19.9 (Me); 29.1; 34.4 (CH2); 52.4 (MeO); 108.1 (t,
J(C,F) ¼ 1.9, C(1)); 119.6 (t, J(C,F) ¼ 8.8, C(5)); 125.3 (t, J(C,F) ¼ 289.7, CF2Cl); 126.0, 128.4, 128.4, 132.6
(Ph); 133.1 (t, J(C,F) ¼ 25.8, C(6)); 141.8, 142.5, 159.3 (C); 170.3 (COO). 19F-NMR (282 MHz): ꢀ 44.4
(CF2Cl). GC/MS (EI, 70 eV): 354 (Mþ, 26), 322 (15), 286 (13), 263 (21), 233 (34), 232 (11), 231 (100),
193 (10), 91 (39). Anal. calc. for C18H17ClF2O3 (354.78): C 60.94, H 4.83; found: C 60.88, H 4.77.

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Methyl 6-[Chloro(difluoro)methyl]-3-[(4-fluorophenyl)methyl]-2-hydroxy-4-methylbenzoate (3v).
Compound 1 (0.242 g, 1.0 mmol), 4-(4-fluorophenyl)-1-methoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene
(2v; 0.737 g, 2.0 mmol), and TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml) gave 3v (0.232 g, 65%). Colorless
oil. Rf (hexane/CH2Cl2 3 :2) 0.68. IR (ATR): 3040w, 3004w, 2955w, 2901w, 2855w, 1672m, 1604m, 1508m,
1
1438m, 1392m, 1274s, 1144s, 970s, 839s, 804s. H-NMR (300 MHz): 2.32 (s, Me); 3.97 (s, MeO); 4.06 (s,
ArCH2); 6.92 (s, HꢀC(5)); 7.04 – 7.28 (m, 4 arom. H); 10.71 (s, OH). 13C-NMR (100 MHz): 21.4 (Me);
32.1 (ArCH2); 53.6 (MeO); 109.6 (C(1)); 116.1 (Ar); 120.8 (t, J(C,F) ¼ 8.7, C(5)); 126.3 (t, J(C,F) ¼ 289.8,
CF2Cl); 130.6 (Ar); 134.9 (t, J(C,F) ¼ 26.0, C(6)); 132.4; 135.6; 144.4 (C); 160.3 (Ar); 161.2 (C); 171.2
(COO). 19F-NMR (282 MHz): ꢀ 44.6 (CF2Cl), ꢀ 44.7 (ArF). GC/MS (EI, 70 eV): 358 (Mþ, 18), 338
(12), 327 (18), 323 (21), 322 (36), 318 (14), 308 (13), 307 (14), 306 (42), 305 (24), 303 (32), 302 (33), 291
(18), 290 (100), 289 (34), 288 (19), 287 (95), 219 (13), 215 (14), 214 (17), 212 (12), 183 (28). Anal. calc.
for C17H14ClF3O3 (358.74): C 56.92, H 3.93; found: C 56.93, H 4.12.
Methyl 3-Chloro-6-[chloro(difluoro)methyl]-2-hydroxy-4-methylbenzoate (3w). Compound 1
(0.242 g, 1.0 mmol), 4-chloro-1-methoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene (2w; 0.589 g, 2.0 mmol),
and TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml) yielded 3w (0.101 g, 35%). Slightly yellow solid. M.p. 86 –
878. Rf (heptane/AcOEt 3 :2) 0.55. IR (ATR): 3377 m, 3047w, 2995w, 2961w, 2925w, 2850w, 1717s, 1601m,
1
1566m, 1455m, 1434m, 1409m, 1280s, 1121 s, 1112s, 974s, 950s, 853s, 807s. H-NMR (300 MHz): 2.46 (s,
Me); 3.99 (s, MeO); 7.17 (s, CH); 10.17 (s, OH). 13C-NMR (75 MHz): 20.8 (Me); 52.9 (MeO); 110.7 (t,
J(C,F) ¼ 1.9, C(1)); 119.4 (t, J(C,F) ¼ 8.5, C(5)); 124.7 (t, J(C,F) ¼ 288.3, CF2Cl); 125.9 (C(3)); 133.3 (t,
J(C,F) ¼ 26.2, C(6)); 142.0; 155.6 (C); 168.8 (OꢀCO). 19F-NMR (282 MHz): ꢀ 45.5 (CF2Cl). GC/MS
(EI, 70 eV): 285 (Mþ, 3), 284 (28), 256 (12), 255 (16), 254 (67), 253 (26), 252 (199), 29 (16), 217 (25), 214
(11), 191 (13), 189 (41). Anal. calc. for C10H8Cl2F2O3 (285.07): C 42.13, H 2.83; found: C 42.23, H 3.04.
Methyl 6-[Chloro(difluoro)methyl]-3-(3-chloropropyl)-2-hydroxy-4-methylbenzoate (3x). Com-
pound 1 (0.242 g, 1.0 mmol), 7-chloro-1-methoxy-1,3-bis(trimethylsilyloxy)hepta-1,3-diene (2x; 0.674 g,
2.0 mmol), and TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (5 ml) furnished 3x (0.205 g, 66%). Slightly yellow oil.
Rf (hexane/CH2Cl2 3 :2) 0.72. IR (ATR): 2955w, 2862w, 1671m, 1608w, 1573w, 1438m, 1392w, 1331m,
1280s, 1143s, 1109m, 973s, 802s. 1H-NMR (300 MHz): 1.95 – 2.05 (m, CH2); 2.39 (s, Me); 2.85 (t, 3J ¼ 7.7,
ArCH2); 3.60 (t, 3J ¼ 6.5, CH2Cl); 3.96 (s, MeO); 7.09 (s, HꢀC(5)); 10.65 (s, OH). 13C-NMR (75 MHz):
20.1 (Me); 24.1; 31.2; 45.0 (CH2); 52.5 (MeO); 108.1 (t, J(C,F) ¼ 1.9, C(1)); 119.7 (t, J(C,F) ¼ 8.8, C(5));
125.2 (t, J(C,F) ¼ 289.7, CF2Cl); 131.8 (C(3)); 133.3 (t, J(C,F) ¼ 25.7, C(6)); 142.6; 159.2 (C); 170.2
(COO). 19F-NMR (282 MHz): ꢀ 44.6 (CF2Cl). GC/MS (EI, 70 eV): 326 (Mþ, 11), 290 (14), 261 (33),
260 (12), 259 (100), 255 (16), 212 (13). HR-MS (EI, 70 eV): 326.028160 (C13H14Cl2F2O3; calc.
326.02826).
Methyl 6-[Chloro(difluoro)methyl]-3-(4-chlorobutyl)-2-hydroxy-4-methylbenzoate (3y). Compound
1
(0.242 g, 1.0 mmol), 8-chloro-1-methoxy-1,3-bis(trimethylsilyloxy)octa-1,3-diene (2y; 0.413 g,
2.0 mmol), and TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (5.0 ml) gave 3y (0.212 g, 62%). Colorless oil. Rf
(hexane/CH2Cl2 3 :2) 0.57. IR (ATR): 3000w, 2955w, 2869w, 1671s, 1607w, 1438m, 1274s, 1143s, 1109m,
1
976s, 862 m, 802m, 739w. H-NMR (300 MHz): 1.64 – 1.72 (m, CH2); 1.83 – 1.92 (m, CH2); 2.37 (s, Me);
3
3
2.72 (t, J ¼ 7.8, CH2); 2.58 (t, J ¼ 6.6, CH2); 3.96 (s, MeO); 7.08 (s, HꢀC(5)); 10.61 (s, OH). 13C-NMR
(75 MHz): 20.0 (Me); 25.6 (Me); 25.7 (CH2); 32.5 (CH2); 44.8 (CH2); 52.5 (MeO); 108.15 (C(1)); 119.7
(t, J(C,F) ¼ 8.9, C(5)); 125.3 (t, J(C,F) ¼ 287.8, CF2Cl); 132.9 (t, J(C,F) ¼ 25.4, C(6)); 132.9; 142.4; 159.1
(C); 170.3 (COO). 19F-NMR (282 MHz): ꢀ 44.5 (CF2Cl). GC/MS (EI, 70 eV): 341 (Mþ, 2), 340 (13),
293 (15), 275 (35), 274 (16), 273 (100), 231 (19). Anal. calc. for C14H16Cl2F2O3 (341.18): C 49.29, H 4.73;
found: C 49.31, H 5.01.
S. Reimann gratefully acknowledges the University of Rostock (scholarship of the Faculty of
Interdisciplinary Science of the University of Rostock/Dept. LLM) for financial support. Financial
support by the State of Mecklenburg-Vorpommern is also gratefully acknowledged.
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Received December 8, 2011