Novel Fluorination of Small-ring Tertiary Cycloalkanols: Reaction of Diethylaminosulfur Trifluoride with Tertiary Cyclobutanols

Article abstract of DOI:10.1039/a804786c

The reaction of diethylaminosulfur trifluoride with a tertiary cyclobutanol afforded a fluorocyclobutane, a (fluoromethyl)cyclopropane or a homoallylic fluoride.

Full text of DOI:10.1039/a804786c

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652 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 652±653$
Novel Fluorination of Small-ring Tertiary
Cycloalkanols: Reaction of Diethylaminosulfur
Trifluoride with Tertiary Cyclobutanols$
Masayuki Kirihara,* Tomofumi Takuwa, Toshihiro Kambayashi,
Takefumi Momose and Yoshio Takeuchi
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University,
Sugitani 2630, Toyama 930-0194, Japan
The reaction of diethylaminosulfur trifluoride with a tertiary cyclobutanol afforded a fluorocyclobutane, a (fluoromethyl)-
cyclopropane or a homoallylic fluoride.
Table 1
There has been much e€ort to develop novel methods
of ¯uorination, because ¯uorine-containing molecules have
become increasingly important in scienti®c and industrial
®elds.1 Diethylaminosulfur tri¯uoride (DAST), an agent
converting aliphatic alcohols or silyl ethers into alkyl
¯uorides under mild conditions, is one of the most con-
venient reagents in organic synthesis.2 There have been
several reports concerning new ¯uorinating methods using
DAST.3±15 Among these methods, we reported that the
reaction of DAST with tertiary cyclopropyl silyl ethers
causes ring opening to give allylic ¯uorides.11
Entry
Starting material
Products
1
2
3
4
Scheme 1 Reagents and conditions: i, DAST, CH2Cl2, room
temperature
5
6
We now report that
a tertiary cyclobutanol reacts
with DAST to a€ord a ¯uorocyclobutane, a (¯uoromethyl)-
cyclopropane or a homoallylic ¯uoride, Scheme 1. The
results of this reaction are summarized in Table 1. Fluoro-
cyclobutanes 2 were obtained from the substrates 1a, 1b
bearing electron-donating substituents at C-1 (R1=n-C9H19
or Ph). (Fluoromethyl)cyclopropanes 3 resulted with the
electron-withdrawing group at C-1 (R1=CN or CO2Me)
*An inseparable mixture. The ratio of the products was
determined on the basis of the 1H and 19F NMR spectral data.
(1c±1e). The compound 1f bearing both an electron-
withdrawing group at C-1 and electron-donating sub-
stituents at C-3 (R1=CN, R3=Ph) gave a homoallylic
¯uoride 4 as the main product.
A plausible reaction mechanism is depicted in Scheme 2.
The ®rst step is nucleophilic displacement of a ¯uorine
atom in DAST by the oxygen of the substrate 1. Next, the
elimination of sul®nyl dimethylamide ¯uoride generates a
carbocation triad (equilibrium mixture of A, B and C).16
In the cases of compounds bearing electron-donating substi-
tuents at C-1, cyclobutyl cations (A) were predominant.
On the other hand, cyclopropylmethyl cations (B) predomi-
nated in the cases of compounds bearing an electron-
withdrawing group at C-1. The homoallylic cation (C)
predominated only in the case of the compound having an
electron-withdrawing group at C-1 and electron-donating
substituents at C-3. Finally, the ¯uoride ion attacks the
carbocations to a€ord the ®nal products.
Experimental
Scheme 2
Infrared spectra were measured with a Perkin-Elmer 1600 series
FT-IR spectrophotometer, 1H and 19F NMR spectra on a JEOL
GX270 instrument with tetramethylsilane (for 1H) and chloro-
tri¯uoromethane (for 19F) as an internal standard, mass (MS)
and high-resolution mass spectra (HRMS) on a JEOL JMS D-200
spectrometer.
*To receive any correspondence.
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).

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J. CHEM. RESEARCH (S), 1998 653
General Procedure for the Reaction of DAST with Tertiary Cyclo-
butanols.ÐTo a solution of tertiary cyclobutanol (1.0 mmol) in
dichloromethane (3 ml) was added DAST (1.0 mmol) at room tem-
perature under an inert atmosphere, and the mixture was stirred for
30 min. A saturated sodium hydrogencarbonate solution was added,
and the resulting mixture extracted with dichloromethane. The
extract was dried over anhydrous sodium sulfate, ®ltered, and evap-
orated to a€ord the crude product. Puri®cation by chromatography
(silica gel, hexane±dichloromethane) gave a pure sample.
2-(2-Fluoro-2,2-diphenylethyl)prop-2-enenitrile 4f.ÐColorless crys-
tals; mp 101±102 8C; ꢀH (CDCl3) 3.32 (2 H, d, JHF 23.0), 5.69 (1 H,
s), 5.94 (1 H, s), 7.30±7.40 (10 H, m); ꢀF (CDCl3) 148.74 (t,
J 23.0 Hz); IR 3104, 3053, 2231, 1913, 1600, 1497, 1451, 1326, 1250,
1
1211, 1057, 1038, 1015, 982, 958, 910, 871, 770, 774, 704, 668 cm
MS m/z 251 (M ); HRMS Calc. for C17H14FN (M ) 251.1092,
;
‡
‡
Found 251.1187.
This work was supported in part by the Foundation for
the Promotion of Higher Education in Toyama Prefecture
and Grant-in-Aid (No. 09771900) for Scienti®c Research
from the Ministry of Education, Science, Sports and
Culture, Japan.
1-Fluoro-1-nonylcyclobutane 2a.ÐColorless oil; ꢀH (CDCl3) 0.88
(3 H, t, J 7.0 Hz), 1.22±1.35 (12 H, m), 1.35±1.41 (2 H, m),
1.41±1.50 (1 H, m), 1.61±1.72 (2 H, m), 1.75±1.84 (1 H, m),
2.02±2.15 (2 H, m), 2.20±2.34 (2 H, m); ꢀF (CDCl3) 130.8 to
131.1 (m); IR 2882, 1556, 1538, 1504, 1392, 1336, 1200, 1116,
1
‡
1057, 980, 803, 707, 666 cm
([M HF] ); HRMS Calc. for C13H24
;
MS m/z 199 ([M H] ), 180
F
‡
‡
([M H] ) 199.1993,
Received, 23rd June 1998; Accepted, 25th June 1998
Paper E/8/04786C
Found 199.1929.
1-Fluoro-1-phenylcyclobutane 2b.ÐColorless oil; ꢀH (CDCl3)
1.16±1.19 (1 H, m), 1.69±1.80 (1 H, m), 2.02±2.17 (1 H, m),
2.52±2.74 (3 H, m), 7.30±7.35 (1 H, m), 7.37±7.42 (2 H, m),
7.46±7.50 (2 H, m); ꢀF (CDCl3) 126.8 to 127.1 (m); IR 3047,
3018, 2970, 1567, 1556, 1538, 1484, 1360, 1270, 1200, 1093, 1036,
References
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972, 926, 902, 834, 794, 723, 677, 660 cm 1; MS m/z 149 ([M H] );
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‡
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‡
Inseparable mixture of 1-( ¯uoromethyl)cyclopropanecarbonitrile 3c
and 2-(2-¯uoroethyl)prop-2-enenitrile 4c.ÐColorless oil; ꢀH (CDCl3)
1.08±1.11 (16/9 H, m), 1.39±1.42 (16/9 H, m), 2.50 (2/9 H, dt, JHF
25.0, JHH 6.0), 4.34 (16/9 H, d, JHF 47.0), 4.62 (2/9 H, dt, JHF 47.0,
JHH 6.0 Hz), 5.88 (1/9 H, s), 6.01 (1/9 H, s); ꢀF (CDCl3) 212.09
(8/9 F, t, J 47.0), 220.15 (1/9 F, tt, J 47.0 and 25.0 Hz); IR 2970,
2248, 1654, 1617, 1435, 1387, 1289, 1041, 1010 cm 1; MS m/z 100
‡
‡
([M ‡ H] ); 79 ([M HF] ).
Methyl 1-( ¯uoromethyl)cyclopropanecarboxylate 3d.ÐColorless
oil; ꢀH (CDCl3) 0.99±1.00 (2 H, m), 1.37±1.38 (2 H, m), 3.73 (3 H,
s), 4.52 (2 H, d, JHF 49.0 Hz); ꢀF (CDCl3) 213.10 (t, J 49.0 Hz);
IR 2956, 1732, 1438, 1356, 1283, 1248, 1200, 1167, 1003, 755 cm
1
;
‡
‡
‡
MS m/z 133 ([M ‡ H] ), 132 (M ), 113 ([M F] ); HRMS Calc.
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37, 8759.
‡
for C6H9O2F (M ) 132.0586, Found 132.0584.
1-(Fluorodiphenylmethyl)cyclopropanecarbonitrile 3e.ÐColorless
oil; ꢀH (CDCl3) 1.25±1.30 (2 H, m), 1.42±1.46 (2 H, m), 7.19±7.45
(10 H, m); ꢀF (CDCl3) 142.90 (s); IR 2926, 2240, 1780, 1654, 1600,
1493, 1449, 1277, 1191, 1078, 1049, 1011, 752, 700 cm 1; MS m/z
251 (M ); HRMS Calc. for C17H14FN (M ) 251.1092, Found
251.1116.
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‡
‡
1-Fluoro-3,3-diphenylcyclobutanecarbonitrile 2f.ÐColorless oil; ꢀH
(CDCl3) 3.34±3.43 (2 H, m), 3.61±3.68 (2 H, m), 7.16±7.37 (10 H,
m); ꢀF (CDCl3) 143.91 to 144.17 (m); IR 3854, 3752, 3736, 3712,
3676, 3650, 3630, 3023, 2362, 1719, 1654, 1597, 1491, 1447, 1415,
14 P. Borrachero-Moya, F. Cabrera-Escribano, M. Gomez-Guillen
and F. Madrir-Dõaz, Tetrahedron Lett., 1997, 38, 1231.
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571.
16 G. A. Olah, V. P. Reddy and G. K. S. Prakash, Chem. Rev.,
1992, 92, 69.
‡
1236, 1120, 1075, 1025, 928, 756, 701 cm 1; MS m/z 251 (M );
‡
HRMS Calc. for C17H14FN (M ) 251.1092, Found 251.1085.