Regiospecific synthesis of α-chloro- and α-fluoro-1,2-diones

Article abstract of DOI:10.1016/j.tetlet.2009.04.049

α-Chloro-1,2-diones and α-fluoro-1,2-diones were prepared from the corresponding α-chloroaldimines by a sequence of reactions involving cyanation to α-cyanoenamines, α-halogenation to form α-chloro- or α-fluoroimidoyl cyanides and addition of organolithiu

Full text of DOI:10.1016/j.tetlet.2009.04.049

Tetrahedron Letters 50 (2009) 3877–3880
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Regiospecific synthesis of a-chloro- and a-fluoro-1,2-diones
*
Riccardo Surmont , Bart De Corte, Norbert De Kimpe
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Gent, Belgium
a r t i c l e i n f o
a b s t r a c t
Article history:
a
-Chloro-1,2-diones and
by a sequence of reactions involving cyanation to
or -fluoroimidoyl cyanides and addition of organolithium reagents across the nitrile moiety, followed
a
-fluoro-1,2-diones were prepared from the corresponding
a
-chloroaldimines
Received 13 March 2009
Revised 8 April 2009
Accepted 14 April 2009
Available online 17 April 2009
a
-cyanoenamines, -halogenation to form
a
a-chloro-
a
by acidic hydrolysis. All steps are straightforward and occur without side reactions finally leading to reg-
iospecifically chlorinated and fluorinated 1,2-diones in good yields.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Cyanoenamines
Chlorination
Fluorination
Diones
1,2-Dicarbonyl compounds have found widespread applications
in the synthesis of several heterocyclic compounds1 and many
good synthetic approaches for substituted 1,2-diketones have been
described.2 Also halogenated 1,2-diones are useful in pharmaceuti-
cal and agrochemical development,3 although their regiospecific
ogenated 1,2-diimines 11 and 13 are hydrolyzed toward regiospe-
cifically -halogenated 1,2-diketones, an interesting class of
trifunctional building blocks.
-Cyanoenamines 8 were prepared from aldehydes 5 via imina-
tion to aldimines 6,
-chlorination to form chloroaldimines 7,18
and cyanation resulting in
-cyanoenamines 8.19 The obtained com-
pounds 8 were well chlorinated at the -position in quantitative
yield using N-chlorosuccinimide in carbon tetrachloride (Scheme
2).10,11 Fluorination of
-cyanoenamines 8 was performed with N-
a
a
a
synthesis remained problematic.4
a
-Chloro-1,2-diones have found
a
application in the synthesis of chlorinated (2-amino)-4-acylthiaz-
a
oles5 and 3,4-dihydroxythiophenes6 while
a-fluoro-1,2-diones
are building blocks for fluorinated (bicyclic) pyrazines,7 tetra-
hydrofurans,8 and imidazoles.9 The synthesis and reactivity of
a
fluorobenzenesulfonimide (NFSI) or 1-chloromethyl-4-fluoro-1,4-
diazoniabicyclo[2.2.2]octane bistetrafluoroborate (Selectfluor) as
fluorination reagents in acetonitrile at room temperature to afford
a
-chlorinated and
extensively discussed in previous papers10,11 but until now
rinated imidoyl cyanides remained unknown. As a part of our
investigations in the chemistry of
-fluorinated imines,12 the syn-
a
-brominated imidoyl cyanides have been
a
-fluo-
a
-fluoroimidoyl cyanides for the first time.20 Selectfluor was the re-
a
agent of choice because the workup of the reaction mixture was less
complicated due to the lower solubility of Selectfluor in organic sol-
vents during extraction, resulting in an easier purification by distil-
thesis and reactivity of fluorinated imidoyl cyanides, which consti-
tute a promising new class of building blocks for the synthesis of
fluorinated azaheterocyclic compounds,13 were studied. It is
known that the addition of organolithium compounds across the
nitrile function of N,N-disubstituted
a-cyanoenamines 1 leads to
adducts14 which can be hydrolyzed into 1,2-diones 3 (Scheme
1).15 On the other hand, tautomerizable
a-cyanoenamines 2
(R1 = H; R2 = alkyl) react with organolithium compounds16 or Grig-
nard reagents17 to give deprotonation at nitrogen followed by
elimination of cyanide to afford ketenimines 4. We report now
on the selective addition of organolithium compounds across the
nitrile function of
a-chloroimidoyl cyanides 9 and
a-fluoroimidoyl
cyanides 10, thereby not affecting the
a-halogen. The resulting hal-
* Corresponding author. Tel.: +32 9 2645951; fax: +32 9 2646243.
E-mail address: norbert.dekimpe@UGent.be (N. De Kimpe).
Aspirant of the Research Foundation—Flanders (FWO—Vlaanderen).
Scheme 1. Reaction of organolithium or Grignard reagents with
1 and 2.
a-cyanoenamines
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.04.049

3878
R. Surmont et al. / Tetrahedron Letters 50 (2009) 3877–3880
Scheme 3. Reaction of a-chloroimidoyl cyanides 9 with organolithium compounds
and subsequent hydrolysis.
tions leads to an interesting class of trifunctional compounds 12,
the chemistry of which has been only scarcely unraveled.23
Analogously,
a-fluoroimidoyl cyanide 10a was treated with
1.1 equiv of methyllithium (1.6 M in Et2O) (Table 2). However, this
reaction at room temperature in diethyl ether only gave traces of
diimine 13a. The major product found was ketenimine 14b17 that
was formed by a fluorine–metal exchange and expulsion of cyanide
(entry 1). Lowering the temperature to 0 °C did favor the attack at
the nitrile but did not exclude the lithium fluorine exchange (entry
2). Also the aggregation of organolithium compounds is important
for their reactivity, and is highly solvent dependent. In hexane,
organolithium compounds are more aggregated and less reactive,
compared to etheral solutions. Indeed we observed that MeLi in
Scheme 2. Synthesis of
tion to a-halogenated imidoyl cyanides 9 and 10.
a-cyanoenamines 8 followed by chlorination or fluorina-
lation. Although a-fluoroimidoyl cyanides 10 were obtained in high
yields, the purification by distillation resulted in some product
decomposition and consequently in lower isolated yields.
Reaction of
(lithium bromide complex) or phenyllithium (1.8 M in Bu2O) in
diethyl ether at À78 °C afforded -chloro-1,2-diimines 11 after
a-chloroimidoyl cyanides 9 with methyllithium
a
hexane (at 0 °C) was less reactive for attack at the
a-fluorine and
careful aqueous workup at 0 °C (Scheme 3, Table 1).21 If the reac-
tion was performed at –20 °C only decomposition products were
formed. Surprisingly, the use of butyllithium at À78 °C did not
result in the selective addition of butyllithium across the nitrile
function but yielded ketenimine 14a17 through a chlorine–metal
exchange and expulsion of cyanide. A possible explanation for
the different behaviors between BuLi and MeLi or PhLi is that BuLi
is more basic and reactive than MeLi and PhLi. Consequently BuLi is
more prone to induce a lithium halogen exchange. Methyllithium
and phenyllithium did not attack the chlorine at À78 °C. The labile
1,2-diimines 11, bearing an unsubstituted and a substituted
nitrogen atom, were fully characterized by spectrometric methods
(1H NMR, 13C NMR, IR, GC–MS). In some cases E/Z isomerism of
these imines was observed. Upon hydrolysis with aqueous hydro-
chloric acid at room temperature in a two-phase system with
carbon tetrachloride, these chlorinated 1,2-diimines 11a–d were
Table 2
Synthesis of 1,2-diimine 13a from
a
-fluoroimidoyl cyanide 10a
Entry
Reaction conditions
10a
13a
14a
1
2
3
4
5
6
Et2O, rt, 30 min
Et2O, 0 °C, 30 min
0
0
0
48
51
0
6
94a
37
25
0
0
0
63
75
52
49
83b
Hexane, 0 °C, 30 min
Hexane, À78 °C, 30 min
Hexane, À78 °C, 2 h
almost quantitatively converted into the corresponding
a-chloro-
1,2-diones 12a–c.22 The hydrolysis of phenyldiimine 11e into
1,2-dione 12d required more concentrated acid at reflux tempera-
ture. The present methodology allows the regiospecific synthesis of
Hexane, À48 °C, 30 min
a
Not isolated.
Isolated.
b
1,2-diones, chlorinated at the
a-position. This sequence of reac-
Table 1
Synthesis of 1,2-diimines 11 and
a
-chloro-1,2-diones 12 from
a
-chloroimidoyl cyanides 9
Reaction conditions 9?11
R1
R2
R3
R
11 Yielda (%)
12 Yieldb (%)
Me
Me
Et
Et
Et
Me
Me
Me
Et
i-Pr
Et
i-Pr
i-Pr
i-Pr
Me
Me
Me
Me
Ph
1.1 equiv MeLi.LiBr, Et2O, À78 °C, 1 h
1.1 equiv MeLi.LiBr, Et2O, À78 °C, 5 min
1.1 equiv MeLi.LiBr, Et2O, À78 °C, 1 h
1.1 equiv MeLi.LiBr, Et2O, À78 °C, 1 h
1.1 equiv PhLi (1.8 M in Bu2O), Et2O, À78 °C, 1 h
11a: 87
11b: 90
11c: 80
11d: 79
11e: 96
12a: 96b
12a: 94b
12b: 98b
12c: 95b
12d: 84c
Et
a
b
c
Compounds 11 were isolated as pure liquids (purity > 95%), which were used as such in the next reaction step.
Compounds 12a–c were obtained from 11a–d by hydrolysis with 10 mol equiv 4 M HCl in the presence of CCl4 during 16 h at room temperature.
Compound 12d was obtained from 11e by hydrolysis with 24 mol equiv 6 M HCl in the presence of CH2Cl2 during 16 h at reflux.

R. Surmont et al. / Tetrahedron Letters 50 (2009) 3877–3880
3879
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1979, 88, 695.
12. Verniest, G.; Van Hende, E.; Surmont, R.; De Kimpe, N. Org. Lett. 2006, 8, 4767.
13. For the importance of fluorinated compounds in agrochemical and medicinal
chemistry see: (a) Welch, J. T.; Eswarakrishnan, S. Fluorine in Bioorganic
Chemistry; John Wiley & Sons: New York, 1991. and references cited herein; (b)
Bégué, J.-P.; Bonnet-Delpon, D. Bioorganic and Medicinal Chemistry of Fluorine;
John Wiley & Sons: Hoboken, NJ, 2008; (c) O’Hagan, D. Chem. Soc. Rev. 2008, 37,
308; (d) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev.
2008, 37, 320; (e) Kirk, K. L. Org. Proc. Res. Dev. 2008, 12, 305; (f) Müller, K.;
Faeh, C.; Diederich, F. Science 2007, 317, 1881; (g) Isanbor, C.; O’Hagan, D. J.
Fluorine Chem. 2006, 127, 303.
14. Fang, J.-M.; Chang, H.-T. J. Chem. Soc., Perkin Trans. 1 1988, 1945.
15. Toye, J.; Ghosez, L. J. Am. Chem. Soc. 1975, 97, 2276.
16. De Kimpe, N.; Verhé, R.; De Buyck, L.; Schamp, N. Org. Prep. Proced. Int. 1982, 14,
213.
17. De Kimpe, N.; Verhé, R.; De Buyck, L.; Chys, J.; Schamp, N. J. Org. Chem. 1978, 43,
2670.
18. De Kimpe, N.; Verhé, R.; De Buyck, L.; Hasma, H.; Schamp, N. Tetrahedron 1976,
32, 2457.
Scheme 4. Reaction of
pounds and subsequent hydrolysis.
a-fluoroimidoyl cyanides 10 with organolithium com-
led to less ketenimine byproduct, in comparison to MeLi in diethyl
ether (entry 3). At À78 °C the reaction could not be driven to com-
pletion (entries 4 and 5). Finally, at À48 °C the reaction of 10a and
1.1 equiv methyllithium in hexane led to a selective addition of
methyllithium across the nitrile function resulting in diimine 13a
in 83% isolated yield and complete conversion (entry 6).24
a-Flu-
oroimidoyl cyanides 10a-b did not react with Grignard reagents,
for example, i-PrMgBr or s-BuMgBr, possibly due to the sterical
hindrance of the N-tert-butyl substituent.
Upon hydrolysis using aqueous oxalic acid at room temperature
in a two-phase system with dichloromethane, fluorinated 1,2-dii-
mines 13a–b were converted into new
a-fluorinated 1,2-diones
15a–b.25 The hydrolysis of phenyldiimine 13c required more con-
centrated acid at reflux temperature (Scheme 4).
In conclusion, a new synthetic pathway for the regiospecific
synthesis of 1,2-diones, chlorinated or fluorinated at the
19. De Kimpe, N.; Verhé, R.; De Buyck, L.; Hasma, H.; Schamp, N. Tetrahedron 1976,
32, 3063.
a-posi-
tion, was developed. This class of compounds with potential as
building blocks in organic chemistry, was synthesized via the
20. Fluorination of
a-cyanoenamines 8: The fluorination procedure is exemplified
for the synthesis of (2E)-2-(tert-butylimino)-3-ethyl-3-fluoropentanenitrile
10a. In a flame-dried 100 mL flask, a solution of 2.00 g (11.11 mmol) of 2-
(tert-butylamino)-3-ethylpent-2-enenitrile 8e in 50 mL of acetonitrile was
cooled to 0 °C and was treated portionwise with 3.94 g (13.33 mmol; 1.2 equiv)
of Selectfluor. The mixture was allowed to warm up to room temperature and
stirred for 1.5 h. The reaction mixture was poured in 50 mL of water and
extracted with 3 Â 50 mL of dichloromethane. The combined organic phases
were dried over MgSO4 and the solvents were evaporated in vacuo after
filtration of the drying agents. The residual oil was distilled to yield 1.21 g
selective attack of organolithium compounds across
and new -fluoroimidoyl cyanides resulting in novel
a
-chloro-
a
a-haloge-
nated 1,2-diimines followed by aqueous hydrolysis.
Acknowledgments
(6.11 mmol,
55%)
of
pure
(2E)-2-(tert-butylimino)-3-ethyl-3-
The authors are indebted to the Research Foundation—Flanders
(FWO—Flanders), Ghent University (GOA), and Janssen Pharmaceu-
tica (Johnson & Johnson) for financial support.
fluoropentanenitrile 10a (bp 80 °C, 19 mmHg) as a colorless oil. 1H NMR
(CDCl3, 300 MHz): d 0.91 (6H, t, J = 7.4 Hz, 2 Â CH3); 1.43 (9H, s, 3 Â CH3); 1.89
(2H, dq, J = 17.1 Hz, 7.4 Hz, CH2); 1.91 (2H, dq, J = 24.3 Hz, 7.4 Hz, CH2). 19F
NMR (CDCl3, 282 MHz): d À162.3 (1F, t  t, J = 24.3 Hz, 17.1 Hz). 13C NMR
(CDCl3, 75 MHz): d 6.9 (d, J = 5.8 Hz); 29.0; 29.5 (d, J = 23.1 Hz); 58.6; 99.9 (d,
J = 180.0 Hz); 110.5; 141.1 (d, J = 33.5 Hz). IR (ATR, cmÀ1):
m = 2975; 2942;
References and notes
2886; 2218 (CN); 1641 (C@N); 1462; 1366; 1240; 1210; 1160; 1092; 1040;
955; 912; 860. GC–MS (EI) m/z (%): 198 (M+, 1); 183 (M+ÀCH3, 14); 155 (4);
143 (4); 124 (8); 114 (17); 69 (5); 57 (+C(CH3)3; 100); 41 (19).
1. (a) Babudri, F.; Fiandanese, V.; Marchese, G.; Punzi, A. Tetrahedron Lett. 1995,
40, 7305. and references cited therein; (b) De Kimpe, N.; Stanoeva, E.;
Boeykens, M. Synthesis 1994, 427. and references cited therein; (c) McKenna,
J. M.; Halley, F.; Souness, J. E.; McLay, I. M.; Pickett, S. D.; Collis, A. J.; Page, K.;
Ahmed, I. J. Med. Chem. 2002, 45, 2173; (d) Singh, S. K.; Saibaba, V.; Ravikumar,
V.; Rudrawar, S. V.; Daga, P.; Rao, C. S.; Akhila, V.; Hegde, P.; Razo, C. S.; Akhila,
V.; Hegde, P.; Rao, Y. K. Bioorg. Med. Chem. 2004, 12, 1881.
2. (a) Landais, Y.; Vincent, J. M. Sci. Synth. 2005, 26, 647; (b) Zhao, X.-F.; Zhang, C.
Synthesis 2007, 551. and references cited therein; (c) Wan, Z.; Jones, C. D.;
Mitchell, D.; Pu, J. Y.; Zhang, T. Y. J. Org. Chem. 2006, 71, 826; (d) Katritzky, A. R.;
Zhang, D.; Kirichencko, K. J. Org. Chem. 2005, 70, 3271. and references cited
therein.
3. (a) Imuda, J.; Ono, H.; Tan, H.; Kihara, N. Jpn. Kokai Tokkyo Koho 1988, JP
63222140 A 19880916, 1988; Chem. Abstr. 1988, 111, 6925.; (b) Lavallee, J.-F.;
Doyle, T. W.; Rioux, E.; Belec, L.; Rabouin, D.; Billot, X. U.S. Pat. Appl. Publ. US
2005032802 A1 20050210, 2005; Chem. Abstr. 2005, 142, 219436.; (c) Hoeffkes,
H.; Fuhr, D.; Gross, W.; Knuebel, G.; Oberkobusch, D. Eur. Pat. Appl. EP 1900393
A2 20080319, 2008; Chem. Abstr. 2008, 148, 362850.
4. (a) Ogloblin, K. A.; Potekhin, A. A. Zh. Org. Khim. 1965, 1, 408; (b) Rappe, C.;
Norstrom, A. Acta Chem. Scand. 1968, 22, 1853; (c) Zbiral, E.; Rasberger, M.
Tetrahedron 1968, 24, 2419; (d) Woolsey, N. F.; Khalil, M. H. J. Org. Chem. 1975,
40, 3521; (e) Makosza, M.; Kwast, A.; Kwast, E.; Jonczyk, A. J. Org. Chem. 1985,
21. Reaction of a-chloroimidoyl cyanides with organolithium compounds: The general
procedure is exemplified for the synthesis of N-[(3E)-2-chloro-4-imino-2-
methylpentan-3-ylidene]propan-2-amine 11a. A solution of 5.17 g (0.03 mol)
of (2E)-3-chloro-3-methyl-2-(propan-2-ylimino)butanenitrile 9a in 40 mL of
freshly distilled diethyl ether was cooled to À78 °C and was treated dropwise,
while stirring under nitrogen, with 22 mL of 1.5 M methyllithium–lithium
bromide complex (0.033 mol) in diethyl ether. After stirring for 5 min at
À78 °C, the cooling bath was removed and stirring was continued for 15 min.
The reaction mixture was then poured into 100 mL of iced water, to which
10 mL of 2 M sodium hydroxide solution was added, and the organic phase was
isolated. The aqueous phase was extracted with diethyl ether and the
combined organic extracts were dried (K2CO3). Filtration of the drying agent
and evaporation of the solvent in vacuo afforded compound 11a (4.90 g, 87%)
as a light yellow oil (purity > 96%; 1H NMR). These labile 1,2-diimines 11 were
used immediately in the next hydrolysis step. N-[(3E)-2-Chloro-4-imino-2-
methylpentan-3-ylidene]isopropylamine 11a. 1H NMR (CDCl3, 60 MHz): d 1.08
(6H, d, J = 6 Hz, NCH(CH3)2); 1.77 (6H, s, (CH3)2CCl); 2.20 (3H, s, CH3C@N); 3.48
(1H, septet, J = 6 Hz, NCH); NH invisible. 13C NMR (CDCl3, 20 MHz): d 23.6;
28.8; 30.9; 53.1; 68.8; 168.3; 176.6. IR (NaCl, cmÀ1):
GC–MS (EI) m/z (%): 188/190 (M+, 0.5); 173/175 (3); 153 (3); 152 (3); 146/148
m = 1628–1650 (C@N).

3880
R. Surmont et al. / Tetrahedron Letters 50 (2009) 3877–3880
(29); 137 (54); 111 (9); 104/106 (79); 96 (7); 94 (5); 77/79 (53); 70 (47); 69
(43); 68 (13); 54 (9); 43 (90); 42 (100); 42 (50); 40 (43).
22. Hydrolysis of -chloro-1,2-diimines 11 into -chloro-1,2-diones 12: The
Ethyl-4-fluoro-2-iminohexan-3-ylidene]-tert-butylamine 13a. Yield 83%. 1H
NMR (CDCl3, 300 MHz): d 0.92 (6H, t, J = 7.4 Hz, (CH2CH3)2); 1.24 (9H, s,
NC(CH3)3); 1.67–2.05 (4H, m, (CH2CH3)2); 2.20 (3H, s, CH3C@N); NH invisible.
19F NMR (CDCl3, 282 MHz): À168.3 (1F, s(br), CF, dE-isomer); 169.3 (1F, ttd,
J = 34.9 Hz, 13.4 Hz, 7.7 Hz, CF, dZ-isomer). 13C NMR (CDCl3, 75 MHz): dE-isomer
7.4; 7.5; 28.4; 30.5; 30.5; 56.4; 102.1 (d, J = 174.2 Hz); 166.5 (d, J = 35.8 Hz);
181.4; dZ-isomer 7.4; 7.5; 28.4; 30.5; 30.5; 56.9; 103.3 (d, J = 171.9 Hz); 165.1 (d,
a
a
procedure is exemplified by the conversion of 11a into 12a. A solution of
5.65 (0.03 mol) of 3-chloro-1,2-diimine 11a in 50 mL of carbon tetrachloride
was treated with 75 mL of 4 M hydrochloric acid (0.3 mol). The two-phase
system was vigorously stirred during 16 h at room temperature after which the
organic phase was separated, washed with brine, and dried (MgSO4).
Evaporation in vacuo of the solvent from the filtrate afforded 4.27 g (96%) of
pure 4-chloro-4-methylpentane-2,3-dione 12a, bp 44–46 °C (18 mmHg). 1H
NMR (CDCl3, 60 MHz): d 1.83 (6H, s, (CH3)2CCl); 2.42 (3H, s, CH3C@O). 13C NMR
J = 34.6 Hz); 179.8. IR (NaCl, cmÀ1):
m = 2971; 2941; 2884; 1672; 1634 (C@N);
1524; 1460; 1362; 1213; 1119; 1056; 948; 896; 835. GC–MS (EI) m/z (%): 214
(M+, 1); 199 (M+ÀMe, 1); 179 (M+ÀHFÀMe, 1); 172 (Et2CFC„N+-t-Bu, 10); 157
(4); 125 (2); 116 (Et2CFC„NH+, 1); 97 (3); 89 (Et2CF+, 5); 69 (23); 57 (Me3C+,
100); 42 (MeC„NH+, 14); 41 (16).
(CDCl3, 20 MHz): d 26.7; 28.7; 68.6; 196.5; 199.1. IR (NaCl, cmÀ1):
m = 1725
(C@O); 1720 (C@O). GC–MS (EI) m/z (%): 148 (M+, 0.5); 113 (M+ÀCl, 0.5); 77/79
((CH3)2CCl+, 10); 70 (33); 57 (2); 43 (CH3CO+, 100); 42 (10); 41 (18). Anal. Calcd
for C6H9ClO2: C, 48.5; H, 6.1; Cl, 23.9. Found: C, 48.4; H, 6.1; Cl, 23.7.
25. Hydrolysis of a-fluoro-1,2-diimines 13 into a-fluoro-1,2-diones 15: a-Fluoro-1,2-
diimines 13 were dissolved in dichloromethane and treated with 4 equiv of
oxalic acid (4 M in H2O). The two-phase system was vigorously stirred during
2 h at room temperature. Aqueous workup, isolation of the organic phase,
drying (Mg2SO4) and evaporation of the solvent gave after distillation
compounds 15 (59–71%) as yellow oil. 4-Ethyl-4-fluorohexane-2,3-dione 15a.
Yield 59%. Bp 65 °C (25 mmHg). 1H NMR (CDCl3, 300 MHz): d 0.93 (6H, t,
J = 7.7 Hz, 2 Â CH3); 1.95 (2H, dq, J = 17.1 Hz, 7.7 Hz, CH2); 2.02 (2H, dq,
J = 27.6 Hz, 7.7 Hz, CH2); 2.36 (3H, s, CH3). 19F NMR (CDCl3, 282 MHz): d À170.4
(1F, tt, J = 27.6 Hz, 17.1 Hz). 13C NMR (CDCl3, 75 MHz): d 7.5 (d, J = 5.8 Hz);
25.5; 29.2 (d, J = 23.1 Hz); 103.2 (d, J = 183.5 Hz); 199.7; 201.9 (d, J = 32.3 Hz).
23. For some leading references on 1,2-diones, halogenated at the a-position with
respect to the carbonyls, see for instance: Wegmann, J.; Dahn, H. Helv. Chim.
Acta 1946, 29, 1247; Wanzlick, H.-W.; Sucrow, W. Chem. Ber. 1958, 91, 2727;
Hamer, N. K. Tetrahedron Lett. 1986, 27, 2167.
24. Reaction of
procedure is analogous to the reaction of
organolithium compounds. -Fluoroimidoyl cyanides 10 were dissolved in
a
-fluoroimidoyl cyanides 10 with organolithium compounds: The
a-chloroimidoyl cyanides 9 with
a
hexane and treated with a methyllithium solution (1.6 M in Et2O) at À48 °C
(acetonitrile/N2 bath) for 30 min. Careful aqueous workup (0 °C) yielded
compounds 13 (83–63%) as a yellow oil (purity > 95%; 1H NMR). These labile
1,2-diimines 13 were used immediately in the next hydrolysis step. N-[(3E)-4-
IR (ATR, cmÀ1):
m = 2979; 2943; 2887; 1717 (C@O); 1462; 1356; 1245; 1160;
1041; 950; 870. GC–MS (EI) m/z (%): 160 (M+, 4); 134 (2); 115 (3); 98 (15); 88
(10); 69 (51); 59 (10); 43 (CH3CO+, 100).