Selective multiple magnesiations of the thieno[3,2-b]thiophene scaffold

Article abstract of DOI:10.1002/chem.201002506

A full functionalization of all four positions of the thieno[3,2-b] thiophene scaffold was achieved. Starting from 2,5-dichlorothieno[3,2-b] thiophene, magnesiation of the 3- and 6-position using tmpMgClLiCl furnishes, after trapping with various electrop

Full text of DOI:10.1002/chem.201002506

DOI: 10.1002/chem.201002506
Selective Multiple Magnesiations of the ThienoACTHNUTRGNE[UNG 3,2-b]thiophene Scaffold
Thomas Kunz and Paul Knochel*[a]
À
Abstract: A full functionalization of all
four positions of the thieno[3,2-b]thio-
phene scaffold was achieved. Starting
from 2,5-dichlorothieno[3,2-b]thio-
phene, magnesiation of the 3- and 6-
position using tmpMgCl·LiCl furnishes,
after trapping with various electro-
dichlorothieno
quent dechlorination and regioselective
metalation or regioselective magnesi-
G
um insertion into the C Cl bond pro-
vides fully functionalized thieno[3,2-
E
ACHTUNGTRENNUNG
b]thiophenes. Furthermore, new con-
densed heterocycles and small oligo-
mers of these compounds with poten-
tial applications in material chemistry
have been prepared.
AHCTUNGTRENNUNG
Keywords: C H activation · cross-
coupling · magnesium · metalation ·
regioselectivity
philes,
3,6-difunctionalized
Introduction
more, organolithium reagents are not compatible with sever-
al important functional groups, such as aldehydes, ketones,
or esters.[9] Direct magnesiation of this scaffold as an alter-
native strategy has to the best of our knowledge, not been
explored.[10] Directed magnesiations of aromatic and hetero-
aromatic substrates using the recently developed Mg/Li–
amide tmpMgCl·LiCl (1; tmp=2,2,6,6-tetramethylpiperidyl)
have shown broad applicability and exceptional functional
group tolerance.[11]
In the research field of materials chemistry, molecular elec-
tronics and electronic devices have rapidly gained interest.
Besides organic light-emitting diodes (OLEDs)[1] and organ-
ic field-effect transistors (FETs),[2] organic photovoltaics[3]
have attracted considerable attention in the search for a reli-
able alternative energy supply. The different approaches to
construct organic solar cells are based on bulk heterojunc-
tion, small-molecule, or nanorod systems,[4] consisting of var-
ious donor–acceptor interactions.[5] Improvement of these
donor–acceptor systems depends on advances in the mor-
phology of the materials as well as in their molecular struc-
ture.[6] Among the donor polymers, functional oligothio-
phenes or fused S-heterocycles are predominant.[7] More re-
Herein, we report the full functionalization of the thieno-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
tmpMgCl·LiCl base (1). This allows the incorporation of
sensitive functional groups that are tolerated in further
modifications leading to highly diverse compounds that
were so far inaccessible. In a general reaction sequence, the
thienothiophene 2 is metalated sequentially at the 3- and 6-
position with base 1 and leads, after quenching with various
electrophiles, to substituted thienothiophenes of type 5.
cently thienothiophenes, in particular the thienoACTHNUTRGNE[UNG 3,2-b]thio-
phene scaffold, have attracted considerable attention, as
these moieties comprise some significant advantages, such as
centrosymmetry and higher rigidity, over the universally em-
ployed thiophene building block.[8]
Direct lithiations are known for all positions of the fused
thienothiophene ring, although selective lithiations on the 3-
and 6-positions are only possible by halogen–lithium ex-
change and therefore require low temperatures. Further-
À
After the reductive cleavage of the C Cl bonds, the inter-
mediate 6 is then regioselectively deprotonated at the 2- and
5-position, again using tmpMgCl·LiCl (1), leading to fully
functionalized thienoACHTUNTGRNEUNG[3,2-b]thiophenes of type 8 (Scheme 1).
Results and Discussion
[a] M. Sc. T. Kunz, Prof. Dr. P. Knochel
Department Chemie, Ludwig-Maximilians-Universtꢀt Mꢁnchen
Butenandtstrasse 5–13, 81377 Mꢁnchen (Germany)
Fax : (+49)89-2180-77680
Preparation of 3,6-disubstituted 2,5-dichlorothienoACHTUNGTRENNUNG[3,2-b]-
thiophenes of type 5: The reaction of 2,5-dichlorothienoACHTUNGTRENNUNG[3,2-
b]thiophene (2) with tmpMgCl·LiCl (1; 1.1 equiv, 258C,
45 min) leads to the corresponding 3-magnesiated thieno-
thiophene 3, which can be trapped with PhSO2SMe to give
E-mail: paul.knochel@cup.uni-muenchen.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201002506.
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FULL PAPER
Table 1. Synthesis of 3,6-disubstituted thienothiophenes of type 5.
Entry
E1 (Yield)[a]
E2 (Yield)[a]
Product
1
PhSO2SMe
NCCO2Et
A
R
5a
2
3
4
5
6
7
8
9
G
G
5b
Scheme 1. Reaction sequence allowing the conversion of 2,5-dichlorothie-
E
5c
no-[3,2-b]thiophene (2) to fully functionalized thieno
type 8.
ACHTUNGTREN[NUNG 3,2-b]thiophenes of
the thiomethylated thienothiophene 4a[13] in 96% yield. A
subsequent deprotonation of 4a using base 1 (258C, 45 min)
yields the ester 5a in 89% yield after reaction with ethyl cy-
anoformate (entry 1, Table 1). Similarly, treatment of inter-
mediate 3 with PhSO2SPh provides the thioether 4b in 85%
yield. A further deprotonation of 4b (258C, 45 min) and
quenching with di-tert-butyl dicarbonate gives the ester 5b
in 70% yield (entry 2, Table 1). The reaction of the 3-mag-
nesiated thienothiophene 3 with TMSCN affords compound
4c in 85% yield. Metalation of 4c (258C, 45 min) followed
by a CuI-catalyzed acylation[14] with benzoyl chloride gives
the difunctionalized thienothiophene 5c in 95% yield
(entry 3, Table 1). A Pd-catalyzed cross-coupling reaction[15]
of 3 with 1-iodo-4-methoxybenzene or 1-chloro-4-iodoben-
A
5d: R=p-C6H4OMe
5e: R=p-C6H4OMe
5 f: R=p-C6H4Cl
5g: R=p-C6H4Cl
5h
A
A
G
zene (3 mol% [PdACHTUNGTRENNUNG(dba)2], 6 mol% tfp, tfp=tri-(2-furyl)-
phosphine) leads to thienothiophenes 4d and 4 f in 71–91%
yield (entries 4–7, Table 1). After metalation of 4d (258C,
1 h), the magnesiated intermediate reacts directly with
Boc2O giving product 5d in 73% yield (entry 4, Table 1).
Alternatively, a CuI-catalyzed acylation reaction with pivalo-
yl chloride leads to ketone 5e in 85% yield (entry 5,
Table 1). Similarly, the deprotonation of 4 f (258C, 45 min)
affords after subsequent acylation with pivaloyl choride 5 f
in 75% yield (entry 6, Table 1). The reaction with ethyl cya-
noformate as second electrophile gives 5g in 81% yield
(entry 7, Table 1). The ester 4h is obtained in 92% yield
(entry 8, Table 1) by trapping the 3-magnesiated thienothio-
phene 3 with ethyl cyanoformate. After a successive metala-
tion (À208C, 20 min) and quenching again with ethyl cyano-
formate the diester 5h is isolated in 81% yield. Treatment
of intermediate 3 with PhSO2SBu yields thioether 4i in
94% yield. A subsequent deprotonation (258C, 45 min) and
trapping with ethyl cyanoformate provides the ester 5i in
83% yield (entry 9).
N
N
5i
[a] Yield of isolated analytically pure product. [b] After transmetalation
using ZnCl2 (1.1 equiv) and cross-coupling reaction ([Pd(dba)2]
3 mol%, tfp 6 mol%). [c] After transmetalation using CuCN·2LiCl
(20 mol%).
ACHTUNGTRENNUNG
ation (100 W, 1208C) was used. This enhances the reaction
rate, so that the reduction of the dichlorothienoACTHNUTRGNE[UNG 3,2-b]thio-
phene 5a is complete within 6 h, yielding 6a in 77% yield.
This procedure has also been used for the reduction of
the dichlorothienothiophenes 5b–g (4-6 h, 100 W, 1208C),
furnishing the dechlorinated products 6b–g in 71–85% yield
(Scheme 2). Remarkably, this reduction is compatible with
À
other aromatic C Cl bonds (see Scheme 2, compound 6e).
Preparation of 3,6-disubstituted thieno
G
Preparation of fully functionalized thienoACTHUNGTERNNU[G 3,2-b]thiophenes
type 6: The best method for the reductive cleavage of a C
Cl bond was the reduction developed by Schlosser and co-
workers using Pd/C and ammonium formate.[16] As conven-
tional heating leads to a sluggish reaction, microwave irradi-
of type 8: A further deprotonation of the dechlorinated thie-
nothiophenes of type 6 is achieved with complete regioselec-
tivity. When treating the thienothiophene 6a with
tmpMgCl·LiCl (1; 1.1 equiv, À208C, 40 min), the ester
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867

P. Knochel and T. Kunz
gives compound 8a in 80% yield. After metalation of 7c
(À408C, 15 min) and a Pd-catalyzed cross-coupling reaction
with 1-fluoro-4-iodobenzene, the fully functionalized thieno-
AHCTUNGTREG[NNUN 3,2-b]thiophene 8b is isolated in 81% yield. Similarly, prod-
uct 8c is obtained in 81% yield after deprotonating thieno-
thiophene 7e (08C, 90 min) and trapping the resulting mag-
nesiated reagent with ethyl cyanoformate. The treatment of
the diester 6b with tmpMgCl·LiCl (1) directly leads to a bis-
magnesiated intermediate (2.2 equiv, À408C, 20 min), which
could be acylated with pivaloyl chloride in 72% yield (8d)
or allylated with ethyl 2-(bromomethyl)acrylate in 77%
yield (8e, Scheme 3).
Scheme 2. Synthesis of thienothiophenes of type
NH4HCO2 under microwave irradiation.
6 using Pd/C and
Direct magnesium insertion for the preparation of thieno-
AHCTUNGTREG[NNNU 3,2-b]thiophenes of type 10: Recently, we have reported a
LiCl-mediated magnesium insertion into aryl chlorides and
bromides under mild and convenient conditions.[18] By using
this method, the dichlorothienothiophenes of type 5 can also
be directly magnesiated. Thus, the addition of the dichloro-
thienothiophene 5a to Mg turnings (2.5 equiv), LiCl
(1.25 equiv), and ZnCl2 (1.1 equiv) in THF regioselectively
gives the zincated intermediate 9 (258C, 1 h), which can be
arylated by a Pd-catalyzed cross-coupling reaction with 4-io-
doanisole or tert-butyl 4-iodobenzoate, leading to the arylat-
ed products 10a and 10b in 75–83% yield. After a similar
insertion/cross-coupling sequence, compound 5g affords the
arylated thienothiophene 10c in 74% yield (Scheme 4).
moiety acts as a directing group[17] and magnesiation occurs
regioselectively on the adjacent carbon atom (Scheme 3).
Pd-catalyzed cross-coupling reactions with 4-iodoanisole or
4-iodobenzotrifluoride, CuI-catalyzed acylation reactions
with pivaloyl chloride, or quenching with PhSO2SPh afford
the expected products 7a–d in 77–94% yield. Similarly, a
ketone proved to be an efficient directing group. After de-
protonation of 6g (À508C, 20 min), thioether 7e is isolated
in 94% yield after trapping with PhSO2SMe, and product 7 f
is obtained in 77% yield after an acylation with 4-chloro-
benzoyl chloride.
The remaining 5-position can again be metalated with
tmpMgCl·LiCl (1). Deprotonation of 7b (À208C, 40 min)
followed by a CuI-catalyzed acylation using pivaloyl chloride
Scheme 4. Magnesium insertion into dichlorothienothiophenes of type 5.
Preparation of condensed pyridazines: Furthermore, we
have prepared a new class of condensed heterocycles of
type 11. The metalation of unsubstituted thienoACHTNUTRGNE[NUG 3,2-b]thio-
phene[19] (12) with tmpMgCl·LiCl (1, 258C, 1 h) followed by
a of CuI-catalyzed acylation reaction gives the ketone 13 in
89% yield (Scheme 5). When treating this compound again
with tmpMgCl·LiCl (1, À508C, 30 min), the keto group acts
as a directing group[17] and magnesiation occurs regioselec-
Scheme 3. Synthesis of fully substituted thienothiophenes of type 8.
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Functionalized ThienoACTHNUGRTNEUNG[3,2-b]thiophenes
FULL PAPER
tion[15] with dibromothienothiophene[12] 20 using Pd
(2.5 mol%) and SPhos (5 mol%, SPhos=2-dicyclohexyl-
phosphino-2’,6’-dimethoxybiphenyl). Br/Mg exchange
ACHTUNGTRENNUNG(OAc)2
A
(iPrMgCl·LiCl, À508C, 20 min) on the bromothienothio-
phenes 17 and 18 affords the oligomers 22 and 23 after a
PEPPSI-iPr-catalyzed cross-coupling reaction[20] in 48–51%
yield (PEPPSI-iPr=[1,3-bis(2,6-diisopropylphenyl)imidazol-
2-ylidene](3-chloropyridyl)palladium(II) dichloride). Depro-
tonation of 19 using tmpMgCl·LiCl (1, 258C, 1 h) and a
PEPPSI-iPr-catalyzed cross-coupling reaction with dibromo-
thienothiophene 20 gives the trimer 24 in 47% yield. The
oligomer 25 is isolated in 43% yield after a double Br/Li ex-
change on compound 20 and cross-coupling with the thieno-
thiophene 7g. The effect of ring fusion on the electronic ab-
sorption and emission properties of oligothiophenes has
been reported in the literature.[21] In agreement with these
results, the compounds 21–25 show similar absorption
maxima (lmax =413–416 nm). However, the stability of the
trimers varies widely. While the compounds 22–24 are very
sensitive towards light and air, the trimeric species of 21 and
25 were found to be stable in air at room temperature over
several weeks. This confirms that the appropriate functional-
Scheme 5. Synthesis of new condensed pyridazine heterocycles.
tively at the ortho position. A further acylation affords the
diketone 14a in 74% yield, which can be condensed with
hydrazine hydrate to give the pyridazine 15a in 95% yield.
Repetition of this reaction sequence leads to the pyridazino-
pyridazine 11 in 54% yield.
In an analogous reaction sequence, the diketone 14b is
obtained from 13 after metalation with tmpMgCl·LiCl (1,
À508C, 30 min) and acylation with 4-chlorobenzoyl chloride.
The crude product is directly condensed with hydrazine hy-
drate to give the pyridazine 15b in 72% yield (over two
steps). Similarly, the functionalized thienothiophene 7 f is
converted to the pyridazine 15c in 91% yield (Scheme 6).
These compounds represent an interesting scaffold as tail-
ored building blocks for material applications.
ization of the thienoACTHNUTRGNE[NUG 3,2-b]thiophene scaffold allows the
preparation of tailored building blocks with specifically
tuned properties for use in material synthesis. Further elabo-
ration of polyfunctional thienothiophenes for material appli-
cations is underway in our laboratories.
Conclusion
Direct metalation using tmpMgCl·LiCl (1) or magnesium in-
sertion in the presence of zinc chloride and lithium chloride
allow a full and regioselective functionalization of the
thienoACTHNURTGNEU[GN 3,2-b]thiophene scaffold. A large variety of function-
al groups can be introduced as substituents, affording vari-
ous highly functionalized thienothiophenes that so far have
not been accessible. This may allow one to fine-tune materi-
al properties of such heterocycles (e.g absorption band,
overlap of frontier orbitals) by introducing specific side
chains in monomeric building blocks, as could be shown in
the oligomer synthesis (21–25). The condensation reaction
of diketones with hydrazine hydrate leads to fused pyrida-
zines (15b and 15c) and pyridazinopyridazines (11). These
compounds represent a new class of sulfur- and nitrogen-
containing heterocycles that should also be of interest as
new materials.
Scheme 6. Synthesis of condensed pyridazine heterocycles of type 15.
Experimental Section
For the complete experimental procedures, analytical data, and NMR
spectra see the Supporting Information.
Preparation of thienoACTHNUTRGNE[NUG 3,2-b]thiophene oligomers: Finally,
Metalation of thienothiophenes using tmpMgCl·LiCl (1): ethyl 2,5-
we have assembled small oligomers of these functionalized
thienothiophenes (Scheme 7). The trimer 21 is obtained in
43% yield after metalation of 16 with tmpMgCl·LiCl (1,
258C, 1 h) followed by a Pd-catalyzed cross-coupling reac-
dichlorothieno
flushed Schlenk flask equipped with a magnetic stirrer and a septum was
charged with 2,5-dichlorothieno[3,2-b]thiophene (2; 6.27 g, 30.0 mmol)
and THF (30 mL). tmpMgCl·LiCl (28.7 mL, 1.15m in THF, 33.0 mmol)
ACHTUNGTERN[NUGN 3,2-b]thiophene-3-carboxylate (4h): A dry and argon-
AHCTUNGTRENNUNG
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869

P. Knochel and T. Kunz
Scheme 7. Synthesis of functionalized oligomers.
was added at 258C and the reaction mixture was stirred for 45 min (the
completion of the reaction was checked by GC analysis of reaction ali-
quots quenched with a solution of I2 in THF). Ethyl cyanoformate
(3.57 g, 24.0 mmol) was added at À408C and the reaction mixture stirred
for 1 h while warming to room temperature. The reaction was quenched
with half-concentrated aqueous NH4Cl solution, extracted three times
with Et2O, dried (MgSO4), and concentrated in vacuo. Flash column
chromatographic purification on silica gel (pentane/CH2Cl2 3:1) afforded
4h (7.73 g, 92%) as a white solid. M.p. 115.3–117.08C; 1H NMR (C6D6,
400 MHz): d=6.17 (s, 1H), 3.99 (q, J=7.13 Hz, 2H), 0.97 ppm (t, J=
7.13 Hz, 3H); 13C NMR (C6D6, 100 MHz): d=160.1, 137.6, 135.7, 133.1,
131.3, 122.7, 118.2, 61.3, 14.0 ppm; IR (ATR): n˜ =3087 (m), 1715 (vs),
1500 (m), 1468 (s), 1224 (vs), 1174 (w), 1078 (s), 1021 (m), 1010 (m), 868
(m), 842 (m), 772 cmÀ1 (m); MS (EI, 70 eV): m/z (%): 280 (94) [M+],
252 (100), 235 (44), 207 (18), 103 (19); HRMS (EI) for C9H6O235L232S2
(279.9186): 279.9172.
Magnesium insertion in 3,6-disubstituted-2,5-dichlorothieno
phenes of type 5: ethyl 5-chloro-2-(4-methoxyphenyl)-6-
(methylthio)thieno[3,2-b]thiophene-3-carboxylate (10a): dry and
argon-flushed Schlenk flask equipped with a magnetic stirrer and a
septum was charged with LiCl (160 mg, 3.75 mmol) and magnesium turn-
ings (182 mg, 7.5 mmol), and was dried under vacuum. ZnCl2 solution
(3.3 mL, 3.3 mmol) and THF (6 mL) were added and the magnesium was
activated with DIBAL-H (0.3 mL, 0.1 m in THF, 0.03 mmol). After the
ACHTUNGTREN[NUNG 3,2-b]thio-
G
A
mixture had been stirred for 5 min, 2,5-dichlorothienoACHTUNTRGNEU[GN 3,2-b]thiophene
(5a; 982 mg, 3.0 mmol) was added in one portion at room temperature.
The reaction mixture was stirred for 1 h and then canulated to a new
Schlenk flask. A cross-coupling reaction was performed by using 4-iodoa-
nisole (702 mg, 3.0 mmol), [PdACTHNUTRGNE(NUG dba)2] (34 mg, 3%), and tfp (28 mg, 6%)
over 3 h at 258C. The reaction mixture was quenched with half-concen-
trated aqueous NH4Cl solution, extracted three times with Et2O, dried
(Na2SO4), and concentrated in vacuo. Flash column chromatographic pu-
rification on silica gel (pentane/CH2Cl2 2:1) afforded 10a (898 mg, 75%)
as a yellow solid. M.p. 108.7–109.98C; 1H NMR (CDCl3, 600 MHz): d=
7.51 (m, 2H), 6.95 (m, 2H), 4.30 (q, J=7.13 Hz, 2H), 3.86 (s, 3H), 2.48
(s, 3H), 1.31 ppm (t, J=7.13 Hz, 3H); 13C NMR (CDCl3, 150 MHz): d=
161.8, 160.6, 152.7, 137.1, 135.2, 133.6, 131.5, 125.3, 122.8, 120.7, 113.6,
61.2, 55.5, 17.6, 14.2 ppm; IR (ATR): n˜ =2983 (w), 2925 (w), 2831 (w),
1716 (vs), 1671 (w), 1607 (m), 1572 (w), 1525 (m), 1487 (s), 1458 (m),
1439 (m), 1431 (m), 1414 (w), 1391 (m), 1365 (w), 1298 (m), 1267 (s),
1252 (vs), 1190 (s), 1172 (vs), 1113 (m), 1085 (w), 1061 (m), 1045 (m),
1031 (s), 1015 (s), 976 (w), 963 (w), 951 (w), 943 (w), 912 (m), 873 (w),
834 (s), 827 (m), 822 (m), 811 (m), 802 (w), 795 (m), 778 (s), 752 (w),
740 cmÀ1 (m); MS (EI, 70 eV): m/z (%): 398 (100) [M+], 370 (20), 355
(15), 185 (4); HRMS (EI) for C17H15O335L132S3 (397.9872): 397.9857.
Dechlorination of 3,6-disubstituted-2,5-dichlorothieno
ACHTUNGTREN[NUGN 3,2-b]thiophenes
of type 5: diethyl thieno[3,2-b]thiophene-3,6-dicarboxylate (6b): A micro-
ACHTUNGTRENNUNG
wave vial equipped with a stirring bar was charged with the 2,5-dichloro-
thienothiophene 5h (5.51 g, 15.6 mmol) in EtOH (30 mL). NH4 HCO2
(2.95 g, 46.8 mmol) and Pd/C (664 mg, 2 mol%) were added, and the re-
action mixture was heated by using a Biotage Initiatior 2.5 system
(100 W, 1208C) for 1 h. The mixture was allowed to cool to 258C, another
portion of Pd/C was added, and the mixture was again heated. This pro-
cedure was repeated for a total of four reaction cycles. The mixture was
allowed to cool to 258C and filtered through Celite. Flash column chro-
matographic purification on silica gel (pentane/CH2Cl2 2:1) afforded 6b
(3.61 g, 81%) as a pale yellow solid. M.p. 119.5–121.58C; 1H NMR
(C6D6, 300 MHz): d=7.77 (s, 2H), 4.06 (q, J=7.13 Hz, 4H), 1.01 ppm (t,
J=7.13 Hz, 6H); 13C NMR (C6D6, 75 MHz): d=161.5, 140.2, 139.0, 134.5,
127.2, 126.2, 125.5, 61.0, 16.9, 14.2 ppm; IR (ATR): n˜ =3107 (w), 2989
(w), 1711 (vs), 1678 (m), 1499 (s), 1472 (m), 1452 (w), 1388 (w), 1377 (w),
1355 (w), 1230 (vs), 1159 (m), 1141 (m), 1117 (m), 1026 (s), 1003 (m), 876
(s), 849 (m), 831 (m), 821 (m), 725 (vs), 696 cmÀ1 (m); MS (EI, 70 eV):
m/z (%): 284 (100) [M+], 256 (20), 239 (78), 211 (74), 183 (27), 69 (19);
HRMS (EI) for C12H12O432S2 (284.0177): 284.0176.
Preparation of fused pyridazines by condensation reactions with hydra-
zine hydrate: 5,8-di-tert-butylthieno[2’,3’:4,5]thienoACTHNUTRGNEU[GN 2,3-d]pyridazine
(15a): A dry and argon-flushed Schlenk flask, equipped with a magnetic
stirrer and a septum was charged with 13 (1.57 g, 7.0 mmol) and THF
(7.0 mL). tmpMgCl·LiCl (6.70 mL, 1.15 m in THF, 7.7 mmol) was added
at À508C and the reaction mixture was stirred for 30 min (the completion
of the reaction was checked by GC analysis of reaction aliquots
quenched with a solution of I2 in THF). An acylation reaction was per-
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Functionalized ThienoACTHNUGRTNEUNG[3,2-b]thiophenes
FULL PAPER
fomed by using CuCN·2LiCl (1.4 mL, 1 m in THF, 20 mol%) and pivalo-
yl chloride (1.01 g, 8.4 mmol) at À408C over 2 h. The reaction was
quenched with half-concentrated aqueous NH4Cl solution, extracted
three times with Et2O, dried (MgSO4), and concentrated in vacuo. The
crude product 14a (1.83 g, 87% purity by 1H NMR, 74%) was obtained
as a white solid, which was used in the next step without further purifica-
tion. Compound 14a (1.54 g, 5.0 mmol) was dissolved in ethanol (20 mL).
Hydrazine hydrate (751 mg, 64%, 15.0 mmol) was added and the reac-
tion mixture stirred for 12 h at 258C. The solvent was evaporated and the
reaction was quenched with half-concentrated aqueous NH4Cl solution,
extracted three times with CH2Cl2, dried (MgSO4), and concentrated in
vacuo. Flash column chromatographic purification on silica gel (CH2Cl2)
afforded 15a (1.45 g, 95%) as a light yellow solid. M.p. 198.2–200.98C;
1H NMR (C6D6, 400 MHz): d=6.99 (d, J=5.37 Hz, 1H), 6.73 (d, J=
5.37 Hz, 1H), 1.78 (s, 9H), 1.68 ppm (s, 9H); 13C NMR (C6D6, 150 MHz):
d=162.7, 159.9, 141.5, 140.6, 133.0, 132.7, 129.7, 119.1, 38.8, 38.5, 29.4,
29.3 ppm; IR (ATR): n˜ =3052 (m), 2966 (m), 2928 (m), 2904 (w), 2900
(w), 2868 (w), 1637 (m), 1497 (m), 1476 (m), 1418 (vs), 1399 (m), 1365
(s), 1348 (m), 1334 (m), 1278 (w), 1252 (w), 1220 (s), 1196 (s), 1160 (s),
1154 (s), 1109 (w), 1101 (w), 1075 (m), 1024 (w), 930 (m), 913 (vs), 883
(w), 858 (w), 835 (w), 803 (m), 797 (m), 785 (w), 767 (m), 749 (w), 738
(vs), 733 (vs), 710 (w), 702 (w), 690 (s), 674 (w), 669 (w), 666 (w),
658 cmÀ1 (w); MS (EI, 70 eV): m/z (%): 304 (9) [M+], 289 (29), 262
(100), 246 (13), 191 (7), 41 (5); HRMS (EI) for C16H20N232S2 (304.1068):
304.1043.
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The research leading to these results has received funding from the Euro-
pean Research Council under the European Communityꢃs Seventh
Framework Program (FP7/2007-2013) ERC grant agreement n8 227763.
We thank W. C. Heraeus GmbH (Hanau), Chemetall GmbH (Frankfurt),
and BASF AG (Ludwigshafen) for the generous gift of chemicals.
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Received: August 30, 2010
Published online: November 24, 2010
872
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