Propargylic dithioacetal as an allene 1,3-dication synthon. Nickel-catalyzed cross-coupling reactions of propargylic dithioacetals with Grignard reagents

Full text of DOI:10.1021/jo961514c

J . Org. Chem. 1996, 61, 8685-8686
8685
Ta ble 1. NiCl2(d p p e)-Ca ta lyzed Cr oss-Cou p lin g
Rea ction s of 1 w ith Gr ign a r d Rea gen ts
P r op a r gylic Dith ioa ceta l a s a n Allen e
1,3-Dica tion Syn th on . Nick el-Ca ta lyzed
Cr oss-Cou p lin g Rea ction s of P r op a r gylic
Dith ioa ceta ls w ith Gr ign a r d Rea gen ts†
reactant
n
R1
R2
R3
product (% yield)
1a
1b
1c
1d
1b
1e
1f
1b
1c
1c
2
1
1
1
1
1
1
1
1
1
Ph
Ph
Ph
Bu
Ph
Me3Si
PhCtC
Ph
H
Me
Me
Me
Me3SiCH2
Me3SiCH2
Me3SiCH2
Me
Ph
Et
Bu
3a (88)a
3b (90)
3c (79)
3d (90)
3e (92)
3f (95)a
3g (78)a
3h (56)
3i (55)a,b
3j (57)a,b
Me
Ph
Me
Me
Me
Me
Me
Ph
Ph
Hsian-Rong Tseng and Tien-Yau Luh*
Department of Chemistry, National Taiwan Universtiy,
Taipei, Taiwan 106, Republic of China
Received August 5, 1996
Ph
Ph
The synthesis of allenes from propargylic derivatives
is well documented.1,2 In general, a good leaving group
is required to facilitate the SN2′ reaction leading to the
formation of allenes. A series of the nickel-catalyzed
cross-coupling reactions of dithioacetals with Grignard
reagents was recently reported.3-5 To illustrate, the
reactions of allylic compound under these conditions give
the corresponding geminal dimethylation4 or the olefin-
ation products.5
a
b
NiCl2(dppf) was employed as the catalyst. The reaction was
carried out in benzene solvent at room temperature.
The analogous coupling reactions with propargylic
dithioacetals (1) have not been investigated. Since the
SN2′ reaction is so facile in the propargylic substrates, it
was felt that the nickel-catalyzed cross-coupling reactions
of 1 with the Grignard reagent R3MgX would lead to an
allenyl thioether 2 intermediate that can further couple
with the Grignard reagent affording the substituted
allenes 3. Thus, the reaction can be viewed as employing
the 1 as an allene 1,3-dication synthon 4.
The reaction can formally be considered as using the
dithioacetal functionality as a geminal dication synthon.
Interestingly, the NiCl2(dppe)-catalyzed cross couplings
of allylic trithioorthoesters with MeMgI afford the cor-
responding 1,1,3-trimethylation products, the first methyl
group being introduced at the γ-position.5a
The propargylic dithioacetals 1 were obtained con-
veniently from the BF3‚OEt2-catalyzed reactions of the
corresponding ketones 5 with 1,2-ethanedithiol or 1,3-
propanedithiol in methanol.6 A benzene solution of 1 and
2.5 equiv of the Grignard reagent in the presence of 5
mol % of NiCl2(dppe) or NiCl2(dppf) was warmed at 65
°C for 4-12 h. After usual workup, the corresponding
allenes 3 were obtained in good to excellent yield. No
corresponding geminal dialkylation products were de-
tected at all. Representative results are summarized in
Table 1. The reaction proceeded extremely well when
methyl or silylmethyl Grignard reagent was employed.
Aryl or primary alkyl Grignard reagents gave the corre-
sponding coupling products in moderate yields. However,
secondary alkyl Grignard reagents afforded a mixture of
products that were difficult to separate. No reaction was
observed in the absence of the nickel catalyst.
Both tri- and tetrasubstituted allenes were efficiently
synthesized by this procedure (Table 1). Silyl as well as
alkynyl substituents are stable under these conditions.
Allenylsilanes and silylmethyl-substituted allenes 3d -f
were prepared accordingly. Bisallene 7 was obtained in
81% yield from the reaction of bisdithioacetal 6 under
the same conditions.
† Dedicated to Professor Y.-S. Cheng on the occasion of her 65th
birthday.
(1) For reviews, see: (a) Tsuji, J .; Mandai, T. J . Organomet. Chem.
1993, 451, 15. (b) Tsuji, J . Angew. Chem., Int. Ed. Engl. 1995, 34, 2589.
(c) Tsuji, J .; Mandai, T. Synthesis 1996, 1. (d) Landor, S. R., Ed. The
Chemistry of Allenes; Academic Press: London, 1982.
(2) For recent syntheses, see: (a) Meyer, C.; Marek, I.; Courte-
manche, G.; Normant, J .-F. J . Org. Chem. 1995, 60, 863. (b) Sugimoto,
Y.; Hanamoto, T.; Inanaga, J . Appl. Organomet. Chem. 1995, 9, 369.
(c) Hojo, F.; Ando, W. Synlett 1995, 880. (d) Kirms, M. A.; Salcido, S.
L.; Kirms, L. M. Tetrahedron Lett. 1995, 36, 7979. (e) Baldwin, J . E.;
Adlington, R. M.; Crouch, N. P.; Hill, R. L.; Laffey, T. G. Tetrahedron
Lett. 1995, 36, 7925. (f) Holmann, M.; Krause, M. Chem. Ber. 1995,
128, 851. (g) Besson, L.; Gore, J .; Gazes, B. Tetrahedron Lett. 1995,
36, 3853. (h) Yamamoto, Y.; Almasum, M.; Asao, N. J . Am. Chem. Soc.
1995, 117, 2379. (i) Ogoshi, S.; Nishiguchi, S.; Tsutsumi, K. J . Org.
Chem. 1995, 60, 4650. (j) Brown, H. C.; Khire, U. R.; Narla, G. J . Org.
Chem. 1995, 60, 8130.
(3) For reviews, see: (a) Luh, T.-Y. Acc. Chem. Res. 1991, 24, 257.
(b) Luh T.-Y.; Ni, Z.-J . Synthesis 1990, 89. (c) Luh T.-Y.; Leung, M.-K.
In Advances in the Use of Synthons in Organic Chemistry; Dondoni,
A., Ed.; J AI: London, 1996; Vol. 2, p 109. (d) Luh, T.-Y. In Modern
Methodology in Organic Synthesis; Shono, T., Ed.; Kodansha: Tokyo,
1992; p 229. (e) Luh, T.-Y. Pure Appl. Chem. 1996, 68, 105. (f) Luh,
T.-Y. Synlett 1996, 201.
(4) (a) Ni, Z.-J .; Mei, N.-W.; Shi, X.; Wang, M. C.; Tzeng Y.-L.; Luh,
T.-Y. J . Org. Chem. 1991, 56, 4035 and references therein. (b) Shiu,
L.-L.; Yu, C. C.; Wong, K.-T.; Chen, B.-L.; Cheng, W.-L.; Yuan, T.-M.;
Luh, T.-Y.Oragnometallics 1993, 12, 1018. (c) Wong, K.-T.; Yuan, T.-
M.; Wang, M. C.; Tung, H.-H.; Luh, T.-Y. J . Am. Chem. Soc. 1994,
116, 8920 and references therein. (d) Cheng W.-L.; Luh, T.-Y. J . Chem.
Soc., Chem. Commun. 1992, 1392.
(5) (a) Tzeng, Y.-L.; Yang, P.-F.; Mei, N.-W.; Yuan, T.-M.; Yu C. C.;
Luh, T.-Y. J . Org. Chem. 1991, 56, 5289. (b) Yuan, T.-M.; Luh, T.-Y.
J . Org. Chem. 1991, 57, 4550.
(6) Methanol solvent is essential for this transformation. (Cf.
Williams, J . R.; Sarkisian, G. M. Synthesis 1974, 32. Yuan, T.-M.; Luh,
T.-Y. Org. Synth. 1996, 74, in press).
S0022-3263(96)01514-9 CCC: $12.00 © 1996 American Chemical Society

8686 J . Org. Chem., Vol. 61, No. 24, 1996
Notes
1,2-ethanedithiol (5.5 mL, 55 mmol) in the presence of BF3‚OEt2
(9.6 mL, 59 mmol) in methanol (60 mL) to yield 1e (5.85 g, 59%),
bp 65-68 °C (0.9 mmHg), which solidified upon standing: mp
48-50 °C; 1H NMR (200 MHz, CDCl3) δ 0.13 (s, 9 H), 1.98 (s, 3
H), 3.39-3.56 (m, 4 H); 13C NMR (75 MHz, CDCl3) δ -0.1, 31.0,
40.5, 54.3, 86.8, 108.7; IR (KBr) 2157 cm-1; HRMS calcd for
C9H16S2Si 216.0463, found 216.0467.
2-Eth yn yl-2-m eth yld ith iola n e. Dithiolane 1e (432 mg, 20.0
mmol) and K2CO3 (100 mg) in 20 mL methanol was stirred at
room temperature for 3 h. Water (20 mL) was then added, and
the mixture was extracted with ether (20 mL × 3). The organic
layer was dried (MgSO4), and the solvent was removed in vacuo
to give a pale yellow oil that was distilled (275 mg, 96%), bp
40-42 °C (0.9 mmHg), and that solidified upon standing; mp
36-38 °C; 1H NMR (300 MHz, CDCl3) δ 2.00 (s, 3 H), 2.65 (s, 1
H), 3.44-3.58 (m, 4 H); 13C NMR (75 MHz, CDCl3) δ 30.6, 40.6,
53.6, 70.9, 87.8; IR (KBr) 2108 cm-1; HRMS calcd for C6H8S2
144.0067, found 144.0068.
The reaction may occur via a similar pathway for the
cross-coupling reaction of allylic dithioacetals. However,
the regioselective carbon-carbon bond formation at C1
and C3 appears to be different from the allylic counter-
part. Presumably, the first coupling process may occur
at the γ-position leading to an allenyl thioether inter-
mediate 2 that undergoes further coupling with the
Grignard reagent.
2-(4-P h en ylbu ta d iyn yl)-2-m eth yld ith iola n e (1f). To a
mixture of NH2OH‚HCl (0.5 g, 7.0 mmol), diethylamine (2 mL,
20 mmol), 2-ethynyl-2-methyldithiolane (710 mg, 5.00 mmol),
and CuCl (75 mg, 0.75 mmol) in methanol/H2O (14 mL, v/v )
5/9) was added at room temperature 1-bromo-2-phenylacetylene
(1.09 g, 6.00 mmol) under a nitrogen atomsphere. The mixture
was stirred for 30 min. A solution of KCN (0.25 g, 4.0 mmol)
and NH4Cl (1.0 g, 20 mmol) in water (15 mL) was then added
with vigorous stirring. The mixture was extracted with ether.
The organic layer was dried (MgSO4), and the solvent was
removed in vacuo to give a pale yellow solid, which was
chromatographed on silica gel (1% EtOAc in hexane) to give 1f
as a white solid (1.10 g, 90%):; mp 65-67 °C; 1H NMR (300 MHz,
CDCl3) δ 2.05 (s, 3 H), 3.46-3.62 (m, 4 H), 7.28-7.34 (m, 3 H),
7.45 (dd, J ) 1.5, 6.0 Hz, 2 H); 13C NMR (75 MHz, CDCl3) δ
29.8, 40.7, 54.5, 67.6, 73.3, 80.9, 85.1, 121.6, 128.4, 129.2, 132.4;
IR (KBr) 2172, 2231 cm-1; HRMS calcd for C14H12S2 244.0380,
found 244.0378.
Dod eca -3,9-d iyn e-2,11-d ion e Bis(eth ylen e d ith ioa ceta l)
(6). To a sodium-dried methanol solution (40 mL) of dodeca-
3,9-diyne-2,11-dione (1.90 g, 10.9 mmol) and 1,2-ethanedithiol
(1.92 mL, 25.1 mmol) at 0 °C was added dropwise BF3‚OEt2 (3.29
mL, 26.2 mmol). The mixture was stirred at 0 °C for 30 min,
quenched with aqueous NaOH (10%), and extracted with ether.
The organic layer was dried (MgSO4), and the solvent was
removed in vacuo to give a pale yellow solid, which was
chromatographed on silica gel (5% EtOAc in hexane) to give 6
as a white solid (1.76 g, 47%): mp 54-56 °C; 1H NMR (300 MHz,
CDCl3) δ 1.54-1.59 (m, 2 H), 1.98 (s, 3 H), 2.20-2.24 (m, 2 H),
3.40-3.56 (m, 4 H); 13C NMR (75 MHz, CDCl3) δ 18.5, 27.6, 31.9,
40.5, 54.7, 83.2, 84.3; IR (KBr) 2213, 2233 cm-1; MS (20eV) m/z
(rel intensity) 342 (M+, 1), 316 (6), 280 (2), 242 (4), 209 (5), 171
(5), 131 (6), 119 (100).
2-P h en yl-2,3-p en ta d ien e (3a ). An ether solution of MeMgI
(2.0 mL of 2 M solution, 4.0 mmol) was evacuated to remove
the ether solvent. Under nitrogen atmosphere, a mixture of 1a
(220 mg, 1.00 mmol) and NiCl2(dppf) (34 mg, 0.05 mmol) in
benzene/THF (5mL, 19/1) was stirred at 65 °C for 12 h, quenched
with saturated NH4Cl (10 mL), and extracted with ether (10 mL
× 3). The organic layer was dried (MgSO4), and the solvent was
removed in vacuo to give a pale yellow oil, which was chromato-
graphed on silica gel (hexane) to give 3a as a colorless oil (124
mg, 88%): 1H NMR (300 MHz, CDCl3) δ 1.74 (d, J ) 6.9 Hz, 3
H), 2.07 (d, J ) 3.0 Hz, 3 H), 5.43 (qq, J ) 3.0, 6.9 Hz, 1 H), 7.17
(t, J ) 7.6 Hz, 1 H), 7.32 (dd, J ) 7.6, 7.8 Hz, 2 H), 7.45 (d, J )
7.8 Hz, 2 H); 13C NMR (75 MHz, CDCl3) δ 14.3, 17.1, 87.5, 99.7,
125.6, 126.3, 128.2, 137.8, 204.9; IR (neat) 1955 cm-1; HRMS
calcd for C11H12 144.0939, found 144.0935.
An attempt to synthesize cumulene 8 from 1f by this
procedure was unsuccessful. Rather, the corresponding
alkynylallene 3g was obtained. Again, a γ-attack may
occur first followed by a similar displacement of the
allenyl thioether intermediate to give 3g.
Exp er im en ta l Section
2- (P h en yleth yn yl)d ith ia n e (1a ). To a sodium-dried 2-pro-
panol solution (30 mL) of 3-phenylpropynal (5a ) (3.40 g, 39
mmol) and 1,3-propanedithiol (3.2 mL, 31 mmol) at 0 °C was
added dropwise BF3‚OEt2 (4.2 mL, 33 mmol). The mixture was
stirred at 0 °C for 30 min, quenched with aqueous NaOH (10%),
and extracted with ether (50 mL × 3). The organic layer was
dried (MgSO4) and the solvent was removed in vacuo to give a
pale yellow oil, which was chromatographed on silica gel (1%
EtOAc in hexane) to give 1a as a white solid (4.21 g, 73%): mp
51-53 °C (lit.7 54-55.5 °C).
2- (P h en yleth yn yl)-2-m eth yld ith ola n e (1b). In a manner
similar to that described for 1a , a mixture of 4-phenylbutyn-2-
one (5b) (5.61 g, 39 mmol), 1,2-ethanedithiol (3.9 mL, 47 mmol)
and BF3‚OEt2 (6.3 mL, 50 mmol) in methanol (125 mL) was
converted to 1b as a white solid (7.80 g, 91%): mp 43-45 °C;
1H NMR (300 MHz, CDCl3) δ 2.11 (s, 3 H), 3.44-3.62 (m, 4 H),
7.25-7.28 (m, 3 H), 7.38-7.42 (m, 2 H); 13C NMR (75 MHz,
CDCl3) δ 31.1, 40.5, 54.6, 82.6, 92.8, 122.6, 128.0, 128.1, 131.4;
IR (KBr) 2220 cm-1; HRMS calcd for C12H12S2 220.0380, found
220.0380.
2- (P h en yleth yn yl)-2-p h en yld ith ola n e (1c). In a manner
similar to that described for 1a , phenyl phenylethynyl ketone
(5c) (1.03 g, 5.0 mmol) was allowed to react with 1,2-ethanedi-
thiol (0.5 mL, 6.0 mmol) in the presence of BF3‚OEt2 (0.9 mL,
6.4 mmol) in methanol (25 mL) to yield 1c as a white solid (0.71
g, 50%): mp 52-54 °C; 1H NMR (200 MHz, CDCl3) δ 3.64-3.84
(m, 4 H), 7.28-7.41 (m, 6 H), 7.45-7.52 (m, 2 H), 7.96-8.03 (m,
2 H); 13C NMR (75 MHz, CDCl3) δ 41.3, 62.2, 86.8, 91.1, 122.7,
127.6, 128.2, 128.3, 128.4, 131.6, 138.7; IR (KBr) 2208 cm-1
HRMS calcd for C17H14S2 282.0537, found 282.0532.
;
2- (Hex-1-yn -1-yl)-2-m eth yld ith ola n e (1d ). In a manner
similar to that described for 1a , oct-3-yn-2-one (5d ) (3.80 g, 30
mmol) was allowed to react with 1,2-ethanedithiol (3.0 mL, 36
mmol) in the presence of BF3‚OEt2 (4.8 mL, 38 mmol) in
methanol (40 mL) to yield 1d as a colorless oil (2.39 g, 40%):
1H NMR (200 MHz, CDCl3) δ 0.87 (t, J ) 7.3 Hz, 3 H), 1.24-
1.47 (m, 4 H), 1.98 (s, 3 H), 2.19 (t, J ) 6.8 Hz, 2 H), 3.40-3.58
(m, 4 H); 13C NMR (50 MHz, CDCl3) δ 13.6, 18.6, 21.9, 30.6,
32.0, 40.5, 54.8, 83.7, 83.9; IR (neat) 2236 cm-1; HRMS calcd
for C10H16S2 200.0693, found 220.0703.
Ack n ow led gm en t. This work was supported by the
National Science Council of the Republic of China.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for 3b-j and 7 and 1H NMR spectra for 3a -j and 7
(14 pages). This material is contained in libraries on micro-
fiche, immediately follows this article in the microfilm version
of the journal, and can be ordered from the ACS; see any
current masthead page for ordering information.
2-[(Tr im eth ylsilyl)eth yn yl]-2-m eth yld ith ola n e (1e). In
a manner similar to that described for 1a , 4- (trimethylsilyl)-
butyn-2-one (5e) (6.56 g, 46 mmol) was allowed to react with
(7) Arai, K.; Iwamura, H.; Oki, M. Bull. Chem. J pn. 1975, 48, 3319.
(8) J acobs, T. L.; Prempree, P. J . Am. Chem. Soc. 1967, 89, 6177.
(9) Ziegler, K.; Sauermilch, W. Ber. 1930, 63, 1851.
J O961514C