Rhodium-Catalyzed Carbene-Transfer Reactions via Thienylcarbene Complexes Generated from Thiocarbamoyl-ene-yne Compounds

Abstract

Catalytic thienylcarbene-transfer reactions have been developed. The rhodium-catalyzed reaction of alkenes, furans, and thiophenes with a thiocarbamoyl-ene-yne compound as a carbene source gave the cyclopropanation products or ring-opened products of heterocycles. These processes provide efficient synthetic methods for thiophene-containing complex molecules.

Key words

thiocarbamoyl-ene-yne - rhodium - carbene complex - cyclopropanation - ring-opening reaction

References and Notes

• 1a Zaragozasm Dörward F. Metal Carbenes in Organic Synthesis   Wiley-VCH; Weinheim: 1999. 
• 1b Metal Carbenes in Organic Synthesis, In Topics in Organometallic Chemistry   Vol. 13:  Dötz KH. Springer; Berlin: 2004. 
• 2 Doyle MP. McKervey MA. Ye T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds   Wiley-Interscience; New York: 1998. 
• 3a Miki K. Uemura S. Ohe K. Chem. Lett.  2005,  34:  1068 
• 3b Kusama H. Iwasawa N. Chem. Lett.  2006,  35:  1082 
• 3c Ohe K. Bull. Korean Chem. Soc.  2007,  28:  2153 
• 3d Ohe K. Miki K. J. Synth. Org. Chem. Jpn.  2009,  67:  1161 
• 4a Miki K. Nishino F. Ohe K. Uemura S. J. Am. Chem. Soc.  2002,  124:  5260 
• 4b Nishino F. Miki K. Kato Y. Ohe K. Uemura S. Org. Lett.  2003,  5:  2615 
• 4c Miki K. Yokoi T. Nishino F. Kato Y. Washitake Y. Ohe K. Uemura S. J. Org. Chem.  2004,  69:  1557 
• 5 Thiocarbamoyl moiety was also used for the generation of vinylcarbene complexes. See: Ikeda Y. Murai M. Abo T. Miki K. Ohe K. Tetrahedron Lett.  2007,  48:  6651 
• 6 Thiocarbamoyl-ene-yne 1 was synthesized in two steps from 1,2-dibromocyclohexene, which was prepared according to the known procedure. See: Voigt K. von Zezschwitz P. Rosauer K. Lansky A. Adams A. Reiser O. de Meijere A. Eur. J. Org. Chem.  1998,  1521 
• In sharp contrast, the reaction of carbamoyl-ene-yne compounds with a chromium complex gives not furyl carbene-chromium complexes but pyranylidene-chromium complexes. Theoretical investigations are in progress and will be published in due course. See:
• 9a Ohe K. Miki K. Yokoi T. Nishino F. Uemura S. Organometallics  2000,  19:  5525 
• 9b Miki K. Yokoi T. Nishino F. Ohe K. Uemura S. J. Organomet. Chem.  2002,  645:  228 
• 11a Pirrung MC. Zhang J. Lackey K. Strenbach DD. Brown F. J. Org. Chem.  1995,  60:  2112 
• 11b Shieh CP. Ong CW. Tetrahedron  2001,  57:  7303 
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• 13 Katritzky AR. Ramsden CA. Joule JA. Zhdankin VV. Handbook of Heterocyclic Chemistry   3rd ed.:  Elsevier; Amsterdam: 2010.  p.126-128  
• 14 Rhodium-catalyzed ring-opening reaction of 2-methoxy-thiophene with ethyl diazoacetate has been reported. See: Tranmer GK. Capreta A. Tetrahedron  1998,  54:  15499 
• 16 2-Aminothiophenes were synthesized according reported procedures. See: Lu Z. Twieg RJ. Tetrahedron  2005,  61:  903 
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7

Synthesis of 1-Bromo-2-trimethylsilylethynylcyclohex-1-ene
To a solution of trimethylsilylacetylene (1.96 g, 20 mmol) in toluene (40 mL) were added tert-butylamine (5 mL) and 1,2-dibromocyclohexene (9.6 g, 40 mmol) at r.t. under N₂. CuI (0.68 g, 3.6 mmol) and Pd(PPh₃)₄ (1.35 g 1.2 mmol) were added to the solution, and the mixture was stirred at 60 ˚C for 2 h. The reaction mixture was filtered through a pad of silica gel with Et₂O. The filtrate was removed under reduced pressure, and the residue was purified by column chromatog-raphy on silica gel with hexane to afford 1-bromo-2-trimethylsilylethynylcyclohex-1-ene (4.6 g. 18 mmol, 45%) as a colorless oil. ^¹H NMR (300 MHz, CDCl₃): δ = 0.21 (s, 9 H), 1.55-1.75 (m, 4 H), 2.21-2.26 (m, 2 H), 2.50-2.55 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = -0.1, 21.8, 24.1, 31.7, 36.3, 98.3, 104.9, 121.4, 129.8.

8

Synthesis of N , N -Dimethyl 2-Ethynyl-1-cyclohexene-thiocarboxamide (1)
To a solution of 1-bromo-2-trimethylsilylethynylcyclohex-1-ene (2.56g, 10 mmol) in THF (20 mL) was added dropwise n-BuLi (7.5 mL, 12.0 mmol) at -78 ˚C under N₂. The mixture was stirred at -78 ˚C for 30 min, and then N,N-dimethylthiocarbamoyl chloride (1.5g, 15.0 mmol) was added to it. After further stirring at r.t. for 2 h, the organic solution was washed with H₂O, and the aquous phase was extracted with Et₂O (3 × 10 mL). The combined organic phase was dried over MgSO₄. The solvent was removed under reduced pressure. The residue was filtered through a pad of silica gel. The filtrate was removed under reduced pressure. To a solution of the residue in DMSO (20 mL) were added KF (0.59 g, 10 mmol) and H₂O (1 mL). The mixture was stirred at r.t. for 2 h. The reaction mixture was poured into H₂O, and the aqueous phase was extracted with Et₂O (3 × 10 mL). The combined organic phase was dried over MgSO₄. The solvent was removed under reduce pressure, and the residue was purified by column chroma-tography on silica gel with hexane-EtOAc (v/v = 4:1) as an eluent to afford N,N-dimethyl 2-ethynyl-1-cyclohexenethio-carboxamide (640 mg, 3.3 mmol 33% yield) as a dark brown solid; mp 42.1-43.0 ˚C. IR (KBr): 1061, 1123, 1140, 1395, 1520, 2858, 2931, 3223 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 1.60-1.79 (m, 4 H), 2.01-2.07 (m, 1 H), 2.20-2.26
(m, 2 H), 2.68-2.78 (m, 1 H), 3.04 (s, 1 H), 3.28 (s, 3 H), 3.47 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 21.7, 21.8, 28.7, 29.0, 41.8, 41.9, 80.7, 82.4, 113.29, 147.7, 201.0. HRMS-FAB: m/z calcd for C₁₁H₁₆NS [M + H⁺], 194.1003; found: 194.1003.

10

The use of platinum or gold catalyst precursors (PtCl₂, AuCl, AuCl₃) was not effective in this reaction.

12

Typical Procedure for Rhodium-Catalyzed Ring-Opening Reaction of Thiocarbamoyl-ene-yne 1 with 2-Methoxyfuran
To a solution of [Rh(OAc)₂]₂ (3.3 mg, 0.0075 mmol) in anhyd DCE (3.0 mL) were added thiocarbamoyl-ene-yne 1 (59 mg. 0.30 mmol) and 2-methoxyfuran (150 mg, 1.50 mmol) under N₂. The mixture was stirred at r.t. for appropriate time. The mixture was diluted with EtOAc (10 mL), and the solution was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel with hexane-EtOAc (v/v = 10:1).
Compound 3a
Orange solid; yield 90%; 1E,4E/1Z,4E = 99:1; mp 108.5-109.5 ˚C. IR (KBr): 877, 1008, 1237, 1332, 1394, 1590, 1701, 2831, 2938 cm^-¹.
Compound (1E,4E)-3a: ^¹H NMR (300 MHz, CDCl₃): δ = 1.63-1.78 (m, 4 H), 2.41-2.56 (m, 2 H), 2.62-2.71 (m, 2 H), 2.79 (s, 6 H), 3.73 (s, 3 H), 5.80 (d, J = 15.0 Hz, 1 H), 6.38 (dd, J = 15.0, 11.3 Hz, 1 H), 6.96 (d, J = 15.0 Hz, 1 H), 7.39 (dd, J = 15.0, 11.3 Hz, 1 H). ^¹³C NMR (75.5 MHz, CDCl₃): δ = 22.9, 23.2, 25.2, 25.4, 44.7, 51.2, 116.7, 120.5, 123.5, 124.5, 132.1, 140.9, 145.7, 154.9, 167.9.
Compound (1Z,4E)-3a: ^¹H NMR (300 MHz, CDCl₃): δ = 1.63-1.78 (m, 4 H), 2.41-2.56 (m, 2 H), 2.62-2.71 (m, 2 H), 2.82 (s, 6 H), 3.76 (s, 3 H), 5.51 (d, J = 11.5 Hz, 1 H), 6.66 (dd, J = 11.5, 11.5 Hz, 1 H), 6.89 (d, J = 15.0 Hz, 1 H), 7.69 (dd, J = 15.0, 11.5 Hz, 1 H). ^¹³C NMR (75.5 MHz, CDCl₃): δ = 23.1, 23.1, 25.2, 25.4, 44.8, 50.1, 112.7, 119.8, 123.9, 124.3, 133.0, 140.9, 146.0, 155.3, 167.4. Anal. Calcd for C₁₆H₂₁NO₂S: C, 65.95; H, 7.26. Found: C, 66.06; H, 7.22.
Compound 4e Red solid; yield 76%; mp 79.0-80.0 ˚C. IR (KBr): 1119, 1269, 1396, 1558 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 1.60-1.75 (m, 4 H), 2.50-2.55 (m, 2 H), 2.68-2.77 (m, 2 H), 2.80 (s, 6 H), 3.78 (br s, 8 H), 4.20-4.40 (m, 2 H,), 6.45 (t, J = 13.2 Hz, 1 H), 6.52 (d, J = 14.2 Hz, 1 H), 7.03 (d, J = 15.1 Hz, 1 H), 7.73 (t, J = 12.7 Hz, 1 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 15.2, 22.9, 23.2, 25.2, 25.5, 44.7, 50.3, 65.8, 66.6, 121.5, 123.3, 124.0, 124.7, 131.9, 141.1, 147.9, 154.8, 194.9. HRMS-FAB: m/z calcd for C₁₉H₂₆N₂OS₂ [M⁺]: 362.1487; found: 362.1473.

15

Catalytic ring-opening reaction of 2-methoxythiophene with propargyl acetates as carbene sources has been reported. See ref. 11c.

18

The reaction of 1,1-dimethyl-2-propynyl acetate and 2-pyrrolidinothiophene in the presence of [RuCl₂(CO)₃]₂ or PtCl₂ as a catalyst gave no ring-opening product. Compared with ref. 13, the reactivity of 2-aminothiophenes towards ring opening seems to be lower than that of furans or 2-methoxythiophene.