Thieme Chemistry Journal Awardees - Where are They Now? Synthesis of Diamantane-Derived N-Heterocyclic Carbenes and Applications in Catalysis

Abstract

Novel diamantyl-substituted imidazolium salts have been synthesized, characterized and, in addition, analyzed by single-crystal structural analysis. The corresponding NHCs (a-IDAd and m-IDAd) have been prepared in solution and have been characterized by NMR. They exhibit increased steric demand and increased lipophilicity relative to the well-known IAd. In comparative studies, these NHCs were tested as ligands in palladium-catalyzed Sonogashira reactions of primary alkyl halides and, in addition, as catalysts in an organocatalyzed silyl enol ether formation.

diamondoids - N-heterocyclic carbene - organocatalysis - Sonogashira coupling

References and Notes

<A NAME="RS09208ST-1A">1a</A> Herrmann WA. Köcher C. Angew. Chem., Int. Ed. Engl.  1997,  36:  2162 

<A NAME="RS09208ST-1B">1b</A> Arduengo AJ. Acc. Chem. Res.  1999,  32:  913 

<A NAME="RS09208ST-1C">1c</A> Bourissou D. Guerret O. Gabbaï FP. Bertrand G. Chem. Rev.  2000,  100:  39 

<A NAME="RS09208ST-1D">1d</A> Hahn FE. Jahnke MC. Angew. Chem. Int. Ed.  2008,  47:  3122 

For applications of NHCs as ligands in catalysis, see:

<A NAME="RS09208ST-2A">2a</A> N-Heterocyclic Carbenes in Synthesis   Nolan SP. Wiley-VCH; Weinheim: 2006. 

<A NAME="RS09208ST-2B">2b</A> N-Heterocyclic Carbenes in Transition-Metal Catalysis, In Topics in Organometallic Chemistry   Vol. 21:  Glorius F. Springer; : 2007. 

<A NAME="RS09208ST-3">3</A> Hahn FE. Angew. Chem. Int. Ed.  2006,  45:  1348 

<A NAME="RS09208ST-4">4</A> Arduengo AJ. Harlow RL. Kline M. J. Am. Chem. Soc.  1991,  113:  361 

<A NAME="RS09208ST-5A">5a</A> Gstöttmayr CWK. Böhm VPW. Herdtweck E. Grosche M. Herrmann WA. Angew. Chem. Int. Ed.  2002,  41:  1363 

<A NAME="RS09208ST-5B">5b</A> Altenhoff G. Goddard R. Lehmann CW. Glorius F. Angew. Chem. Int. Ed.  2003,  42:  3690 

<A NAME="RS09208ST-5C">5c</A> Altenhoff G. Goddard R. Lehmann CW. Glorius F. J. Am. Chem. Soc.  2004,  126:  15195 

<A NAME="RS09208ST-5D">5d</A> Kantchev EA. B. O’Brien CJ. Organ MG. Angew. Chem. Int. Ed.  2007,  46:  2768 

<A NAME="RS09208ST-5E">5e</A> Würtz S. Glorius F. Acc. Chem. Res.  2008,  41:  1523 

<A NAME="RS09208ST-6">6</A> Review: Schwertfeger H. Fokin AA. Schreiner PR. Angew. Chem. Int. Ed.  2008,  47:  1022 

<A NAME="RS09208ST-7">7</A> Landa S. Machacek V. Coll. Czech. Chem. Commun.  1933,  5:  1 

<A NAME="RS09208ST-8">8</A> Hala S. Landa S. Hanus V. Angew. Chem., Int. Ed. Engl.  1966,  5:  1045 

<A NAME="RS09208ST-9">9</A> Dahl JE. Liu SG. Carlson RMK. Science  2003,  299:  96 

<A NAME="RS09208ST-10A">10a</A> Fokin AA. Tkachenko BA. Gunchenko PA. Gusev DV. Schreiner PR. Chem. Eur. J.  2005,  11:  7091 

<A NAME="RS09208ST-10B">10b</A> Schreiner PR. Fokina NA. Tkachenko BA. Hausmann H. Serafin M. Dahl JEP. Liu S. Carlson RMK. Fokin AA. J. Org. Chem.  2006,  71:  6709 

<A NAME="RS09208ST-10C">10c</A> Fokin AA. Schreiner PR. Fokina NA. Tkachenko BA. Hausmann H. Serafin M. Dahl JEP. Liu S. Carlson RMK. J. Org. Chem.  2006,  71:  8532 

<A NAME="RS09208ST-10D">10d</A> Fokina NA. Tkachenko BA. Merz A. Serafin M. Dahl JEP. Carlson RMK. Fokin AA. Schreiner PR. Eur. J. Org. Chem.  2007,  4738 

<A NAME="RS09208ST-10E">10e</A> Tkachenko BA. Fokina NA. Chernish LV. Dahl JEP. Liu S. Carlson RMK. Fokin AA. Schreiner PR. Org. Lett.  2006,  8:  1767 

<A NAME="RS09208ST-11">11</A> Schwertfeger H. Würtele C. Serafin M. Hausmann H. Carlson RMK. Dahl JEP. Schreiner PR. J. Org. Chem.  2008,  73:  7789 

<A NAME="RS09208ST-12A">12a</A> Arduengo AJIII. inventors; US  5077414. 

<A NAME="RS09208ST-12B">12b</A> Herrmann WA. Köcher C. Gooßen LJ. Artus GRJ. Chem. Eur. J.  1996,  2:  1627 

<A NAME="RS09208ST-12C">12c</A> For a sequential procedure, see: Arduengo AJ. Krafczyk R. Schmutzler R. Craig HA. Goerlich JR. Marshall WJ. Unverzagt M. Tetrahedron  1999,  55:  14523 

<A NAME="RS09208ST-13">13</A>

General Procedure for the Synthesis of 1,3-Dialkyl-imidazolium Tetrafluoroborate
Paraformaldehyde (1 equiv) was dissolved in toluene and alkyl amine (1.03 equiv) were added slowly. The mixture was stirred at r.t. for 1 h. After cooling to 0 ˚C another 1.03 equiv of alkyl amine were added. A 3 N solution of HBF₄
(1 equiv, 50% in H₂O) was added as dropwise and after removal of cooling glyoxal (1 equiv) was added dropwise. The reaction mixture was stirred at 60-75 ˚C for 32-70 h. The solvent was removed under reduced pressure. After column chromatography (SiO₂; CH₂Cl₂-MeOH, 10:1) the crude product was obtained, which was further purified by recrystallization from CH₂Cl₂-hexane mixture.
1,3-Diadamantylimidazolium Tetrafluoroborate A total of 0.66 mmol adamantyl amine and 0.32 mmol of other substrates were used. Reaction mixture was stirred for 32 h at 60 ˚C. Yield 95 mg (0.22 mmol, 70%).
^¹H NMR (400 MHz, CDCl₃): δ = 8.80 (t, ⁴ J _HH = 1.6 Hz, 1 H, NCHN), 7.55 (d, ⁴ J _HH = 1.6 Hz, 2 H, NCHCHN.), 2.30 (s, 6 H, CH), 2.20 (br, 12 H, CH₂), 1.78 (s, 12 H, CH₂). ^¹³C NMR (100 MHz, CDCl₃): δ = 130.71 (NCHN), 119.09 (NCHCHN), 60.83 (NCR₃), 42.52 (CH₂) 35.38 (CH), 29.59 (CH₂). ESI-MS: m/z = 337.2638 [M - BF₄ ^-]⁺. R _f = 0.66 (CH₂Cl₂-MeOH, 10:1).
1,3-Di-4-diamantylimidazolium Tetrafluoroborate ( a -IDAd˙HBF ₄ ) A total of 1.11 mmol diamantyl amine and 0.54 mmol of other substrates were used. Reaction mixture was stirred for 70 h at 60 ˚C. Yield 152 mg (0.29 mmol, 53%).
^¹H NMR (400 MHz, CDCl₃): δ = 8.84 (t, ⁴ J _HH = 1.3 Hz, 1 H, NCHN), 7.50 (d, ⁴ J _HH = 1.3 Hz, 2 H, NCHCHN), 2.16 (s, 12 H, CH₂), 2.10 (s, 6 H, CH), 1.85 (m, 8 H), 1.77 (s, 12 H, CH₂). ^¹³C NMR (100 MHz, CDCl₃): δ = 131.03 (NCHN), 119.46 (NCHCHN), 60.01 (NCR₃), 43.11 (CH₂), 38.52, 36.98, 35.70, 25.31. Anal. Calcd for C₃₁H₄₁BF₄N₂: C, 70.45; H, 7.82; N, 5.30. Found: C, 70.00; H, 7.82; N, 5.21. ESI-MS: m/z = 441.3254 [M - BF₄ ^-]⁺. R _f = 0.51 (CH₂Cl₂-MeOH, 10:1). IR (ATR): ν = 2901, 2883, 2846, 1562, 1355, 1287, 1073, 1052, 1029, 714 cm^-¹.
1,3-Di-1-diamantylimidazolium Tetrafluoroborate ( m -IDAd˙HBF ₄ ) A total of 1.47 mmol diamantyl amine and 0.72 mmol of other substrates were used. Reaction mixture was stirred for 65 h at 75 ˚C. Yield 110 mg (0.21 mmol, 29%).
^¹H NMR (300 MHz, CDCl₃): δ = 8.79 (s, 1 H, NCHN), 7.48 (s, 2 H, NCHCHN), 2.58 (s, 4 H), 2.18 (s, 4 H), 2.09 (s, 2 H), 1.56-1.95 (m, 28 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 132.52 (NCHN), 119.02 (NCHCHN), 65.63 (NCR₃), 47.11, 38.76, 38.32, 37.24, 36.19, 35.94, 32.13, 28.84, 24.26. Anal. Calcd for C₃₁H₄₁BF₄N₂: C, 70.45; H, 7.82; N, 5.30. Found: C, 69.73; H, 7.63; N, 5.21. ESI-MS: m/z = 441.3268 [M - BF₄ ^-]⁺. R _f = 0.49 (CH₂Cl₂-MeOH, 10:1).
IR (ATR): ν = 2905, 2854, 1540, 1463, 1444, 1139, 1055, 1037, 1015, 891, 819, 657 cm^-¹.

<A NAME="RS09208ST-14A">14a</A>

X-ray crystal structure analysis of a-IDAd HBF₄: formula C₃₁H₄₁N₂BF₄˙CH₂Cl₂, M = 613.39, colorless crystals 0.30 × 0.25 × 0.25 mm, a = 8.0712 (3), b = 14.4584 (5), c = 25.7643 (9) Å, β = 91.599 (1)˚, V = 3005.44 (19) Å^³, ρ_calc = 1.356 g cm^-³, µ = 2.364 mm^-¹, empirical absorption correction (0.537 ≤ T ≤ 0.589), Z = 4, monoclinic, space group P2₁/n (No. 14), λ = 1.54178 Å, T = 223 (2) K, ω and φ scans, 28618 reflections collected (±h, ±k, ±l), [(sinθ)/λ] = 0.60 Å^-¹, 5321 independent (R _int = 0.046) and 4684 observed reflections [I ÷2 σ(I)], 438 refined parameters, R = 0.054, wR ^² = 0.145, max. (min.) residual electron density 0.37
(-0.30) e Å^-³, anion BF₄ and solvent molecule CH₂Cl₂ heavily disordered, refined with split positions (PART command) using geometrical (SADI) and thermal (ISOR) restraints, hydrogen atoms calculated and refined as riding atoms.
X-ray crystal structure analysis of m-IDAd HBF₄: formula C₃₁H₄₁N₂BF₄˙2 CH₂Cl₂, M = 698.32, colorless crystal 0.20 × 0.20 × 0.10 mm, a = 11.6878 (5), b = 18.6313 (8), c = 15.5260 (7) Å, β = 96.909 (2)˚, V = 3356.4 (3) Å^³, ρ_calc = 1.382 g cm^-³, µ = 3.615 mm^-¹, empirical absorption correction (0.532 ≤ T ≤ 0.714), Z = 4, monoclinic, space group P2₁/c (No. 14), λ = 1.54178 Å, T = 223 (2) K, ω and φ scans, 25753 reflections collected (±h, ±k, ±l), [(sinθ)/λ] = 0.60 Å^-¹, 5866 independent (R _int = 0.060) and 4210 observed reflections [I ÷2 σ(I)], 481 refined parameters, R = 0.086, wR ^² = 0.247, max. (min.) residual electron density 0.54
(-0.35) e Å^-³, anion BF₄ and both solvent molecules CH₂Cl₂ heavily disordered, refined with split positions (PART command) using geometrical (SADI) and thermal (SIMU and ISOR) restraints, hydrogen atoms calculated and refined as riding atoms.
Data sets were collected with a Nonius KappaCCD diffractometer. Programs used: data collection COLLECT (Nonius B.V., 1998), data reduction Denzo-SMN, [¹4b] absorption correction Denzo, [¹4c] structure solution SHELXS-97, [¹4d] structure refinement SHELXL-97, [¹4e] graphics SCHAKAL (E. Keller, 1997).
CCDC 702245 & 702246 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: [phone], e-mail: [e-mail]].

<A NAME="RS09208ST-14B">14b</A> Otwinowski Z. Minor W. Methods Enzymol.  1997,  276:  307 

<A NAME="RS09208ST-14C">14c</A> Otwinowski Z. Borek D. Majewski W. Minor W. Acta Crystallogr., Sect. A: Found. Crystallogr.  2003,  59:  228 

<A NAME="RS09208ST-14D">14d</A> Sheldrick GM. Acta Crystallogr., Sect. A: Found. Crystallogr.  1990,  46:  467 

<A NAME="RS09208ST-14E">14e</A> Sheldrick GM. Acta Crystallogr., Sect. A: Found. Crystallogr.  2008,  64:  112 

<A NAME="RS09208ST-15">15</A> Nonnenmacher M. Kunz D. Rominger F. Oeser T. Chem. Commun.  2006,  11378 

<A NAME="RS09208ST-16">16</A>

1,3-Di-4-diamantylimidazolin-2-ylidene ( a -IDAd)
a-IDAd HBF₄ (20.5 mg, 0.038 mmol, 1.0 equiv) and KOt-Bu (5.0 mg, 0.045 mmol, 1.2 equiv) were mixed in an NMR tube, THF-d ₈ (0.5 mL) was added and the NMR experiment was carried out.
^¹H NMR (300 MHz, 300 K, THF-d ₈): δ = 7.04 (s, 2 H, imid.), 2.12-2.11 (m, 12 H, diam.), 1.97 (s, 6 H, diam.), 1.81 (s, 20 H, diam.). ^¹³C NMR (75 MHz, 300 K, THF-d ₈): δ = 211.90 (C, carbene), 114.58 (C, imid.), 55.14 (NCR₃, diam.), 45.92 (3 × CH), 40.28 (3 × CH), 38.40 (3 × CH₂), 37.82 (3 × CH₂), 26.98 (1 × CH).
1,3-Di-1-diamantylimidazolin-2-ylidene ( m -IDAd) m-IDAd HBF₄ (20.5 mg, 0.038 mmol, 1.0 equiv) and KOt-Bu (7.0 mg, 0.06 mmol, 1.6 equiv) were mixed in an NMR tube, THF-d ₈ (0.5 mL) was added and the NMR experiment was carried out.
^¹H NMR (400 MHz, 300 K, THF-d ₈): δ = 6.98 (s, 2 H, imid.), 2.71 (s, 4 H, diam.), 2.08-2.04 (m, 8 H, diam.), 1.96 (m, 2 H, diam.), 1.82-1.72 (m, 18 H, diam.), 1.62 (m, 2 H, diam.), 1.42-1.36 (m, 4 H, diam.). ^¹³C NMR (100 MHz, 300 K, THF-d ₈): δ = 215.19 (C, carbene), 114.69 (C, imid.), 60.56 (NCR₃), 49.71 (1 × C), 40.63 (2 × C,), 39.66 (1 × C), 38.63 (2 × C), 38.56 (1 × C), 33.95 (2 × C), 33.63 (2 × C), 26.70 (1 × C), 25.50 (1 × C).

<A NAME="RS09208ST-17A">17a</A> Chemistry and Biology of Naturally-Occuring Acetylenes and Related Compounds   Lam J. Breteler H. Arnason T. Hansen L. Elsevier; Amsterdam: 1988. 

<A NAME="RS09208ST-17B">17b</A> Nicolaou KC. Dai W.-M. Angew. Chem., Int. Ed. Engl.  1991,  30:  1387 

<A NAME="RS09208ST-17C">17c</A> Frigoli S. Fuganti C. Malpezzi L. Serra S. Org. Process Res. Dev.  2005,  9:  646 

<A NAME="RS09208ST-18">18</A> Eckhardt M. Fu GC. J. Am. Chem. Soc.  2003,  125:  13642 

<A NAME="RS09208ST-19">19</A> Altenhoff G. Würtz S. Glorius F. Tetrahedron Lett.  2006,  47:  2925 

For excellent reviews of NHCs in organocatalysis, see:

<A NAME="RS09208ST-20A">20a</A> Enders D. Niemeier O. Henseler A. Chem. Rev.  2007,  107:  5606 

<A NAME="RS09208ST-20B">20b</A> Marion N. Díez-Gonzalez S. Nolan SP. Angew. Chem. Int. Ed.  2007,  46:  2988 

<A NAME="RS09208ST-20C">20c</A> Enders D. Balensiefer T. Acc. Chem. Res.  2004,  37:  534 

This becomes obvious in the NHC-catalyzed conjugate Umpolung, for which many different NHCs have been screened:

<A NAME="RS09208ST-21A">21a</A> Burstein C. Tschan S. Xie X. Glorius F. Synthesis  2006,  2418 

<A NAME="RS09208ST-21B">21b</A> Hirano K. Piel I. Glorius F. Adv. Synth. Catal.  2008,  350:  984 

For initial reports see:

<A NAME="RS09208ST-21C">21c</A> Burstein C. Glorius F. Angew. Chem. Int. Ed.  2004,  43:  6205 

<A NAME="RS09208ST-21D">21d</A> Sohn SS. Rosen EL. Bode JW. J. Am. Chem. Soc.  2004,  126:  14370 

<A NAME="RS09208ST-22">22</A> Song JJ. Tan Z. Reeves JT. Fandrick DR. Yee NK. Senanayake C. Org. Lett.  2008,  10:  877