One-Pot Synthesis of Conjugated (E)-Enynones via Two Types of Cross-Coupling Reaction

Abstract

(Trimethylsilyl)ethynyl bromide can be easily transformed into conjugated (E)-enynones, whose skeleton consists of consecutive carbonyl, ethynyl, and (E)-ethenyl units, via a one-pot multicomponent Suzuki-type reaction-Sonogashira reaction sequence. Thus, a three-component coupling of (trimethylsilyl)ethynyl bromide, (E)-alk-1-enyldisiamylborane and acid chloride is achieved in a two-step, one-pot procedure, in which (E)-alk-1-enyl group is installed as nucleophile in the sp-carbon atom attached to bromine atom and acyl group is installed as electrophile in the other sp-carbon atom.

(trimethylsilyl)ethynyl bromide - conjugated enynone - cross-coupling - alkenylborane - acid chloride

References and Notes

For example, see:

<A NAME="RU06510ST-1A">1a</A> Thompson CF. Jamison TF. Jacobsen EN. J. Am. Chem. Soc.  2001,  123:  9974 

<A NAME="RU06510ST-1B">1b</A> Marco-Contelles J. de Opazo E. J. Org. Chem.  2002,  67:  3705 

<A NAME="RU06510ST-1C">1c</A> Aoki S. Matsui K. Wei H. Murakami N. Kobayashi M. Tetrahedron  2002,  58:  5417 

For example, see:

<A NAME="RU06510ST-2A">2a</A> Arcadi A. Marinelli F. Rossi E. Tetrahedron  1999,  55:  13233 

<A NAME="RU06510ST-2B">2b</A> Adlington RM. Baldwin JE. Pritchard GJ. Spencer KC. Tetrahedron Lett.  2000,  41:  575 

<A NAME="RU06510ST-2C">2c</A> Wang X.-J. Tan J. Zhang L. Org. Lett.  2000,  2:  3107 

<A NAME="RU06510ST-2D">2d</A> Jeevanandam A. Narkunan K. Ling Y.-C. J. Org. Chem.  2001,  66:  6014 

<A NAME="RU06510ST-2E">2e</A> Grotjahn DB. Van S. Combs D. Lev DA. Schneider C. Rideout M. Meyer C. Hernandez G. Mejorado L. J. Org. Chem.  2002,  67:  9200 

For example, see:

<A NAME="RU06510ST-3A">3a</A> Dodero VI. Koll LC. Faraoni MB. Mitchell TN. Podestá JC. J. Org. Chem.  2003,  68:  10087 

<A NAME="RU06510ST-3B">3b</A> Trost BM. Ball ZT. J. Am. Chem. Soc.  2004,  126:  13942 

<A NAME="RU06510ST-4A">4a</A> Tohda Y. Sonogashira K. Hagihara N. Synthesis  1977,  777 

<A NAME="RU06510ST-4B">4b</A> Chowdhury C. Kundu NG. Tetrahedron Lett.  1996,  37:  7323 

<A NAME="RU06510ST-4C">4c</A> Chowdhury C. Kundu NG. Tetrahedron  1999,  55:  7011 

<A NAME="RU06510ST-4D">4d</A> Wang J.-X. Wei B. Huang D. Hu Y. Bai L. Synth. Commun.  2001,  31:  3337 

<A NAME="RU06510ST-4E">4e</A> Wang J.-X. Wei B. Hu Y. Liu Z. Fu Y. Synth. Commun.  2001,  31:  3527 

<A NAME="RU06510ST-4F">4f</A> Karpov AS. Müller TJJ. Org. Lett.  2003,  5:  3451 

<A NAME="RU06510ST-4G">4g</A> Guo M. Li D. Zhang Z. J. Org. Chem.  2003,  68:  10172 

<A NAME="RU06510ST-4H">4h</A> Yin J. Wang X. Liang Y. Wu X. Chen B. Ma Y. Synthesis  2004,  331 

<A NAME="RU06510ST-4I">4i</A> Alonso DA. Nájera C. Pacheco MC. J. Org. Chem.  2004,  69:  1615 

<A NAME="RU06510ST-4J">4j</A> Chen L. Li C.-J. Org. Lett.  2004,  6:  3151 

<A NAME="RU06510ST-4K">4k</A> Cox RJ. Ritson DJ. Dane TA. Berge J. Charmant JPH. Kantacha A. Chem. Commun.  2005,  1037 

<A NAME="RU06510ST-4L">4l</A> Palimkar SS. Kumar PH. Jogdand NR. Daniel T. Lahoti RJ. Srinivasan KV. Tetrahedron Lett.  2006,  47:  5527 

<A NAME="RU06510ST-4M">4m</A> Likhar PR. Subhas MS. Roy M. Roy S. Kantam ML. Helv. Chim. Acta  2008,  91:  259 

<A NAME="RU06510ST-4N">4n</A> Lv Q.-R. Meng X. Wu J.-S. Gao Y.-J. Li C.-L. Zhu Q.-Q. Chen B.-H. Catal. Commun.  2008,  9:  2127 

<A NAME="RU06510ST-4O">4o</A> Chen J.-Y. Lin T.-C. Chen S.-C. Chen A.-J. Mou C.-Y. Tsai F.-Y. Tetrahedron  2009,  65:  10134 

<A NAME="RU06510ST-4P">4p</A> Bakherad M. Keivanloo A. Bahramian B. Rajaie M. Tetrahedron Lett.  2010,  51:  33 

<A NAME="RU06510ST-5">5</A> Alkynyllithium: Stefani HA. Cella R. Dörr FA. de Pereira CMP. Gomes FP. Zeni G. Tetrahedron Lett.  2005,  46:  2001 

Alkynylborane:

<A NAME="RU06510ST-6A">6a</A> Oh CH. Reddy VR. Tetrahedron Lett.  2004,  45:  8545 

<A NAME="RU06510ST-6B">6b</A> Nishihara Y. Saito D. Inoue E. Okada Y. Miyazaki M. Inoue Y. Takagi K. Tetrahedron Lett.  2010,  51:  306 

Alkynylaluminium:

<A NAME="RU06510ST-7A">7a</A> Wakamatsu K. Okuda Y. Oshima K. Nozaki H. Bull. Chem. Soc. Jpn.  1985,  58:  2425 

<A NAME="RU06510ST-7B">7b</A> Wang B. Bonin M. Micouin L. J. Org. Chem.  2005,  70:  6126 

Alkynylsilane:

<A NAME="RU06510ST-8A">8a</A> Ito H. Arimoto K. Sensui H. Hosomi A. Tetrahedron Lett.  1997,  38:  3977 

<A NAME="RU06510ST-8B">8b</A> Yadav JS. Reddy BVS. Reddy MS. Synlett  2003,  1722 

<A NAME="RU06510ST-8C">8c</A> Yadav JS. Reddy BVS. Reddy MS. Parimala G. Synthesis  2003,  2390 

<A NAME="RU06510ST-9">9</A> Alkynylzinc: Negishi E. Bagheri V. Chatterjee S. Luo F.-T. Miller JA. Stoll AT. Tetrahedron Lett.  1983,  24:  5181 

<A NAME="RU06510ST-10">10</A> Alkynylcopper: Qian H. Shao L.-X. Huang X. Synlett  2001,  1571 

<A NAME="RU06510ST-11">11</A> Alkynylgallate: Han Y. Fang L. Tao W.-T. Huang Y.-Z. Tetrahedron Lett.  1995,  36:  1287 

Alkynylindium:

<A NAME="RU06510ST-12A">12a</A> Pérez I. Sestelo JP. Sarandeses LA. J. Am. Chem. Soc.  2001,  123:  4155 

<A NAME="RU06510ST-12B">12b</A> Augé J. Lubin-Germain N. Seghrouchni L. Tetrahedron Lett.  2003,  44:  819 

Alkynyltin:

<A NAME="RU06510ST-13A">13a</A> Logue MW. Teng K. J. Org. Chem.  1982,  47:  2549 

<A NAME="RU06510ST-13B">13b</A> Kuhn H. Neumann WP. Synlett  1994,  123 

<A NAME="RU06510ST-13C">13c</A> Lerebours B. Camacho-Soto A. Wolf C. J. Org. Chem.  2005,  70:  8601 

Alkynylstibine:

<A NAME="RU06510ST-14A">14a</A> Kakusawa N. Yamaguchi K. Kurita J. Tsuchiya T. Tetrahedron Lett.  2000,  41:  4143 

<A NAME="RU06510ST-14B">14b</A> Kakusawa N. Tobiyasu Y. Yasuike S. Yamaguchi K. Seki H. Kurita J. J. Organomet. Chem.  2006,  691:  2953 

<A NAME="RU06510ST-15">15</A> Alkynylthallium: Marko IE. Southern JM. J. Org. Chem.  1990,  55:  3368 

<A NAME="RU06510ST-16A">16a</A> Kobayashi T. Tanaka M. J. Chem. Soc., Chem. Commun.  1981,  333 

<A NAME="RU06510ST-16B">16b</A> Delaude L. Masdeu AM. Alper H. Synthesis  1994,  1149 

<A NAME="RU06510ST-16C">16c</A> Arcadi A. Cacchi S. Marinelli F. Pace P. Sanzi G. Synlett  1995,  823 

<A NAME="RU06510ST-16D">16d</A> Kang S.-K. Lim K.-H. Ho P.-S. Kim W.-Y. Synthesis  1997,  874 

<A NAME="RU06510ST-16E">16e</A> Mohamed Ahmed MS. Mori A. Org. Lett.  2003,  5:  3057 

<A NAME="RU06510ST-16F">16f</A> Liang B. Huang M. You Z. Xiong Z. Lu K. Fathi R. Chen J. Yang Z. J. Org. Chem.  2005,  70:  6097 

<A NAME="RU06510ST-16G">16g</A> Sans V. Trzeciak AM. Luis S. Ziókowski JJ. Catal. Lett.  2006,  109:  37 

<A NAME="RU06510ST-16H">16h</A> Rahman MT. Fukuyama T. Kamata N. Sato M. Ryu I. Chem. Commun.  2006,  2236 

<A NAME="RU06510ST-16I">16i</A> Ma W. Li X. Yang J. Liu Z. Chen B. Pan X. Synthesis  2006,  2489 

<A NAME="RU06510ST-16J">16j</A> Liu J. Chen J. Xia C. J. Catal.  2008,  253:  50 

<A NAME="RU06510ST-16K">16k</A> Tambade PJ. Patil YP. Nandurkar NS. Bhanage BM. Synlett  2008,  886 

<A NAME="RU06510ST-16L">16l</A> Liu J. Peng X. Sun W. Zhao Y. Xia C. Org. Lett.  2008,  10:  3933 

<A NAME="RU06510ST-16M">16m</A> Fusano A. Fukuyama T. Nishitani S. Inouye T. Ryu I. Org. Lett.  2010,  12:  2410 

<A NAME="RU06510ST-17">17</A> Vong BG. Kim SH. Abraham S. Theodorakis EA. Angew. Chem. Int. Ed.  2004,  43:  3947 

<A NAME="RU06510ST-18">18</A> Inhülsen I. Margaretha P. Org. Lett.  2010,  12:  728 

<A NAME="RU06510ST-19A">19a</A> Shergina SI. Sokolov IE. Zanina AS. Mendeleev Commun.  1994,  4:  207 

<A NAME="RU06510ST-19B">19b</A> Van den Hoven BG. El Ali B. Alper H. J. Org. Chem.  2000,  65:  4131 

<A NAME="RU06510ST-20A">20a</A> Hoshi M. Nakayabu H. Shirakawa K. Synthesis  2005,  1991 

<A NAME="RU06510ST-20B">20b</A> Hoshi M. Suzuki S. Saitoh S. Okimoto M. Shirakawa K. Tetrahedron Lett.  2007,  48:  119 

<A NAME="RU06510ST-20C">20c</A> Hoshi M. Iizawa T. Okimoto M. Shirakawa K. Synthesis  2008,  3591 

<A NAME="RU06510ST-21A">21a</A> Hoshi M. Shirakawa K. Synlett  2002,  1101 

<A NAME="RU06510ST-21B">21b</A> Hoshi M. Kawamura N. Shirakawa K. Synthesis  2006,  1961 

<A NAME="RU06510ST-22">22</A>

Compound 2a was formed in about 75% GC yield based on Me₃SiC≡CBr employed, see ref. 21.

<A NAME="RU06510ST-23">23</A>

Considering that acid chloride would be consumed by reaction with residual both NaOMe and MeOH, an excess amount of benzoyl chloride was employed in this one-pot reaction. Indeed, using a stoichiometric amount of benzoyl chloride (0.5 mmol), a decrease in the yield of product 3aa was observed.

<A NAME="RU06510ST-24">24</A>

Among amine bases including i-Pr₂NEt, Et₃N was the base of choice for the cross-coupling reaction with benzoyl chloride.

<A NAME="RU06510ST-25">25</A>

To a solution of BH₃ (1 mmol) in THF (3 mL) was added 2-methylbut-2-ene (0.14 g, 2 mmol) dropwise at -15 ˚C under argon, and the mixture was stirred for 2 h at 0 ˚C to form a solution of disiamylborane in THF. To this solution was added oct-1-yne (0.11 g, 1 mmol) dropwise at -15 ˚C, and the mixture was stirred for 2 h at 0 ˚C. A solution of (E)-oct-1-enyldisiamylborane (1a, 1 mmol) in THF, thus prepared, was cooled to -15 ˚C, and Cu(acac)₂ (0.013 g, 0.05 mmol) was added to the solution under a flow of argon, followed by dropwise addition of (trimethylsilyl)ethynyl bromide (0.119 g, 0.67 mmol) and NaOMe (1 M, 0.75 mL, 0.75 mmol). The resulting mixture was allowed to warm gradually to r.t. and stirred overnight. Methanol resulting from 1 M NaOMe was removed under reduced pressure, accompanied by the solvent. After addition of THF (3 mL) to the residue under argon, the resulting mixture including (E)-dec-3-en-1-yne (2a) was cooled to 0 ˚C, and Pd(OAc)₂ (0.002 g, 0.01 mmol) and Ph₃P (0.005 g, 0.02 mmol) were added successively under a flow of argon, followed by dropwise addition of benzoyl chloride (0.141 g, 1 mmol) and Et₃N (0.101 g, 1 mmol). The resultant mixture was stirred for 2 h at r.t. and then oxidized by the successive addition of 3 M NaOH (1 mL) and 30% H₂O₂ (0.5 mL) at 0 ˚C. After being stirred for 1 h at this temperature, the mixture was extracted three times with Et₂O. The combined extracts were washed with brine, dried over Na₂SO₄, and concentrated. The residue was purified by flash chromatography on silica gel, with hexane-CH₂Cl₂ (1:1) as eluent, to give (E)-1-phenylundec-4-en-2-yn-1-one (3aa, 0.103 g, 86%).
Compound 3aa: ^¹H NMR (500 MHz, CDCl₃): δ = 0.89 (t, J = 7.1 Hz, 3 H), 1.25-1.35 (m, 6 H), 1.42-1.49 (m, 2 H), 2.21-2.26 (m, 2 H), 5.74 (dt, J = 16.1, 1.5 Hz, 1 H), 6.63 (dt, J = 16.1, 7.1 Hz, 1 H), 7.46-7.50 (m, 2 H), 7.58-7.62 (m, 1 H), 8.13-8.16 (m, 2 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 14.06 (CH₃), 22.56 (CH₂), 28.22 (CH₂), 28.78 (CH₂), 31.59 (CH₂), 33.64 (CH₂), 86.05 (≡C), 92.85 (≡C), 107.65 (=CH), 128.50 (2 × =CH), 129.50 (2 × =CH), 133.90 (=CH), 136.92 (=C), 153.10 (=CH), 178.11 (C=O). IR (neat): 2954, 2927, 2856, 2183, 1641, 1620, 1596, 1579, 1448, 1313, 1265, 1174, 956, 937, 700 cm^-¹. HRMS (EI): m/z calcd for C₁₇H₂₀O: 240.1514; found: 240.1508.

<A NAME="RU06510ST-26">26</A>

Compounds 2b-d were formed in 72-74% GC yields based on Me₃SiC≡CBr employed; unpublished results.