CuI/l-Proline-Catalyzed Intramolecular Aryl Amination: An Efficient Route for the Synthesis of 1,4-Benzodiazepinones

Abstract

An effective protocol for the synthesis of potentially bioactive benzo[e]chromeno[6,5-b][1,4]diazepine-3,8(7H,13H)-dione and dibenzo[b,e][1,4]diazepin-11(10H)-one derivatives in good to excellent yields has been achieved by CuI/l-Proline catalyzed coupling reaction as the key step. The methodology offers clean reaction conditions and easy isolation of the products in 61-92% yields.

CuI - l-proline - 1,4-benzodiazepinones - intramolecular cyclization

References and Notes

<A NAME="RB04911ST-1A">1a</A> Baldessarini RJ. In The Pharmacologic Basis of Therapeutics   Vol. 1:  Gilman AG. Goodman LS. Ralland TW. Murad F. Macmillan; New York: 1985.  p.391 

<A NAME="RB04911ST-1B">1b</A> Landquist JK. In Comprehensive Heterocyclic Chemistry   Vol. 1:  Katritzky AR. Rees CW. Pergamon; Oxford: 1984.  Chap. 1/06.

<A NAME="RB04911ST-1C">1c</A> Sharp JT. In Comprehensive Heterocyclic Chemistry   Vol. 7:  Katritzky AR. Rees CW. Pergamon; Oxford: 1984.  Chap. 5/18.

<A NAME="RB04911ST-1D">1d</A> Vida JA. In Medicinal Chemistry   Part III:  Wolf MV. Burger A. Wiley; New York: 1981. 

<A NAME="RB04911ST-2">2</A> Lehner H. Gauch R. Michaelis W. Arzneim.-Forsch.  1967,  17:  185 

<A NAME="RB04911ST-3">3</A> Hunziker F. Lauener H. Smutz J. Arzneim.-Forsch.  1963,  13:  324 

<A NAME="RB04911ST-4A">4a</A> Joergensen TK, Andersen KE, Andersen HS, Hohlweg R, Madsen P, and Olsen UB. inventors; WO  9631497.  ; Chem. Abstr. 1997, 126, 8146

<A NAME="RB04911ST-4B">4b</A> Ohkuma H, and Kobaru S. inventors; US 94  249518.  ; Chem. Abstr. 1996, 125, 140671

<A NAME="RB04911ST-5">5</A> Grigorseva EK, Kaverina NV, Likhosherstov AM, Lyskovtsev VV, Skoldinov AP, Stavrovskaya AV, Tolmacheva EA, Chichkanov GG, and Barch R. inventors; RU  2026862.  ; Chem. Abstr. 1996, 124, 106663

<A NAME="RB04911ST-6">6</A> Yoshino H, Ueda N, Niijma J, Haneda T, Kotake Y, Yoshimatsu K, Watanabe T, Nagasu T, and Tsukahara N. inventors; WO  9503279.  ; Chem. Abstr. 1995, 122, 314588

<A NAME="RB04911ST-7">7</A> Squires RF. Saederup E. Neurochem. Res.  1993,  18:  787 

<A NAME="RB04911ST-8">8</A> Schmidt G. inventors; US  3,406,168.  ; Chem. Abstr. 1969, 70, 87866d

<A NAME="RB04911ST-9">9</A> Boyd DR. Sharma ND. Barr SA. Carroll JG. Mackerracher D. Malone JF. J. Chem. Soc., Perkin Trans. 1  2000,  3397 

<A NAME="RB04911ST-10">10</A> Bar G. Parson AF. Thomas CB. Tetrahedron  2001,  57:  4719 

<A NAME="RB04911ST-11">11</A> Lee YR. Kim BS. Kweon HI. Tetrahedron  2000,  56:  3867 

<A NAME="RB04911ST-12">12</A> Pirrung MC. Blume F. J. Org. Chem.  1999,  64:  3642 

<A NAME="RB04911ST-13">13</A> Dickinson JM. Nat. Prod. Rep.  1993,  10:  71 

<A NAME="RB04911ST-14A">14a</A> Beccalli EM. Broggini G. Paladino G. Pilati T. Pontremoli G. Tetrahedron: Asymmetry  2004,  15:  687 

<A NAME="RB04911ST-14B">14b</A> Surman MD. Mulvihill MJ. Miller MJ. Org. Lett.  2002,  4:  139 

<A NAME="RB04911ST-14C">14c</A> Broggini G. Molteni G. Terraneo A. Zecchi G. Tetrahedron  1999,  55:  14803 

<A NAME="RB04911ST-14D">14d</A> Keenan RM. Callahan JF. Samanen JM. Bondinell WE. Calvo RR. Chen L. DeBrosse C. Eggleston DS. Haltiwanger RC. Hwang SM. Jakas DR. Ku TW. Miller WH. Newlander KA. Nichols A. Parker MF. Southhall LS. Uzinskas I. Vasko-Moser JA. Venslavsky JW. Wong AS. Huffman WF. J. Med. Chem.  1999,  42:  545 

<A NAME="RB04911ST-14E">14e</A> Sugimori T. Okawa T. Eguchi S. Kakehi A. Yashima E. Okamoto Y. Tetrahedron  1998,  54:  7997 

<A NAME="RB04911ST-14F">14f</A> Matsunaga N. Harada H. Aoyama T. Shioiri T. Heterocycles  1992,  33:  235 

<A NAME="RB04911ST-14G">14g</A> Walser A. Fryer RI. In Bicyclic Diazepines   Wiley; New York: 1991.  Chap. 8.

<A NAME="RB04911ST-15A">15a</A> Matthews JM. Dyatkin AB. Evangelisto M. Gauthier DA. Hecker LR. Hoekstra WJ. Liu F. Poulter B. Sorgi KL. Maryanoff BE. Tetrahedron: Asymmetry  2004,  15:  1259 

<A NAME="RB04911ST-15B">15b</A> Hemming K. Loukou C. Tetrahedron  2004,  60:  3349 

<A NAME="RB04911ST-15C">15c</A> Herrero S. Garcìa-López MT. Herranz R. J. Org. Chem.  2003,  68:  4582 

<A NAME="RB04911ST-15D">15d</A> Abrous L. Hynes JJr. Friederich SR. Smith AB. Hirschmann R. Org. Lett.  2001,  3:  1089 

<A NAME="RB04911ST-15E">15e</A> Wang T. Lui AS. Cloudsdale IS. Org. Lett.  1999,  1:  1835 

<A NAME="RB04911ST-15F">15f</A> Ammadi F. Boukhris S. Souizi A. Coudert G. Tetrahedron Lett.  1999,  40:  6517 

<A NAME="RB04911ST-15G">15g</A> Grunewald GL. Dahanukar VH. Ching P. Criscione KR. J. Med. Chem.  1996,  39:  3539 

<A NAME="RB04911ST-16A">16a</A> Yang BH. Buchwald SL. J. Organomet. Chem.  1999,  576:  125 

<A NAME="RB04911ST-16B">16b</A> Wolfe JP. Wagaw S. Marcoux J.-F. Buchwald SL. Acc. Chem. Res.  1998,  31:  805 

<A NAME="RB04911ST-16C">16c</A> Hartwig JF. Angew. Chem. Int. Ed.  1998,  37:  2046 

<A NAME="RB04911ST-16D">16d</A> Klapars A. Antilla JC. Huang X. Buchwald SL.
J. Am. Chem. Soc.  2001,  123:  7727 

<A NAME="RB04911ST-16E">16e</A> Klapars A. Huang X. Buchwald SL. J. Am. Chem. Soc.  2002,  124:  7421 

<A NAME="RB04911ST-16F">16f</A> Jiang L. Job GE. Klapars A. Stephen L. Buchwald SL. Org. Lett.  2003,  5:  20 

<A NAME="RB04911ST-16G">16g</A> Mallesham B. Rajesh BM. Reddy PR. Srinivas D. Trehan S. Org. Lett.  2003,  5:  7 

<A NAME="RB04911ST-17A">17a</A> Klapars A. Antilla JC. Huang X. Buchwald SL. J. Am. Chem. Soc.  2001,  123:  7727 

<A NAME="RB04911ST-17B">17b</A> Wolter M. Klapars A. Buchwald SL. Org. Lett.  2001,  3:  23 

<A NAME="RB04911ST-17C">17c</A> Kwong FY. Klapars A. Buchwald SL. Org. Lett.  2002,  4:  4 

<A NAME="RB04911ST-17D">17d</A> Martin R. Larsen HC. Ana Cuenca A. Buchwald SL. Org. Lett.  2007,  9:  17 

<A NAME="RB04911ST-17E">17e</A> Zheng N. Buchwald SL. Org. Lett.  2007,  9:  23 

<A NAME="RB04911ST-18A">18a</A> Guo L. Li B. Huang W. Pei G. Ma D. Synlett  2008,  1833 

<A NAME="RB04911ST-18B">18b</A> Ma D. Cai Q. Org. Lett.  2003,  5:  21 

For reviews on Cu-catalyzed C-N bond-forming reactions:

<A NAME="RB04911ST-19A">19a</A> Beletskaya IP. Cheprakov AV. Coord. Chem. Rev.  2004,  248:  2337 

<A NAME="RB04911ST-19B">19b</A> Ley SV. Thomas AW. Angew. Chem. Int. Ed.  2003,  42:  5400 

<A NAME="RB04911ST-19C">19c</A> Kunz K. Scholz U. Ganzer D. Synlett  2003,  2428 

<A NAME="RB04911ST-20">20</A> Beccalli EM. Broggini G. Paladino G. Zoni C. Tetrahedron  2005,  61:  61 

For some of our recent synthesis of heterocycles, see:

<A NAME="RB04911ST-21A">21a</A> Majumdar KC. Ray K. Ganai S. Tetrahedron Lett.  2010,  51:  1736 

<A NAME="RB04911ST-21B">21b</A> Majumdar KC. Ray K. Ganai S. Ghosh T. Synthesis  2010,  858 

<A NAME="RB04911ST-21C">21c</A> Majumdar KC. Ray K. Ganai S. Synthesis  2010,  2101 

<A NAME="RB04911ST-21D">21d</A> Majumdar KC. Ray K. Ganai S. Synlett  2010,  2122 

<A NAME="RB04911ST-21E">21e</A> Majumdar KC. Ponra S. Ganai S. Synlett  2010,  2575 

<A NAME="RB04911ST-21F">21f</A> Majumdar KC. Cahttopadhyay B. Samanta S. Tetrahedron Lett.  2009,  50:  3178 

<A NAME="RB04911ST-21G">21g</A> Majumdar KC. Samanta S. Chattopadhyay B. Tetrahedron Lett.  2009,  50:  4866 

<A NAME="RB04911ST-21H">21h</A> Majumdar KC. De R N. Chattopadhyay B. Roy B. Synlett  2009,  2083 

<A NAME="RB04911ST-21I">21i</A> Majumdar KC. Ansary I. Sinha B. Chattopadhyay B. Synthesis  2009,  3593 

<A NAME="RB04911ST-21J">21j</A> Majumdar KC. Mondal S. De N. Synlett  2008,  2851 

<A NAME="RB04911ST-22">22</A>

Procedure for the Synthesis of Compound 8a
To a solution of the compound 6a (160 mg, 0.50 mmol) in DMSO (5 mL), CuI (9.5 mg, 0.05 mmol), l-proline (12 mg, 0.1 mmol), and Cs₂CO₃ (325.8 mg, 1 mmol) were added. The reaction mixture was stirred at 120 ˚C for 8 h. The reaction was monitored by TLC. After completion, the reaction mixture was diluted with CH₂Cl₂ (3 × 15 mL) and washed with H₂O (3 × 15 mL). The combined organic layer was filtered and dried over Na₂SO₄. The solvent was distilled off, and the crude product was purified by column chromatography over silica gel (60-120 mesh) using PE and EtOAc (4:1) as eluent to give a white solid product 8a. Analytical Data of Compound 8a
Yield 72%, solid; mp 156-158 ˚C. IR (KBr): ν_max = 1609, 3328 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 2.28 (s, 3 H), 3.51 (s, 3 H), 5.27 (s, 1 H), 6.72 (s, 1 H), 6.77 (d, 1 H, J = 7.6 Hz), 6.91 (s, 1 H), 7.01-7.07 (m, 2 H), 7.29 (d, 1 H, J = 8.8 Hz), 7.87 (d, 1 H, J = 7.6 Hz). ^¹³C NMR (100 MHz, CDCl₃): δ = 20.61, 38.06, 118.39, 120.73, 122.59, 123.04, 124.85, 124.97, 132.45, 132.90, 135.76, 143.01, 150.60, 168.57. HRMS: m/z calcd for C₁₅H₁₄N₂O [M⁺ + Na]: 261.1004; found: 261.1029.

<A NAME="RB04911ST-23">23</A>

Procedure for the Synthesis of Compound 8e To a solution of the compound 7f (0.50 mmol) in DMSO-H₂O (4:1; 5 mL), CuI (0.05 mmol), l-proline (0.1 mmol), and DABCO (3 mmol) were added. The reaction mixture was stirred at 120 ˚C for 9 h. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with CH₂Cl₂ (3 × 15 mL) and washed with H₂O (3 × 15 mL). The combined organic layer was filtered and dried over Na₂SO₄. The solvent was distilled off, and the crude product was purified by column chromatography over silica gel (60-120 mesh) using PE and EtOAc (1:1) as eluent to give a white solid product 8e.
Analytical Data of Compound 8e Yield 88%, white solid; mp 240-242 ˚C. IR (KBr): ν_max = 1162, 1600, 1644, 1659 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 1.35 (t, 3 H, J = 6.4 Hz), 2.43 (s, 3 H), 3.28 (q, 1 H, J = 6.4 Hz), 3.46 (q, 1 H, J = 6.8 Hz), 3.71 (s, 3 H), 6.90 (d, 1 H, J = 10.0 Hz), 7.24 (s, 2 H), 7.35-7.50 (m, 5 H), 7.56-7.61 (m, 2 H), 7.78 (d, 1 H, J = 7.6 Hz), 8.42 (d, 1 H, J = 9.6 Hz). ^¹³C NMR (100 MHz, CDCl₃): δ = 14.14, 21.65, 29.79, 45.92, 115.58, 120.57, 123.65, 124.12, 127.39, 128.90, 129.29, 129.84, 132.22, 132.56, 132.83, 134.77, 135.74, 136.41, 138.52, 141.10, 144.42, 161.54, 165.17. HRMS: m/z calcd for C₂₆H₂₃N₃O₄S [M⁺ + Na]: 496.1307; found: 496.1311.

<A NAME="RB04911ST-24">24</A> Zhang H. Cai Q. Ma D. J. Org. Chem.  2005,  70:  5164