Asymmetric Organocatalytic Synthesis of cis-Substituted ­Dihydrobenzofuranols via Intramolecular Aldol Reactions

Abstract

The diastereo- and enantioselective synthesis of 3-hydroxy 2,3-dihydrobenzofurans via an intramolecular cis-selective aldol reaction employing proline-type organocatalysts is described enabling a new entry to coumarine natural products.

organocatalysis - aldol reaction - asymmetric synthesis - proline - dihydrobenzofuran

References and Notes

<A NAME="RG31106ST-1">1</A> Khanum SA. Shashikanth S. Sudha BS. Sriharsha SN. J. Chem. Res., Synop.  2003,  463 

<A NAME="RG31106ST-2">2</A> Zou Y. Lobera M. Snider BB. J. Org. Chem.  2005,  70:  1761 

<A NAME="RG31106ST-3A">3a</A> Lemmich J. Havelund S. Thastrup O. Phytochemistry  1983,  22:  553 

<A NAME="RG31106ST-3B">3b</A> Vilegas W. Pozetti GL. Vilegas JHY. J. Nat. Prod.  1993,  56:  416 

<A NAME="RG31106ST-3C">3c</A> Jiménez B. Grande MC. Anaya J. Torres P. Grande M. Phytochemistry  2000,  53:  1025 

<A NAME="RG31106ST-3D">3d</A> Appendino G. Bianchi F. Bader A. Campagnuolo C. Fattorusso E. Taglialatela-Scafati O. Blanco-Molina M. Macho A. Fiebich BL. Bremmer P. Heinrich M. Ballero M. Muñoz E. J. Nat. Prod.  2004,  67:  532 

<A NAME="RG31106ST-4A">4a</A> Seshadri TR. ; Vishwapaul; Indian J. Chem.  1971,  9:  418 

<A NAME="RG31106ST-4B">4b</A> Gupta BD. Banerjee SK. Handa KL. Phytochemistry  1976,  15:  576 

<A NAME="RG31106ST-4C">4c</A> Shimomura H. Sashida Y. Nakata H. Kawasaki J. Ito Y. Phytochemistry  1982,  21:  2213 

<A NAME="RG31106ST-5A">5a</A> Asymmetric Organocatalysis   Berkessel A. Gröger H. Wiley-VCH; Weinheim: 2005. 

<A NAME="RG31106ST-5B">5b</A> Dalko PI. Moisan L. Angew. Chem. Int. Ed.  2004,  43:  5138 

<A NAME="RG31106ST-5C">5c</A> Seayad J. List B. Org. Biomol. Chem.  2005,  3:  719 

<A NAME="RG31106ST-6A">6a</A> Mahrwald R. Chem. Rev.  1999,  99:  1095 

<A NAME="RG31106ST-6B">6b</A> Modern Aldol Reactions   Mahrwald R. Wiley-VCH; Weinheim: 2004. 

<A NAME="RG31106ST-6C">6c</A> Palomo C. Oiarbide M. Garcia JM. Chem. Soc. Rev.  2004,  33:  65 

<A NAME="RG31106ST-7A">7a</A> List B. Lerner RA. Barbas CF. J. Am. Chem. Soc.  2000,  122:  2395 

<A NAME="RG31106ST-7B">7b</A> Notz W. List B. J. Am. Chem. Soc.  2000,  122:  7386 

Reviews:

<A NAME="RG31106ST-8A">8a</A> List B. Synlett  2001,  1675 

<A NAME="RG31106ST-8B">8b</A> List B. Tetrahedron  2002,  58:  5573 

<A NAME="RG31106ST-8C">8c</A> List B. Acc. Chem. Res.  2004,  37:  548 

<A NAME="RG31106ST-8D">8d</A> Notz W. Tanake F. Barbas CF. Acc. Chem. Res.  2004,  37:  580 

<A NAME="RG31106ST-9A">9a</A> Northrup AB. MacMillan DWC. J. Am. Chem. Soc.  2002,  124:  6798 

<A NAME="RG31106ST-9B">9b</A> Córdova A. Notz W. Barbas CF. J. Org. Chem.  2002,  67:  301 

<A NAME="RG31106ST-9C">9c</A> Storer AI. MacMillan DWC. Tetrahedron  2004,  60:  7705 

<A NAME="RG31106ST-10A">10a</A> Hajos ZG, and Parrish DR. inventors; DE  2102623. 

<A NAME="RG31106ST-10B">10b</A> Eder U, Sauer GR, and Wiechert R. inventors; DE  2014757. 

<A NAME="RG31106ST-10C">10c</A> Eder U. Sauer G. Wiechert R. Angew. Chem., Int. Ed. Engl.  1971,  10:  496 

<A NAME="RG31106ST-10D">10d</A> Hajos ZG. Parrish DR. J. Org. Chem.  1974,  39:  1615 

Reviews:

<A NAME="RG31106ST-11A">11a</A> Cohen N. Acc. Chem. Res.  1976,  9:  412 

<A NAME="RG31106ST-11B">11b</A> Drauz K. Kleemann A. Martens J. Angew. Chem., Int. Ed. Engl.  1982,  21:  584 

<A NAME="RG31106ST-11C">11c</A> Dalko PI. Angew. Chem. Int. Ed.  2001,  40:  3726 

<A NAME="RG31106ST-11D">11d</A> Jarvo ER. Miller SJ. Tetrahedron  2002,  58:  2481 

<A NAME="RG31106ST-11E">11e</A> List B. Tetrahedron  2002,  58:  5572 

<A NAME="RG31106ST-12A">12a</A> Pidathala C. Hoang L. Vignola N. List B. Angew. Chem. Int. Ed.  2003,  42:  2785 

<A NAME="RG31106ST-12B">12b</A> Itagaki N. Kimura M. Sugahara T. Iwabuchi Y. Org. Lett.  2005,  7:  4185 

<A NAME="RG31106ST-13A">13a</A> Enders D. Kallfass U. Angew. Chem. Int. Ed.  2002,  41:  1743 

<A NAME="RG31106ST-13B">13b</A> Enders D. Niemeier O. Synlett  2004,  2111 

<A NAME="RG31106ST-13C">13c</A> Enders D. Niemeier O. Balensiefer T. Angew. Chem. Int. Ed.  2006,  45:  1463 

Reviews:

<A NAME="RG31106ST-14A">14a</A> Enders D. Balensiefer T. Acc. Chem. Res.  2004,  37:  534 

<A NAME="RG31106ST-14B">14b</A> Christmann M. Angew. Chem. Int. Ed.  2005,  44:  2632 

<A NAME="RG31106ST-14C">14c</A> Enders D. Balensiefer T. Niemeier O. Christmann M. Nucleophilic N-Heterocyclic Carbenes in Asymmetric Synthesis, In Enantioselective Organocatalysis - Reactions and Experimental Procedures   Dalko PI. Wiley-VCH; Weinheim: 2006.  p.in press 

<A NAME="RG31106ST-15">15</A> Enders D. Niemeier O. Raabe G. Synlett  2006,  2431 

<A NAME="RG31106ST-16A">16a</A> Enders D. Seki A. Synlett  2002,  26 

<A NAME="RG31106ST-16B">16b</A> Enders D. Grondal C. Angew. Chem. Int. Ed.  2005,  44:  1210 

<A NAME="RG31106ST-16C">16c</A> Enders D. Grondal C. Vrettou M. Raabe G. Angew. Chem. Int. Ed.  2005,  44:  4079 

<A NAME="RG31106ST-16D">16d</A> Enders D. Hüttl MRM. Synlett  2005,  991 

<A NAME="RG31106ST-16E">16e</A> Grondal C. Enders D. Tetrahedron  2006,  62:  329 

<A NAME="RG31106ST-16F">16f</A> Enders D. Paleček J. Grondal C. Chem. Commun.  2006,  655 

<A NAME="RG31106ST-16G">16g</A> Enders D. Vrettou M. Synthesis  2006,  2155 

<A NAME="RG31106ST-16H">16h</A> Enders D. Hüttl MRM. Grondal C. Raabe G. Nature (London)  2006,  441:  861 

<A NAME="RG31106ST-17">17</A>

Aldehyde ketones of type 4 can be synthesized by reaction of the corresponding salicyl aldehydes, K₂CO₃ and α-bromo ketones in DMF at r.t.

<A NAME="RG31106ST-18">18</A>

CCDC 617162 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

<A NAME="RG31106ST-19A">19a</A> Bahmanyar S. Houk KN. J. Am. Chem. Soc.  2001,  123:  11273 

<A NAME="RG31106ST-19B">19b</A> Bahmanyar S. Houk KN. J. Am. Chem. Soc.  2001,  123:  12911 

<A NAME="RG31106ST-19C">19c</A> Hoang L. Bahmanyar S. Houk KN. List B. J. Am. Chem. Soc.  2003,  125:  16 

<A NAME="RG31106ST-19D">19d</A> Bahmanyar S. Houk KN. Martin HJ. List B. J. Am. Chem. Soc.  2003,  125:  2475 

<A NAME="RG31106ST-19E">19e</A> List B. Hoang L. Martin HJ. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  5839 

<A NAME="RG31106ST-20">20</A>

All new compounds were fully characterized (IR, NMR, MS, elemental analysis, optical rotation, melting point).
Asymmetric Organocatalytic Intramolecular cis -Aldol Reaction to 5b - Typical Procedure.
To a suspension of (S)-proline (17.3 mg, 0.15 mmol, 30 mol%) in DMF (0.5 mL) was added the aldehyde-ketone 4b (96 mg, 0.5 mmol) and stirred at r.t. for 24 h. The mixture was quenched with a pH 7 buffer solution, extracted with Et₂O (3 ×) and dried over MgSO₄. The solvent was evaporated and the crude product was purified by flash chromatography on silica gel (Et₂O-n-pentane, 1:2) to yield 5b (71 mg, 74%) as a colorless solid; mp. 106 °C; de 88% (99% after recrystallization, determined by GC); ee 77% [99% after recrystallization, determined by chiral stationary phase HPLC (Daicel Chiralpak IA)]; [α]_D ²³ -149.5 (c 1.7, CHCl₃). IR (KBr): 3363, 2971, 2927, 1720, 1601, 1469, 1394, 1311, 1237, 1166, 1024, 981, 939, 847, 748, 634, 490 cm^-1. ¹H NMR (400 MHz, CDCl₃, TMS): δ = 1.09 (t, 3 H, J = 7.3 Hz, CH₃), 2.58 (s, 1 H, OH), 2.63 (dq, 1 H, J = 7.2, 18.7 Hz, CHH), 2.80 (dq, 1 H, J = 7.2, 18.7 Hz, CHH), 4.98 (d, 1 H, J = 6.6 Hz, CH), 5.54 (d, 1 H, J = 6.6 Hz, CH), 6.95-6.97 (m, 1 H, ArH), 6.98-7.01 (m, 1 H, ArH), 7.29-7.33 (m, 1 H, ArH), 7.40-7.42 (m, 1 H, ArH). ¹³C NMR (100 MHz, CDCl₃): d = 6.7 (CH₃), 34.1 (CH₂), 73.0, 89.9, 110.6, 121.6, 125.7 (CH), 126.6 (C), 131.0 (CH), 159.3 (C), 208.7 (CO). MS (EI): m/z (%) 192 (25) [M⁺], 121 (7), 119 (9), 118 (100), 107 (7), 79 (10), 77 (11), 57 (13). Anal. Calcd for C₁₁H₁₂O₃: C, 68.74; H, 6.29. Found: C, 68.96; H, 6.65.