Download PDF
Synlett 2008(5): 739-744  
DOI: 10.1055/s-2008-1042765
CLUSTER
© Georg Thieme Verlag Stuttgart · New York

An Unexpected Reversal of Diastereoselectivity in the [4+3]-Cycloaddition Reaction of Nitrogen-Stabilized Oxyallyl Cations with Methyl 2-Furoate

Jennifer E. Antoline, Richard P. Hsung*
Division of Pharmaceutical Sciences and Department of Chemistry, University of Wisconsin-Madison, 777 Highland Avenue, Rennebohm Hall, Madison, WI 53705, USA
Fax: +1(608)2625345; e-Mail: rhsung@wisc.edu;
Further Information

Publication History

Received 27 November 2007
Publication Date:
26 February 2008 (online)

    Permissions and Reprints All articles of this category

Abstract

An unexpected reversal of diastereoselectivity in the [4+3] cycloaddition of methyl 2-fuorate with nitrogen-stabilized oxyallyl cations derived from epoxidation of chiral allenamides is described here. This intriguing reversal in favor of the endo-II cycloaddition pathway is likely a result of minimizing the dipole interaction between the oxyallyl cation and ester carbonyl of methyl 2-fuorate.

Key words

stereoselective [4+3] cycloadditions - allenamides - nitrogen-stabilized oxyallyl cations - endo-I versus endo-II selectivity - dipole interaction

    References and Notes

  • For excellent reviews on heteroatom-substituted oxyallyl cations, see:
  • 1a Harmata M. Adv. Synth. Catal.  2006,  348:  2297 
    Google Scholar
  • 1b Harmata M. Recent Res. Dev. Org. Chem.  1997,  1:  523 
    Google Scholar
  • For general reviews, see:
  • 2a Hartung IV. Hoffmann HMR. Angew. Chem. Int. Ed.  2004,  43:  1934 
    Google Scholar
  • 2b Harmata M. Rashatasakhon P. Tetrahedron  2003,  59:  2371 
    Google Scholar
  • 2c Harmata M. Acc. Chem. Res.  2001,  34:  595 
    Google Scholar
  • Also see:
  • 2d Davies HML. In Advances in Cycloaddition   Vol. 5:  Harmata M. JAI; Greenwich: 1998.  p.119 
    Google Scholar
  • 2e West FG. In Advances in Cycloaddition   Vol. 4:  Lautens M. JAI; Greenwich: 1997.  p.1 
    Google Scholar
  • 2f Rigby JH. Pigge FC. Org. React.  1997,  51:  351 
    Google Scholar
  • 2g Harmata M. Tetrahedron  1997,  53:  6235 
    Google Scholar
  • For some examples of other heteroatom-substituted oxyallyl cations, see:
  • 3a Harmata M. Wacharasindhu S. Org. Lett.  2005,  7:  2563 
    CrossrefGoogle Scholar
  • 3b Sáez JA. Arnó M. Domingo LR. Tetrahedron  2005,  61:  7538 
    CrossrefGoogle Scholar
  • 3c Harmata M. Kahraman M. Adenu G. Barnes CL. Heterocycles  2004,  62:  583 
    CrossrefGoogle Scholar
  • 3d Sáez JA. Arnó M. Domingo LR. Org. Lett.  2003,  5:  4117 
    CrossrefGoogle Scholar
  • 3e Funk RL. Aungst RA. Org. Lett.  2001,  3:  3553 
    CrossrefGoogle Scholar
  • 3f Harmata M. Sharma U. Org. Lett.  2000,  2:  2703 
    CrossrefGoogle Scholar
  • 3g Lee K. Cha JK. Org. Lett.  1999,  1:  523 
    CrossrefGoogle Scholar
  • 3h Masuya K. Domon K. Tanino K. Kuwajima I. J. Am. Chem. Soc.  1998,  120:  1724 
    CrossrefGoogle Scholar
  • 3i Harmata M. Elomari S. Barnes CJ. J. Am. Chem. Soc.  1996,  118:  2860 ; and references cited within
    CrossrefGoogle Scholar
  • For recent stereoselective attempts, see:
  • 4a Davies HML. Dai X. J. Am. Chem. Soc.  2004,  126:  2693 
    Google Scholar
  • 4b Prié G. Prévost N. Twin H. Fernandes SA. Hayes JF. Shipman M. Angew. Chem. Int. Ed.  2004,  43:  6517 
    Google Scholar
  • 4c Grainger RS. Owoare RB. Tisselli P. Steed JW. J. Org. Chem.  2003,  68:  7899 
    Google Scholar
  • 4d Montanã A. M., Grima P. M.; Tetrahedron; 2002, 58: 4769
    Google Scholar
  • 4e Beck H. Stark CBW. Hoffman HMR. Org. Lett.  2000,  2:  883 ; and reference 11 cited within
    Google Scholar
  • 4f Harmata M. Rashatasakhon P. Synlett  2000,  1419 
    Google Scholar
  • 4g Cho SY. Lee JC. Cha JK. J. Org. Chem.  1999,  64:  3394 
    Google Scholar
  • 4h Harmata M. Jones DE. Kahraman M. Sharma U. Barnes CL. Tetrahedron Lett.  1999,  40:  1831 
    Google Scholar
  • 4i Kende AS. Huang H. Tetrahedron Lett.  1997,  38:  3353 
    Google Scholar
  • 4j Harmata M. Jones DE. J. Org. Chem.  1997,  62:  4885 
    Google Scholar
  • 5 Harmata M. Ghosh SK. Hong X. Wacharasindu S. Kirchhoefer P. J. Am. Chem. Soc.  2003,  125:  2058 
    CrossrefGoogle Scholar
  • 6 For a recent account that constitutes an enantioselective formal [4+3] cycloaddition, see: Dai X. Davies HML. Adv. Synth. Catal.  2006,  348:  2449 
    CrossrefGoogle Scholar
  • 7 For a compendium on the chemistry of allenes, see: Krause N. Hashmi ASK. Modern Allene Chemistry   Vol. 1 and 2:  Wiley-VCH; Weinheim: 2004. 
    Google Scholar
  • For reviews on the chemistry and synthesis of allenamides, see:
  • 8a Hsung RP. Wei L.-L. Xiong H. Acc. Chem. Res.  2003,  36:  773 
    CrossrefPubMedGoogle Scholar
  • 8b Tracey MR. Hsung RP. Antoline J. Kurtz KCM. Shen L. Slafer BW. Zhang Y. In Science of Synthesis, Houben-Weyl Methods of Molecular Transformations   Weinreb SM. Thieme; Stuttgart: 2005.  Chap. 21.4.
    CrossrefPubMedGoogle Scholar
  • For recent reports on the allenamide chemistry, see:
  • 9a Watanabe T. Oishi S. Fuji N. Ohno H. Org. Lett.  2007,  9  in press
    CrossrefGoogle Scholar
  • 9b Hyland CJT. Hegedus LS. J. Org. Chem.  2006,  71:  8658 
    CrossrefGoogle Scholar
  • 9c Parthasarathy K. Jeganmohan M. Cheng C.-H. Org. Lett.  2006,  8:  621 
    CrossrefGoogle Scholar
  • 9d Fenández I. Monterde MI. Plumet J. Tetrahedron Lett.  2005,  46:  6029 
    CrossrefGoogle Scholar
  • 9e de los Rios C. Hegedus LS. J. Org. Chem.  2005,  70:  6541 
    CrossrefGoogle Scholar
  • 9f Alouane N. Bernaud F. Marrot J. Vrancken E. Mangeney P. Org. Lett.  2005,  7:  5797 
    CrossrefGoogle Scholar
  • 9g Hyland CJT. Hegedus LS. J. Org. Chem.  2005,  70:  8628 
    CrossrefGoogle Scholar
  • For our recent efforts, see:
  • 10a Song Z. Hsung RP. Lu T. Lohse AG. J. Org. Chem.  2007,  72: in press
    Google Scholar
  • 10b Song Z. Hsung RP. Org. Lett.  2007,  9:  2199 
    Google Scholar
  • 10c Huang J. Ianni JC. Antoline JE. Hsung RP. Kozlowski MC. Org. Lett.  2006,  8:  1565 
    Google Scholar
  • 10d Berry CR. Hsung RP. Antoline JE. Petersen ME. Rameshkumar C. Nielson JA. J. Org. Chem.  2005,  70:  4038 
    Google Scholar
  • 10e Shen L. Hsung RP. Zhang Y. Antoline JE. Zhang X. Org. Lett.  2005,  7:  3081 
    Google Scholar
  • For leading examples of nitrogen-stabilized oxyallyl cations in [4+3] cycloadditions, see:
  • 11a MaGee DI. Godineau E. Thornton PD. Walters MA. Sponholtz DJ. Eur. J. Org. Chem.  2006,  3667 
    CrossrefGoogle Scholar
  • 11b Myers AG. Barbay JK. Org. Lett.  2001,  3:  425 
    CrossrefGoogle Scholar
  • 11c Sung MJ. Lee HI. Chong Y. Cha JK. Org. Lett.  1999,  1:  2017 
    CrossrefGoogle Scholar
  • 11d Walters MA. Arcand HR. J. Org. Chem.  1996,  61:  1478 
    CrossrefGoogle Scholar
  • 11e Walters MA. Arcand HR. Lawrie DJ. Tetrahedron Lett.  1995,  36:  23 
    CrossrefGoogle Scholar
  • 11f Dennis N. Ibrahim B. Katritzky AR. J. Chem. Soc., Perkin Trans. 1  1976,  2307 
    CrossrefGoogle Scholar
  • 12 Rameshkumar C. Xiong H. Tracey MR. Berry CR. Yao LJ. Hsung RP. J. Org. Chem.  2002,  67:  1339 
    CrossrefGoogle Scholar
  • 13 For our asymmetric [4+3] cycloaddition, see: Xiong H. Hsung RP. Berry CR. Rameshkumar C. J. Am. Chem. Soc.  2001,  123:  7174 
    Google Scholar
  • 14 Antoline JE. Hsung RP. Huang J. Song Z. Li G. Org. Lett.  2007,  9:  1275 
    CrossrefGoogle Scholar
  • 15 Xiong H. Huang J. Ghosh SK. Hsung RP. J. Am. Chem. Soc.  2003,  125:  12694 
    CrossrefGoogle Scholar
  • Rameshkumar C. Hsung RP. Angew. Chem. Int. Ed.  2004,  43:  615 
    Google Scholar
  • For a very recent account on intramolecular [4+3] cycloadditions of allenyl dienes employing PtCl2 as a catalyst, see:
  • 16b Trillo B. López F. Gulías M. Castedo L. Mascareñas LJ. Angew. Chem. Int. Ed.   2008,  47:  951 
    Google Scholar
  • For a review, see:
  • 17a Hoffmann HMR. Angew. Chem., Int. Ed. Engl.  1973,  12:  819 ; Angew. Chem. 1973, 85, 877
    CrossrefGoogle Scholar
  • 17b Also see: Hoffmann HMR. Joy DR. J. Chem. Soc. B  1968,  1182 
    CrossrefGoogle Scholar
  • 18 Huang J. Hsung RP. J. Am. Chem. Soc.  2005,  127:  50 
    CrossrefGoogle Scholar
  • 22 Sibi MP. Porter NA. Acc. Chem. Res.  1999,  32:  163 
    CrossrefGoogle Scholar
19

General Procedure for the [4+3] Cycloaddition To a solution of the allenamide in CH2Cl2 [0.10 M] was added the appropriate furan (3.0-6.0 equiv) and 4 Å pulverized MS (0.50 g). The reaction solution was cooled to -78 °C, and ZnCl2 (2.0 equiv, 1.0 M in Et2O) was added. Then, DMDO in acetone (4.0-6.0 equiv) was added as a chilled solution (at -78 °C) via syringe pump over 3-4 h. The syringe pump was cooled by dry ice the entire addition time. After the addition the reaction mixture was stirred for another 14 h. The reaction was then quenched with sat. aq NaHCO3, filtered through Celite®, concentrated in vacuo, partitioned with CH2Cl2, extracted [4 × 20 mL], dried over Na2SO4, and concentrated in vacuo. The crude residue was purified via silica gel column chromatography (gradient eluent: 10-75% EtOAc in hexane).

20

In our intermolecular nitrogen stabilized oxyallyl cation [4+3] cycloadditions, for electron-rich furans, while some of the low-yielding reactions are due to decomposition of the epoxidized starting allenamide, most are due to noticeable competing epoxidation of the respective electron-rich furan. This issue can be circumvented using 6-10 equiv of furan, leading to higher yields (see references 13 and 18). For electron-deficient furans, the competing furan-epoxidation is not a problem, and thus, we can employ a much lower loading. However, we have found that reactions with electron-deficient furans such as those shown in this study are overall slower and more sluggish. This is consistent with the fact that oxyallyl cation based [4+3] cycloadditions proceed in an electrophilic manner.

21

Analytical Data
Compound 4b: R f = 0.10 (50% EtOAc in hexane); [α]D 23
-86.2 (c 0.10, CH2Cl2). 1H NMR (500 MHz, CDCl3): δ = 2.53 (d, 1 H, J = 16.2 Hz), 2.83 (dd, 1 H, J = 5.4, 16.0 Hz), 3.67 (s, 3 H), 3.96 (s, 1 H), 4.18 (t, 1 H, J = 8.1 Hz), 4.66 (t, 1 H, J = 8.0 Hz), 4.82 (t, 1 H, J = 9.2 Hz), 5.06 (dd, 1 H, J = 5.2, 1.6 Hz), 6.28 (dd, 1 H, J = 6.0, 2.0 Hz), 7.15 (d, 1 H, J = 6.4 Hz), 7.28-7.46 (m, 5 H). 13C NMR (75 MHz, CDCl3): δ = 14.5, 21.3, 45.4, 53.1, 64.4, 68.6, 70.6, 79.1, 89.3, 128.4, 129.5, 129.4, 140.2, 167.4, 171.4, 199.4 cm-1. IR (thin film): 3280 (w), 2911 (w), 1766 (s) cm-1. MS (APCI): m/e (%) = 344.1 (90) [M + H]+.
Compound 4b-D: R f = 0.10 (50% EtOAc in hexane); [α]D 23 -132.6 (c 0.30, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 2.52 (d, 1 H, J = 16.8 Hz), 2.84 (dd, 1 H, J = 5.2, 16.4 Hz), 3.65 (s, 3 H), 3.96 (s, 0.35 H), 4.20 (dd, 1 H, J = 8.8, 6.8 Hz), 4.74 (t, 1 H, J = 8.4 Hz), 4.96 (t, 1 H, J = 7.6 Hz), 5.05 (m, 1 H) 6.28 (dd, 1 H, J = 1.6, 5.6 Hz), 7.11 (d, 1 H, J = 6.0 Hz), 7.23-7.44 (m, 5 H). 13C NMR (125 MHz, CDCl3): δ = 29.5, 45.4, 53.0, 64.3, 70.5, 79.1, 89.2, 128.4, 129.5, 129.9, 132.6, 133.6, 136.4, 158.3, 167.3, 199.4. IR (thin film): 3300 (w), 2910 (w), 1748 (s) cm-1. MS (APCI): m/e (%) = 345.1 (60) [M + H]+.
Compound 5b: R f = 0.23 (50% EtOAc in hexane); [α]D 23
-72.8 (c 6.4, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 2.51 (d, 1 H, J = 16.0 Hz), 2.84 (dd, 1 H, J = 16.4, 6.0 Hz), 4.00 (s, 1 H), 4.17 (t, 1 H, J = 8.8 Hz), 4.39 (ddt, 1 H, J = 13.2, 5.6, 1.3 Hz), 4.66 (t, 1 H J = 8.4 Hz), 4.69 (m, 1 H), 4.83 (t, 1 H, J = 8.4 Hz), 5.07 (dd, 1 H, J = 5.6, 1.9 Hz), 5.27 (ddd, 1 H, J = 10.4, 2.5, 1.3 Hz) 5.34 (ddd, 1 H, J = 17.2, 3.0, 1.4 Hz) 5.84 (ddt, 1 H, J = 6.0, 11.6, 16.4), 6.28 (dd, 1 H, J = 6.0, 2.0 Hz), 6.72 (d, 1 H, 6.0 Hz), 7.28-7.41 (m, 5 H). 13C NMR (125 MHz, CDCl3): δ = 45.4, 64.4, 66.7, 68.6, 70.6, 79.1, 89.3, 119.6, 128.5, 129.5, 129.9, 131.3, 132.8, 133.7, 136.5, 158.2, 166.8, 199.5. IR (thin film): 3629 (w), 3445 (w), 3065 (w), 1764 (s), 1726 (s) cm-1. MS (APCI):
m/e (%) = 370.1 (100) [M + H]+.
Compound 9b: R f = 0.13 (50% EtOAc in hexane); [α]D 23
-78.5 (c 2.0, CH2Cl2). 1H NMR (500 MHz, CDCl3): δ = 2.52 (d, 1 H, J = 16.5 Hz), 2.79 (dd, 1 H, J = 17.0, 5.5 Hz), 3.84 (s, 1 H), 4.26 (dd, 1 H, J = 9.0, 7.0 Hz), 4.77 (t, 1 H, J = 8.5 Hz), 5.08 (d, 1 H, J = 4.0 Hz), 5.16 (t, 1 H, J = 8.0 Hz) 6.34 (br d, 1 H, J = 4.5 Hz), 6.37 (dd, 0.5 H, J = 6.0, 2.0 Hz), 6.61 (d, 0.5 H, J = 6.0 Hz), 7.41-7.48 (m, 5 H). 13C NMR (125 MHz, CDCl3): δ = 29.6, 44.8, 45.3, 65.1, 71.4, 79.3, 79.7, 128.2, 128.8, 129.9, 130.2, 130.6, 132.8, 135.7, 197.2. IR (thin film): 3509 (w), 3110 (w), 2897 (w), 1755 (s), 1729 (s) cm-1. MS (APCI): m/e (%) = 311.1 (10) [M + H]+.
Compounds 10a,b: R f = 0.31 (50% EtOAc in hexane). 1H NMR (400 MHz, CDCl3): δ = 1.31 (s, 3 H), 1.43 (s, 3 H), 2.43 (d, 1 H, J = 16.5 Hz), 2.49 (d, 1 H, J = 15.5 Hz), 2.65 (d, 1 H, J = 15.5 Hz), 2.75-2.82 (br, 1 H), 4.08 (dd, 1 H, J = 8.0, 4.4 Hz), 4.19 (dd, 1 H, J = 8.4, 8.4 Hz), 4.74 (t, 2 H, J = 8.8 Hz), 4.82 (dd, 1 H, J = 9.2, 4.4 Hz), 4.87 (dd, 2 H, J = 8.4, 4.8 Hz), 4.92 (d, 2 H, J = 4.4 Hz), 4.99 (dd, 1 H, J = 5.6, 0.8 Hz), 5.92 (d, 1 H, J = 6.0 Hz), 6.06 (br, 1.8 H), 6.13 (dd, 0.50 H, J = 6.4, 2.0 Hz), 6.45 (d, 0.20 H, J = 5.6 Hz), 6.48 (dd, 0.50 H, J = 4.4, 1.0 Hz), 7.27-7.44 (m, 10 H). IR (thin film): 3425 (w), 2927 (m), 1751 (s), 1719 (s) cm-1. MS (APCI): m/e (%) = 300.1 (100) [M + H]+.

23

When the reaction was carried out in the absence of ZnCl2, it was very sluggish and inconclusive.