Regioselectivity in a Highly Efficient, Microwave-Assisted Epoxide Aminolysis

Abstract

We have developed a microwave-assisted aminolysis of epoxides as an efficient method for synthesizing a number of β-amino alcohols. In most cases, including in reactions of amines with a trisubstituted epoxide, only one equivalent of amine is required to obtain good yields. The reactions are consistently regioselective for amine nucleophiles of varying strengths and for both hindered and unhindered epoxides. In some cases, this regioselectivity could be enhanced by using a polar aprotic or a non-polar solvent.

Key words

amino alcohols - amines - epoxides - regioselectivity - solvent effects

References

• 1 Bergmeier SC. Tetrahedron  2000,  56:  2561 ; and references cited therein
• 2 Lee H.-S. Kang SH. Synlett  2004,  1673 
• For reviews, see:
• 3a Ager DJ. Prakash I. Schaad DR. Chem. Rev.  1996,  96:  835 
• 3b Kolb HC. Sharpless KB. In Transition Metals for Organic Synthesis   Beller M. Bolm C. Wiley-VCH; Weinheim: 1998.  p.243 
• 3c Pu L. Yu H.-B. Chem. Rev.  2001,  101:  757 
• 3d de Parrodi AC. Juaristi E. Synlett  2006,  2699 
• For recent examples, see:
• 3e Garcia-Delgado N. Fontes M. Pericas MA. Riera A. Verdaguer X. Tetrahedron: Asymmetry  2004,  15:  2085 
• 3f Castellnou D. Sola L. Jimeno C. Fraile JM. Mayoral JA. Riera A. Pericas MA. J. Org. Chem.  2005,  70:  433 
• 3g Yamashita M. Yamada K. Tomioka K. Org. Lett.  2005,  7:  2369 
• 3h Huang J. Ianni JC. Antoline JE. Hsung RP. Kozlowski MC. Org. Lett.  2006,  8:  1565 
• 3i Schiffers I. Rantanen T. Schmidt F. Bergmans W. Zani L. Bolm C. J. Org. Chem.  2006,  71:  2320 
• Two powerful alternate methods for synthesizing β-amino alcohols are the Sharpless aminohydroxylation and the Mannich-type reaction. Aminohydroxylation:
• 4a Li G. Chang H.-T. Sharpless KB. Angew. Chem. Int. Ed.  1996,  35:  451 
• 4b O’Brien P. Angew. Chem. Int. Ed.  1999,  38:  326 
• Mannich-type reaction:
• 4c Trost BM. Terrell LR. J. Am. Chem. Soc.  2003,  125:  338 ; and references cited therein
• 5 For an excellent leading reference listing metal-mediated epoxide aminolyses published through 2001, see: Cossy J. Bellosta V. Hamoir C. Desmurs J.-R. Tetrahedron Lett.  2002,  43:  7083 
• Recent examples:
• 6a LiClO₄: Heydari A. Mehrdad M. Maleki A. Ahmadi N. Synthesis  2004,  1563 
• 6b See also: Azizi N. Saidi MR. Can. J. Chem.  2005,  83:  505 
• 6c LiBr: Chakraborti AK. Rudrawar S. Kondaskar A. Eur. J. Org. Chem.  2004,  3597 
• 6d

  LiNTf₂: see reference 5

• 6e Ca(OTf)₂: Cepanec I. Litvic M. Mikuldas H. Bartolincic A. Vinkovic V. Tetrahedron  2003,  59:  2435 
• 6f See also: Babic A. Sova M. Gobec S. Pecar S. Tetrahedron Lett.  2006,  47:  1733 
• 6g Al(OTf)₃: Fringuelli F. Pizzo F. Tortoioli S. Vaccaro L. J. Org. Chem.  2004,  69:  7745 
• 6h see also: Williams DBG. Lawton M. Tetrahedron Lett.  2006,  47:  6557 
• 6i BiCl₃: Swamy NR. Kondaji G. Nagaiah K. Synth. Commun.  2002,  32:  2307 
• 6j See also: McCluskey A. Leitch SK. Garner J. Caden CE. Hill TA. Odell LR. Stewart SG. Tetrahedron Lett.  2005,  46:  8229 
• 6k Bi(OTf)₃ and Bi(TFA)₃: Khodaei MM. Khosropour AR. Ghozati K. Tetrahedron Lett.  2004,  45:  3525 
• 6l Sc(OTf)₃: Placzek AT. Donelson JL. Trivedi R. Gibbs RA. De S K. Tetrahedron Lett.  2005,  46:  9029 
• 6m ZrCl₄: Chakraborti AK. Kondaskar A. Tetrahedron Lett.  2003,  44:  8315 
• 6n CoCl₂: Sundararajan G. Vijayakrishna K. Varghese B. Tetrahedron Lett.  2004,  45:  8253 
• 6o Cu(BF₄)₂: Kamal A. Ramu R. Azhar MA. Khanna GBR. Tetrahedron Lett.  2005,  46:  2675 
• 6p See also: Yarapathy VR. Mekala S. Rao BV. Tammishetti S. Catal. Commun.  2006,  7:  466 
• 6q ZnCl₂: Pachon LD. Gamez P. van Brussel JJM. Reedijk J. Tetrahedron Lett.  2003,  44:  6025 
• 6r Yb(OTf)₃: Shi M. Chen Y. J. Fluorine Chem.  2003,  122:  219 
• 6s K₅CoW₁₂O₄₀·3H₂O and (NH₄)₈[CeW₁₀O₃₆]·20H₂O: Mirkhani V. Tangestaninejad S. Yadollahi B. Alipanah L. Catal. Lett.  2005,  101:  93 
• 6t See also: Rafiee E. Tangestaninejad S. Habibi MH. Mirkhani V. Synth. Commun.  2004,  34:  3673 
• 6u Cyclodextrin: Surendra K. Krishnaveni NS. Rao KR. Synlett  2005,  506 
• 6v Silica gel: Kotsuki H. Hayashida K. Shimanouchi T. Nishizawa H. J. Org. Chem.  1996,  61:  984 
• 6w See also: Chakraborti A. Rudrawar S. Kondaskar A. Org. Biomol. Chem.  2004,  2:  1277 
• 6x Montmorillonite K 10: Chakraborti A. Kondaskar A. Rudrawar S. Tetrahedron  2004,  60:  9085 
• 6y [Cr(salen)Cl]: Bartoli G. Bosco M. Carlone A. Locatelli M. Massaccesi M. Melchiorre Sambri L. Org. Lett.  2004,  6:  2173 
• 6z See also: Kureshy RI. Sing S. Khan N. Abdi SHR. Agrawal S. Jasra RV. Tetrahedron: Asymmetry  2006,  17:  1638 
• 6aa Zeolite: Onaka M. Kawai M. Izumi Y. Chem. Lett.  1985,  779 
• 7a Kotsuki H. Hayakawa H. Wakao M. Shimanouchi T. Ochi M. Tetrahedron: Asymmetry  1995,  6:  2665 
• 7b Kotsuki H. Wakao M. Hayakawa H. Shimanouchi T. Shiro M. J. Org. Chem.  1996,  61:  8915 
• 7c

  See also refs 6s and 6t.

• 8 Huerta G. Contreras-Ordonez G. Alvarez-Toledano C. Santes V. Gomez E. Toscano RA. Synth. Commun.  2004,  34:  2393 
• 9a Chrisman W. Camara JN. Marcellini K. Singaram B. Goralski CT. Hasha DL. Rudolf PR. Nicholson LW. Borodychuk KK. Tetrahedron  2001,  42:  5805 
• 9b Azizi N. Saidi MR. Org. Lett.  2005,  7:  3649 
• 9c Bonollo S. Fringuelli F. Pizzo F. Vaccaro L. Green Chem.  2006,  8:  960 
• For exceptions giving S_N1 regioselectivity with better amine nucleophiles, see refs 6p and 8. For S_N2 selectivity using poorer nucleophiles, see:
• 10a Fu X.-L. Wu S.-H. Synth. Commun.  1997,  27:  1677 
• 10b

  Ref. 6s.

• 11a Chini M. Crotti P. Favero L. Macchia F. Pineschi M. Tetrahedron Lett.  1994,  35:  433 
• 11b Meguro M. Asao N. Yamamoto Y. J. Chem. Soc., Perkin Trans. 1  1994,  2598 
• 11c Van de Wedghe P. Collin J. Tetrahedron Lett.  1995,  36:  1649 
• 13 For a recent example of an alternate approach, see: Metro T.-X. Appenzeller J. Pardo DG. Cossy J. Org. Lett.  2006,  8:  3509 
• For books, see:
• 14a Microwave Assisted Organic Synthesis   Tierney JP. Lidstrom P. Blackwell; Oxford: 2005. 
• 14b Kappe O. Stadler A. Microwaves in Organic and Medicinal Chemistry   Wiley-VCH; Weinhiem: 2005. 
• 14c Microwaves in Organic Synthesis   Loupy A. Wiley-VCH; Weinheim: 2006. 
• For reviews, see:
• 15a Varma RS. Pure Appl. Chem.  2001,  73:  193 
• 15b Perreux L. Loupy A. Tetrahedron  2001,  57:  9199 
• 15c Lidstrom P. Tierney J. Wathey B. Westman J. Tetrahedron  2001,  57:  9225 
• 15d Kuhnert N. Angew. Chem. Int. Ed.  2002,  41:  1863 
• 15e Nuchter M. Ondruschka B. Bonrath W. Gum A. Green Chem.  2004,  6:  128 
• 15f Kappe O. Angew. Chem. Int. Ed.  2004,  43:  6250 
• 16a McCarthy TJ. Dence CS. Welch JM. Appl. Radiat. Isot.  1993,  44:  1129 
• 16b Gupta R. Paul S. Gupta AK. Kachroo PL. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  1997,  36:  281 
• 16c Glas H. Thiel WR. Tetrahedron Lett.  1998,  39:  5509 
• 16d Mojtahedi MM. Saidi MR. Bolourtchian M. J. Chem. Res., Synop.  1999,  128 
• 16e Sabitha G. Subba Reddy BV. Abraham S. Yadav JS. Green Chem.  1999,  3:  251 
• 16f Lindstrom UM. Olofsson B. Somfai P. Tetrahedron Lett.  1999,  40:  9273 
• 16g Lindsay KB. Pyne SG. Tetrahedron  2004,  60:  4173 
• 16h Alikhani V. Beer D. Bentley D. Bruce I. Cuenoud BM. Fairhurst RA. Gedeck P. Haberthuer S. Hayden C. Janus D. Jordan L. Lewis C. Smithies E. Wissler E. Bioorg. Med. Chem. Lett.  2004,  14:  4705 
• 16i Eshghi H. Rahimizadeh M. Shoryabi A. Synth. Commun.  2005,  35:  791 
• 16j Rodriquez-Escrich S. Popa D. Jimeno C. Vidal-Ferran A. Pericas MA. Org. Lett.  2005,  7:  3829 
• 16k Sello G. Orsini F. Bernasconi S. Di Gennaro P. Tetrahedron: Asymmetry  2006,  17:  372 
• 16l Schirok H. J. Org. Chem.  2006,  71:  5538 
• 17 Bis-alkylation is common in these reactions; see, for example, ref. 6f. For suppression of bis-alkylation in the aminolysis of styrene oxide with primary amines, see: Randall K. Atkins RK. Frazier J. Moore LL. Weigel LO. Tetrahedron Lett.  1986,  27:  2451 
• 18 For an example of solvent-dependent regioselectivity in epoxide aminolysis, see: Anderson SR. Ayers JT. DeVries KM. Ito F. Mendenhall D. Vanderplas BC. Tetrahedron: Asymmetry  1999,  10:  2655 
• 19a Overman LE. Kakimoto M. Okazaki ME. Meier GP. J. Am. Chem. Soc.  1983,  105:  6622 
• 19b Cooke A. Bennett J. McDaid E. Tetrahedron Lett.  2002,  43:  903 
• 19c

  See also refs 5 and 6n.

• For examples of regioselectivity for allylamino alcohol 11 via Pd or Rh π-allyl, see:
• 20a Fagnou K. Lautens M. Org. Lett.  2000,  2:  2319 
• 20b Trost BM. Bunt RC. Lemoine RC. Calkins TL. J. Am. Chem. Soc.  2000,  122:  5968 
• 20c Trost BM. Jiang C. Hammer K. Synthesis  2005,  3335 
• 21 Chini M. Crotti P. Macchia F. J. Org. Chem.  1991,  56:  5939 
• 22 Kotsuki H. Hayashida K. Shimanouchi T. Nishizawa H. J. Org. Chem.  1996,  61:  984 
• 23 Chamchaang W. Pinhas AR. J. Org. Chem.  1990,  55:  2943 

12

For an example of a rapid, zeolite-catalyzed aminolysis of a hindered epoxide, see ref. 6aa.