Register      Login
Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
Shopping Cart: ( empty )
You are here: Home > Journals > CH > CH14531
RESEARCH ARTICLE
Contents Vol 68(4)

Epoxidation of trans-4-Aminocyclohex-2-en-1-ol Derivatives: Competition of Hydroxy-Directed and Ammonium-Directed Pathways*

Méabh B. Brennan A , Stephen G. Davies A B , Ai M. Fletcher A , James A. Lee A , Paul M. Roberts A , Angela J. Russell A and James E. Thomson A
+ Author Affiliations
- Author Affiliations

A Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.

B Corresponding author. Email: steve.davies@chem.ox.ac.uk

Australian Journal of Chemistry 68(4) 610-621 https://doi.org/10.1071/CH14531
Submitted: 30 August 2014  Accepted: 22 October 2014   Published: 25 February 2015

Abstract

N-Substituted trans-4-aminocyclohex-2-en-1-ols undergo epoxidation upon treatment with Cl3CCO2H followed by meta-chloroperbenzoic acid (m-CPBA) via competitive pathways resulting from hydrogen-bonding delivery by both the hydroxy group and the in situ formed ammonium ion. The absence of epoxide ring-opening in these reactions renders these substrates a unique platform for analysing the effect of the two competing directing groups on the rate of the epoxidation reaction: the diastereoisomeric ratio of the epoxide products is also the ratio of the rate constants describing the competing epoxidation processes (the group with the higher directing ability dominating the stereochemical course of the reaction). Analysis of the diastereoisomeric epoxide mixtures obtained from these reactions allowed the following order of directing group ability to be defined: NHBn >> NMeBn > OH > NBn2. The large difference in rate between the secondary and tertiary amino groups is consistent with superior directing ability of the former due to the presence of two hydrogen-bond donor sites on the secondary ammonium ion and/or an increased conformational flexibility to adopt an optimum geometry. The rate of an ammonium-directed epoxidation proceeds ~10 times slower in the presence of an allylic hydroxy group than in its absence, consistent with the presence of the additional, inductively electron-withdrawing heteroatom abating the nucleophilicity of the olefin. The relative rate of the hydroxy-directed epoxidation process in the presence of a more sterically demanding ammonium substituent is greater than that in the presence of a less sterically demanding one: this effect is attributed to an increased bias for the half-chair conformer in which the bulky ammonium substituent and, hence, the hydroxy group occupy pseudo-equatorial sites, thus allowing the latter to direct the reaction more efficiently.


References

[1]  N. Prileschajew, Ber. Dtsch. Chem. Ges. 1909, 42, 4811.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaD28XnvFc%3D&md5=4aefd4ff6ad7d60544080a9dfb90ad16CAS |

[2]  H. B. Henbest, R. A. L. Wilson, J. Chem. Soc. 1957, 1958.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaG2sXosFGhsw%3D%3D&md5=74ae5c7f77185efdde957d4151b334d7CAS |

[3]  P. Chamberlain, M. L. Roberts, G. H. Whitham, J. Chem. Soc. B 1970, 1374.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE3cXkvFygsrw%3D&md5=1a6f6aa4092e0bc80a8d280e1db0432cCAS |

[4]  P. D. Bartlett, Rec. Chem. Prog. 1950, 11, 47.
         | 1:CAS:528:DyaG3cXjsFWitg%3D%3D&md5=39c8b8aaeaa1ceef45cdb64ff37ae371CAS |

[5]  A. H. Hoveyda, D. A. Evans, G. C. Fu, Chem. Rev. 1993, 93, 1307.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXktVyisLg%3D&md5=04ced8a1aaa6a28e2cd58c940670d01eCAS |

[6]  K. B. Sharpless, T. R. Verhoeven, Aldrichim Acta 1979, 12, 63.
         | 1:CAS:528:DyaL3cXnsFensw%3D%3D&md5=86e7620be324bd3e136c8a06f8710f10CAS |

[7]  For a discussion and molecular modelling calculations, see: M. Freccero, R. Gandolfi, M. Sarzi-Amadè, A. Rastelli, J. Org. Chem. 2000, 65, 8948.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXotlKgt7o%3D&md5=d83a73b48654824380c45fb066db7964CAS | 11149837PubMed |

[8]  B. A. McKittrick, B. Ganem, Tetrahedron Lett. 1985, 26, 4895.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL28Xkslymtrg%3D&md5=53e1955c20055411a7886c83309347ccCAS |

[9]  D. K. Fukushima, M. Smulowitz, J. S. Liang, G. J. Lukacs, J. Org. Chem. 1969, 34, 2702.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF1MXkvFWkt7w%3D&md5=ae0385c4e6978cf8e8c294eb61f83e38CAS |

[10]  P. O’Brien, A. C. Childs, G. J. Ensor, C. L. Hill, J. P. Kirby, M. J. Dearden, S. J. Oxenford, C. M. Rosser, Org. Lett. 2003, 5, 4955.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXptlOlu78%3D&md5=5c74098d6f1f7f22368b17b73b66bfd8CAS | 14682738PubMed |

[11]  P. Kocovsky, I. Stary, J. Org. Chem. 1990, 55, 3236.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3cXitFOgtrg%3D&md5=c76c3522a3820bd02dcbb67d48cd1f7cCAS |

[12]  W. J. Brouillette, A. Saeed, A. Abuelyaman, T. L. Hutchison, P. E. Wolkowicz, J. B. McMillin, J. Org. Chem. 1994, 59, 4297.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXitFSgtA%3D%3D&md5=c3d49798e644e60f87af1f3539cbbe88CAS |

[13]  L. Goodman, S. Winstein, R. Boschan, J. Am. Chem. Soc. 1958, 80, 4312.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaG1MXitlehuw%3D%3D&md5=1b2b85ff5a0cafd7037a4d4bd870c64aCAS |

[14]  G. Lukacs, D. K. Fukushima, J. Org. Chem. 1969, 34, 2707.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF1MXkvFWkt78%3D&md5=bf7bb943c1902f5cfe265ccfee45c06dCAS | 5803817PubMed |

[15]  R. Vince, S. Daluge, J. Med. Chem. 1974, 17, 578.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE2cXltFGitrc%3D&md5=913166e38e5f6bc014f2ed3d41e27de8CAS | 4598021PubMed |

[16]  J. E. Baldwin, R. M. Adlington, J. Chondrogianni, M. S. Edenborough, J. W. Keeping, C. B. Ziegler, J. Chem. Soc., Chem. Commun. 1985, 816.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2MXmtFSnu7o%3D&md5=a50fa83f8a57f601bedd094d306590f1CAS |

[17]  G. Asensio, R. Mello, C. Boix-Bernardini, M. E. Gonzàlez-Núñez, G. Castellano, J. Org. Chem. 1995, 60, 3692.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXlvFWrur4%3D&md5=56e97538b967e944972cc5efb825e184CAS |

[18]  A. S. Edwards, R. A. J. Wybrow, C. Johstone, H. Adams, J. P. A. Harrity, Chem. Commun. 2002, 1542.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XkvFKmtr4%3D&md5=56bf93434a30f6cdb00de1c71045583eCAS |

[19]  V. K. Aggarwal, G. Y. Fang, Chem. Commun. 2005, 3448.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXlslOqtb0%3D&md5=c61f9c5830d6d981667f2f12a312947aCAS |

[20]  C. Aciro, T. D. W. Claridge, S. G. Davies, P. M. Roberts, A. J. Russell, J. E. Thomson, Org. Biomol. Chem. 2008, 6, 3751.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXht1Wkur3M&md5=d4dce6a665af1168802e0eb907f7a8c5CAS | 18843405PubMed |

[21]  C. Aciro, S. G. Davies, P. M. Roberts, A. J. Russell, A. D. Smith, J. E. Thomson, Org. Biomol. Chem. 2008, 6, 3762.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXht1Wkur3N&md5=aa224d2442fd9212031661458bc8383cCAS | 18843406PubMed |

[22]  C. W. Bond, A. J. Cresswell, S. G. Davies, W. Kurosawa, J. A. Lee, A. M. Fletcher, P. M. Roberts, A. J. Russell, A. D. Smith, J. E. Thomson, J. Org. Chem. 2009, 74, 6735.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXpt1Gqsb8%3D&md5=dcc8db5891e2b89582b8c864bea83a77CAS | 19642691PubMed |

[23]  M. B. Brennan, T. D. W. Claridge, R. G. Compton, S. G. Davies, A. M. Fletcher, M. C. Henstridge, D. S. Hewings, W. Kurosawa, J. A. Lee, P. M. Roberts, A. K. Schoonen, J. E. Thomson, J. Org. Chem. 2012, 77, 7241.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtVygu7fK&md5=4f33e34f8d94b5881269bb252fceb27dCAS | 22827448PubMed |

[24]  (a) For reviews, see: W. Kurosawa, P. M. Roberts, S. G. Davies, Yuki Gosei Kagaku Kyokaishi (J. Synth. Org. Chem. Jpn.) 2010, 68, 1295.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsFOgtbnM&md5=edeabebface541f8eeef3b02e1a16995CAS |
      (b) S. G. Davies, A. M. Fletcher, J. E. Thomson, Org. Biomol. Chem. 2014, 12, 4544.
         | Crossref | GoogleScholarGoogle Scholar |

[25]  S. K. Bagal, S. G. Davies, A. M. Fletcher, J. A. Lee, P. M. Roberts, P. M. Scott, J. E. Thomson, Tetrahedron Lett. 2011, 52, 2216.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXkt1ykt7Y%3D&md5=a4b7d13f5410a18b2a5d628af47ed207CAS |

[26]  K. Csatayová, S. G. Davies, J. G. Ford, J. A. Lee, P. M. Roberts, J. E. Thomson, J. Org. Chem. 2013, 78, 12397.
         | Crossref | GoogleScholarGoogle Scholar | 24256461PubMed |

[27]  S. K. Bagal, S. G. Davies, J. A. Lee, P. M. Roberts, A. J. Russell, P. M. Scott, J. E. Thomson, Org. Lett. 2010, 12, 136.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsFShs7%2FM&md5=14a94c9d4b51c2fbeaca952635e6ed0fCAS | 19954199PubMed |

[28]  S. K. Bagal, S. G. Davies, J. A. Lee, P. M. Roberts, P. M. Scott, J. E. Thomson, J. Org. Chem. 2010, 75, 8133.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtlOnsLvN&md5=daf3ef97b6296b47a9493b5eb6343fd9CAS | 21043433PubMed |

[29]  A. J. Cresswell, S. G. Davies, J. A. Lee, M. J. Morris, P. M. Roberts, J. E. Thomson, J. Org. Chem. 2012, 77, 7262.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtVyns7fK&md5=01b6e72a7778e90a211417396a482c8eCAS | 22827338PubMed |

[30]  See pp. 191–193 in M. J. Pilling, P. W. Seakins, Reaction Kinetics 1996 (Oxford University Press: New York, NY).

[31]  J.-E. Bäckvall, J.-E. Nyström, R. E. Nordberg, J. Am. Chem. Soc. 1985, 107, 3676.
         | Crossref | GoogleScholarGoogle Scholar |

[32]  J. Tsuji, H. Takahashi, M. Morikawa, Tetrahedron Lett. 1965, 6, 4387.
         | Crossref | GoogleScholarGoogle Scholar |

[33]  B. M. Trost, D. L. Van Vranken, Chem. Rev. 1996, 96, 395.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XjsVOiuw%3D%3D&md5=eb2828277603cff841d363fd86ce45f0CAS | 11848758PubMed |

[34]  The corresponding cis-amino alcohols 30–32 were also observed in the 1H NMR spectra of the crude reaction mixtures.

[35]  The preparation of both cis-30 and trans-36 has been previously reported; see: R. G. P. Gatti, A. L. E. Larsson, J.-E. Bäckvall, J. Chem. Soc., Perkin Trans. 1 1997, 577.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXhvFWitLo%3D&md5=9c48eb2aec439fba156be22da2dee2f1CAS |

[36]  Full crystallographic data have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication numbers CCDC 1021308 (32) and 1021309 (53). Copies of these data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

[37]  O. Mitsunobu, M. Yamada, T. Mukaiyama, Bull. Chem. Soc. Jpn. 1967, 40, 935.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF2sXksVegtrc%3D&md5=d2a9602547d34dcf61d9b02a06580fc3CAS |

[38]  O. Mitsunobu, Y. Yamada, Bull. Chem. Soc. Jpn. 1967, 40, 2380.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF1cXht1Citw%3D%3D&md5=165e3e6e7ee270fb80b6df3ae14b035fCAS |

[39]  K. C. Kumara Swamy, N. N. Bhuvan Kumar, E. Balaraman, K. V. P. Pavan Kumar, Chem. Rev. 2009, 109, 2551.
         | Crossref | GoogleScholarGoogle Scholar |

[40]  This method to determine the amount of Cl3CCO2H (or any Brønsted acid) required to protect the nitrogen atom against oxidation has been shown to give excellent agreement with results derived from experiment (see Ref. [20]).

[41]  R. E. Parker, N. S. Isaacs, Chem. Rev. 1959, 59, 737.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaG1MXhtVGit7o%3D&md5=d5966f053711778c8445306578d73d00CAS |

[42]  J. K. Addy, R. E. Parker, J. Chem. Soc. 1963, 915.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF3sXlt1Grug%3D%3D&md5=910c71909babb26106e4c600a8278420CAS |

[43]  D. Swern, Org. React. 1953, VII, 392.

[44]  P. W. Betteridge, J. R. Carruthers, R. I. Cooper, C. K. Prout, D. J. Watkin, J. Appl. Cryst. 2003, 36, 1487.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXptFekt78%3D&md5=8b033fc538a9dd99e4736dbd95b8272eCAS |