ORGANIC
LETTERS
2005
Vol. 7, No. 19
4145-4148
Some New Aspects of the Boyer
Reaction
Rupak Chakraborty, Veronica Franz, Ghanashyam Bez, Dipali Vasadia,†
Chenchu Popuri,† and Cong-Gui Zhao*
Department of Chemistry, UniVersity of Texas at San Antonio, 6900 North Loop 1604
West, San Antonio, Texas 78249-0698
Received June 21, 2005
ABSTRACT
The reaction outcome of 2-azidoethanol and aliphatic aldehyde is found to be dependent on the catalyst and the structure of the azido alcohol.
Under the catalysis of Cu(II) triflate, the corresponding acetal is obtained. A similar reaction between 2-aryl-2-azidoethanol and aldehyde
catalyzed by BF3 yields a mixture of 3-oxazoline and 2-oxazoline. The latter reaction has been used for the preparation of 3-oxazolines in good
enantioselectivity.
The reaction of an azido compound with an aldehyde or
ketone catalyzed by a Brønsted acid or a Lewis acid, which
is generally known as the Schmidt reaction,1 may yield an
amide, a lactam, or a heterocyclic product, depending on
the structure of the azido compound and the carbonyl
compound. Through recent efforts in developing an asym-
metric version of this reaction, the Schmidt reaction has
become a new strategy for the synthesis of optically active
lactams and nitrogen-containing heterocyclic compounds.2
For example, Aube´ and co-workers have synthesized poten-
tial peptide â- and γ-turn mimics by using this method.3
Mechanistically akin to the Schmidt reaction, the Boyer
reaction refers to the reaction of 2-azidoethanol or 3-azi-
dopropanol and an aldehyde, where 2-oxazoline or dihy-
drooxazine form as the product (eq 1). This reaction was
originally studied by Boyer with H2SO4 as the catalyst, with
a very limited substrate scope;4 however, Aube´ and co-
workers demonstrated that this can be much improved by
using Lewis acids, such as BF3‚Et2O, as the catalyst.5
Recently, we accidentally found some new pathways of this
reaction when we studied the Lewis acid catalyzed ring-
† Undergraduate student.
(1) For reviews, see: (a) Wolff, H. Org. React. 1946, 3, 307-336. (b)
Fodor, G.; Nagubandi, S. Tetrahedron 1980, 36, 1279-1300. (c) Krow, G.
R. Tetrahedron 1981, 37, 1283-1307.
(2) (a) Smith, B. T.; Gracias, V.; Aube´, J. J. Org. Chem. 2000, 65, 3771-
3774. (b) Desai, P.; Schildknegt, K.; Agrios, K. A.; Mossman, C.; Milligan,
G. L.; Aube´, J. J. Am. Chem. Soc. 2000, 122, 7226-7232. (c) Wrobleski,
A.; Aube´, J. J. Org. Chem. 2001, 66, 886-889. (d) Sahasrabudhe, K.;
Gracias, V.; Furness, K.; Smith, B. T.; Katz, C. E.; Reddy, D. S.; Aube´, J.
J. Am. Chem. Soc. 2003, 125, 7914-7922. (e) Katz, C. E.; Aube´, J. J. Am.
Chem. Soc. 2003, 125, 13948-13949.
(3) (a) Reddy, D. S.; Vander Velde, D.; Aube´, J. J. Org. Chem. 2004,
69, 1716-1719. (b) Ramanathan, S. K.; Keeler, J.; Lee, H.-L.; Reddy, D.
S.; Lushinton, G.; Aube´, J. Org. Lett. 2005, 7, 1059-1062.
(4) (a) Boyer, J. H.; Hamer, J. J. Am. Chem. Soc. 1955, 77, 951-954.
(b) Boyer, J. H.; Canter, F. C.; Hamer, J.; Putney, R. K. J. Am. Chem. Soc.
1956, 78, 325-327. (c) Boyer, J. H.; Morgan, L. R., Jr. J. Org. Chem.
1959, 24, 561-562.
(5) (a) Badiang, J. G.; Aube´, J. J. Org. Chem. 1996, 61, 2484-2487.
(b) Gracias, V.; Frank, K. E.; Milligan, G. L.; Aube´, J. Tetrahedron 1997,
53, 16241-16252.
10.1021/ol051442o CCC: $30.25
© 2005 American Chemical Society
Published on Web 08/24/2005