Using the 9-BBN Group as a Transient Protective Group for the Functionalization of Reactive Chains of α-Amino Acids

In a recent article¹ we presented the use of 9-BBN as a transient protection for the side chain of α-amino acids. This work is an extension of the pioneering work of Fields et al.² who first disclosed the use of 9-BBN as a protective group for the functionalization of the side chain of α-amino acids. Even though the formation of boron complexes between α-amino acids and boron reagents had been known for a while,³ it is the work of Fields that must be recognized as the starting point of the extensive use of this technology for the protection/deprotection of the α-amino and carboxy group amino acids under mild conditions, allowing further transformations on the functionalities present on the side chains of these molecules. Following the report of Fields, several examples of its use, including our work, has been reported in the literature. In order to acknowledge this work, we would like to add some references which were involuntarily missed during the writing process of our manuscript.

For instance, Rokita⁴ used 9-BBN to form a complex with tyrosine which allowed him to prepare 3-ethynyl-tyrosine using a palladium-mediated coupling. In 2004, Kihlberg⁵ prepared hydroxylysine and galactosylated hydroxylysine forming the complex between 9-BBN and (5R)-5-hydroxylysine, followed by some manipulations of the side chain. In the same year, Fields and Graupner^6a reported the use of B-BBN for the preparation of the ornithine-based natural products pyridazocidin, octicidin, and N-(phosphonoacetyl)-l-ornithine (PALO). Dussault^6b also reported the preparation of PALO using the same approach. Zhao⁷ reported the preparation of Fmoc-Lys(Boc)-OH [i.e., N ⁶-[(1,1-dimethylethoxy)carbonyl]-N ²-[(9H-fluoren-9-ylmethoxy)carbonyl]-l-lysine] via the 9-BBN technology. The use of oxazaborolidinones, derived from α-amino acids and 9-BBN, was successfully used for the preparation of γ-hydroxy-d-valine (d-Hyv),⁸ which later was used in solid-phase peptide synthesis. On the other hand, Clement⁹ successfully employed the technology introduced by Fields² to prepare derivatives of l-arginine, l-citrulline and l-ornithine. Most recently, Lewis¹⁰ exploited the use of 9-BBN as a protective group for α-aminoa cids in the preparation of catalytically active metallopeptides.

In conclusion, the introduction of 9-BBN as a transient protective group for α-amino acids must be credited to Fields et al.,² and the references discussed herein must be considered for future work on this area.

References

(1) Sánchez, A.; Calderón, E.; Vázquez, A. Synthesis 2013, 45, 1364.

(2) Dent III, W. H.; Erickson, W. R.; Fields, S. C.; Parker, M. H.; Tromiczak, E. G. Org. Lett. 2002, 4, 1249.

(3) (a) Skoog, I. H. J. Org. Chem. 1964, 29, 492. (b) Baum, G. J. Organomet. Chem. 1970, 22, 269. (c) Koster, R.; Rothgery, E. Liebigs Ann. Chem. 1974, 112. (d) Miller, N. E. Inorg. Chem. 1974, 13, 1459. (e) Halstrom, J.; Nebelin, E.; Pedersen, E. J. J. Chem. Res. 1978, 80. (f) Brown, H. C.; Gupta, A. K. J. Organomet. Chem. 1988, 34, 73.

(4) Walker IV, W. H.; Rokita, S. E. J. Org. Chem. 2003, 68, 1563.

(5) Syed, B. M.; Gustafsson, T.; Kihlberg, Tetrahedron 2004, 60, 5571.

(6) (a) Graupner, P. R.; Fields, S. 36th Central Regional Meeting of the American Chemical Society, Indianapolis, IN, United States, June 2–4 (2004), INV-404. (b) Johnson, B. M.; Steadman, R.; Dussault, P. H. 44th Midwest Regional Meeting of the American Chemical Society, Iowa City, IA, United States, October 21–24 (2009), MWRM-349.

(7) Wang, D.; Wang, G.-C.; Lu, J.-X.; Zhao, L.-X. Chin. J. Pharmaceuticals 2006, 37, 659.

(8) Cudic, M.; Marí, F.; Fields, G. B. J. Org. Chem. 2007, 72, 5581.

(9) Schade, D.; Töpker-Lehmann, K.; Kotthaus, J.; Clement, B. J. Org. Chem. 2008, 73, 1025.

(10) Zhang, Z.; Yang, H.; Zhang, C. Lewis, J. C. Organometallics 2012, 31, 7328.

Synthesis 2013, 45, 1364.