Practical One-Pot Double Functionalizations of Proline

Abstract

Solubilization of proline as the triethylammonium salt allows N-protection (as the Boc, Cbz or Moc derivative) and subsequent esterification or amidation of the carboxy terminus to be performed in an efficient one-pot fashion. Based on this concept, highly practical protocols were developed to prepare a series of proline derivatives (including Pro-Ser dipetides, Weinreb amides and N-protected proline esters), which are important intermediates, for instance, for the synthesis of proline-derived peptides, chiral reagents and catalysts for asymmetric synthesis.

proline derivatives - peptides - carbamates - N-protecting groups - solvent effects - coupling reagents

References

Selected references:

<A NAME="RT56010SS-1A">1a</A> Gentilucci L. Cerisoli L. De Marco R. Tolomelli A. Tetrahedron Lett.  2010,  51:  2576 

<A NAME="RT56010SS-1B">1b</A> Dai N. Etzkorn FA. J. Am. Chem. Soc.  2009,  131:  13728 

<A NAME="RT56010SS-1C">1c</A> Chiba K. Sugihara M. Yoshida K. Mikami Y. Kim S. Tetrahedron  2009,  65:  8014 

<A NAME="RT56010SS-1D">1d</A> Heiser U, Niestroj AJ, and Schulz I. inventors; WO Patent 007415  A2. 

<A NAME="RT56010SS-1E">1e</A> Sun H. Martin C. Kesselring D. Keller R. Moeller KD. J. Am. Chem. Soc.  2006,  128:  13761 

<A NAME="RT56010SS-1F">1f</A> Pfeifer ME. Linden A. Robinson JA. Helv. Chim. Acta  1997,  80:  1513 

<A NAME="RT56010SS-1G">1g</A> Falorni M. Porcheddu A. Giacomelli G. Tetrahedron: Asymmetry  1996,  7:  1999 

Selected references:

<A NAME="RT56010SS-2A">2a</A> Woodin KS. Jamison TF. J. Org. Chem.  2007,  72:  7451 

<A NAME="RT56010SS-2B">2b</A> Ni Y. Zhao G. Ding Y. J. Chem. Soc., Perkin Trans. 1  2000,  3264 

<A NAME="RT56010SS-2C">2c</A> Sibi M. Christensen J. J. Org. Chem.  1999,  64:  6434 

<A NAME="RT56010SS-2D">2d</A> Céliméne C. Dhimane H. Lhommet G. Tetrahedron  1998,  54:  10457 

See, for example:

<A NAME="RT56010SS-3A">3a</A> Chena Z. Ye T. New J. Chem.  2006,  30:  518 

<A NAME="RT56010SS-3B">3b</A> Yokokawa F. Sameshima H. In Y. Minoura K. Ishida T. Shioiri T. Tetrahedron  2002,  58:  8127 

<A NAME="RT56010SS-4A">4a</A> Corey EJ. Bakshi RK. Shibata S. J. Am. Chem. Soc.  1987,  109:  5551 

<A NAME="RT56010SS-4B">4b</A> Corey EJ. Helal CJ. Angew. Chem. Int. Ed.  1998,  37:  1986 

<A NAME="RT56010SS-4C">4c</A> Stemmler RT. Synlett  2007,  997 

<A NAME="RT56010SS-5">5</A> Corey EJ. Angew. Chem. Int. Ed.  2002,  41:  1650 

For recent reviews, see:

<A NAME="RT56010SS-6A">6a</A> Bertelsen S. Jørgensen KA. Chem. Soc. Rev.  2009,  38:  2178 

<A NAME="RT56010SS-6B">6b</A> MacMillan DWC. Nature (London)  2008,  455:  304 

<A NAME="RT56010SS-6C">6c</A> Dondoni A. Massi A. Angew. Chem. Int. Ed.  2008,  47:  4638 

<A NAME="RT56010SS-7">7</A> Zaminer J. Brockmann C. Huy P. Opitz R. Reuter C. Beyermann M. Freund C. Müller M. Oschkinat H. Kühne R. Schmalz H.-G. Angew. Chem. Int. Ed.  2010,  49:  7111 

<A NAME="RT56010SS-8A">8a</A> Anderson GW. McGregor AC. J. Am. Chem. Soc.  1957,  79:  6180 

<A NAME="RT56010SS-8B">8b</A> Kaname M. Mashige H. Yoshifuji S. Chem. Pharm. Bull.  2001,  49:  531 

<A NAME="RT56010SS-9A">9a</A> Takeda K. Akiyama A. Nakamura H. Takizawa Y. Mizuno Y. Takayanagi H. Harigaya Y. Synthesis  1994,  1063 

<A NAME="RT56010SS-9B">9b</A> Held I. Von Den Hoff P. Stephenson DS. Zipse H. Adv. Synth. Catal.  2008,  350:  1891 

<A NAME="RT56010SS-10">10</A> Hayashi Y. Matsuzawa M. Yamaguchi J. Yonehara S. Matsumoto Y. Shoji M. Hashizume D. Koshino H. Angew. Chem. Int. Ed.  2006,  45:  4593 

To the best of our knowledge, the only one-step protocols for the synthesis of compounds of type 2 described so far lead to N-Moc (or N-Eoc)-protected proline esters; see:

<A NAME="RT56010SS-11A">11a</A> Kanth JVB. Perlasamy M. Synth. Commun.  1995,  25:  1523 

<A NAME="RT56010SS-11B">11b</A> Oliveira DF. Miranda PCML. Correia Carlos RD. J. Org. Chem.  1999,  64:  6646 

<A NAME="RT56010SS-12">12</A>

Protic solvents such as water or alcohols are rival nucleophiles.

<A NAME="RT56010SS-13">13</A>

The esterification step requires DMAP as a nucleophilic catalyst, which activates both Boc₂O (to react with the carboxylate) and the resulting mixed anhydride (to react with t-BuOH); see ref. 9a.

<A NAME="RT56010SS-14">14</A> Zhou ZH. Tang YL. Li KY. Liu B. Tang CC. Heteroat. Chem.  2003,  14:  603 

<A NAME="RT56010SS-15A">15a</A> König W. Geiger R. Chem. Ber.  1970,  103:  788 

<A NAME="RT56010SS-15B">15b</A> Deng S. Taunton J. Org. Lett.  2005,  7:  299 

<A NAME="RT56010SS-16">16</A>

DCC-mediated coupling of 10 in the presence of DMAP led to the isolation of 2e in only 48% yield, along with 21% of the tert-butyl ester 2b resulting from the reaction of 7a with tert-butyl alcohol.

<A NAME="RT56010SS-17A">17a</A> Ho G.-J. Mathre DJ. J. Org. Chem.  1995,  60:  2271 

<A NAME="RT56010SS-17B">17b</A> Soloshonok VA. Ueki H. Jiang C. Cai C. Hruby VJ. Helv. Chim. Acta  2002,  85:  3616 

<A NAME="RT56010SS-18">18</A> Kim S. Lee JI. Kim YC. J. Org. Chem.  1985,  50:  560 

<A NAME="RT56010SS-19">19</A>

Methyl ester 2j was synthesized in 93% yield with K₂CO₃ instead of Et₃N.^¹¹b

<A NAME="RT56010SS-20">20</A>

For example, the yield of tert-butyl ester 2k (Table  [²] , entry 9) dropped to 42% when MocCl was added undiluted.

<A NAME="RT56010SS-21">21</A> Mayr H. Ofial AR. Angew. Chem. Int. Ed.  2006,  45:  1844 ; and references cited therein

<A NAME="RT56010SS-22">22</A> Beckett RP. Davies SG. Mortlock AA. Tetrahedron: Asymmetry  1992,  3:  123 

<A NAME="RT56010SS-23">23</A> Gibson FS. Bergmeier SC. Rapoport H. J. Org. Chem.  1994,  59:  3216 

<A NAME="RT56010SS-24">24</A> Anderson GW. Callahan FM. J. Am. Chem. Soc.  1960,  82:  3359 

<A NAME="RT56010SS-25">25</A> Irie K. Ishida A. Nakamura T. Oh-ishi T. Chem. Pharm. Bull.  1984,  32:  2126