Synthesis of γ-Amino Acid Esters by 1,4-Addition of Deprotonated α-Aminonitriles and α-(Alkylideneamino)nitriles to α,β-Unsaturated Esters

Abstract

α-Aminonitriles and α-(alkylideneamino)nitriles can serve as readily available α-aminocarbanion equivalents. Their conjugate addition to α,β-unsaturated esters followed by reduction furnishes polysubstituted γ-amino acid esters in moderate to high yield.

Michael addition - reduction - α-aminonitriles - α-amino­carbanions - γ-amino acids

References

<A NAME="RT14506SS-1">1</A> Analgesics   Buschmann H. Christoph T. Friderichs E. Maul C. Sundermann B. Wiley-VCH; Weinheim: 2002. 

<A NAME="RT14506SS-2">2</A> Trabocchi A. Guarna F. Guarna A. Curr. Org. Chem.  2005,  9:  1127 

<A NAME="RT14506SS-3">3</A> Bryans JS. Wustrow DJ. Med. Res. Rev.  1999,  19:  149 

<A NAME="RT14506SS-4">4</A> Satzinger G. Arzneim.-Forsch.  1994,  44:  261 

<A NAME="RT14506SS-5">5</A> Silverman RB. Andruszkiewicz R. Nanavati SM. Taylor CP. Vartanian MG. J. Med. Chem.  1991,  34:  2295 

<A NAME="RT14506SS-6">6</A> Baldauf C. Guenther R. Hofmann H.-J. Helv. Chim. Acta  2003,  86:  2573 

<A NAME="RT14506SS-7">7</A> Seebach D. Brenner M. Rueping M. Jaun B. Chem. Eur. J.  2002,  8:  573 

<A NAME="RT14506SS-8">8</A> Seebach D. Schaeffer L. Brenner M. Hoyer D. Angew. Chem. Int. Ed.  2003,  42:  776 ; Angew. Chem. 2003, 115, 800

<A NAME="RT14506SS-9">9</A> Hintermann T. Gademann K. Jaun B. Seebach D. Helv. Chim. Acta  1998,  81:  983 

<A NAME="RT14506SS-10">10</A> Andruszkiewicz R. Silverman RB. Synthesis  1989,  953 

<A NAME="RT14506SS-11">11</A> Brenner M. Seebach D. Helv. Chim. Acta  1999,  82:  2365 

<A NAME="RT14506SS-12">12</A> Masson G. Cividino P. Py S. Vallee Y. Angew. Chem. Int. Ed.  2003,  42:  2265 ; Angew. Chem. 2003, 115, 2367

<A NAME="RT14506SS-13">13</A> Masson G. Zeghida W. Cividino P. Py S. Vallee Y. Synlett  2003,  1527 

<A NAME="RT14506SS-14">14</A> Kison C. Meyer N. Opatz T. Angew. Chem. Int. Ed.  2005,  44:  5662 ; Angew. Chem. 2005, 117, 5807

<A NAME="RT14506SS-15">15</A> von Miller W. Plöchl J. Ber. Dtsch. Chem. Ges.  1898,  31:  2718 

<A NAME="RT14506SS-16">16</A> Bodforss S. Ber. Dtsch. Chem. Ges.  1931,  64:  1111 

<A NAME="RT14506SS-17">17</A> Treibs A. Derra R. Liebigs Ann. Chem.  1954,  589:  176 

<A NAME="RT14506SS-18">18</A> Meyer N. Opatz T. Synlett  2003,  1427 

<A NAME="RT14506SS-19">19</A> Meyer N. Werner F. Opatz T. Synthesis  2005,  945 

<A NAME="RT14506SS-20A">20a</A> Albright JD. Tetrahedron  1983,  39:  3207 ; and references cited therein

For an asymmetric variant of the 1,4-addition, see:

<A NAME="RT14506SS-20B">20b</A> Enders D. Gerdes P. Kipphardt H. Angew. Chem. Int. Ed.  1990,  29:  179 ; Angew. Chem. 1990, 102, 226

<A NAME="RT14506SS-21">21</A> Mattalia J.-M. Marchi-Delapierre C. Hazimeh H. Chanon M. ARKIVOC  2006,  (iv):  90 

<A NAME="RT14506SS-22">22</A> Opatz T. Ferenc D. Org. Lett.  2006,  8:  4473 

<A NAME="RT14506SS-23">23</A> Tsuge O. Ueno K. Kanemasa S. Yorozu K. Bull. Chem. Soc. Jpn.  1987,  60:  3347 

<A NAME="RT14506SS-24">24</A> Tsuge O. Kanemasa S. Yorozu K. Ueno K. Bull. Chem. Soc. Jpn.  1987,  60:  3359 

<A NAME="RT14506SS-25">25</A> Tsuge O. Kanemasa S. Yamada T. Matsuda K. J. Org. Chem.  1987,  52:  2523 

<A NAME="RT14506SS-26">26</A> Roux-Schmitt MC. Croisat D. Seyden-Penne J. Wartski L. Cossentini M. Pol. J. Chem.  1996,  70:  325 

<A NAME="RT14506SS-27">27</A> O’Donnell MJ. Aldrichimica Acta  2001,  34:  3 

<A NAME="RT14506SS-28">28</A> Zymalkowski F. Katalytische Hydrierungen im Organisch-Chemischen Laboratorium (Sammlung Chemischer und Chemisch-Technischer Beiträge, Neue Folge Nr. 61)   Enke; Stuttgart: 1965. 

<A NAME="RT14506SS-29">29</A>

A NOESY-spectrum of trans-8d was recorded and the distance between H4 and H5 was calculated from the cross-peak volume integrals using the diastereotopic NCH₂ protons as a reference. The obtained value (3.3 Å) was in good accordance with a 3D model of the trans-isomer (3.1 Å) but not with the cis-isomer (2.4 Å). Moreover, a transient NOE experiment on trans-8d revealed a close contact between H4 and one of the benzylic protons of the substituent in 5-position. The γ-lactam obtained by cyclization of 7d was not identical with trans-8d.

<A NAME="RT14506SS-30">30</A> O’Donnell MJ. Polt RL. J. Org. Chem.  1982,  47:  2663 

<A NAME="RT14506SS-31">31</A> Meyer N. Opatz T. Synlett  2004,  787 

<A NAME="RT14506SS-32">32</A> Paventi M. Edward JT. Can. J. Chem.  1987,  65:  282 

<A NAME="RT14506SS-33">33</A> Lagriffoul P.-H. Tadros Z. Taillades J. Commeyras A. J. Chem. Soc., Perkin Trans. 2  1992,  1279 

<A NAME="RT14506SS-34">34</A> Liu J. Zhao Y. Zhou Y. Li L. Zhang H. Zhang TY. Org. Biomol. Chem.  2003,  1:  3227 

<A NAME="RT14506SS-35">35</A> Ahmad S. Doweyko LM. Dugar S. Grazier N. Ngu K. Wu SC. Yost KJ. Chen B.-C. Gougoutas JZ. DiMarco JD. Lan S.-J. Gavin BJ. Chen AY. Dorso CR. Serafino R. Kirby M. Atwal KS. J. Med. Chem.  2001,  44:  3302 

<A NAME="RT14506SS-36">36</A>

CCDC 621580 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.