The Baylis-Hillman Reaction with Chiral α-Amino Aldehydes under Racemization-Free Conditions

Abstract

The Baylis-Hillman reaction with chiral α-amino aldehydes has been revisited. The reaction carried out under the influence of ultrasound avoids the aldehyde racemization almost completely, providing useful chiral substrates which can be used as starting materials for the synthesis of natural products. To demonstrate the synthetic applicability of these adducts, the easy preparation of a bicyclic lactam with an indolizidinic skeleton was accomplished.

aldehydes - amino aldehydes - alkaloids - ring closure - stereoselectivity

References and Notes

For comprehensive reviews on the Baylis-Hillman reaction, see:

<A NAME="RS10105ST-1A">1a</A> Basavaiah D. Rao AJ. Satyanarayama T. Chem. Rev.  2003,  103:  811 

<A NAME="RS10105ST-1B">1b</A> Almeida WP. Coelho F. Quim. Nova  2000,  23:  98 ; Chem. Abstr. 2000, 132, 236562e

<A NAME="RS10105ST-1C">1c</A> Ciganek E. Org. React.  1997,  51:  201 

<A NAME="RS10105ST-1D">1d</A> Basavaiah D. Rao PD. Hyma RS. Tetrahedron  1996,  52:  8001 

For some new insights about the mechanism of the Baylis-Hillman reaction, see:

<A NAME="RS10105ST-1E">1e</A> Santos LS. Pavam CH. Almeida WP. Coelho F. Eberlin MN. Angew. Chem. Int. Ed.  2004,  43:  4330 

<A NAME="RS10105ST-1F">1f</A> Price KE. Broadwater SJ. Walker BJ. McQuade DT. J. Org. Chem.  2005,  70:  3980 

<A NAME="RS10105ST-1G">1g</A> Aggarwal VK. Fulford SY. Llyod-Jones GC. Angew. Chem. Int. Ed.  2005,  44:  1706 

For some recent examples concerning the utilization of Baylis-Hillman adduct as substrate for the synthesis of natural products and drugs, see:

<A NAME="RS10105ST-2A">2a</A> Mateus CR. Coelho F. J. Braz. Chem. Soc.  2005,  16:  386-396  ; available free-of-charge at http://jbcs.sbq.org.br/online/2005/vol16_n3A/11-238-04.pdf

<A NAME="RS10105ST-2B">2b</A> Porto RS. Coelho F. Synth. Commun.  2004,  34:  3037 

<A NAME="RS10105ST-2C">2c</A> Feltrin MA. Almeida WP. Synth. Commun.  2003,  33:  1141 

<A NAME="RS10105ST-2D">2d</A> Rossi RC. Coelho F. Tetrahedron Lett.  2002,  42:  2797 

<A NAME="RS10105ST-2E">2e</A> Mateus CR. Feltrin MP. Costa AM. Coelho F. Almeida WP. Tetrahedron  2001,  57:  6901 

<A NAME="RS10105ST-2F">2f</A> Iwabuchi Y. Furukawa M. Esumi T. Hatakeyama S. Chem. Commun.  2001,  2030 

<A NAME="RS10105ST-2G">2g</A> Iwabuchi Y. Sugihara T. Esumi T. Hatakeyama S. Tetrahedron Lett.  2001,  42:  7867 

<A NAME="RS10105ST-2H">2h</A> Masunari A. Trazzi G. Ishida E. Coelho F. Almeida WP. Synth. Commun.  2001,  31:  2100 

<A NAME="RS10105ST-3A">3a</A> Roos G. Manickum T. Synth. Commun.  1991,  21:  2269 

<A NAME="RS10105ST-3B">3b</A> Drewes SE. Khan AA. Rowland K. Synth. Commun.  1993,  23:  183 

<A NAME="RS10105ST-3C">3c</A> Ameer F. Drewes SE. Houston-McMillan MS. Kaye PT. S. Afr. J. Chem.  1986,  39:  57 ; Chem. Abstr. 1986, 105, 114809

<A NAME="RS10105ST-4">4</A> Manickum T. Roos GHP. S. Afr. J. Chem.  1994,  47:  1 ; Chem. Abstr. 1994, 122, 159795

<A NAME="RS10105ST-5A">5a</A> Alcaide B. Almendros P. Aragoncillo C. J. Org. Chem.  2001,  66:  1612 

<A NAME="RS10105ST-5B">5b</A> Alcaide B. Almendros P. Aragoncillo C. Rodríguez-Acebes R. J. Org. Chem.  2004,  69:  826 ; and references cited therein

<A NAME="RS10105ST-6">6</A> Nayak SK. Thijs L. Zwanenburg B. Tetrahedron Lett.  1999,  40:  981 

<A NAME="RS10105ST-7">7</A> Haner R. Olano B. Seebach D. Helv. Chim. Acta  1987,  70:  1676 

<A NAME="RS10105ST-8">8</A> Almeida WP. Coelho F. Tetrahedron Lett.  2003,  44:  937 

<A NAME="RS10105ST-9">9</A> Einhorn J. Einhorn C. Luche J.-L. Synlett  1991,  37 

<A NAME="RS10105ST-10A">10a</A> Bodanszky M. Bodanszky A. In The Practice of Peptide Synthesis   2nd ed.:  Springer-Verlag; Berlin/Heidelberg: 1994. 

<A NAME="RS10105ST-10B">10b</A> Yoshifuji S. Tanaka K. Kawai T. Nitta Y. Chem. Pharm. Bull.  1986,  34:  3873 

<A NAME="RS10105ST-10C">10c</A> Esquerra J. Pedregal C. Rubio A. Yruretagoyena B. Escribano A. Sanchez-Ferrando F. Tetrahedron  1993,  49:  8665 

<A NAME="RS10105ST-11A">11a</A> Gobiowske A. Jurczak J. Jacobsson U. Tetrahedron  1987,  43:  3063 

<A NAME="RS10105ST-11B">11b</A> Luly JR. Dellaria JF. Palttner JJ. Soderquist JL. Yi N. J. Org. Chem.  1987,  52:  1487 

<A NAME="RS10105ST-11C">11c</A> Fehrentz JA. Castro B. Synthesis  1983,  676 

<A NAME="RS10105ST-11D">11d</A> Saari WS. Fisher TE. Synthesis  1990,  453 

<A NAME="RS10105ST-11E">11e</A> Kemp DJ. J. Org. Chem.  1986,  3921 

<A NAME="RS10105ST-12">12</A> D’Aniello F. Taddei M. J. Org. Chem.  1992,  57:  5247 

<A NAME="RS10105ST-13">13</A> Romo D. Meyer SD. Johnson DD. Schreiber SL. J. Am. Chem. Soc.  1993,  115:  7906 

<A NAME="RS10105ST-14">14</A> For a study concerning the optical stability of amino aldehydes that are N-Boc protected, see: Myers AG. Zhong BY. Movassaghi M. Kung DW. Lanman BA. Kwon S. Tetrahedron Lett.  2000,  41:  1359 ; and references cited therein

For the anti relationship, an increment up to 1.9% was expected, see:

<A NAME="RS10105ST-15A">15a</A> Schuch CM. Pilli RA. Tetrahedron: Asymmetry  2000,  11:  753 

For some examples describing the utilization of oxazolidines as a tool for the determination of relative stereochemistry, see:

<A NAME="RS10105ST-15B">15b</A> Dias LC. Ferreira AA. Diaz G. Synlett  2002,  1845 

<A NAME="RS10105ST-15C">15c</A> Dias LC. Meira PRR. Synlett  2000,  37 

<A NAME="RS10105ST-15D">15d</A> Benedetti F. Miertus S. Norbedo S. Tossi A. Zlatoidzky P. J. Org. Chem.  1997,  62:  9348 

<A NAME="RS10105ST-15E">15e</A> Vara Prasad JVN. Rich DH. Tetrahedron Lett.  1991,  32:  5857 

<A NAME="RS10105ST-16A">16a</A> Cherest M. Felkin H. Prudent N. Tetrahedron Lett.  1968,  18:  2199 

<A NAME="RS10105ST-16B">16b</A> Ahn NT. Top. Curr. Chem.  1980,  88:  144 

<A NAME="RS10105ST-16C">16c</A> Hoffmann RW. Chem. Rev.  1989,  89:  1841 

For some examples in which chiral bicyclic lactam were used as advanced substrates for the synthesis of alkaloids see:

<A NAME="RS10105ST-17A">17a</A> Muroni D. Saba A. Culeddu N. Tetrahedron: Asymmetry  2004,  15:  2609 

<A NAME="RS10105ST-17B">17b</A> Dieter RK. Lu K. J. Org. Chem.  2002,  67:  847 

<A NAME="RS10105ST-17C">17c</A> Sibi MP. Christensen JW. J. Org. Chem.  1999,  64:  6434 

<A NAME="RS10105ST-17D">17d</A> Lim SH. Ma S. Beak P. J. Org. Chem.  2001,  66:  9056 

<A NAME="RS10105ST-18">18</A> Clive DLJ. Yu M. Li Z. Chem. Commun.  2005,  906