Rhodium-Catalyzed Synthesis of α-Amido- and α-Carboxylic-β-Ketoesters

Abstract

The rhodium-catalyzed N-H and O-H insertion of amides and carboxylic acids with α-diazo-β-ketoesters to give different α-amido- and α-carboxylic-β-ketoesters is presented. Investigations were carried out to establish an efficient N-H and O-H insertion reaction using a range of different amides and carboxylic acids for the synthesis of intermediates e.g. for receptor antagonists. The reactions were performed under mild conditions with 1 mol% of catalyst and the products were formed in good yields.

amides - carboxylic acids - catalysis - diazo compounds - insertions - rhodium

References

See, for example:

<A NAME="RT01605SS-1A">1a</A> Robinson AJ. Stanislawski P. Mulholland D. J. Org. Chem.  2001,  66:  4148 

<A NAME="RT01605SS-1B">1b</A> Bagley MC. Buck RT. Hind SL. Moody CJ. Slawin AMZ. Synlett  1996,  825 

<A NAME="RT01605SS-1C">1c</A> Bagley MC. Buck RT. Hind SL. Moody CJ. J. Chem. Soc., Perkin Trans. 1  1998,  591 

<A NAME="RT01605SS-1D">1d</A> Noyori R. Ikeda T. Ohkuma T. Widhalm M. Kitamura M. Takaya H. Akutagawa S. Sayo N. Saito T. Taketomi T. Kumobayashi H. J. Am. Chem. Soc.  1989,  111:  9134 

<A NAME="RT01605SS-1E">1e</A> Kuwano R. Okuda S. Yoshihiko I. J. Org. Chem.  1998,  63:  3499 

<A NAME="RT01605SS-1F">1f</A> Kuwano R. Ito Y. J. Am. Chem. Soc.  1999,  121:  3236 

<A NAME="RT01605SS-2">2</A> For further reading of this antagonist, see: Norman MH. Chen N. Chen Z. Fotsch C. Hale C. Han N. Hurt R. Jenkins T. Kincaid J. Liu L. Lu Y. Moreno O. Santora VJ. Sonnenberg JD. Karbon W. J. Med. Chem.  2000,  43:  4288 

<A NAME="RT01605SS-3">3</A> Turnbull AV. Ellershaw L. Masters DJ. Birtles S. Boyer S. Carroll D. Clarkson P. Loxham SJG. McAulay P. Teague JL. Foote KM. Pease JE. Block MH. Diabetes  2002,  51:  2441 

<A NAME="RT01605SS-4">4</A> Genet JP. Pinel C. Mallart S. Juge S. Thorimbert S. Laffitte JA. Tetrahedron: Asymmetry  1991,  2:  555 

See, for example:

<A NAME="RT01605SS-5A">5a</A> Salzmann TN. Ratcliffe RW. Christensen BG. Bouffard FA. J. Am. Chem. Soc.  1980,  102:  6161 

<A NAME="RT01605SS-5B">5b</A> Melillo DG. Shinkai I. Liu T. Ryan K. Sletzinger M. Tetrahedron Lett.  1980,  21:  2783 

<A NAME="RT01605SS-6">6</A> For a comprehensive overview, see: Doyle MP. McKervey MA. Ye T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds: From Cyclopropanes to Ylides   Wiley-Interscience; New York: 1998. 

See, for example:

<A NAME="RT01605SS-7A">7a</A> Bachmann S. Fielenbach D. Jørgensen KA. Org. Biomol. Chem.  2004,  2:  3044 

<A NAME="RT01605SS-7B">7b</A> Karche NP. Jachak SM. Dhavale DD. J. Org. Chem.  2003,  68:  4531 

<A NAME="RT01605SS-7C">7c</A> Lee S.-H. Yoshida K. Matsushita H. Clapham B. Koch G. Zimmermann J. Janda KD. J. Org. Chem.  2004,  69:  8829 

<A NAME="RT01605SS-7D">7d</A> Davis FA. Yang B. Deng J. J. Org. Chem.  2003,  68:  5147 

<A NAME="RT01605SS-7E">7e</A> Davies JR. Kane PD. Moody CJ. Tetrahedron  2004,  60:  3967 

<A NAME="RT01605SS-7F">7f</A> Bashford KE. Cooper AL. Kane PD. Moody CJ. Muthusamy S. Swann E. J. Chem. Soc., Perkin Trans. 1  2002,  1672 

<A NAME="RT01605SS-7G">7g</A> Lee S.-H. Clapham B. Zimmermann J. Janda KD. Org. Lett.  2003,  5:  511 

<A NAME="RT01605SS-8">8</A>

Pd(II), Co(II), Cu(I), Ni(II) and Rh(II) were tried. Besides Rh(II), no other metal gave satisfying results. No conversion was observed for Co(II) and Cu(I). Pd(II) and Ni(II) only afforded 10% yield in the initial studies, whereas Rh(II) gave roughly 70% yield.

For examples on the use of phenol to accelerate Rh(II)-catalyzed insertion reactions, see:

<A NAME="RT01605SS-9A">9a</A> Yamazaki K. Kondo Y. Chem. Commun.  2002,  210 

<A NAME="RT01605SS-9B">9b</A> Haigh D. Tetrahedron  1994,  50:  3177 

<A NAME="RT01605SS-10">10</A> For the insertion of α-diazo-β-ketoesters into aromatic C-H bonds, see: Tsutsui H. Yamaguchi Y. Kitagaki S. Nakamura S. Anada M. Hashimoto S. Tetrahedron: Asymmetry  2003,  14:  817 

<A NAME="RT01605SS-11">11</A> For an example on slow addition of the diazo compound see: Davies JR. Kane PD. Moody CJ. Tetrahedron  2004,  60:  3967 

<A NAME="RT01605SS-12">12</A> For acid-promoted O-H insertion of aliphatic diazo compounds, see: Bradley W. Robinson R. J. Chem. Soc.  1928,  1310 

<A NAME="RT01605SS-13">13</A>

No O-H insertion product could be isolated from entry 11 in Table [1] . Therefore the presence of O-H insertion product is believed to be due to the presence of an amide in the para position.

For an easy and efficient synthesis of α-diazo-β-keto-esters see, for example:

<A NAME="RT01605SS-14A">14a</A> Davies HML. Cantrell WR. Romines KR. Baum JS. Org. Synth. Coll. Vol. 9   Wiley; New York: 1998.  p.422 

<A NAME="RT01605SS-14B">14b</A> Davies HML. Cantrell WR. Romines KR. Baum JS. Org. Synth.  1992,  70:  93 

<A NAME="RT01605SS-14C">14c</A> Moody CJ. Slawin AMZ. Willows D. Org. Biomol. Chem.  2003,  1:  2716 

<A NAME="RT01605SS-15">15</A> For another example of β-hydride elimination, see: Cox GG. Haigh D. Hindley RM. Miller DJ. Moody CJ. Tetrahedron Lett.  1994,  35:  3139