Catalyst-free, High-yield, and Stereospecific Synthesis of 3-Phenylthio β-Lactam Derivatives

Abstract

α-Diazocarbonyl compounds are good precursors of ketenes in the Staudinger reaction. On the basis of the reactions of S-phenyl diazothioacetate with imines under the catalysis of Rh₂(OAc)₄ a method for the synthesis of 3-phenylthio β-lactam derivatives has been developed previously. In this paper, a more convenient and improved procedure was achieved, which simplified the synthesis of S-phenyl diazothioacetate and made the reaction work well without the expensive Rh₂(OAc)₄ catalyst. The catalyst-free reactions of S-phenyl diazothioacetate with a variety of imines produced monocyclic and polycyclic β-lactams stereospecifically in good to excellent yields.

catalyst-free - imine - β-lactam - S-phenyl diazothioacetate - Staudinger reaction

References

For reviews on β-lactam antibiotics, see:

<A NAME="RF12805SS-1A">1a</A> Chemistry and Biology of β-Lactam Antibiotics   Vol. 1-3:  Morin RB. Gorman M. Academic Press; New York: 1982. 

<A NAME="RF12805SS-1B">1b</A> Southgate R. Branch C. Coulton S. Hunt E. In Recent Progress in the Chemical Synthesis of Antibiotics and Related Microbial Products   Vol. 2:  Luckacs G. Springer-Verlag; Berlin: 1993.  p.621 

<A NAME="RF12805SS-1C">1c</A> Southgate R. Contemp. Org. Synth.  1994,  1:  417 

For some recent reviews on β-lactam syntheses, see:

<A NAME="RF12805SS-2A">2a</A> van der Steen FH. van Koten G. Tetrahedron  1991,  47:  7503 

<A NAME="RF12805SS-2B">2b</A> Palomo C. Aizpurua JM. Ganboa I. Oiarbide M. Eur. J. Org. Chem.  1999,  3223 

<A NAME="RF12805SS-3">3</A> For a review, see: The Organic Chemistry of β-Lactams   Georg GI. Verlag Chemie; New York: 1993. 

<A NAME="RF12805SS-4A">4a</A> Podlech J. Linder MR. J. Org. Chem.  1997,  62:  5873 

<A NAME="RF12805SS-4B">4b</A> Linder MR. Podlech J. Org. Lett.  1999,  1:  869 

<A NAME="RF12805SS-4C">4c</A> Maier TC. Frey WU. Podlech J. Eur. J. Org. Chem.  2002,  2686 

<A NAME="RF12805SS-4D">4d</A> Linder MR. Frey WU. Podlech J. J. Chem. Soc., Perkin Trans. 1  2001,  2566 

<A NAME="RF12805SS-4E">4e</A> Linder MR. Podlech J. Org. Lett.  2001,  3:  1849 

<A NAME="RF12805SS-5A">5a</A> Narizuka S. Fuchigami T. J. Org. Chem.  1993,  58:  4200 

<A NAME="RF12805SS-5B">5b</A> van der Veen JM. Bari SS. Krishnan L. Manhas MS. Bose AK. J. Org. Chem.  1989,  54:  5758 

<A NAME="RF12805SS-6">6</A> Bari SS. Venugopalan P. Arora R. Tetrahedron Lett.  2003,  44:  895 

<A NAME="RF12805SS-7">7</A> Hirai K. Iwano Y. Tetrahedron Lett.  1979,  22:  2031 

<A NAME="RF12805SS-8">8</A> Manhas MS. Bari SS. Bhawal BM. Bose AK. Tetrahedron Lett.  1984,  25:  4733 

<A NAME="RF12805SS-9A">9a</A> Lawlor MD. Lee TW. Danheiser RL. J. Org. Chem.  2000,  65:  4375 

<A NAME="RF12805SS-9B">9b</A> Danheiser RL. Okamoto I. Lawlor MD. Lee TW. Org. Synth.  2003,  80:  160 

<A NAME="RF12805SS-10">10</A> Bestmann HJ. Soliman FM. Angew. Chem., Int. Ed. Engl.  1979,  18:  947 

<A NAME="RF12805SS-11A">11a</A> For the synthesis of phenyl chlorothioformate, see: Olah GA. Schilling P. Justus Liebigs Ann. Chem.  1972,  761:  77 

<A NAME="RF12805SS-11B">11b</A> For the synthesis of diazothioacetates, see: Hixson SS. Hixson SH. J. Org. Chem.  1972,  37:  1279 

<A NAME="RF12805SS-12">12</A>

We also attempted chiral Rh(II) and Cu(I) complexes as catalysts (Figure [2] ), hoping to achieve the asymmetric ketene-imine reaction. However, in all cases, the ee of the product 3a was 0%, though the yields were quite good (>90%).

<A NAME="RF12805SS-13">13</A>

The relative configurations of β-lactams 3a-d were determined by the coupling constants between the protons at C-3 and C-4 of the β-lactam rings (J _C-3,C-4 = 2.1-2.7 Hz for trans-β-lactams; J _C-3,C-4 = 5.4 Hz for cis-β-lactams).

<A NAME="RF12805SS-14">14</A> Liang Y. Jiao L. Zhang SW. Xu JX. J. Org. Chem.  2005,  70:  334 

<A NAME="RF12805SS-15">15</A>

The Rh₂(OAc)₄ catalyzed reactions of 1 with 2g, 2h, and 2l were also conducted, and the yields of β-lactam derivatives 3g, 3h, and 3l are 96%, 97%, and 99%, respectively. This indicates that for complex cyclic imines the transition metal-catalyzed reactions are better than catalyst-free reactions due to the lower reaction temperature, which is appropriate for thermally sensitive substrates.

<A NAME="RF12805SS-16">16</A>

CCDC 277470 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, by emailing [e-mail], or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax:[phone].

<A NAME="RF12805SS-17A">17a</A> Szöllösy A. Kotovych G. Tóth G. Lévai A. Can. J. Chem.  1988,  66:  279 

<A NAME="RF12805SS-17B">17b</A> Xu JX. Zuo G. Chan WL. Heteroat. Chem.  2001,  12:  636 

<A NAME="RF12805SS-17C">17c</A> Xu JX. Zuo G. Zhang QH. Chan WL. Heteroat. Chem.  2002,  13:  276 

<A NAME="RF12805SS-17D">17d</A> Huang X. Xu JX. Heteroat. Chem.  2003,  14:  564 

<A NAME="RF12805SS-18">18</A> When imine 2f was employed, the product 4f (Scheme 4) was generated in 27% yield instead of β-lactam 3f. The product 4f has the following spectroscopic data: ¹H NMR (300 MHz): δ = 1.43 (s, 3 H), 1.71 (s, 3 H), 3.74 (s, 3 H), 3.85 (d, J = 13.8 Hz, 1 H), 4.29 (d, J = 13.8 Hz, 1 H), 4.78 (s, 1 H), 6.65 (s, 1 H), 7.12-7.47 (m, 10 H). However, the relative configuration of this product was not determined. This type of product was obtained previously in the reaction of phenylketene with 2,4-diaryl-2,3-dihydro-1,5-benzothi­-azepines, see: Xu JX. Wang C. Zhang QH. Chin. J. Chem.  2004,  22:  1012 

<A NAME="RF12805SS-19">19</A> Georg GI. Ravikumar VT. In The Organic Chemistry of β-Lactams   Georg GI. Verlag Chemie; New York: 1993.  p.295-368  

<A NAME="RF12805SS-20">20</A> Hegedus LS. Montgomery J. Narukawa Y. Snustad DC. J. Am. Chem. Soc.  1991,  113:  5784 

<A NAME="RF12805SS-21">21</A> Bigelow LA. Eatough H. Org. Synth. Coll. Vol. I  1967,  80 

<A NAME="RF12805SS-22">22</A> Wenker H. J. Am. Chem. Soc.  1935,  57:  1079 

<A NAME="RF12805SS-23">23</A> Bell MR. Carlson JA. Oesterlin R. J. Org. Chem.  1972,  37:  2733 

<A NAME="RF12805SS-24">24</A> Wardrop AWH. Sainsbury GL. Harrison JM. Inch TD. J. Chem. Soc., Perkin Trans. 1  1976,  1279 

<A NAME="RF12805SS-25">25</A> Nagarajan K. Venkateswarlu A. Kulkarni CL. Shah RK. Indian J. Chem.  1974,  12:  227 

<A NAME="RF12805SS-26">26</A> Xu JX. Jin S. Xing QY. Phosphorus, Sulfur Silicon Relat. Elem.  1998,  141:  57 

<A NAME="RF12805SS-27">27</A> Sugano Y. Naruto S. Chem. Lett.  1989,  1331