Efficient Two-Step Synthesis of Salicylaldehydes via Directed ortho-Lithiation of in situ N-Silylated O-Aryl N-Isopropylcarbamates

Abstract

O-Aryl N-isopropylcarbamates, conveniently prepared from phenols and isopropyl isocyanate, are subjected to an efficient ortho-lithiation protocol to afford the corresponding salicylaldehydes in a one-pot operation in high yields.

carbanions - formylation - lithiation - phenols - salicylaldehydes

References

Reviews:

1a Katsuki T. Synlett  2003,  281 

1b Katsuki T. Chem. Soc. Rev.  2004,  33:  437 

Examples:

2a Wakamatsu H. Blechert S. Angew. Chem. Int. Ed.  2002,  41:  794 

2b Wakamatsu H. Blechert S. Angew. Chem. Int. Ed.  2002,  41:  2403 

2c Van Veldhuizen JJ. Gillingham DG. Garber SB. Kataoka O. Hoveyda AH. J. Am. Chem. Soc.  2003,  125:  12502 

3 For a general review, see: Olah GA. Ohannesian L. Arvanaghi M. Chem. Rev.  1987,  87:  671 

4a Casiraghi G. Casnati G. Cornia M. Pochini A. Puglia G. Sartori G. Ungaro R. J. Chem. Soc., Perkin Trans. 1  1978,  318 

4b Wang RX. You XZ. Meng QJ. Mintz EA. Bu XR. Synth. Commun.  1994,  24:  1757 

5 Aldred R. Johnston R. Levin D. Neilan J. J. Chem. Soc., Perkin Trans. 1  1994,  1823 

6 Hofsløkken NU. Skattebøl L. Acta Chem. Scand.  1999,  53:  258 

Reviews:

7a Snieckus V. Chem. Rev.  1990,  90:  879 

7b Clayden J. In The Chemistry of Organolithium Compounds   Rappoport Z. Marek I. Wiley; Chichester: 2004.  p.495 

8a Kauch M. Snieckus V. Hoppe D. J. Org. Chem.  2005,  70:  7149 

8b Kauch M. Hoppe D. Can. J. Chem.  2001,  79:  1736 

9 Casiraghi G. Casnati G. Puglia G. Sartori G. Terenghi G. J. Chem. Soc., Perkin Trans. 1  1980,  1862 

10 Antonisse MMG. Snellink-Ruël BHM. Ion AC. Engbersen JFJ. Reinhoudt DN. J. Chem. Soc., Perkin Trans. 2  1999,  1211 

11 van Doorn AR. Bos M. Harkema S. van Eerden J. Verboom W. Reinhoudt DN. J. Org. Chem.  1991,  56:  2371 

12 Christensen H. Synth. Commun.  1975,  5:  65 

13 Aymes DJ. Paris MR. Bull. Soc. Chim. Fr.  1980,  175 

14 Mitani M. Furuyama R. Mohri J.-i. Saito J. Ishii S. Terao H. Nakano T. Tanaka H. Fujita T. J. Am. Chem. Soc.  2003,  125:  4293 

15 García O. Nicolás E. Albericio F. Tetrahedron Lett.  2003,  44:  4961 

16 Spagnolo P. Tiecco M. Tundo A. Martelli G. J. Chem. Soc., Perkin Trans. 1  1972,  556 

17 Narasimhan NS. Mali RS. Barve MV. Synthesis  1979,  906 

18 The synthesis of 3-iodo- and 3-bromosalicylaldehyde by ipso-halodesilylation reactions of 4d is described in the accompanying paper: Kauch M. Hoppe D. Synthesis  2006,  xxx 

19

Carbamate 1d can either be obtained by ortho-lithiation [8b] or by reaction of 2-(trimethylsilyl)phenol with isopropyl isocyanate (96%).