Synlett 2003(14): 2261-2262  
DOI: 10.1055/s-2003-42111
SPOTLIGHT
© Georg Thieme Verlag Stuttgart · New York

Titanium Tetraisopropoxide

Óscar López*
Departamento Química Orgánica, Facultad Química, Universidad Sevilla, Apartado 553, 41071 Sevilla, Spain
e-Mail: osc-lopez@mixmail.com;

Further Information

Publication History

Publication Date:
29 October 2003 (online)

Biographical Sketches

Óscar López was born in Seville (Spain) in 1976 and studied ­chemistry in the University of Seville, where he received his diploma in 1999. He is currently finishing his PhD studies at the same University, in the Department of Organic Chemistry, under the ­supervision of Professor José G. Fernández-Bolaños. His research field is new synthetic approaches to carbohydrate-derived thioureas, isoureas, ureas, and selenoureas.

Introduction

Titaniun tetraisopropoxide is a mild Lewis acid that has been extensively used as a catalyst in organic synthesis, specially in those reactions involving asymmetric inductions, [1] such as Sharpless epoxidation, additions to carbonyl compounds, and oxidations; its catalytic activity in asymmetric synthesis is based on the formation of complexes with chiral auxiliaries. [2] Its mild nature enables the use of this catalyst in the presence of some acid-sensitive functional groups, such as acetonides, OTBDMS, and lactams.
Titanium tetraisopropoxide is a non-expensive catalyst, commercially available as a low-melting point solid.

Abstracts

(A) Ti(i-PrO)4 is a mild catalyst for transesterification reactions; it is used in macrolide synthesis to facilitate ring size equilibration. [3] For instance, macrolide 1 was transformed [4] into 2 by treatment with Ti(i-PrO)4 and this macrolide was used in the synthesis of Scytophycin C.

(B) Ti(i-PrO)4 has been used in the selective oxidation of sulfides to sulfoxides. An asymmetric oxidation of sulfides with high enantioselectivity has been reported [5] using (R)-(+)-BINOL as the chiral auxiliary and Ti(i-PrO)4 as catalyst. Recently, some Ti(i-PrO)4 derivatives supported on silica have been investigated [6] as catalysts for these oxidation reactions.

(C) Sharpless asymmetric epoxidation of allylic alcohols using tert-butyl hydroperoxide, diethyl tartrate, and Ti(i-PrO)4 is the key step in the preparation of many products of synthetic and biological interest. [7] The reaction usually takes place with good yield and high stereoselectivity. Sharpless epoxidation conditions have been used to prepare the phenylalkylamine motif of several calcium channel blockers, such as verapamil and emopamil. [8]

(D) A dimethylsulfide-Ti(i-PrO)4 mixture has been used to reduce hydroperoxides, [9] obtained by photooxygenation of olefins. The reaction takes place at room temperature in 10 minutes with a high yield (93%).

(E) Ti(i-PrO)4 enables the opening of 2,3-epoxy alcohols in the presence of nucleophiles. This occurs usually in high regioselectivity, as the ring-opening normally takes place at C-3. By this type of reaction, chiral benzosultams [10] and amino acid derivatives [11] have been obtained. This reaction can also be extended to 2,3-epoxycarboxylic acids and amides.

(F) Titanium-derived complexes can be used to catalyze aldol-Tishchenko reaction to afford stereoselectively 1,3-anti-diol monoesters. Mahrwald et al. [12] reported the one-pot synthesis of these compounds using a titanium ate complex, obtained in situ by mixing equimolecular amounts of Ti(i-PrO)4 and BuLi. The reaction took place at room temperature with high anti-stereoselectivity.

(G) Ti(i-PrO)4 has been used, together with a chiral ligand, in the preparation of optically active cyanohydrins via asymmetric trimethylsilylcyanation of aldehydes [13] or ketones. [14] In particular, the chiral Ti(IV) salen complex 17 has been used [15] in the preparation of fluoroepinephrine derivatives with high enantioselectivity.

(H) The title compound can be used [16] to catalyze the addition of alkyl groups to aldehydes and ketones, an area where much effort has been devoted. This reaction was studied by Walsh et al. using bis(sulfonamido) or BINOL/ Ti(i-PrO)4 complexes, applied to aldehydes, [17] ketones [18] and a,b-unsaturated ketones. [19] In the case of 18, the reaction is totally chemoselective, as no conjugate addition compound was detected.
Chan et al. have reported [20] the preparation of chiral propargylic alcohols via enantioselective alkynylation of aldehydes using BINOL/ Ti(i-PrO)4 catalysts.

    References

  • 1 Söderberg BCG. Coord. Chem. Rev.  2003,  241:  147 
  • 2 North M. Tetrahedron: Asymmetry  2003,  14:  147 
  • 3 Kigoshi H. Suenaga K. Mutou T. Ishigaki T. Atsumi T. Ishiwata H. Sakakura A. Ogawa T. Ojika M. Yamada K. J. Org. Chem.  1996,  61:  5326 
  • 4 Paterson I. Watson C. Yeung K.-S. Ward RA. Wallace PA. Tetrahedron  1998,  54:  11955 
  • 5 Komatsu N. Hashizume M. Sugita T. Uemura S. J. Org. Chem.  1993,  58:  4529 
  • 6 Fraile JM. García JI. Lázaro B. Mayoral JA. Chem. Commun.  1998,  1807 
  • 7a Liu D.-G. Wang B. Lin G.-Q. J. Org. Chem.  2000,  65:  9114 
  • 7b Yadav JS. Geetha V. Raju AK. Gnaneshwar D. Chandrasekhar S. Tetrahedron Lett.  2003,  44:  2983 
  • 8 Kimura T. Yamamoto N. Suzuki Y. Kawano K. Norimine Y. Ito K. Nagato S. Iimura Y. Yonaga M. J. Org. Chem.  2002,  67:  6228 
  • 9 Gültekin MS. Salamci E. Balci M. Carbohydr. Res.  2003,  338:  1615 
  • 10 Ahn KH. Baek H.-H. Lee SJ. Cho C.-W. J. Org. Chem.  2000,  65:  7690 
  • 11a Martín R. Alcón M. Pericàs MA. Riera A. J. Org. Chem.  2002,  67:  6896 
  • 11b Medina E. Vidal-Ferran A. Moyano A. Pericàs MA. Riera A. Tetrahedron: Asymmetry  1997,  8:  1581 
  • 12 Mahrwald R. Costisella B. Synthesis  1996,  1087 
  • 13 Gama A. Flores-López LZ. Aguirre G. Parra-Hake M. Somanathan R. Walsh PJ. Tetrahedron: Asymmetry  2002,  13:  149 
  • 14 Shen Y. Feng X. Li Y. Zhang G. Jiang Y. Tetrahedron  2003,  59:  5667 
  • 15 Lu S.-F. Herbert B. Haufe G. Laue KW. Padgett WL. Oshunleti O. Daly JW. Kirk KL. J. Med. Chem.  2000,  43:  1611 
  • 16a Yus M. Ramón DJ. Prieto O. Tetrahedron: Asymmetry  2003,  14:  1103 
  • 16b You J.-S. Hsieh S.-H. Gau H.-M. Chem. Commun.  2001,  1546 
  • 17a Walsh PJ. Acc. Chem. Res.  2003, in press
  • 17b Balsells J. Walsh PJ. J. Am. Chem. Soc.  2000,  122:  1802 
  • 18 García C. LaRochelle LK. Walsh PJ. J. Am. Chem. Soc.  2002,  124:  10970 
  • 19 Jeon S.-J. Walsh PJ. J. Am. Chem. Soc.  2003,  125:  9544 
  • 20a Lu G. Li X. Chen G. Chan WL. Chan ASC. Tetrahedron: Asymmetry  2003,  14:  449 
  • 20b Lu G. Li X. Chan WL. Chan ASC. Chem. Commun.  2002,  172 

    References

  • 1 Söderberg BCG. Coord. Chem. Rev.  2003,  241:  147 
  • 2 North M. Tetrahedron: Asymmetry  2003,  14:  147 
  • 3 Kigoshi H. Suenaga K. Mutou T. Ishigaki T. Atsumi T. Ishiwata H. Sakakura A. Ogawa T. Ojika M. Yamada K. J. Org. Chem.  1996,  61:  5326 
  • 4 Paterson I. Watson C. Yeung K.-S. Ward RA. Wallace PA. Tetrahedron  1998,  54:  11955 
  • 5 Komatsu N. Hashizume M. Sugita T. Uemura S. J. Org. Chem.  1993,  58:  4529 
  • 6 Fraile JM. García JI. Lázaro B. Mayoral JA. Chem. Commun.  1998,  1807 
  • 7a Liu D.-G. Wang B. Lin G.-Q. J. Org. Chem.  2000,  65:  9114 
  • 7b Yadav JS. Geetha V. Raju AK. Gnaneshwar D. Chandrasekhar S. Tetrahedron Lett.  2003,  44:  2983 
  • 8 Kimura T. Yamamoto N. Suzuki Y. Kawano K. Norimine Y. Ito K. Nagato S. Iimura Y. Yonaga M. J. Org. Chem.  2002,  67:  6228 
  • 9 Gültekin MS. Salamci E. Balci M. Carbohydr. Res.  2003,  338:  1615 
  • 10 Ahn KH. Baek H.-H. Lee SJ. Cho C.-W. J. Org. Chem.  2000,  65:  7690 
  • 11a Martín R. Alcón M. Pericàs MA. Riera A. J. Org. Chem.  2002,  67:  6896 
  • 11b Medina E. Vidal-Ferran A. Moyano A. Pericàs MA. Riera A. Tetrahedron: Asymmetry  1997,  8:  1581 
  • 12 Mahrwald R. Costisella B. Synthesis  1996,  1087 
  • 13 Gama A. Flores-López LZ. Aguirre G. Parra-Hake M. Somanathan R. Walsh PJ. Tetrahedron: Asymmetry  2002,  13:  149 
  • 14 Shen Y. Feng X. Li Y. Zhang G. Jiang Y. Tetrahedron  2003,  59:  5667 
  • 15 Lu S.-F. Herbert B. Haufe G. Laue KW. Padgett WL. Oshunleti O. Daly JW. Kirk KL. J. Med. Chem.  2000,  43:  1611 
  • 16a Yus M. Ramón DJ. Prieto O. Tetrahedron: Asymmetry  2003,  14:  1103 
  • 16b You J.-S. Hsieh S.-H. Gau H.-M. Chem. Commun.  2001,  1546 
  • 17a Walsh PJ. Acc. Chem. Res.  2003, in press
  • 17b Balsells J. Walsh PJ. J. Am. Chem. Soc.  2000,  122:  1802 
  • 18 García C. LaRochelle LK. Walsh PJ. J. Am. Chem. Soc.  2002,  124:  10970 
  • 19 Jeon S.-J. Walsh PJ. J. Am. Chem. Soc.  2003,  125:  9544 
  • 20a Lu G. Li X. Chen G. Chan WL. Chan ASC. Tetrahedron: Asymmetry  2003,  14:  449 
  • 20b Lu G. Li X. Chan WL. Chan ASC. Chem. Commun.  2002,  172