Skip to main content
SpringerLink
Log in

Cp2TiCl in Natural Product Synthesis

  • Chapter
  • First Online:
Radicals in Synthesis II

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 264))

Abstract

The synthesis of complex natural products constitutes one of the most exigent tests to prove the usefulness of a new reagent or catalyst. During the past 10 years, methods based on the Cp2TiCl -promoted and/or -catalyzed radical epoxide opening have been used by several authors as the key step for the synthesis of more than 50 natural products and advanced synthons. At first, owing to its selectivity and the extremely mild experimental conditions employed, stoichiometric Cp2TiCl was chosen for deoxygenation and reductive epoxide opening on densely functionalized substrates, but during the last 5 years catalytic Cp2TiCl has been increasingly employed to achieve radical cyclizations of different epoxyalkenes and epoxyalkynes, affording straightforward strategies for the synthesis of complex natural products. In these fields Cp2TiCl -based methods have already largely proved their synthetic usefulness but other Cp2TiCl-mediated reactions have as yet been scarcely applied. This review focuses on the increasing scope of applications that employ the Cp2TiCl -mediated procedures in the synthesis of natural products. We also present the basic concepts of these methods to facilitate and encourage further synthetic applications.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Abbreviations

col:

2,4,6-Collidine

Cp:

Cyclopentadienyl

DMP:

Dess–Martin periodinane

m-CPBA:

3-Chloroperbenzoic acid

min:

Minutes

Py:

Pyridine

THF:

Tetrahydrofuran

References

  1. Nicolaou KC, Vourloumis D, Winssinger N, Baran PS (2000) Angew Chem Int Ed 39:45

    Google Scholar 

  2. Enemærke RJ, Hjøllund GH, Daasbjerg K, Skrydstrup T (2001) CR Acad Sci 4:435

    Google Scholar 

  3. Dunlap MS, Nicholas KM (2001) J Organomet Chem 630:125

    Article  CAS  Google Scholar 

  4. Enemærke RJ, Larsen J, Skrydstrup T, Daasbjerg K (2004) J Am Chem Soc 126:7853

    CAS  Google Scholar 

  5. Sekutowski D, Jungst R, Stucky GD (1978) Inorg Chem 17:1848

    Article  CAS  Google Scholar 

  6. Stephan DW (1992) Organometallics 11:996

    Article  CAS  Google Scholar 

  7. Nugent WA, RajanBabu TV (1988) J Am Chem Soc 110:8561

    Article  CAS  Google Scholar 

  8. Gansäuer A, Pierobon M, Bluhm H (1998) Angew Chem Int Ed 37:101

    Article  Google Scholar 

  9. Gansäuer A, Bluhm H, Pierobon M (1998) J Am Chem Soc 120:12849

    Google Scholar 

  10. Gansäuer A, Bluhm H (2000) Chem Rev 100:2771

    Google Scholar 

  11. Gansäuer A, Pierobon M (2001) Rearrangements of cyclopropanes and epoxides. In: Renaud P, Sibi MP (eds) Radicals in organic synthesis, vol 2. Wiley, Weinheim, p 207

    Google Scholar 

  12. Gansäuer A, Rinker B (2002) Tetrahedron 58:7017

    Google Scholar 

  13. Gansäuer A, Narayan S (2002) Adv Synth Catal 344:465

    Google Scholar 

  14. Gansäuer A, Rinker B (2002) Titanocene-catalyzed epoxide opening. In: Marek I (ed) Titanium and zirconium in organic synthesis. Wiley, Weinheim, p 435

    Google Scholar 

  15. Gansäuer A, Lauterbach T, Narayan S (2003) Angew Chem Int Ed 42:5556

    Google Scholar 

  16. Larock RC (1999) Comprehensive organic transformations, 2nd edn. Wiley, New York

    Google Scholar 

  17. Smith MB (2002) Organic synthesis, 2nd edn. McGraw-Hill, New York

    Google Scholar 

  18. Rickborn B (1991) Acid-catalyzed rearrangements of epoxides. In: Trost BM, Fleming I, Pattenden G (eds) Comprehensive organic synthesis, vol 3. Pergamon, Oxford, p 733

    Google Scholar 

  19. Mitsunobu O (1991) Synthesis of alcohols and ethers. In: Trost BM, Fleming I, Winterfeldt E (eds) Comprehensive organic synthesis, vol 6. Pergamon, Oxford, p 1

    Google Scholar 

  20. RajanBabu TV, Nugent WA (1989) J Am Chem Soc 111:4525

    CAS  Google Scholar 

  21. RajanBabu TV, Nugent WA, Beattie MS (1990) J Am Chem Soc 112:6408

    Article  CAS  Google Scholar 

  22. RajanBabu TV, Nugent WA (1994) J Am Chem Soc 116:986

    CAS  Google Scholar 

  23. Murai S, Murai T, Kato S (1991) Reduction of epoxides. In: Trost BM, Fleming I (eds) Comprehensive organic synthesis, vol 8. Pergamon, Oxford, p 871

    Google Scholar 

  24. Schobert R (1988) Angew Chem Int Ed 27:855

    Google Scholar 

  25. Yadav JS, Shekaram T, Gadgil VR (1990) Chem Commun 843

    Google Scholar 

  26. Rao AVR, Bhanu MN, Sherma GVM (1993) Tetrahedron Lett 34:707

    CAS  Google Scholar 

  27. Yadav S, Srinivas D, Shekaram T (1994) Tetrahedron Lett 35:3625

    CAS  Google Scholar 

  28. Chakraborty TK, Dutta S (1997) J Chem Soc Perkin Trans 1 1257

    Google Scholar 

  29. Weigand S, Brückner R (1997) Synlett 225

    Google Scholar 

  30. Chakraborty TK, Dutta S (1998) Tetrahedron Lett 39:101

    CAS  Google Scholar 

  31. Jørgensen KB, Suenaga T, Nakata T (1999) Tetrahedron Lett 40:8855

    Google Scholar 

  32. Hardouin C, Chevallier F, Rousseau B, Doris E (2001) J Org Chem 66:1046

    CAS  Google Scholar 

  33. Chakraborty TK, Das S, Raju TV (2001) J Org Chem 66:4091

    Article  CAS  Google Scholar 

  34. Chakraborty TK, Tapadar S (2001) Tetrahedron Lett 42:1375

    CAS  Google Scholar 

  35. Chakraborty TK, Das S (2002) Tetrahedron Lett 43:2313

    CAS  Google Scholar 

  36. Chakraborty TK, Tapadar S (2003) Tetrahedron Lett 44:2541

    CAS  Google Scholar 

  37. Bermejo F, Sandoval C (2004) J Org Chem 69:5275

    Article  CAS  Google Scholar 

  38. Fernández-Mateos A, Martín de la Nava E, Pascual Coca G, Ramos Silvo A, Rubio González R (1999) Org Lett 1:607

    Google Scholar 

  39. Fernández-Mateos A, Mateos Burón I, Rabanedo Clemente R, Ramos Silvo AI, Rubio González R (2004) Synlett 1011

    Google Scholar 

  40. Merlic CA, Xu D (1991) J Am Chem Soc 113:9855

    CAS  Google Scholar 

  41. Merlic CA, Xu D, Nguyen MC, Truong V (1993) Tetrahedron Lett 34:227

    CAS  Google Scholar 

  42. Dötz KH, Gomes da Silva E (2000) Tetrahedron 56:8291

    Article  Google Scholar 

  43. Parrish JD, Little RD (2002) Org Lett 4:1439

    Article  CAS  Google Scholar 

  44. Gansäuer A, Lauterbach T, Geich-Gimbel D (2004) Chem Eur J 10:4983

    Article  CAS  Google Scholar 

  45. Fernández-Mateos A, Mateos Burón L, Martín de la Nava EM, Rabanedo Clemente R, Rubio González R, Sanz González F (2004) Synlett 2553

    Google Scholar 

  46. Friedrich J, Dolg M, Gansäuer A, Geich-Gimbel D, Lauterbach T (2005) J Am Chem Soc 127:7071

    Article  CAS  Google Scholar 

  47. Barrero AF, Oltra JE, Cuerva JM, Rosales A (2002) J Org Chem 67:2566

    CAS  Google Scholar 

  48. Curran DP, Porter NA, Giese B (1996) Stereochemistry of radical reactions. Wiley, Weinheim

    Google Scholar 

  49. Renaud P, Sibi MP (eds) (2001) Radicals in organic synthesis. Wiley, Weinheim

    Google Scholar 

  50. Spiegel DA, Wiberg KB, Schacherer LN, Medeiros MR, Wood JL (2005) J Am Chem Soc 127:12513

    Article  CAS  Google Scholar 

  51. Barrero AF, Rosales A, Cuerva JM, Gansäuer A, Oltra JE (2003) Tetrahedron Lett 44:1079

    Article  CAS  Google Scholar 

  52. Oller-López JL, Campaña AG, Cuerva JM, Oltra JE (2005) Synthesis 2619

    Google Scholar 

  53. Justicia J, Rosales A, Buñuel E, Oller-López JL, Valdivia M, Haïdour A, Oltra JE, Barrero AF, Cárdenas DJ, Cuerva JM (2004) Chem Eur J 10:1778

    Article  CAS  Google Scholar 

  54. Barrero AF, Cuerva JM, Herrador MM, Valdivia MV (2001) J Org Chem 66:4074

    Article  CAS  Google Scholar 

  55. Leca D, Fensterbank L, Lacôte E, Malacria M (2004) Angew Chem Int Ed 43:4220

    Article  CAS  Google Scholar 

  56. Leca D, Song K, Albert M, Grangeio Gonçalves M, Fensterbank L, Lacôte E, Malacria M (2005) Synthesis 1405

    Google Scholar 

  57. Gansäuer A, Bluhm H (1998) Chem Commun 2143

    Google Scholar 

  58. Gansäuer A, Lauterbach T, Bluhm H, Noltemeyer M (1999) Angew Chem Int Ed 38:2909

    Article  Google Scholar 

  59. Gansäuer A, Bluhm H, Lauterbach T (2001) Adv Synth Catal 343:785

    Article  Google Scholar 

  60. Gansäuer A, Bluhm H, Rinker B, Narayan S, Schick M, Lauterbach T, Pierobon M (2003) Chem Eur J 9:531

    Article  Google Scholar 

  61. Gansäuer A, Barchuk A, Fielenbach D (2004) Synthesis 2567

    Google Scholar 

  62. Gansäuer A, Rinker B, Barchuk A, Nieger M (2004) Organometallics 23:1168

    Google Scholar 

  63. Gansäuer A, Pierobon M (2000) Synlett 1357

    Google Scholar 

  64. Gansäuer A, Pierobon M, Bluhm H (2001) Synthesis 2500

    Google Scholar 

  65. Gansäuer A, Pierobon M, Bluhm H (2002) Angew Chem Int Ed 41:3206

    Article  Google Scholar 

  66. Gansäuer A, Rinker B, Pierobon M, Grimme S, Gerenkamp M, Mück-Lichtenfeld C (2003) Angew Chem Int Ed 42:3687

    Google Scholar 

  67. Gansäuer A, Rinker B, Ndene-Schiffer N, Pierobon M, Grimme S, Gerenkamp M, Mück-Lichtenfeld C (2004) Eur J Org Chem 2337

    Google Scholar 

  68. Barrero AF, Rosales A, Cuerva JM, Oltra JE (2003) Org Lett 5:1935

    Article  CAS  Google Scholar 

  69. Justicia J, Oller-López JL, Campaña AG, Oltra JE, Cuerva JM, Buñuel E, Cárdenas DJ (2005) J Am Chem Soc 127:14911

    Article  CAS  Google Scholar 

  70. Fuse S, Hanochi M, Doi T, Takahashi T (2004) Tetrahedron Lett 45:1961

    Article  CAS  Google Scholar 

  71. Handa Y, Inanaga J (1987) Tetrahedron Lett 28:5717

    Article  CAS  Google Scholar 

  72. Enemærke RJ, Larsen J, Hjøllund GH, Skrydstrup T, Daasbjerg K (2005) Organometallics 24:1252

    CAS  Google Scholar 

  73. Gansäuer A (1997) Chem Commun 457

    Google Scholar 

  74. Gansäuer A, Bauer D (1998) J Org Chem 63:2070

    Google Scholar 

  75. Hirao T, Hatano B, Asahara M, Muguruma Y, Ogawa A (1998) Tetrahedron Lett 39:5247

    CAS  Google Scholar 

  76. Barden MC, Schwartz J (1996) J Am Chem Soc 118:5484

    Article  CAS  Google Scholar 

  77. Moisan L, Hardouin C, Rousseau B, Doris E (2002) Tetrahedron Lett 43:2013

    Article  CAS  Google Scholar 

  78. Parrish JD, Shelton DR, Little RD (2003) Org Lett 5:3615

    CAS  Google Scholar 

  79. Jana S, Guin C, Roy SC (2004) Tetrahedron Lett 45:6575

    Article  CAS  Google Scholar 

  80. Rosales A, Oller-López JL, Justicia J, Gansäuer A, Oltra JE, Cuerva JM (2004) Chem Commun 2628

    Google Scholar 

  81. Mandal SK, Jana S, Roy SC (2005) Tetrahedron Lett 46:6115

    CAS  Google Scholar 

  82. Barrero AF, Herrador MM, Quílez del Moral JF, Arteaga P, Arteaga JF, Piedra M, Sánchez E (2005) Org Lett 7:2301

    Article  CAS  Google Scholar 

  83. Zhou L, Hirao T (2003) J Org Chem 68:1633

    CAS  Google Scholar 

  84. Jana S, Guin C, Roy SC (2005) Tetrahedron Lett 46:1155

    Article  CAS  Google Scholar 

  85. Spencer RP, Schwartz J (2000) Tetrahedron 56:2103

    Article  CAS  Google Scholar 

  86. Hansen T, Daasbjerg K, Skrydstrup T (2000) 41:8645

    Google Scholar 

  87. Samuel E, Vedel J (1989) Organometallics 8:237

    Article  CAS  Google Scholar 

  88. Martre AM, Mousset G, Danciu V, Cosoveanu V (1998) Electrochim Acta 43:3217

    Article  CAS  Google Scholar 

  89. Meunier-Prest R, Lamblin G, Mailfert A, Raveau S (2003) J Electroanal Chem 541:175

    Article  CAS  Google Scholar 

  90. Hersant G, Ferjani MBS, Bennet SM (2004) Tetrahedron Lett 45:8123

    Article  CAS  Google Scholar 

  91. Golakoti T, Ogino J, Heltzel CE, Husebo TL, Jensen CM, Larsen LK, Patterson GML, Moore RE, Mooberry SL, Corbett TH, Valeriote FA (1995) J Am Chem Soc 117:12030

    Article  CAS  Google Scholar 

  92. Hardouin C, Doris E, Rousseau B, Mioskowski C (2002) Org Lett 4:1151

    Article  CAS  Google Scholar 

  93. Hardouin C, Doris E, Rousseau B, Mioskowski C (2002) J Org Chem 67:6571

    Article  CAS  Google Scholar 

  94. Bhaskar KV, Mander LN (1996) Tetrahedron Lett 37:719

    Article  CAS  Google Scholar 

  95. Clive DLJ, Magnuson SR (1995) Tetrahedron Lett 36:15

    Article  CAS  Google Scholar 

  96. Clive DLJ, Magnuson SR, Manning HW, Mayhew DL (1996) J Org Chem 61:2095

    CAS  Google Scholar 

  97. Maiti G, Roy SC (1996) J Chem Soc Perkin Trans 1 403

    Google Scholar 

  98. Mandal PK, Maiti G, Roy SC (1998) J Org Chem 63:2829

    CAS  Google Scholar 

  99. Ziegler FE, Sarpong MA (2003) Tetrahedron 59:9013

    Article  CAS  Google Scholar 

  100. Mandal PK, Roy SC (1999) Tetrahedron 55:11395

    Article  CAS  Google Scholar 

  101. Rana KK, Guin C, Roy SC (2000) Tetrahedron Lett 41:9337

    CAS  Google Scholar 

  102. Rana KK, Guin C, Roy SC (2001) Synlett 1249

    Google Scholar 

  103. Roy SC, Rana KK, Guin C (2002) J Org Chem 67:3242

    Article  CAS  Google Scholar 

  104. Banerjee B, Roy SC (2005) Synthesis 2913

    Google Scholar 

  105. Nakai K, Kamoshita M, Doi T, Yamada H, Takahashi T (2001) Tetrahedron Lett 42:7855

    CAS  Google Scholar 

  106. Barrero AF, Cuerva JM, Alvarez-Manzaneda EJ, Oltra JE, Chahboun R (2002) Tetrahedron Lett 43:2793

    Article  CAS  Google Scholar 

  107. Barrero AF, Alvarez-Manzaneda EJ, Alvarez-Manzaneda R (1989) Tetrahedron Lett 30:3351

    CAS  Google Scholar 

  108. Hoshino T, Shimizu K, Sato T (2004) Angew Chem Int Ed 43:6700

    Article  CAS  Google Scholar 

  109. Trost BM, Shen HC, Surivet JP (2003) Angew Chem Int Ed 42:3943

    CAS  Google Scholar 

  110. Ruano G, Grande M, Anaya J (2002) J Org Chem 67:8243

    Article  CAS  Google Scholar 

  111. Anaya J, Fernández-Mateos A, Grande M, Martiáñez J, Ruano G, Rubio-Gonzalez MR (2003) Tetrahedron 59:241

    Article  CAS  Google Scholar 

  112. Ruano G, Martiáñez J, Grande M, Anaya J (2003) J Org Chem 68:2024

    Article  CAS  Google Scholar 

  113. Haruo Y, Hasegawa T, Tanaka H, Takahashi T (2001) Synlett 1935

    Google Scholar 

  114. Rosales A, Estévez R, Cuerva JM, Oltra JE (2005) Angew Chem Int Ed 44:319

    Article  CAS  Google Scholar 

  115. Barrero AF, Oltra JE, Álvarez M (1998) Tetrahedron Lett 39:1401

    CAS  Google Scholar 

  116. Connolly JD, Hill RA (1991) Dictionary of terpenoids, vol 1. Chapman and Hall, London

    Google Scholar 

  117. Fraga BM (2003) Nat Prod Rep 20:392

    Article  CAS  Google Scholar 

  118. Justicia J, Oltra JE, Barrero AF, Guadaño A, González-Coloma A, Cuerva JM (2005) Eur J Org Chem 712

    Google Scholar 

  119. Justicia J, Oltra JE, Cuerva JM (2004) Tetrahedron Lett 45:4293

    Article  CAS  Google Scholar 

  120. Justicia J, Oltra JE, Cuerva JM (2005) J Org Chem 70:8265

    Article  CAS  Google Scholar 

  121. Simpson T (1998) Top Curr Chem 195:1

    CAS  Google Scholar 

  122. Justicia J, Oltra JE, Cuerva JM (2004) J Org Chem 69:5803

    Article  CAS  Google Scholar 

  123. González AG, Martín JD, Rodríguez ML (1973) Tetrahedron Lett 14:3657

    Google Scholar 

  124. González AG, Martín JD, Rodríguez ML (1976) An Quim 72:1004

    Google Scholar 

  125. Gansäuer A, Justicia J, Rosales A, Rinker B (2005) Synlett 1954

    Google Scholar 

  126. Xing X, Demuth M (1999) Synlett 987

    Google Scholar 

  127. Xing X, Demuth M (2001) Eur J Org Chem 537

    Google Scholar 

  128. Trost BM (1991) Science 254:1471

    CAS  Google Scholar 

  129. Trost BM (1995) Angew Chem Int Ed 34:259

    CAS  Google Scholar 

  130. Abe I, Rohmer M, Prestwich GD (1993) Chem Rev 93:2189

    Article  CAS  Google Scholar 

  131. Wendt KU, Schulz GE, Corey EJ, Liu DR (2000) Angew Chem Int Ed 39:2812

    CAS  Google Scholar 

  132. Hoshino T, Sato T (2002) Chem Commun 291

    Google Scholar 

  133. Goldsmith DJ (1962) J Am Chem Soc 84:3913

    Article  CAS  Google Scholar 

  134. van Tamelen EE (1975) Acc Chem Res 8:152

    Google Scholar 

  135. Taylor SK (1992) Org Prep Proc Int 24:247

    Article  Google Scholar 

  136. Dennison ST, Harrowven DC (1996) J Chem Ed 73:697

    Article  CAS  Google Scholar 

  137. Huang AX, Xiong Z, Corey EJ (1999) J Am Chem Soc 121:9999

    CAS  Google Scholar 

  138. Marson CM (2000) Tetrahedron 56:8779

    Article  CAS  Google Scholar 

  139. Zhang J, Corey EJ (2001) Org Lett 3:3215

    CAS  Google Scholar 

  140. Yuan M, Schreiber JV, Corey EJ (2002) J Am Chem Soc 124:11290

    Google Scholar 

  141. van Tamelen EE, Willet J, Schwartz M, Nadeau R (1966) J Am Chem Soc 88:5937

    Google Scholar 

  142. Sharpless KB, van Tamelen EE (1969) J Am Chem Soc 91:1848

    CAS  Google Scholar 

  143. Eliel EL, Wilen SH, Doyle MP (2001) Basic organic stereochemistry. Wiley-Interscience, New York

    Google Scholar 

  144. Naya Y, Kotake M (1968) Tetrahedron Lett 9:1645

    Google Scholar 

  145. Warmers U, König WA (1999) Phytochemistry 52:99

    CAS  Google Scholar 

  146. Cool LG (2001) Phytochemistry 58:969

    Article  CAS  Google Scholar 

  147. Salomon CE, Magarvey NA, Sherman DV (2004) Nat Prod Rep 21:105

    Article  CAS  Google Scholar 

  148. Blunt JW, Copp BR, Munro MHG, Northcote PT, Prinsep MR (2004) Nat Prod Rep 21:1

    Article  CAS  Google Scholar 

  149. Rudi A, Kashman Y (1992) J Nat Prod 55:1408

    Article  CAS  Google Scholar 

  150. Kuniyoshi M, Marma MS, Higa T, Bernardinelli G, Jefford CW (2000) Chem Commun 1155

    Google Scholar 

  151. Kuniyoshi M, Marma MS, Higa T, Bernardinelli G, Jefford CW (2001) J Nat Prod 64:696

    Article  CAS  Google Scholar 

  152. Su JY, Zhong YL, Zeng LM, Wu HM, Ma K (1995) Phytochemistry 40:195

    Article  CAS  Google Scholar 

  153. Urones JG, Marcos IS, Basabe P, Alonso CA, Diez D, Garrido NM, Oliva IM, Rodilla JS, Slawin AMZ, Williams DJ (1990) Tetrahedron Lett 31:4501

    CAS  Google Scholar 

  154. Urones JG, Marcos IS, Basabe P, Alonso C, Oliva IM, Garrido NM, Martín DD, Lithgow AM (1993) Tetrahedron 49:4051

    CAS  Google Scholar 

Download references

Acknowledgments

We are grateful to the “Junta de Andalucia” for the financial support to our research group (FQM339), including the project from the “Consejería de la Presidencia” (AM43/04). J.J. thanks the University of Granada and J.L.O.-L. the Spanish Ministry of Education and Science for their grants.

Author information

Authors and Affiliations

  1. Department of Organic Chemistry, Faculty of Sciences, University of Granada, Campus Fuentenueva s/n, 18071, Granada, Spain

    Juan M. Cuerva, José Justicia, Juan L. Oller-López & J. Enrique Oltra

Authors
  1. Juan M. Cuerva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. José Justicia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juan L. Oller-López
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Enrique Oltra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Enrique Oltra .

Editor information

Andreas Gansäuer

Rights and permissions

Reprints and permissions

About this chapter

Cite this chapter

Cuerva, J.M., Justicia, J., Oller-López, J.L., Oltra, J.E. Cp2TiCl in Natural Product Synthesis. In: Gansäuer, A. (eds) Radicals in Synthesis II. Topics in Current Chemistry, vol 264. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_025

Download citation

Publish with us

Policies and ethics

Search

Navigation