Transition-Metal-Catalyzed Reactions in Steroid Synthesis Rita Skoda-Fo ¨ldes* Department of Organic Chemistry and Research Group for Petrochemistry of the Hungarian Academy of Sciences, University of Veszpre ´m, Egyetem u. 8., P.O. Box 158, H-8200 Veszpre ´m, Hungary La ´szlo ´ Kolla ´r* Department of Inorganic Chemistry and Research Group for Chemical Sensors of the Hungarian Academy of Sciences, University of Pe ´cs, Ifju ´sa ´g u. 6., P.O. Box 266, H-7623 Pe ´cs, Hungary Received April 8, 2003 Contents 1. Introduction 4095 2. Homogeneous Catalytic Hydrogenation of Steroids 4097 2.1. Hydrogenation of the Carbon-Carbon Double Bonds 4097 2.1.1. Hydrogenation of ∆ 4 and ∆ 5 Double Bonds Resulting in A/B cis- and trans-Fused Skeletons 4097 2.1.2. Hydrogenation of Carbon-Carbon Double Bonds 4097 2.1.3. Isotope Labeling of Steroids via Deuteration and Tritiation 4098 2.2. Reduction of the Carbonyl Group in Steroidal Ketones 4098 2.2.1. Hydrogenation of the Carbonyl Group 4098 2.2.2. Transfer Hydrogenation of the Carbon-Oxygen Double Bond 4098 2.2.3. Hydrosilylation of the Carbon-Oxygen Double Bond 4099 2.3. Hydrogenolysis 4099 3. Homogeneous Catalytic Carbonylation Reactions of Carbon-Carbon Double Bonds 4100 3.1. Hydroformylation 4100 3.1.1. Hydroformylation of Carbon-Carbon Double Bonds in the Ring System 4100 3.1.2. Hydroformylation of Carbon-Carbon Double Bonds in the Substituents 4100 3.2. Hydroalkoxycarbonylation of Carbon-Carbon Double Bonds 4100 3.3. Other Carbonylation Reactions 4101 4. 1,4 and 1,6 Additions to Enones 4101 5. Carbon-Carbon Bond-Forming Reactions on Enol Triflates and Iodo Alkenes (Excluding Carbonylation Reactions) 4102 5.1. Coupling Reactions of Steroidal Enol Triflates/Iodo Alkenes with Alkenes (Heck Reaction) 4102 5.2. Coupling Reactions of Steroidal Enol Triflates/Iodo Alkenes with Alkynes 4103 5.3. Coupling Reactions of Steroidal Enol Triflates/Iodo Alkenes with Organometallics 4104 5.4. Carbonylative Coupling Reactions 4106 5.5. Coupling Reactions of Steroidal Alkenes/ Alkynes 4107 6. Carbonylation Reactions of Enol Triflates and Related Structures 4108 6.1. Alkoxycarbonylation and Hydroxycarbonylation Reactions 4108 6.2. Aminocarbonylation and Related Reactions 4110 7. Stereocontrolled Introduction of an Acyclic Substituent onto a 4-Ring Skeleton via π-Allylpalladium Chemistry 4111 8. Transition-Metal-Catalyzed Cyclization Reactions 4112 8.1. Stereoselective Formation of the Basic Steroidal Skeleton via Cyclization Reactions 4112 8.2. Synthesis of Cyclic Systems Attached to the 4-Ring Skeleton 4114 8.3. Synthesis of Vitamin D Derivatives 4117 8.4. Cyclopropanation 4117 9. Catalytic Rearrangements 4118 10. Introduction of Heteroatoms to the Steroidal Backbone 4119 10.1. Amidation of Saturated C-H Bonds 4119 10.2. Aziridination 4119 10.3. Epoxidation 4119 10.4. Oxidation 4120 10.5. Phosphonation and Amination 4123 11. Formation of the Carbon-Oxygen Bond 4123 11.1. O-Acylation 4123 11.2. O-Vinylation, Allylation 4123 11.3. O-Alkylation 4124 12. Steroid-Based Ligands in Homogeneous Catalysis 4124 12.1. Steroidal Ligands with Phosphorus Donors 4124 12.2. Steroidal Ligands with Other Donors 4125 13. Concluding Remarks 4126 14. Acknowledgments 4126 15. References 4126 1. Introduction Organo-transition-metal chemistry, after an unbe- lievable expansion in the last half of the century, * R.S.-F. E-mail: skodane@almos.vein.hu. Phone: 0036-88-422 022. Fax: 0036-88-427 492. L.K. E-mail: kollar@ttk.pte.hu. Phone: 0036-72-503 600 Fax: 0036-72-501 527. 4095 Chem. Rev. 2003, 103, 4095-4129 10.1021/cr020075g CCC: $44.00 © 2003 American Chemical Society Published on Web 09/19/2003