Samarium(II) Iodide Mediated Sequential Reactions Roy Bowman January 16, 2004

Samarium(II) Iodide Mediated Sequential Reactions

• Roy Bowman

• January 16, 2004

Sequential Reactions

• Multiple bonds formed in a one pot process

• No need to collect and purify intermediates

• Access to elaborate products

• Although conceptually attractive, design of sequential reactions can be overwhelming

• Cationic, anionic, radical, pericyclic, carbenoid, and transition metal catalyzed sequential processes have been realized

Samarium(II) Iodide

• Totleben, M. J.; Curran, D. P.; Wipf, P. Journal of Organic Chemistry 1992, 57, 1740-4.

• Concellon, J. M.; Rodriguez-Solla, H.; Bardales, E.; Huerta, M. European Journal of Organic Chemistry 2003, 1775-1778

Samarium(II) Iodide

Samarium(II) Iodide

• Promotes several individual reactions important in synthesis:

• - Radical Cyclizations - Ketyl-Olefin Coupling

• - Pinacolic Coupling - Barbier Type Reactions

• - Aldol Type Reactions - Reformatsky Type Reactions

• - Conjugate Additions - Nucleophilic Acyl Substitutions

• -Cycloadditions

Samarium(II) Iodide

• Ability to promote both one and two electron processes

• Radical/Anionic

• Anionic/Radical

• Anionic/Anionic

• Radical/Radical

Reactivity

• Reactivity can be manipulated using:

• Co-solvents: HMPA, TMG, DBU

• Additives: Ni(II), Fe(III)

• Irradiation of the reaction mixture

• Allows for highly selective and efficient sequential reactions to be effective

Radical Cyclization/Carbonyl Addition

Formation of Organosamarium

Formation of Organosamarium

Radical Cyclization/Carbonyl Addition

Radical Cyclization/Carbonyl Addition

Radical Cyclization/Carbonyl Addition

Radical Cyclization/Carbonyl Addition

Radical Cyclization/Nucleophilic Addition

Radical Cyclization/ Nucleophilic Addition

Radical Cyclization/ Nucleophilic Addition

Intramolecular Nucleophilic Acyl Substitution/Intramolecular Barbier Cyclization

Intramolecular Nucleophilic Acyl Substitution/Intramolecular Barbier Cyclization

• Ability to sequence formation of the organosamarium species so carbon-carbon bonds may be directed

• Alkyl halides are reduced in the order I > Br > Cl

• Sequences where order is unimportant are performed with diiodides

• Sequenced reactions in which side chain reaction order is significant are performed with alkyl iodide/alkyl chloride substrates

Intramolecular Nucleophilic Acyl Substitution/Intramolecular Barbier Cyclization

Nucleophilic Acyl Substitution/Ketyl Olefin Coupling for Preparation of Oxygen Heterocycles

Nucleophilic Acyl Substitution/Ketyl Olefin Coupling

Nucleophilic Acyl Substitution/Ketyl Olefin Coupling

Ketyl-Olefin Coupling/β-Elimination

Ketyl-Olefin Coupling/β-Elimination

Nucleophilic Acyl Substitution/Alkenyl Transfer Reactions

Nucleophilic Acyl Transfer/Alkenyl Transfer Reactions

Nucleophilic Acyl Transfer/Alkenyl Transfer Reactions

Nucleophilic Acyl Transfer/Alkenyl Transfer Reactions

Epoxide Ring Opening/Ketyl Olefin Coupling

Domino Epoxide Ring Opening/Ketyl Olefin Coupling Reactions

Domino Epoxide Ring Opening/Ketyl Olefin Coupling Reactions

Domino Epoxide Ring Opening/Ketyl Olefin Coupling Reactions

Epoxide Fragmentation/Tandem Radical Cyclizations

Epoxide Fragmentation/Tandem Radical Cyclizations

Epoxide Fragmentation/Tandem Radical Cyclizations

Epoxide Fragmentation/Tandem Radical Cyclizations

Intramolecular Barbier Cyclization/Grob Fragmentation

Ring Expansion by Grob Fragmentation Mediated by SmI2

Ring Expansion by Grob Fragmentation Mediated by SmI2

Reformatsky/Nucleophilic Acyl Substitution

Reformatsky/Nucleophilic Acyl Substitution

Reformatsky/Nucleophilic Acyl Substitution

Reformatsky/Nucleophilic Acyl Substitution

Transformation of Carbohydrate Derivatives into Cyclopentanols

Transformation of Carbohydrate Derivatives into Cyclopentanols

Insertion of Isocyanides into Organic Halides Preparation of -Hydroxy Ketones

Insertion of Isocyanides into Organic Halides Preparation of -Hydroxy Ketones

Insertion of Isocyanides into Organic Halides Preparation of -Hydroxy Ketones

Insertion of Isocyanides into Organic Halides Preparation of -Hydroxy Ketones

Insertion of Isocyanides into Organic Halides Preparation of -Hydroxy Ketones

Insertion of Isocyanides into Organic Halides Preparation of -Hydroxy Ketones

Synthesis of Vicinal Di- and Tri-Carbonyl Compounds

Synthesis of Vicinal Di- and Tri-Carbonyl Compounds

Synthesis of Vicinal Di- and Tri-Carbonyl Compounds

Synthesis of Vicinal Di- and Tri-Carbonyl Compounds

Cyclizations of Indole Derivatives

Cyclizations of Indole Derivatives

Cyclizations of Indole Derivatives

Cascade Radical Cyclizations: Synthesis of Paeonilactone B

Cascade Radical Cyclizations: Synthesis of Paeonilactone B

Synthesis of (±) Hypnophilin

Synthesis of (±) Hypnophilin

Synthesis of Phomoidrides

Synthesis of Phomoidrides

Synthesis of Phomoidrides

Synthesis of Phomoidrides

Synthesis of Phomoidrides

Synthesis of Phomoidrides

Synthesis of Phomoidrides

Summary

• Mild conditions, tolerant to functionality

• Reactivity can be manipulated allowing each

• step in the sequence to be tuned

• Capable of driving sequential reactions

• Highly diastereoselective resulting from highly

• organized transition states

• Sequential radical cyclization mediated by SmI2 have shown

• utility in natural product synthesis

Acknowledgements

• Dr. Jeff Johnson

• Johnson Group