REVIEW 1 Recent Advances in Chromium(II)- and Chromium(III)-Mediated Organic Synthesis Ludger A. Wessjohann, GŸnther Scheid Ludger A. Wessjohann,* GŸnther Scheid Vakgroep Organische en Anorganische Chemie, Faculty of Chemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, NL-1081 HV Amsterdam Fax: +31(20)4447488; E-mail: [email protected] Received 7 September 1998 Dedicated to Professor Dr. Wolfgang Steglich on the occasion of his 65th birthday 4.1 Dehalogenations and Reductions Abstract: Synthetic transformations utilizing chromium(II) or 4.2 CÐC Coupling Reactions: Radicals from Carbonyl Groups chromium(III) reagents, mainly CÐC-coupling reactions, are dis- 4.3 CÐC Coupling Reactions: Radicals from Alkyl Halides cussed. Chromium reagents find increasing application in complex 5 Reactions Catalytic in Chromium(II) total syntheses where other organometallics are difficult to apply. 5.1 General Aspects They are easy to prepare and exhibit extraordinary chemoselectivity 5.2 Chromium(II) Recycled with Reductive Metals and high diastereoselectivity. In this article emphasis is laid on re- 5.3 Electrochemical Reactions cent results in synthetic procedures, on little known general aspects 5.4 Chromium(II/III) Compounds in Alkene Polymerization and of (organo)chromium chemistry, and on areas not reviewed before. Alkane formation The most important recent advances include reactions catalytic in 6 Asymmetric Synthesis with Chromium(II)-Mediated Reac- chromium ions, anti-selective Reformatsky-type aldol reactions tions with excellent asymmetric induction, domino radical/carbanion re- 6.1 Auxiliary Based Methods actions, asymmetric chromium(III) catalyzed epoxide openings and 6.2 Ligand Based Methods homogeneous alkene polymerization catalysts. Some progress is 7 Reactions at Heteroatoms also made in ligand controlled enantioselective reactions with Cr(II) 8 Chromium(III)-Mediated Reactions reagents, but satisfying solutions remain a major challenge in the 9 Conclusion and Outlook field. Key words: chromium(II), chromium(III) alkyls and enolates, rad- ical cyclizations, Reformatsky-type aldol reactions, NozakiÐHiya- ma and TakaiÐKishi reactions. 1 Introduction 1 Introduction The first organic chemical reactions involving chrom- 2 Importance of the Specific Properties of the Central Ions ium(II) made use of the reductive potential of the ion, Chromium(II) and Chromium(III) in the Design of Cr(II/ mainly to achieve dehalogenations.1Ð3 Later, alkene for- III)-Based Reactions mation from organic 1,2-dihalides and the first CÐC-cou- 3 Addition of Organochromium(III) Intermediates to Carbon- 4Ð17 yl Compounds plings were also discovered. Chromium(II) reagents 3.1 The Chromium-Reformatsky Reaction: Chromium(III) Eno- gained their place in modern organic synthesis in the late lates and Related Species 1970s when Nozaki and Hiyama discovered the ion to 3.1.1 General Aspects of the Chromium-Reformatsky Reaction promote chemoselective CÐC-couplings in aprotic solvent 3.1.2 Reactivity and Stereoselectivity with Simple α-Halocarbon- (WurtzÐ and HiyamaÐNozaki reactions).18Ð21 This was the yl Derivatives onset of an ever increasing development of synthetic 3.1.3 Reactions of 4-Bromocrotonates 3.1.4 Chemoselectivity in the Chromium-Reformatsky Reaction methods based on chromium(II) reagents, mainly chrom- 3.2 The NozakiÐHiyama Reaction: Allyl- and Propargylchromi- ium dichloride, and is reflected in the amount of reviews um(III) Intermediates; Benzylchromium(III) Intermediates devoted to the subject in organic chemistry. The early 3.2.1 Reactions Involving Allylchromium(III) Intermediates ones covered mainly reductions,1,22 later organochromium 3.2.2 Reactions Involving Propargyl- and Allenylchromium(III) reactions became the center of interest.15,20,23 In the early 3.2.3 Reactions of Benzylchromium(III) Derivatives 1990s, with applications in total synthesis exploding, the 3.3 Reactions of Alkylchromium(III) Intermediates; Chromium- number of specialized reviews rose rapidly,24Ð32 but chrom- Mediated Alkenation Reactions 3.3.1 General Aspects ium(II) reagents were also covered in other, more general 22,33Ð48 3.3.2 Reactions of Alkyl Halides with an Activating Substituent in reviews and books. Other recent reviews concen- α-Position trate on inorganic and physical chemistry and technical 3.3.3 Alkenation Reactions (TakaiÐHodgson) aspects like the surface chemistry of chromium ions de- 3.3.4 Reactions of Nonactivated Haloalkyl Derivatives posited on oxides;49 structure, reactivity and polymeriza- 3.3.5 Reactions of Halocyclopropanes tion activity of organochromium(III) compounds;50 and 3.4 The TakaiÐKishi (NozakiÐHiyamaÐKishi) Reaction: Vinyl-, complexes and kinetics of organochromium(III).51 Aryl- and Ethynylchromium(III) Intermediates 3.4.1 Vinyl- and Arylchromium(III) Intermediates The purpose of this review is to catch up on recent develop- 3.4.2 Reactions Involving Alkynylchromium(III) ments since the comprehensive review of Saccomano on nu- 4 Reactions of Carbon Centered Radical Intermediates Gener- cleophilic organochromium reagents,29 and the more speci- ated with Chromium(II) and Related Reactions alized one of Cintas which appeared in this journal in 1992.28 Synthesis 1999, No. 1, 1Ð36 ISSN 0039-7881 © Thieme Stuttgart á New York 2 L. A. Wessjohann, G. Scheid REVIEW However, since some aspects of the field have remained un- prox. Ð0.41 V (Figure 1) allows the mild reduction of covered in most reviews, we felt that for some minor areas a alkyl halides but in most cases is not sufficient to attack larger timeframe had to be covered. Often quite underesti- carbonyl groups directly, thus avoiding a problem com- mated is, for instance, the importance of chromium(II/III) in mon to strong and oxophilic ions like samarium(II). Com- technical processes, e.g. as the center of the second most im- pared to most metals used in similar reactions (Grignard, portant family of alkene-polymerization catalysts. Barbier reaction, etc.) chromous salts have little reducing power. They are best comparable to the also highly Most reactions with chromium(II) compounds proceed via 53 chromium(III) intermediates. Thus the properties discussed chemoselective indium metal, but without the disadvan- are usually those of organochromium(III), not of Cr(II). We tage of being a heterogeneous reagent. hope to bring some general aspects of chromium(III) chem- istry into focus, which appear to be less well known to the purely synthetic chemist, in order to aid method design and applications in the future. Recently chromium(III) com- pounds have become of greater importance in their own right, and thus syntheses utilizing defined chromium(III) reagents are reviewed for the first time. Although the reduc- tion properties of Cr(II) are in most cases still the bases for Figure 1 Reduction potentials of some metals and low valent ions the many reactions and applications developed, other prop- commonly used in organic synthesis (vs. standard hydrogen elec- erties of these ions and especially of Cr(III) have become trode)54 the center of interest and account for the immense success of Cr(III)-centered reactions in the total syntheses of com- The reduction potential of chromium(II) can be modified to plex molecules and in other reactions. Some basic proper- a large extent by ligands, or counter ions and solvents if ties of the ions involved and organochomium(III) are these act as ligands. Donor solvents like DMF increase the highlighted in the following section. reduction potential considerably, as do strong donor ligands like cyclopentadienyl (cp) or polydentate nitrogen ligands. Apart from this thermodynamic effect some ligands seem 2 Importance of the Specific Properties of the to improve the kinetics of electron transfer by breaking up Central Ions Chromium(II) and Chromium(III) the common dimeric or clustered structures of chromi- in the Design of Cr(II/III)-Based Reactions um(II) compounds. Monomeric donor complexes like chromocene are extremely reactive even at low temperature Chromium(II) is the strongest reductive metal ion soluble (vide infra). In general, chromium(II) is one of the kineti- but not rapidly reacting in water.52 The potential of ap- cally most labile transition metal ions (Figure 4).55 Biographical Sketches Ludger Wessjohann was Skatteb¿l in Oslo (Norway) completed Habilitation at born in 1961 in Melle, and after his Ph.D. as lectur- the Ludwig-Maximilians- Germany. He studied in er at the Universidade Fed- UniversitŠt MŸnchen in Hamburg (Germany) and eral de Santa Maria in Brazil 1992. Since June 1998 he is Southampton (UK) and re- (1990), where he also was full professor of bio-organic ceived his degrees from the visiting professor in 1993 chemistry at the Vrije Uni- University of Hamburg (Di- and 1995. After a postdoc- versiteit Amsterdam, The ploma 1987, Ph.D. 1990, toral stay with Professor Netherlands. His research both with Professor de Paul Wender at Stanford interests include the devel- Meijere). During his Ph.D. University (USA) working opment of new synthetic he worked 1987/88 as a vis- on the total synthesis of methods, biocatalysis, and iting scientist with Professor Taxol he started his recently natural products chemistry. GŸnther Scheid was born (LMU). The work was car- thesis. His current interest is in Landshut, Bavaria ried out under the supervi- focused on the total synthe- (Germany), in 1971. He ob- sion of Ludger Wessjohann, sis of biologically active tained his diploma in 1997 whom he followed to the compounds. from the Ludwig-Maximi-