The development of enabling synthetic methodologies for the chemical manipulation of unfunctionalized C-H bonds (frequently referred as “C-H activation”) is a long though issue for chemical practitioners. , The astonishing interest by the chemical community in the field has been elegantly addressed recently by a NEWS & VIEWS Q&A article in which R.G. Bergman emphasized Why, When and How, organometallic chemists succeeded in addressing and efficiently solving this challenging task. • Why: C-H bonds are ubiquitous in nature and, consequently, they constitute and undoubted atom economy platform to build up countless new molecular architectures, aiming to the synthesis of natural as well as synthetic compounds. Unfortunately, the C-H content of the largest part of natural hydrocarbons is too inert for taking part to “classic” organic transformations under synthetically accessible reaction parameters. Moreover, the electronic as well as sterical similarity of C-H connections within unfunctionalized organic scaffolds concur to pose extra challenges in selective C-H cleavages. For sure, the pursuing in developing efficient, selective and sustainable C-H activation methodologies would dramatically revolutionize our current way of thinking about planning organic synthetic sequences. • When and How: organometallic chemists opened new horizons up in C-H functionalization in the late 1960s (Ni, Pt, Ru) and early 1970s (Re, Ir). Here, late transition metals were found to activated both Csp3-H and Csp2-H bonds via a well-known process referred as oxidative addition in which a metal center inserts into a C-H connection providing a new chemical entity containing reactive carbon-metal and carbon-hydrogen bonds. Interestingly, a close debate about definition of C-H activation, invested chemical community along the second half of the past century. In particular, the former statement posed by Halpern in 1968: ”dissociation of carbon-hydrogen bonds by metal complexes” was replaced by a more “organometallic definition”, that was formulated with the purpose to distinguish metal-assisted C-H activation processes by radical and ionic substitution: “C-H bond activation refers to the formation of a complex wherein the C-H bond interacts with the metal reagent and catalysts”. Pioneering investigations documented on the need for stoichiometric amount of metal source to reach satisfyingly levels of chemical yields, however these methodologies have never been economically sustainable. Metal catalysis in C-H activation appeared only recently and many shortcomings still have to be fully addressed. Among them, harsh reaction conditions and the mandatory presence of directing groups need to be mentioned. Finally, it is worth mentioning that the transformation of unactivated C-H interatomic connections into C-X bonds (X: C, heteroatoms) is routinely addressed also as C-H bond oxidation, and “traces” of reliable catalytic methodologies were already present in the seminal treatise edited by Trost and Fleming in 1991. In line with these considerations it is not surprising to disclose that also asymmetric catalysis could not be immune by the incredible impact that C-H activation methodologies have had on inspiring organic chemists over the past few years. At this stage, we are adding an extra-challenge to the transformation, as a matter of fact, beside the intrinsic difficulties related to chemo- and regioselectivity of C-H activations, the new dimension of this hot-topic is related to the selective cleavage of diastereotopically and/or enantiotopically disposed C-H bonds in a certain molecule. Despite marvellous advances reached in the recent years, the discovery of efficient chiral catalyst for the stereoselective cleavage/manipulation of C-H molecular frameworks has still remained a non-trivial synthetic task. Concerning the organization of the chapter, it should be mentioned that emphasis will be exclusively devoted to that transformations a...

C-H Activation in Asymmetric Catalysis

BANDINI, MARCO
2012

Abstract

The development of enabling synthetic methodologies for the chemical manipulation of unfunctionalized C-H bonds (frequently referred as “C-H activation”) is a long though issue for chemical practitioners. , The astonishing interest by the chemical community in the field has been elegantly addressed recently by a NEWS & VIEWS Q&A article in which R.G. Bergman emphasized Why, When and How, organometallic chemists succeeded in addressing and efficiently solving this challenging task. • Why: C-H bonds are ubiquitous in nature and, consequently, they constitute and undoubted atom economy platform to build up countless new molecular architectures, aiming to the synthesis of natural as well as synthetic compounds. Unfortunately, the C-H content of the largest part of natural hydrocarbons is too inert for taking part to “classic” organic transformations under synthetically accessible reaction parameters. Moreover, the electronic as well as sterical similarity of C-H connections within unfunctionalized organic scaffolds concur to pose extra challenges in selective C-H cleavages. For sure, the pursuing in developing efficient, selective and sustainable C-H activation methodologies would dramatically revolutionize our current way of thinking about planning organic synthetic sequences. • When and How: organometallic chemists opened new horizons up in C-H functionalization in the late 1960s (Ni, Pt, Ru) and early 1970s (Re, Ir). Here, late transition metals were found to activated both Csp3-H and Csp2-H bonds via a well-known process referred as oxidative addition in which a metal center inserts into a C-H connection providing a new chemical entity containing reactive carbon-metal and carbon-hydrogen bonds. Interestingly, a close debate about definition of C-H activation, invested chemical community along the second half of the past century. In particular, the former statement posed by Halpern in 1968: ”dissociation of carbon-hydrogen bonds by metal complexes” was replaced by a more “organometallic definition”, that was formulated with the purpose to distinguish metal-assisted C-H activation processes by radical and ionic substitution: “C-H bond activation refers to the formation of a complex wherein the C-H bond interacts with the metal reagent and catalysts”. Pioneering investigations documented on the need for stoichiometric amount of metal source to reach satisfyingly levels of chemical yields, however these methodologies have never been economically sustainable. Metal catalysis in C-H activation appeared only recently and many shortcomings still have to be fully addressed. Among them, harsh reaction conditions and the mandatory presence of directing groups need to be mentioned. Finally, it is worth mentioning that the transformation of unactivated C-H interatomic connections into C-X bonds (X: C, heteroatoms) is routinely addressed also as C-H bond oxidation, and “traces” of reliable catalytic methodologies were already present in the seminal treatise edited by Trost and Fleming in 1991. In line with these considerations it is not surprising to disclose that also asymmetric catalysis could not be immune by the incredible impact that C-H activation methodologies have had on inspiring organic chemists over the past few years. At this stage, we are adding an extra-challenge to the transformation, as a matter of fact, beside the intrinsic difficulties related to chemo- and regioselectivity of C-H activations, the new dimension of this hot-topic is related to the selective cleavage of diastereotopically and/or enantiotopically disposed C-H bonds in a certain molecule. Despite marvellous advances reached in the recent years, the discovery of efficient chiral catalyst for the stereoselective cleavage/manipulation of C-H molecular frameworks has still remained a non-trivial synthetic task. Concerning the organization of the chapter, it should be mentioned that emphasis will be exclusively devoted to that transformations a...
Seminars in Organic Synthesis
64
87
M. Bandini
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/117088
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