Silicon-Tethered Strategies for C–H Functionalization Reactions

Abstract

CONSPECTUS Selective and efficient functionalization of ubiquitous C–H bonds is the Holy Grail of organic synthesis. Most advances in this area rely on employment of strongly or weakly coordinating directing groups (DGs) which have proven effective for transition-metal-catalyzed functionalization of C(sp2)–H and C(sp3)–H bonds. Although most directing groups are important functionalities in their own right, in certain cases, the DGs become static entities that possess very little synthetic leverage. Moreover, some of the DGs employed are cumbersome or unpractical to remove, which precludes the use of this approach in synthesis. It is believed, that development of a set of easily installable and removable/modifiable DGs for C–H functionalization would add tremendous value to the growing area of directed functionalization, and hence would promote its use in synthesis and late-stage functionalization of complex molecules. In particular, silicon tethers have long provided leverage in organic synthesis as easily installable and removable/modifiable auxiliaries for a variety of processes, including radical transformations, cycloaddition reactions, and a number of TM-catalyzed methods, including ring-closing metathesis (RCM) and cross-coupling reactions. Employment of Si-tethers is highly attractive for several reasons: (1) they are easy to handle/synthesize and are relatively stable; (2) they utilize cheap and abundant silicon precursors; and (3) Si-tethers are easily installable and removable/modifiable. Hence, development of Si-tethers for C–H functionalization reactions is appealing not only from a practical but also from a synthetic standpoint, since the Si-tether can provide an additional handle for diversification of organic molecules post-C–H functionalization. Over the past few years, we developed a set of Si-tether approaches for C–H functionalization reactions. The developed Si-tethers can be categorized into four types: (Type-1) Si-tethers possessing a reacting group, where the reacting group is delivered to the site of functionalization; (Type-2) Si-tethers possessing a DG, designed for selective C(sp2)–H functionalization of arenes; (Type-3) reactive Si-tethers for C–H silylation of organic molecules; and finally, (Type-4) reactive Si-tethers containing a DG, developed for selective C–H silylation/hydroxylation of challenging C(sp3)–H bonds. In this Account, we outline our advances on the employment of silicon auxiliaries for directed C–H functionalization reactions. The discussion of the strategies for employment of different Si-tethers, functionalization/modification of silicon tethers, and the methodological developments on C–C, C–X, C–O, and C–Si bond forming reactions via silicon tethers will also be presented. While the work described herein presents a substantial advance for the area of C–H functionalization, challenges still remain. The use of noble metals are required for the C–H functionalization methods presented herein. Also, the need for stoichiometric use of high molecular weight silicon aux...

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…Following this general concept several research groups entered the field of Si-based DGs in C–H functionalisation. 735 , 1090 , 1091 Already more than one decade ago several research groups questioned the potential of “SiR 2 H” to play a double role of a DG to drive the C–H activation event at one specific position and to provide, in an intramolecular fashion, a silicone-based coupling partner. The potential of such reactions holds also a major synthetic value as the newly formed C–Si bonds might be further interconverted into several functionalised motifs.…”

Desymmetrization‐Oriented Enantioselective Synthesis of Silicon‐Stereogenic Silanes by Palladium‐Catalyzed C−H Olefinations

“…In fact, only intramolecular C−H bond functionalization approaches have been reported to access cyclic silicon‐stereogenic silanes such as dibenzosiloles and 5,10‐dihydrophenazasiline, including the direct arylation, dehydrogenative silylation, 1,5‐palladium migration reaction, and ring expansion/dehydrogenative silylation reactions. The pioneering work by the group of Gevorgyan showed that pyridine and pyrimidine serve as powerful directing groups in various C−H functionalization reactions of silicon‐tethered arenes (Scheme ). However, to the best of our knowledge, there have been no successful examples on the transition‐metal‐catalyzed intermolecular C−H functionalization of prochiral organosilicon compounds which allow for the synthesis of acyclic silicon‐stereogenic tetraorganosilicons with heteroatom‐containing functional groups.…”

“…In fact, only intramolecular CÀHb ond functionalization approaches have been reportedt oa ccess cyclic siliconstereogenic silanes such as dibenzosiloles and 5,10-dihydrophenazasiline, including the direct arylation, [7] dehydrogenative silylation, [8] 1,5-palladium migration reaction, [9] and ring expansion/dehydrogenative silylation [10] reactions. The pioneering work by the group of Gevorgyan showedt hat pyridine and pyrimidine serve as powerful directing groups in various CÀH functionalization reactions of silicon-tethered arenes [11] (Scheme 1). However,t ot he best of our knowledge, there have been no successful exampleso nt he transition-metal-catalyzed intermolecular CÀHf unctionalization of prochiral organosilicon compounds which allow for the synthesis of acyclic silicon-stereogenic tetraorganosiliconsw ith heteroatom-containingf unctional groups.I nspired by the findings that amino acid can promote the ortho-CÀHa ctivation of phenols with a silicon-tetheredd irectingg roup [12] (Scheme 1a)a nd the MPAA/ Pd complexesa re efficient catalysts for the syntheses of P-and S-chiral compounds [13] via CÀHa ctivation,w ee nvisioned that silicon-stereogenic certers may be produced via desymmetric CÀHf unctionalization of one of two identical aryls at the prochiral silicon under chiral palladium complex catalysis.…”

Iridium‐Catalyzed, Silyl‐Directed, peri‐Borylation of C−H Bonds in Fused Polycyclic Arenes and Heteroarenes

“…[12,13] Thesilyl group adds transiently to the metal center and can be used after the borylation reaction to create ar ange of functional groups by transformations that are orthogonal in most cases to those of the transformations of CÀ Bb onds,thus largely increasing the product diversity. [12,13] Thesilyl group adds transiently to the metal center and can be used after the borylation reaction to create ar ange of functional groups by transformations that are orthogonal in most cases to those of the transformations of CÀ Bb onds,thus largely increasing the product diversity.…”

“…Our group has reported silyl-directed borylations of C À H bonds,i nw hich the borylation occurred at aromatic C À H bonds or C(sp 3 ) À Hbonds ortho to asubstituent containing an SiÀHbond. [12,13] Thesilyl group adds transiently to the metal center and can be used after the borylation reaction to create ar ange of functional groups by transformations that are orthogonal in most cases to those of the transformations of CÀ Bb onds,thus largely increasing the product diversity. [12] We report the peri-borylation of C À Hb onds in 1-hydrosilyl naphthalenes and related polyaromatic hydrocarbons (Scheme 1d).…”