Electronic Effects in Carbene‐Mediated CH Bond Functionalization: An Experimental and Theoretical Study

Abstract

Abstract:In this article, we show that short-distance and long-range electronic effects are strongly affecting the mechanism and stereoselectivity of Rh(II)-carbene mediated C À H functionalization processes. Based on experimental studies with deuterium-labelled carbohydrates and DFT calculations, we show that the orientation of the lone pairs of adjacent heteroatoms, as well as the nature of substituents located far from the reaction center, are inducing a shift from the classical concerted mechanism to the less common stepwise process. Furthermore, we reveal that the stereochemical outcome of these transformations is depending on the relative energies of the C À H bond activation and Rh(II)-carbene isomerization barriers. The formation of a single diastereoisomer is thus resulting from Curtin-Hammet-like kinetics when insertion occurs in poorly activated C À H bonds. However, the formation of diastereoisomeric mixtures is resulting from two disconnected and totally stereoselective transformations when the reactivity of the C À H bonds towards electrophilic metallocarbenes is increased by short-distance or longrange electronic effects.

Mechanism of the Selective Fe-Catalyzed Arene Carbon–Hydrogen Bond Functionalization

“…In agreement with our results, the fact that metal carbenes do not perform a concerted C substrate –H bond insertion for aromatic substrates, contrary to alkane substrates, has been also recently reported for gold carbenes . The same conclusion can also be obtained when comparing the mechanistic literature of the reactions of Au, Cu, Ag, or Rh carbenes with alkanes and with aromatic compounds. , …”

Diastereoselective Pd-Catalyzed Anomeric C(sp3)–H Activation: Synthesis of α-(Hetero)aryl C-Glycosides

“…To functionalize the anomeric C­(sp 3 )–H bond, the easy removable picolinic acid auxiliary has been chosen to be installed on the C3-amino group of the sugar to direct the palladium­(II) catalyst selectively to the weak anomeric C­(sp 3 )–H bond through a bidentate coordinating mechanism. We suggested at this stage that the metal catalyst will approach preferentially the more reactive axial anomeric C–H bond of the substrate ( A ) to generate through the concerted metalation-deprotonation (CMD) mechanism a five membered palladacycle ( B ) (Figure ). This pathway will lead to the 1,3 diaxial complex ( B ), which may be involved in an oxidative addition in the presence of an aryl iodide to furnish the Pd­(IV) complex ( C ).…”

Rhodium‐Catalyzed Alkene Difunctionalization with Nitrenes

“…We used [Rh 2 (O 2 CH) 4 ]( A or [Rh] 2 )a nd Rh 2 (O 2 CH) 4 (NTces) (C or [Rh] 2 = NTces) as model organometallic frameworks. [25] Althought he Lewis acid A and its Lewis base adducts are obviously closedshell species, the spin multiplicity of rhodium nitrenesc an be singlet or triplet. According to calculations, C has at riplet ground state (E st = E singlet ÀE triplet = 1.5 kcal mol À1 ; DG st (solv) = 0.9 kcal mol À1 ), yet as previously noted for related systems, [23] the singlet-triplet gap is rather small, so the two spin states could coexist in solution.…”

“…Solvation correction (benzene) was obtained by the CPCM method. We used [Rh 2 (O 2 CH) 4 ] ( A or [Rh] 2 ) and Rh 2 (O 2 CH) 4 (NTces) ( C or [Rh] 2 =NTces) as model organometallic frameworks . Although the Lewis acid A and its Lewis base adducts are obviously closed‐shell species, the spin multiplicity of rhodium nitrenes can be singlet or triplet.…”