C–H Nickelation of Naphthyl Phosphinites: Electronic and Steric Limitations, Regioselectivity, and Tandem C–P Functionalization

Abstract

This report describes the results of a study on the C–H nickelation of phosphinites derived from variously substituted 1- and 2-naphthols, as well as the C–P functionalization of the Ni-naphthyl moiety arising from the C–H cyclonickelation. Refluxing 4-X-1-naphthyl phosphinites (X = H, 1a; MeO, 1b; Cl, 1c) with {(i-PrCN)­NiBr2} n and Et3N in acetonitrile gave the nickelacyclic complexes {(κP,κC-4-X-1-OP­(i-Pr)2-naphth-2-yl)­Ni­(μ-Br)}2, 2a–c, resulting from cyclonickelation at the C2–H, whereas cyclonickelation of the 2-naphthyl phosphinite analogue 1e under the same conditions occurred at C3–H. Placing a Me substituent at the C3 position of a 2-naphthyl phosphinite (1f) led to a very sluggish nickelation at the C1–H position, whereas 2-ethyl-1-naphthyl phosphinite (1d) failed to nickelate at C8–H. H/D scrambling tests conducted on the deuterated analogue of 1a (1a-d 7 ) confirmed that nickelation occurs exclusively at C2. Similar tests conducted on deuterated analogues of alkyl-substituted 1- and 2-naphthyl phosphinites showed that no nickelation takes place at Csp3 –H sites of the alkyl substituents. In contrast, very facile C–H nickelation was observed with 2-allyl-1-naphthyl phosphinite 1g to give a product featuring a π-allyl-Ni moiety. A series of tests have shown that the nickelation of substrates 1a, 1e, and 1f can be accelerated dramatically at 120–160 °C. On the other hand, conducting the high temperature reaction of 1a in the absence of Et3N resulted in an unanticipated and interesting C–P functionalization of the C2–H site, thus generating a i-Pr2P-substituted bidentate phosphine-phosphinite. A similar tandem C–H nickelation/C–P­(O) functionalization was also observed at the C8–H position of substrate 1d. The mechanisms of these functionalization reactions have been probed and outlined.

The Deuterated “Magic Methyl” Group: A Guide to Site‐Selective Trideuteromethyl Incorporation and Labeling by Using CD3Reagents

“…CD 3 I has also been applied as a reagent in the C−H trideuteromethylation of arenes, a very useful transformation from an atom and a step‐economy point of view. A classical strategy is ortho ‐lithiation with n BuLi followed by trapping with CD 3 I [51] . The scope of this approach is very limited due to the use of very reactive organolithium; milder conditions are needed.…”

“…A classical strategy is ortho ‐lithiation with n BuLi followed by trapping with CD 3 I. [51] The scope of this approach is very limited due to the use of very reactive organolithium; milder conditions are needed. In 2016, ortho C−H trideuteromethylation of acetanilide was achieved based on a method developed in 1984 by Tremont (Scheme 9 a).…”

Influence of the Flexibility of Nickel PCP‐Pincer Complexes on C−H and P−C Bond Activation and Ethylene Reactivity: A Combined Experimental and Theoretical Investigation

“…[81] The Ni1À P1 bond length of 2.2019(5) Å is also indicative of the trans influence of the aryl ligand at C16. It is interesting to recall that reactions related to a "reverse" of the PÀ C bond breaking reaction leading to 15 were observed (i) in Ni II phosphinite/phosphane complexes, [82] (ii) when metallacyclic Pd II complexes containing C,P and P,O chelates were reacted with PPhCl 2 with formation of CÀ P and OÀ P bonds, [83,84] and in Pt cluster chemistry with the reductive coupling of a bridging μ-PPh 2 group with a cis-phenyl ligand to form a PPh 3 ligand. [85] Note, however, that in cases (i) and (ii), the PR 2 group does not originate from a phosphanido ligand.…”

Frontispiece: The Deuterated “Magic Methyl” Group: A Guide to Site‐Selective Trideuteromethyl Incorporation and Labeling by Using CD3 Reagents

“…A classical strategy is ortho-lithiation with nBuLi followed by trapping with CD 3 I. [51] The scope of this approach is very limited due to the use of very reactive organolithium; milder conditions are needed. In 2016, ortho CÀ H trideuteromethylation of acetanilide was achieved based on a method developed in 1984 by Tremont (Scheme 9a).…”