Tandem Intramolecular Carbolithiation‐Lithium/Zinc Transmetallation and Applications to Carbon−Carbon Bond‐Forming Reactions

Abstract

Lithium/zinc transmetallation with the cyclic organolithium intermediate 3 (prepared by intramolecular carbolithiation of the initially formed organolithium 2) gives the corresponding organozinc intermediate 5. Copper‐ or palladium‐promoted SN2′ reactions between compound 5 and allylic or propargylic halides, as well as arylation, vinylation, benzylation, acylation, and conjugate addition to α,β‐unsaturated carbonyl compounds, afford (after hydrolysis) the expected compounds 7−15, which are not accessible directly from the organolithium precursor 3 even with transition metal catalysis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Synthesis of Functionalized Dialkyl Ketones from Carboxylic Acid Derivatives and Alkyl Halides

“…5a,12 The NiCl 2 /Zn-mediated acylation of alkyl iodides with substituted pyridyl carboxylates was reported by Mukaiyama 30 years ago, but access to the esters required extra steps, an excess of R-I (3 equiv) was needed, and a reaction with a more hindered ester provided a low yield. 12c Other studies with either Pd/Zn 5a or Ni/ e -12e–f found that primary benzylic chlorides could be acylated in good yield, but an excess of benzyl halide was required to overcome competing dimerization and no hindered substrates were reported.…”

Intramolecular Carbolithiation Reactions in the Construction of Medium‐Sized Rings. Synthesis of Pyrroloisoquinolines, Benzazepines, and Benzazocines

“…of tBuLi/ TMEDA (see Table 2, Entry 3). The introduction of a phenyl group to the alkene to stabilize the organolithium compound generated by the carbolithiation [26] also did not favor the intramolecular reaction, and deiodinated N-benzylpyrrole 4b was the only product (see Table 2, Entries 4 and 5). The introduction of a phenyl group to the alkene to stabilize the organolithium compound generated by the carbolithiation [26] also did not favor the intramolecular reaction, and deiodinated N-benzylpyrrole 4b was the only product (see Table 2, Entries 4 and 5).…”

“…CI): m/z (%) = 371 (88) [MH] + , 370 (72) [M] + , 284(11), 270(19), 269(13), 258(14), 257(26), 256 (100). HRMS (CI): calcd.…”

Nickel-Catalyzed Synthesis of Ketones from Alkyl Halides and Acid Chlorides: Preparation of Ethyl 4-Oxododecanoate

“…2 While both of these protocols are effective, the organometallic reagents can be limiting with complex, functionalized molecules. More recently, cross-coupling methods based upon the less reactive alkyltin, 4 alkylzinc, 5,6 dialkylzinc, 7 or alkylboron 8 reagents have been developed.…”