Grignard reagents from alkynes

When terminal alkynes are used as substrates, alkylcoppermagnesium dihalides prepared from a cop-peril) bromide-dimethyl sulfide complex typically are used (e.g. equation 31134 and Scheme 7).135 The choice of a Grignard reagent, from which the alkylcopper(I) species is prepared, is important in this instance, alkyllithium-derived alkylcopper reagents usually are less satisfactory.10... 

Another feature of the Pd—C bonds is the excellent functional group tolerance. They are inert to many functional groups, except alkenes and alkynes and iodides and bromides attached to sp carbons, and not sensitive to H2O, ROH, and even RCO H. In this sense, they are very different from Grignard reagents, which react with carbonyl groups and are easily protonated. 

Alkyl- and aryl-pyridazines can be prepared by cross-coupling reactions between chloropyridazines and Grignard reagents in the presence of nickel-phosphine complexes as catalysts. Dichloro[l,2-bis(diphenylphosphino)propane]nickel is used for alkylation and dichloro[l,2-bis(diphenylphosphino)ethane]nickel for arylation (78CPB2550). 3-Alkynyl-pyridazines and their A-oxides are prepared from 3-chloropyridazines and their A-oxides and alkynes using a Pd(PPh3)Cl2-Cu complex and triethylamine (78H(9)1397). 

Jacobi reports using a variant of method A to access the A,B,E-ring system of wortmannin.14 The sequential addition of methyl lithium and acetylenic Grignard reagent followed by triflation proceeds from 7 to the corresponding triflate 8 in 74% yield (Fig. 4.13). Subsequent carbonylation of the alkyne and the phenol produces the acyl oxazole 9, which is smoothly converted into the furanolactone 10 over three more steps. 

Terminal alkynes are acidic, and the end hydrogen can be removed as a proton by strong bases (e.g. organolithiums, Grignard reagents and NaNH2) to form metal acetylides and alkynides. They are strong nucleophiles and bases, and are protonated in the presence of water and acids. Therefore, metal acetylides and alkynides must be protected from water and acids. 

In general, monoaddition was observed when a terminal alkyne was directly treated with an excess of the allenylzinc reagent itself. However, starting from an alkynyl Grignard reagent predominantly led to bis-addition compounds (equation 152)185. 

The best copper reagents are RCu.MgHlg2 and R2Cu.MgHlg derived from Grignard reagents, and R2CuLi (R = primary alkyl). Acetylene is the most reactive alkyne,515 whereas internal acetylenes do not react. 

Acetylenic Grignard reagents of the type RC CMgBr are prepared, not from an acetylenic halide, but by an acid-base reaction in which a Grignard reagent abstracts a proton from a terminal alkyne. 

Chiral Metal Atoms in Optically Active Organo-Transition-Metal Compounds, 18, 151 13C NMR Chemical Shifts and Coupling Constants of Organometallic Compounds, 12, 135 Compounds Derived from Alkynes and Carbonyl Complexes of Cobalt, 12, 323 Conjugate Addition of Grignard Reagents to Aromatic Systems, I, 221 Coordination of Unsaturated Molecules to Transition Metals, 14, 33 Cyclobutadiene Metal Complexes, 4, 95 Cyclopentadienyl Metal Compounds, 2, 365... 

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