Grignard with ethylene derivative

SAMPLE SOLUTION (a) Reaction with ethylene oxide results in the addition of a —CH2CH2OH unit to the Grignard reagent. The Grignard reagent derived from o-bromotoluene (or o-chlorotoluene or o-iodotoluene) is appropriate here. 

The first total synthesis of cinchonamine (277) and 2-epicinchonamine (278) proceeds via the epimers (279), which were prepared by two independent methods.169 Scheme 28 illustrates the more efficient of the two syntheses, which involves as its first stage the condensation of 2-lithio-iV-benzenesulphonyl-indole with N-benzoylmeroquinene aldehyde (280), itself obtained by reduction of the readily available JV-benzoylmeroquinene ester (281). The critical cyclization stage [(279)— (283)+ (284)] that occurs on prolonged heating at 155 °C presumably proceeds via the immonium ion (282), since separation of the epimers of (279) followed by dehydration and cyclization affords the same mixture of (283) and (284). Finally, the hydroxyethyl group was introduced by the reaction of the Grignard derivatives of (283) and (284) with ethylene oxide.169... 

The major product (19) from addition of the crotyl Grignard to ethylene was found to be in equilibrium with a small concentration of isomeric secondary Grignard 20. From the equilibrium constant [19]/[20] = 290 at 70°C, and thermodynamic data for the corresponding alkenes, a value of 3.3 kcal/mole was derived as the difference in free energy between primary and secondary Grignard reagents (46). 

The Grignard reagent (29) derived from the ethylene acetal of 4-bromobutan-2-one, previously reported as unavailable, has now been prepared in THF and undergoes cyclization in refluxing solvent. The reaction of myrcene with magnesium results in the complex myrcene-magnesium which, on treatment with acetyl chloride or acetic... 

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