Indolyl Grignard reagent

Addition of pyrrolyl and indolyl Grignard reagents to 1-acyl salts of 4-methoxy-3-(triisopropylsilyl)pyridine affords the corresponding l-acyl-2-heteroaryl-2,3-dihydro-4(17/)-pyridones, e.g., 443 (main product) and 444... 

Two new successful routes46,47 to the dasycarpidone-uleine type have been described. The first, which has been used to make de-ethyldasycarpidone460 and the (+)-dasycarpidones (34a and b) (Scheme 12466) utilizes, as a key step, the reaction of methyl 3-ethylisonicotinate N-oxide with the indolyl Grignard reagent in the presence of benzoyl chloride. After quaternization, reduction, and hydrolysis of the product (35), cyclization was effected as before,1" using poly-phosphoric acid. 

Some other, apparent cycloadditions probably proceed by non-concerted pathways, for example addition of 1,3-cyclohexadiene in the presence of light and 2,4,6-triphenylpyrylium, probably involves radical intermediates, and reactions of 2-phenylsulfonyl-dienes with indolyl Grignard reagents probably proceed in stepwise fashion as shown. "... 

The reactions of indolyl Grignard reagents, generated in this fashion, have been explored further by others [389-392]. A regioselective Grignard formation at C2 occurred upon tteatment of 2,3-diiodo-iV-(phenylsulfonyl)indole (28) with isopropylmagnesium chloride [393]. 

Indolyl Grignard reagents have also been generated by direct deprotonation with a magnesium base (e.g., jPr2NMgBr) [281] and also by transmetalation of lithioin-dole intermediate 11 (Table 1, entry 2) [61]. 

Majima et al. prepared ethyl y-(3-indolyl)-y-oxobut3rrate (250) in a similar manner by the condensation of the indole Grignard reagent with -ethoxycarboiiylpropionyl chloride.Methyl y-(3-indolyl)-y-oxobutyrate (251) has been obtained by the action of mcthoxycarbonylpropionyl chloride on indole magnesium iodide in ether. Ballantine et al. prepared methyl y-(5-methoxy-3-... 

The related compounds bis(2-mothyl-3-indolyl)glyoxal (263) and bis(3-methyl-l-indolyl)glyoxai (264) - have been prepared by the action of oxalyl chloride on the Grignard reagents derived from 2-methylindole and 3-methylindole, respectively, Eis(l-methyl-3-indolyl)-glyoxal (265) was prepared by the action of oxalyl chloride on 1-methyIindole in ether. 

Sanna reported that l,3-di(3-indolyl)-l,3-dioxo-%-propanc (266) and l,4-di(3-indolyl)-l,4-dioxo-M-butane (267) were formed by the action of malonyl chloride and succinyl chloride, respectively, on the indole Grignard reagent in ether, and analogous products could be obtained from 2-methylindole. 

Majiina and Kotake prepared 2,2-di(3-indolyl)propane (336) by the action of acetone on indole magnesium iodide in other or anisole. Recently 1 -indolyl derivatives have been o btained as primary products by interaction of ketones with indole Grignard reagents for example acetone gave a 75% yield of 2-(l-indolyl)propan-2-ol (337). 

The indole Grignard reagent (Id) was also used for the production of 1-indolyl- (119) and 3-indolyl- (120) phosphonates and phosphinates [113] ... 

Treatment of indole (pKa - 17) with strong bases such as butyl lithium, Grignard reagents, or metal hydrides produces the corresponding indolyl anion, which reacts with electrophiles either on nitrogen or at the C3 position. With lithium, sodium, or potassium as counterion the indolyl anion tends to react on nitrogen, as in the preparation of 7.35. However, with magnesium as the counterion the intermediate has an essentially covalent rather than ionic structure, and reaction tends to occur at the C3 position, as in the preparation of 7.36. 

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