Grignard reagents, reactions with pyridines

Adition of Grignard reagents. Reaction of 2,3-O-isopropylidene-D-ribose (62) with ethynyl magnesium bromide gives l,2-dideoxy-4,5-0-iso-propylidene-D-a//o-hept-l-ynitol (63), which is then converted into its 7-O-trityl ether (64). Treatment of 64 with TsCl/pyridine provides 2,3-0-isopropylidene-5-0-trityl-a-D-ribofuranosylethyne (65) which upon deprotection affords derivative 66 (Scheme 22).89... 

Two isomers of azoniafluoranthene have been reported. The reaction of 2-methylpyridine ALoxide with a Grignard reagent gave the pyridine 244 which, on treatment with HBr, cyclized to 245. The Westphal condensation between 245 and 2,3-dihydroxy-1,4-dioxane in the presence of triethyl-amine yielded lOc-azoniafluoranthene salt (246) (33%) [89AG(E)588]. 

When the additional nitrogen atom is included in one of the aromatic rings, on the other hand, there is obtained a compound with antihistaminic properties. Reaction of the Grignard reagent from 4-chlorobromobenzene with pyridine-2-aldehyde gives the benzhydrol analog (12). The alcohol is then converted to its sodium salt by means of sodium, and this salt is alkylated with W-C2-chloroethyl)dimethylamine. Carbinoxamine (13) is thus obtained. ... 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

Aluminum-free titanocene-methylidene can be generated by thermolysis of titana-cyclobutanes 6, which are prepared by reaction of the Tebbe reagent with appropriate olefins in the presence of pyridine bases [9]. Alternatively, the titanacyclobutanes are accessible from titanocene dichloride and bis-Grignard reagents [10] or from 71-allyl titanocene precursors [11]. The a-elimination of methane from dimethyltitanocene 7 provides a convenient means of preparing titanocene-methylidene under almost neutral conditions [12] (Scheme 14.5). 

Murdoch and coworkers carried out amination reactions of aryl Grignard reagents and aryllithiums with oximes using O-p-toluenesulfonyl tetraphenylcyclopentanone oxime (0-tosyltetracyclone oxime) 6g (Scheme 61). The imine is extracted with benzene, purified, and then converted to amine and oxime by reacting with excess hydroxylamine in aqueous pyridine at room temperature. Amines are obtained following acidic hydrolysis. 

---