Imines, reaction with Grignard reagents

Carbon nucleophiles may react at the sulfur-sulfur bond, or at C-3. Thus Grignard reagents react with monocyclic dithiol-3-ones (3a) and -3-imines (3c) at S-2 (74LA1261,73LA247). The product (84) of reaction of a Grignard reagent with benzo-1,2-dithiol-3-one (77a) (74T4113) could be alternately formed by attack at S-2, at C-3 or at C-5. Phosphonium ylides or other stabilized carbanions react at the 3-position of dithiol-ones... 

Reactions of Nitriles Nitriles undergo acidic or basic hydrolysis to amides, which may be further hydrolyzed to carboxylic acids. Reduction of a nitrile by lithium aluminum hydride gives a primary amine, and the reaction with a Grignard reagent gives an imine that hydrolyzes to a ketone. 

Reaction of Nitriles with Organometallic Reagents Grignard reagents add to a nitrile to give an intermediate imine anion that is hydrolyzed by addition of water to yield a ketone. 

Organomercury compounds undergo a similar reaction. Alkyl and aryl Grignard reagents can be converted to carboxylic esters with Fe(CO)5 instead of CO. Amides have been prepared by the treatment of trialkyl or triarylboranes with CO and an imine, in the presence of catalytic amounts of cobalt carbonyl ... 

The reaction has been applied to nonheterocyclic aromatic compounds Benzene, naphthalene, and phenanthrene have been alkylated with alkyllithium reagents, though the usual reaction with these reagents is 12-20, and Grignard reagents have been used to alkylate naphthalene. The addition-elimination mechanism apparently applies in these cases too. A protected form of benzaldehyde (protected as the benzyl imine) has been similarly alkylated at the ortho position with butyl-lithium. ... 

If the rearrangement of oxime sulfonates is induced by organoaluminum reagents,the intermediate (71) is captured by the nucleophile originally attached to the Al. By this means an oxime can be converted to an imine, an imino thioether (R—N—C—SR), or an imino nitrile (R—N—C—In the last case, the nucleophile comes from added trimethyl si lyl cyanide. The imine-producing reaction can also be accomplished with a Grignard reagent in benzene or toluene. ... 

The intramolecular cyclization route to p-lactams still provides interest. P-Amino esters (obtained by a Reformatsky-type reaction of an imine and bromoacetates derived from chiral alcohols) are cyclized by the action Grignard reagents to 4-substituted P-lactams with impressive e.e. <96TL4095>. A similar approach through a Reformatsky-type reaction uses tricarbonyl(Ti -benzaldimine)chromium complexes and ultrasound <96T4849>. 3-Methyl-azetidin-2-ones (obtained from 3-amino-2-methylpropionates) have been resolved and their... 

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). 

Alvernhe and Laurent first developed a procedure for conversion of Grignard reagents to primary amines using acetone oxime 6c and butanone oxime 6d (Scheme 55) 22 23 However, the yields were low. They expanded their study to investigate how well organo-lithiums perform in their reaction with 6c or 6d 23. Phenyllithium gave a 1 4 mixture of aniline and the addition product of phenyllithium to the imine (Scheme 53, path e product) in the reaction with 6c while aziridine was obtained in the reaction with 6d (Scheme 56). 

When cyclohexanone oxime 6e was used as amination reagent, primary amines were obtained from phenylmagnesium bromide. Reaction of 6e with alkyl Grignard reagents gave aziridines, whereas reaction with phenyllithium gave aziridine and the addition product of phenyllithium to the imine (Scheme 57) 24. 

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. 

Also other reaction types have been dealt with in CHEC(1984) and CHEC-II(19%) like reduction to alcohols (e.g., sodium borohydride), Wolff Kishner reduction, nucleophilic addition via reaction with Grignard reagents or organo-lithium compounds, and formation of imine type functional groups (e.g., hydrazones). New examples are the reaction of... 

Similarly, reaction of enamines such as 218 with benzotriazole affords a-aminoalkyl-benzotriazoles 219, which react smoothly with organomagnesium compounds, giving tertiary alkyl carbylamines 220 (equation 149) . The whole sequence can therefore be considered as the addition of Grignard reagents to imines. 

---