Organolithium and Grignard Additions

In general, nucleophilic addition reactions using Grignard or organolithium reagents to -chiral or other remotely chiral ketones usually yield mixtures of stereoisomers which are not synthetically use-fiil.9,12-27 However, some specific examples of stereoselective organolithium and Grignard additions to these remotely chiral carbonyl compounds have been reported. 

In contrast to the extraordinarily high preference for endo attack observed with camphor (1), nucleophilic additions of organolithium and Grignard reagents to norcamphor (3) proceed with exclusive attack of the nucleophile from the exo face of the carbonyl group. 

Thiazolinc 2 proves to be inert to organometallic attack. However, addition of organolithium and Grignard reagents to the C —N double bond of 2 can easily be achieved by previous activation with boron trifluoridc, providing /r[Pg.696]

Enantiomerically pure alkylboranes arc known to be excellent reagents for asymmetric reduction but they can also be used to generate enantiomerically pure /V-borylimines by partial reduction of nitriles. Addition of organolithium and Grignard reagents to these compounds affords secondary carbinamines in moderate to good yield but low enantioselectivity13,14. The best results reported so far are shown below. 

Addition of an organolithium and Grignard reagent across the peroxy bridge of endoperoxides gives c/s-cyclohex-2-en-l,4-diols. Alkyl, cycloalkyl, alkenyl and aryl moieties can be transferred to oxygen <96TL6635>. 

Organolithiums and Grignard reagents are two key classes of carbanion-like organometallics. In addition to the organolithiums, Holm determined the enthalpies... 

Organolithium and Grignard reagents are capable of addition to the C=N bond of oximes and oxime ethers. Oxime ethers can react directly while addition to oximes requires two equivalents of an organometallic reagent. The majority of experimental... 

Reaction with even harder nucleophiles such as organolithiums and Grignard reagents is substantially limited by virtue of the fact that these carbon nucleophiles add by direct attack at the metal center, as opposed to the softer carbon nucleophiles which add by attack on the allyl ligand. Direct metal addition can lead to the opening of alternative reaction pathways, e.g. 3-H elimination, in competition with reductive elimination which accomplishes nucleophile allylation (equation 40). 

Organolithium and Grignard reagents always afford 3° alcohols when they react with esters and acid chlorides. As soon as the ketone forms by addition of one equivalent of reagent to RCOZ (Part [1] of the mechanism), it reacts with a second equivalent of reagent to form the 3° alcohol. 

Organolithium and Grignard reagents form 1,2-addition products. 

Addition to cyclic iminium salts has been utilized in alkaloid synthesis. A zinc-promoted reductive coupling reaction of iminium salts and alkyl halides has been reported by Shono et al. (Scheme 8). Evidence delineating the mechanistic course (organozinc addition or electron transfer reaction) of the addition has not been established. In contrast to organolithium or Grignard additions, aromatic halogen and alkoxycarbonyl substituents are compatible with this methodology. The intramolecular version of this reaction has been employed for the synthesis of tricyclic amines (53 equation 9). 

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