Nucleophilic addition reactions butyllithium

Deprotonation of oxathiane 16 with butyllithium, addition of an appropriate aldehyde and subsequent oxidation lead to the acylated oxathianes 17 which can be used in diastereose-lective nucleophilic addition reactions. 

The addition of terminal acetylenes to imines is an important reaction because of the importance of these products as building blocks. Conventionally, the addition reaction shown in Scheme 5.2 is performed with stoichiometric amounts of butyllithium in a step that is, separate from the subsequent nucleophilic addition reaction (see (b)). Carreira has recently developed a procedure that utilizes an iridium catalyst to effect the addition reaction to a wide range of aldimines and ketimines (see (a)). ... 

Another interesting example of this type of reaction is the nucleophilic addition of butyllithium to 4,6-dialkoxypyrimidines to give the 2-butyl-4,6-dialkoxy-2,5-dihydropyrimidine (104), probably via the intermediate 1,2-dihydropyrimidine 103178 [Eq. (38)]. A series of dihydropyrimidines of this type was prepared analogously in the author s laboratory.179... 

General methods for the preparation of a.jS-unsaturated iron-acyl complexes are deferred to Section D 1.3.4.2.5.1.1. examples of the alkylation of enolates prepared via Michael additions to ii-0 ,/ -unsaturated complexes prepared in situ are included here. Typical reaction conditions for these one-pot processes involve the presence of an excess of alkyllithium or lithium amide which first acts as base to promote elimination of alkoxide from a /f-alkoxy complex to generate the -a,)S-unsaturated complex which then suffers 1,4-nucleophilic addition by another molecule of alkyllithium or lithium amide. The resulting enolate species is then quenched with an electrophile in the usual fashion. The following table details the use of butyllithium and lithium benzylamide for these processes44,46. 

Crotonaldehyde dimethyl acetal (7 Scheme 1) can undergo metallo-dehydrogenation or nucleophilic addition 9 for the example of n-butyllithium, the products of different experimental conditions are shown. The alternative pathways have been modelled computationally by examining the reactions of (7) with methyllithiurn and methylpotassium. The role of the potassium alkoxide in diverting the reaction towards diene is twofold it de-aggregates (RLi) , and promotes a partial cleavage of the carbon-lithium bond. 

Dinaphtho[2, -d Y,2 7]-[l,3]dithiepins 58 are readily lithiated with -butyllithium at —78°C. Asymmetric nucleophilic addition of the anions to aldehydes afforded 59 with moderate to good diastereoselectivities (Scheme 7) <2002H(57)1487>. For a similar reaction, see <1991JOC4467>. 

R-Li (alkyllithium) Methyllithium Butyllithium sec-Butyllithium fert-Butyllithium Strong base Strong nucleophile when R is not bulky. Deprotonation of weak organic acids, E2 eliminations Sn2/Sn2 displacements, addition reactions, addition-elimination reactions... 

Dimethyl-4,8-dioxaspiro[2.5]oct-l-ene is a synthetically useful precursor for cyclopropenones because of its stability and ready availability. The sodium derivative 1 of the cyclopropenone acetal in liquid ammonia reacted with alkyl halides giving alkyl-substituted cyclopropenone acetals 3. The lithiated cyclopropenone acetal 4 was generated by treating the cyclopropenone acetal with one equivalent of butyllithium in tetrahydrofuran. Reaction of the lithium carbanion 4 with alkyl halides proceeded cleanly in the presence of two equivalents of hexamethylphosphoric triamide (Table 1, entries 1-4). The lithium compound underwent nucleophilic addition to carbonyl compounds smoothly at — 70 C giving hydroxymethyl derivatives 5 (Table 1, entries 5-10). 

Regarding synthetic studies, the syntheses of ( )-latifine (437) (200), of ( )-cherylline (440) and ( )-latifine (437) (201), and of ( )-0,0-dimethylcherylline (445) and ( )-6>,0-dimethyllatifine (446) (202) have been performed using the Pomeranz-Fritsch-type cyclization (Scheme 51), the Bischler-Napieralski-type reaction (Scheme 52), and intramolecular nucleophilic addition of aryllithium (generated by butyllithium) to a carbonyl group (Scheme 53). 

Among the classical (summarized in [11]) reactions of cyanoacetylenes (salt and n-complex formation, nucleophilic addition of, inter alia, amines and alcohols, Diels-Alder additions with 2 (see Section 2.22.2), addition of halogens and hydrogen halides, etc.) their polymerization might deserve a second look since the products formed - polyacetylenes - have attracted much attention during the last two decades. Thus 1, several of its derivatives, and 2 have been polymerized with anionic initiators (triethylamine, sodiiun cyanide, butyllithium) to give black, low-molecular-weight polymers claimed to have structures like 33 [38-40], which is obtained from 2 by treatment with butyllithium. 

Another approach for the anionic synthesis of both bipyridine- and terpyridine-functionalized polymers is the direct reaction of PSIi with either 2,2 -bipyridine or 2,2 6, 2"-terpyri-dine, respectively. This end functionalization is proposed to proceed by nucleophilic addition of PSLi to the 6-position of the pyridine ring, followed by termination and oxidative rearomati-zation as shown in eqn [29] for terpyridine functionalization. One shortcoming of this procedure is that a large excess of terpyridine (e.g., 23-fold molar excess) is required to prevent diaddition. SEC analysis indicated that only small amounts of dimeric coupling products (up to 4.8%) are obtained under these conditions. Once again, in spite of the use of sec-butyllithium as initiator, the lower molecular weight samples... 

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