Bases nucleophiles

Ester Enolates- Esters are susceptible to substitution by the base, even LDA can be problematic. Use very hindered non-nucleophillic base (Li isopropylcyclohexyl amide)... 

Many organic syntheses requHe the use of stericaHy hindered and less nucleophilic bases than //-butyUithium. Lithium diisopropylamide (LDA) and lithium hexamethyldisilazide (LHS) are often used (140—142). Both compounds are soluble in a wide variety of aprotic solvents. Presence of a Lewis base, most commonly tetrahydrofuran, is requHed for LDA solubdity in hydrocarbons. A 30% solution of LHS can be prepared in hexane. Although these compounds may be prepared by reaction of the amine with //-butyUithium in the approprite medium just prior to use, they are also available commercially in hydrocarbon or mixed hydrocarbon—THF solvents as 1.0—2.0 M solutions. 

Certain base adducts of borane, such as triethylamine borane [1722-26-5] (C2H )2N BH, dimethyl sulfide borane [13292-87-OJ, (CH2)2S BH, and tetrahydrofuran borane [14044-65-6] C HgO BH, are more easily and safely handled than B2H and are commercially available. These compounds find wide use as reducing agents and in hydroboration reactions (57). A wide variety of borane reducing agents and hydroborating agents is available from Aldrich Chemical Co., Milwaukee, Wisconsin. Base displacement reactions can be used to convert one adduct to another. The relative stabiUties of BH adducts as a function of Group 15 and 16 donor atoms are P > N and S > O. This order has sparked controversy because the trend opposes the normal order estabUshed by BF. In the case of anionic nucleophiles, base displacement leads to ionic hydroborate adducts (eqs. 20,21). 

We saw in the preceding chapter that the carbon-ha]ogen bond in an alkyl halide is polar and that the carbon atom is electron-poor. Thus, alkyl halides are electrophiles, and much of their chemistry involves polar reactions with nucleophiles and bases. Alkyl halides do one of two things when they react with a nucleophile/base, such as hydroxide ion either they undergo substitution of the X group by the nucleophile, or they undergo elimination of HX to yield an alkene. 

The conversion of a thiolactone to a cyclic ether can also be used as a key step in the synthesis of functionalized, stereochemically complex oxacycles (see 64—>66, Scheme 13). Nucleophilic addition of the indicated higher order cuprate reagent to the C-S double bond in thiolactone 64 furnishes a tetrahedral thiolate ion which undergoes smooth conversion to didehydrooxepane 65 upon treatment with 1,4-diiodobutane and the non-nucleophilic base 1,2,2,6,6-pentamethylpiperidine (pempidine).27 Regio- and diastereoselective hydroboration of 65 then gives alcohol 66 in 89 % yield after oxidative workup. Versatile vinylstannanes can also be accessed from thiolactones.28 For example, treatment of bis(thiolactone) 67 with... 

Water, which can be taken to a minimum by the use of molecular sieves, can produce a lactamide either through direct reaction with the aziridinone intermediate, or upon hydrolysis of oxazolidinone self-condensation products, previously obtained also in the presence of a strong non-nucleophilic base (H ) (ref. 17). The recently reported 0-self-alkylation compound H bears the (S,S)-configurations at the unreacted C-Br and newly formed C-0 bonds. The presence of bromine was expedient for the x-ray assessment of configuration at the two chiral centers of 11 which forms in high diastereoisomeric excess (ref. 5). 

Hydroxide is the nucleophile Water is the nucleophile Water is the nucleophile MeCl is the electrophile Nucleophile Base... 

The analogous dimerization of alkynes over Fe(C0)5 is not applicable, so clearly a different route towards alkynylated derivatives of 25 was needed. Comparison of 25 to cymantrene suggests that metallation of the hydrocarbon ligand should be the route of choice for the synthesis of novel substituted cyclobutadienes. In the literature, addition of organolithium bases (MeLi, BuLi) to the CO ligands with concomitant rearrangement had been observed [25]. But the utilization of LiTMP (lithium tetramethylpiperidide, Hafner [26]) or sec-BuLi as effectively non-nucleophilic bases led to clean deprotonation of the cyclobuta-... 

Steric factors and especially hindered rotations may change the pATa of an acid by up to two pAfa units as has been found for 2,6-disubstituted pyridines 2,6-di-t-butylpyridine [70k] is an unusual (Kanner, 1982) non-nucleophilic base which has a surprisingly low pKa value. When [70k] is compared to other 2,6-dialkylsubstituted pyridines [70] it is found to be the only disubstituted pyridine with a smaller pKa than pyridine itself (see Table 29). The exceptional behaviour of [70k] has been investigated intensively... 

Aregioselective catalytic system for the allylic substitution of non-symmetric allyl carbonates by carbon and nitrogen nucleophiles based on [ Bu N][Fe(NO)(CO)3] and PPhj was developed (Scheme 2.26). The high regioselectivity was ascribed to the slow a-allyl- to Jt-aUyl-isomerisation relative to the rate of substitution. However, the use of high excess of the pro-nucleophile and DMF solvent are drawbacks on the atom efficiency and functional group tolerance of the system. 

Secondary amines, such as pyrrolidine, must be alkylated with care too polar a solvent leads to participation of a second nearby polymer-bound alkylant in the formation of a quaternary ammonium salt, along with the desired immobilized trialkyl amine. The exception, as seen above, is diisopropylamine, which refuses to displace tosylate even in the refluxing pure amine, or in hot dimethyl-formamide or other polar solvent, while metal diisopropylamide is notorious as a powerful non-nucleophilic base. However, carboxamide is not difficult to form from (carboxymethyl)polystyrene, again using toluenesulfonyl chloride as condensing agent this can then be reduced to (diisopropyl-ethylaminoethyl)polystyrene, which is of interest as a polymer-bound non-nucleophilic base. ... 

It also follows that protonation of the triazine ring makes it more susceptible to attack by nucleophilic reagents unless the reagent itself is also protonated. If the triazine ring remains unprotonated when a nucleophilic base, such as an alkylamine, is present as its acid salt the reaction is slower, of course. Cyanuric chloride itself is a very weak base that becomes protonated only under strongly acidic conditions. Thus step 1 in Scheme 11.2 can be carried out in aqueous solution even at pH 2 without risk of undesirable hydrolysis of cyanuric chloride, water being an extremely weak nucleophile. 

Ring transformations were conducted with a variety of organic and inorganic bases <1997T4611>. The results are summarized in Equation (7) and Table 4. Treatment of cycloadduct 30a with strong and non-nucleophilic bases such... 

When the nucleophile (base) attacks a P carbon atom, elimination occurs. 

Reaction Solvent Nucleophile/base Leaving group Substrate structure... 

The predominant nucleophile/base in acid systems is water. Thus we can write equation (44) ... 

Owing to their cationic and radical character, organic cation radicals also participate in a variety of bimolecular reactions with nucleophiles, bases, radicals, etc., as illustrated by the following examples. 

The coordinated macrocycle readily reacts with alkoxide ions to yield products of type (71) (Taylor, Urbach Busch, 1969). In so doing additional flexibility is imparted to the ring which may reduce ring strain and, in part, provide a driving force for the reaction. Thus the coordinated imine carbons appear predisposed to attack by such nucleophiles. Based on this knowledge, elegant template syntheses of three-dimensional derivatives have been performed. The syntheses involved the reaction of [M(taab)]2+ (M = Ni, Cu) with the dialkoxide ions derived from bis(2-hydroxyethyl)sulphide or bis(2-hydroxyethyl)methylamine (Katovic, Taylor Busch, 1969). The products were demonstrated to be monomeric square-pyramidal complexes of type (72). The condensation... 

Nitrobenzofurazan 240 and 4-chloro-7-nitrobenzofurazan 232 also condense with isocyanoacetates in the presence of the non-nucleophilic base l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to give tricyclic pyrrole derivatives 241 in excellent yields (Scheme 60) <2005T11615>. 

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