Base-promoted reactions

The most widely applied precursors for the synthesis of monocyclic NHPs are a-diimines which can be converted to the target heterocycles either in a two-step reaction sequence involving two-electron reduction of the diimine to an enediamide, enediamine, or a-aminoamine and subsequent condensation with PC13 [18-20] or a dichlorophosphine RPC12 [21], or via direct base-promoted reaction with PC13 [20, 22], The latter reaction involves addition of a P-Cl bond to each imine moiety followed by base-promoted elimination of hydrogen chloride leading to 2,4-dichloro-... 

Acid- and base-promoted methods have also been used in the syntheses of pyrazoles. Hydrogenation of methyl 2-Cbz(hydrazine)-3-hydroxy-4,4-dimethoxybutanoate 11 followed by cyclization in the presence of trifluoroacetic acid afforded the first asymmetric synthesis of the (4S,5.R)-5-carbomethoxy-4-hydroxy-A2-pyrazoline 12 <00TL8795>. Reaction of 2-nitrobenzyl triphenylphosphonium ylide (13) with aiyl isocyanates afforded 2-aryl-2H-indazoles 14 <00TL9893>. Base-promoted reaction of nitrobenzenes 15 with aryl imines 16 afforded aryl pyrazoles 17 . 

Both acid- and base-promoted reactions may be affected by acidic surfaces and, hence, by the factors which influence the surface acidity. Kinetic evidence for increased Br nsted acidity at clay surfaces has been presented by McAuliffe and Coleman (80) who studied the hydrolysis of ethylacetate and the inversion of sucrose. They noted that potentionmetrie pH measurements did not explain the catalytically effective H+-concentration at the clay surface. 

The incorporation of two nonidentical chiral residues, each supporting C2 symmetry, into a mactocyclic poly ether affords a chiral crown compound with C2 symmetry provided its structure is constitutionally symmetrical. Thus, base-promoted reaction of the half-crown diol prepared from (5)-birraphthol with the half-crown ditosylate d-72 synthesized tom diacetone-manrritol affords (144) the 20-crown-6 derivative (S)-d-113 with C2 symmetry. When d-72 is condensed in like fashion with (/ 5)-binaphthol, then the diastereoisomeric 20-crown-6 derivative (/ )-d-114 can be separated chromatogiaphically tom (S)-d-113. In this matmer, (/ 5)-binaphthol is resolved by the carbohydrate unit during the synthesis. 

A base-promoted reaction between L-threitol and tetraethylene glycol di-tosylate afforded (165) the chiral bis(15-ctown-5) derivative l-146 as well as the trans-fused bicyclic system l-147 containing 15-crown-5 and 17-crown-5 rings. These constitutional isomers, which were separated chromatographically, were characterized by preparing l-147 unequivocally by a stepwise route from 2,3-O-isopropylidene-L-threitol. 

Novel macrobicyclic compounds have been prepared (151) from the tetraol obtained on de-O-benzylidenation of the bisgalactosido-18-crown-6 derivative aa-DD-117 in Figure 18. Selective tritylation of the two hydroxymethyl groups of the tetraol, followed by a base-promoted reaction with pentaethylene glycol ditosylate afforded aa-DD-155 with a polyether chain bridging the 4 and 4 positions of the D-galactopyranosidic rings across presumably the /3 face of the molecule. 

A number of benzo-15-crown-5 derivatives are known where chirality is associated with side chains or fused ring systems. For example, base-promoted reactions of l,ll-dichloro-3,6,9,-trioxaundecane with apomorphine and adrenaline have afforded the benzo-lS-crown-S derivatives 164 and 165, respectively... 

Order of reactivity 1 > Br > Cl > F, bases promote reactions for R = alkyl... 

Cyclobutylidenecarbene, generated by base-promoted reaction between cyclobutanone and diethyl (diazomethyl)phosphonate at (CC (Method A),1,2 or by treatment of dibro-momethylenecyclobutane with phenyllithium at —40 to +20 C (Method B),3 4 rearranged to a transient entity, thought to be cyclopentyne3 6 or a lumomer of cyclopentyne.7,8 This entity underwent stereospecific cis addition to both (Z)- and ( )-l-melhoxypropene,2 and (Z)- and ( )-but-2-ene,4 and prefers 1,2- over 1,4-addition with buta-1,3-diene.4 These and other examples are collected below. 

Carboxylic acid esters have been studied widely and detailed mechanisms have been worked out for these reactions. Equation (4) shows the overall reaction of a carboxylic add ester with hydroxide via the nucleophilic attack of hydroxide at the carbonyl oxygen, with the subsequent loss of the alcohol moiety (HOR). Esters generally have larger ly, than kH+ values, with the result that they hydrolyze by base-promoted reactions at pH 5-6 (Mabey and Mill, 1978). 

The [1,2]-Wittig Rearrangement is the base-promoted reaction of ethers to yield secondary or tertiary alcohols. 

Azetidin-3-ones have been used as precursors of N-substituted 3-azetidinylidenecarbenes 116 (Scheme 25). The 1-benzhydryl- and l-tosylazetidin-3-ylcarbenes 116, generated in situ by base-promoted reactions of 1-benzhydryl-azetidin-3-one 30 and of l-tosylazetidin-3-one 40 with diethyldiazomethylphosphinate (DAMP), were trapped by cyclohexene to afford the corresponding methylenecyclopropanes 117 <1996TL8101>. 

Addition of nitriles to acetylenic compounds proceeds with chemoselectivity in contrast with the corresponding base-promoted reactions, where the products derived from acetylides are contaminants. The RuH2(PPh3)4-catalyzed reaction of ethyl 2-cyanopropionate (12) with methyl propiolate (14) at room temperature gave 15 in 90 % yield. 

An alternative mechanism for the base-promoted reaction of silanes with silica has been described by Blitz et al.83 In this mechanism, the base attacks directly to the surface silanols. The bonded amine renders the silanol more nucleophilic which then attacks the silicon atom of an approaching silane, giving rise to a pentacoordinate intermediate. 

In another example, the base-promoted reaction of ammonium salt 36 led to cw-alkene 37 in 72% yield. Interestingly, desilylation of the related... 

Sulfur ylides, derived from benzyl bromides and an optically active alkyl sulfide, undergo base-promoted reactions with aryl aldehydes to produce optically active 1,2-diatyl epoxides.The reaction is illustrated by equation (17) and produces epoxides with optical purities in the range of 28-47% ee. The bicyclic sulfide shown in equation (17) was derived from (-t-)-camphor8ulfonic acid and produces the (RiO-enantiomer of the epoxide in excess. 

Halogenation of aldehydes and koUmes fiocura under boch baaic and conditions. As you naight cxpc ct, the base-promoted reaction occurs t1 an enolate ion intermediate. Even relatively weak bases such as hvdi ion are effective for halo nntion because it s not necessary to convert ketone completely into its enolate too. As soon as a. small amount of eoo late is generated, it reacts immediately with the halogen. 

In base promoted reactions with rate-determining proton transfer, it is possible to observe a substrate isotope effect by comparison of the rates of the substrates HS and DS, both in light water [127, 128]. In almost all known examples, HS reacts faster than DS. 

Base-promoted reaction of nitrobenzenes 680 with aryl imines 681 afforded arylindazoles 682 (Equation 144) <20000L413>. /3-Tosylhydrazono phosphonates 683, novel and bifunctional reagents, were employed in a concise approach to give polysubstituted pyrazoles 684 in the presence of aromatic and aliphatic aldehydes under basic conditions (Equation 145) <1999SL299>. 

The base-promoted reaction of fluoroalcohols RfOH (Rf=CF3CH2 H(CF2)CH2, C2F5CH2, C3F7CH2, (CF3)2CH with alkyl phosphonic dichlorides is an excellent method for the synthesis of bis(fluoroalkyl) alkylphosphonates (Rf0)2P(0)R. ... 

Strictly speaking, a part of carbanion chemistry, this is perhaps the best place to take it up, since it shows a striking parallel in every aspect to the base-promoted reaction we have just left. 

Sugihara, T., Yamaguchi, M., Nishizawa, M. Lewis base promoted reactions of alkyne-dicobalt hexacarbonyls. Rev. on Heteroa. Chem. 1999, 21, 179-194. 

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