Alkoxide nucleophile

A number of reaction variables or parameters have been examined. Catalyst solutions should not be prepared and stored since the resting catalyst is not stable to long term storage. However, the catalyst solution must be aged prior to the addition of allylic alcohol or TBHP. Diethyl tartrate and diisopropyl tartrate are the ligands of choice for most allylic alcohols. TBHP and cumene hydroperoxide are the most commonly used terminal oxidant and are both extremely effective. Methylene chloride is the solvent of choice and Ti(i-OPr)4 is the titanium precatalyst of choice. Titanium (IV) t-butoxide is recommended for those reactions in which the product epoxide is particularly sensitive to ring opening from alkoxide nucleophiles. ... 

Kinetics of the reaction between BNP- and 24b C104 in dry DMF at 35°C was studied (24). The second-order rate constant Ae(BNP ) of 1.1 M-1sec-1 with respect to [BNP ] and [24b] was obtained. Comparison of the rate constants (BNP") in DMF and aqueous solution showed that the Znn-bound alkoxide nucleophile acts 1700 times more effectively in this aprotic solvent than in water, which is accounted for by a... 

For substitution at a carbonyl carbon, the nucleophilicity order is not the same as it is at a saturated carbon, but follows the basicity order more closely. The reason is presumably that the carbonyl carbon, with its partial positive charge, resembles a proton more than does the carbon at a saturated center. That is, a carbonyl carbon is a much harder acid than a saturated carbon. The following nucleophilicity order for these substrates has been de-termmined 321 Me2C=NO- > EtO" > MeO > OH" > OAr- > N-f > F" > H20 > Br" I". Soft bases are ineffective at a carbonyl carbon.322 In a reaction carried out in the gas phase with alkoxide nucleophiles OR solvated by only one molecule of an alcohol R OH, it was found that both RO and R O" attacked the formate substrate (HCOOR") about equally, though in the unsolvated case, the more basic alkoxide is the better nucleophile.323 In this study, the product ion R"0 was also solvated by one molecule of ROH or R OH. 

Chloro substituted pyrazino[2,3 -d]pyridazines react readily with amine and alkoxide nucleophiles to give the corresponding amino and alkoxy substituted products (66JHC512). 5,8-Dichloropyrazino[2,3-d]pyridazine (102) can be hydrolyzed in 2% aqueous sodium hydroxide to yield 5-chloropyrazino[2,3-d]pyridazin-8-one (103). Displacement of only one halogen substituent is also observed in the basic hydrolysis of the 5,8-dibromo analog (68JHC53). 

SAMPLE SOLUTION (a) The ether linkage of cyclopentyl ethyl ether involves a primary carbon and a secondary one. Choose the alkyl halide corresponding to the primary alkyl group, leaving the secondary alkyl group to arise from the alkoxide nucleophile. 

The analogous p-dichlotobenzene complex will react rapidly with phenoxide and alkoxide nucleophiles in the first substitution and more slowly in the second monosubstitution can be readily achieved.78 Simple amines give only monosubstitution, even in the presence of excess amine (equation 24). 

Baldwin and co-workers (56, 57) have reported that all attempts to cyclize hydroxy-enones 162 and 164 (R=H or OCH3) under basic conditions failed to give the corresponding furanones 163 and 165 (R=H or 0CH3). The susceptibility of these systems to conjugate addition of alkoxide nucleophile was verified by conducting the attempted cyclization with sodium methoxide in deute-... 

It is well known that bicyclic B-diketones are readily cleaved by hydroxide or alkoxide nucleophiles. For instance, diketone 395 gives readily the keto-acid 397 via intermediate 396 (112). This is a stereoelectronically allowed... 

Tagaki et al. [24] and Fomasier et al. [25] reported another type of metallomicelle attached with a metal-bound alkoxide nucleophile. Tagaki s zinc(II) and copper(II) complexes (with possible structures 6a and b) promoted the hydrolysis of 4-nitrophenyl picolinate in a comicellar system with hexadecyl trimethy-lammonium bromide. However, no detailed mechanistic study was reported. Scrimin s zinc(II) and copper(II) complexes (proposed structures 7a and b) also promoted the hydrolysis of 4-nitrophenyl picolinate. A postulated mechanism for the catalytic activity of 7 is shown in Figure 4. An aggregate of 7 more effectively... 

A considerable number of nucleophiles have been shown to react through this mechanism stabilized carbanions, anions derived from elements of the VIA group (S, Se, Te) and anions from elements of the V A group (P, As, Sb). More recently cyanide anion, nitrogen and oxygen (e.g. aromatic alkoxides) nucleophiles have been added to the list. These nucleophiles behave as C— rather than as N— or O— nucleophiles. 

We can also make rings using alkoxide nucleophiles, and in this example the phenol (hydroxy-benzene) is deprotonated by the sodium methoxide base to give a phenoxide anion. Intramolecular attack on the conjugated ketone gives the cyclic product in excellent yield. In this case, the methoxide (pkaH about 16) will deprotonate the phenol (pKa about 10) completely, and competitive attack by MeCT acting as a nucleophile is not a problem as intramolecular reactions are usually faster than their intermolecular equivalents. 

Intramolecular nucleophilic addition of alkoxides to vinyl sulfoxides (90) provided a route to (3-alkoxysuIfoxides (91) (Scheme 24). The cij-product was formed with up to 18 1 selectivity.58 Alkoxide nucleophiles undergo an addition/elimi-nation protocol with P-iodo vinyl sulfoxides to yield tetrahydrofurans and tetrahy-dropyrans, which contain either an endo- or an exo-cyclic double bond.59,60... 

The order of reactivity of alkoxides - K > Na Mg - is consistent with the higher electron density on oxygen, hence increasing the alkoxide nucleophilicity. When the a-silylcarbanion contains electron-withdrawing substituents, the Peterson alkenation directly forms the alkene, without the isolation of (3-hydroxysilane. 

For example, the ring opening of ethylene oxide with a OH initiator affords an alkoxide nucleophile, which propagates the chain by reacting with more ethylene oxide. This process yields poly(etbylene glycol), PEG, a polymer used in lotions and creams. The many C-O bonds in these polymers make them highly water soluble. 

Two alkoxide nucleophiles trifluoroethoxide and butoxide were chosen to model the substitution pattern of 18 and 20. The reaction of cyclic thionylphosphazene with NaOBu was found to follow the same order of reactivity as NaOPh however, unlike NaOPh the substitution of the S-Cl bond was facile at room temperature and the substitution of the S-F bond required an excess of nucleophile. Interestingly, although the reaction of the cyclic thionylphosphazenes with the NaOCH2CF3 was found to follow the same general order of reactivity as NaOPh or NaOBu (PC12 > PCl(OPh) > S (O)X), a significant enhancement in reaction rate was detected with each equivalent of trifluoroethoxide added. 

Scheme 33 Proposed reaction pathway for phosphate ester hydrolysis involving an internal alkoxide nucleophile.

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