Secondary alkoxide

In Barton s method, the base used for the enolization step assumes some importance -butoxide is clearly superior, even though enolization could be demonstrated with primary and secondary alkoxides. 

Molecular dynamics free-energy perturbation simulations utilizing the empirical valence bond model have been used to study the catalytic action of -cyclodextrin in ester hydrolysis. Reaction routes for nucleophilic attack on m-f-butylphenyl acetate (225) by the secondary alkoxide ions 0(2) and 0(3) of cyclodextrin giving the R and S stereoisomers of ester tetrahedral intermediate were examined. Only the reaction path leading to the S isomer at 0(2) shows an activation barrier that is lower (by about 3kcal mol ) than the barrier for the corresponding reference reaction in water. The calculated rate acceleration was in excellent agreement with experimental data. ... 

Yields of i,8-anhydro derivatives, after removal of the 3,4-0 isopropyl dene blocking group, were ft-7% for the D-raannitol series, 15-20% for the -sorbitol series, and 55-60% for the L-iditol series. Tho authors asoribed this trend to the fact that formation of these 1,6-anhydrides produced two, one, and zero axial hydroxyl substituents respectively. That seven- in preference to five or aix-mentbered anhydrides were generated was attributed to the preeenoe of the 3,4-0-iflopropylidene function. The products were formulated on the assumption that no inversion had occurred either at or CtS), and that initial attack of an 0H> ion at Ct or Ct was followed by a tautomeric proton transfer to the adjacent secondary alkoxide oxygen (Eq. 597). 

The commonly used reducing agents AlH and BH will reduce aldehydes and ketones to primary and secondary alkoxides.109 Similar reactivity is found for some other main group hydrides, e.g. gallium (equation 33).110... 

Alkoxide and aryloxide ions are not arylated on oxygen. Tertiary alkoxides do not react, thus making them appropriate bases for generation of nucleophiles, and primary and secondary alkoxides undergo a-hydrogen abstraction with aryl radicals normally making them unsuitable for use as bases e.g. isopro-poxide ion reacts with phenyl radicals to give benzene and acetone ketyl.58 The C-arylation of aryloxides is discussed in Section 2.2.3.1.4. 

Chiral induction was also observed in lanthanide(III)-alkoxide-mediated MPV reductions. The optically active ligand (Fig. 35C) was used in enantioselec-tive samarium-catalyzed MPV reductions of arylmethyl ketones (Scheme 30) [253], The resulting mixed alkoxide-iodide complex shows higher reactivity than (rBuO)SmI2. It was pointed out that the tridentate, secondary alkoxide ligand is not oxidized under the reaction conditions and that tridendate ligands... 

In the addition of hydride donors to aldehydes (other than formaldehyde) the tetrahedral intermediate is a primary alkoxide. In the addition to ketones it is a secondary alkoxide. When a primary alkoxide is formed, the steric hindrance is smaller. Also, when the C=0 double bond of an aldehyde is broken due to the formation of the CH(0 M ) group of an alkoxide, less stabilization of the C=0 double bond by the flanking alkyl group is lost than when the analogous transformation occurs in a ketone (cf. Table 9.1). For these two reasons aldehydes react faster with hydride donors than ketones. With a moderately reactive hydride donor such as NaBH4 at low temperature one can even chemoselectively reduce an aldehyde in the presence of a ketone (Figure 10.6, left). 

ROC==CCH -> ROCHjC CH. Propynyl ethers can be obtained from secondary alkoxides by reaction with trichloroethylene followed by dehydrochlorination and methylation. These can be rearranged to propargyl ethers by KAPA. This sequence is applicable to highly hindered secondary alcohols.1... 

Aliphatic alkoxide ions are known to be unreactive as nucleophiles in the S l mechanism. Primary and secondary alkoxides reduce aromatic halides to arenes242 by an ET chain process, which at the same time leads to the oxidation of the alkoxide into the corresponding carbonyl group. Tertiary alkoxides (e.g. r-butoxide) can be used as bases in the reaction media as well as to initiate the photostimulated process. 

The diol 493 cyclized by intramolecular SnAr of the sterically hindered benzimiazole-activated nitro group by the primary or the secondary alkoxide in the presence of NaH to give the 1,5-oxazocine 495 (8%) and the thermodynamically more favored 1,4-oxazepine 494 (70%) (Equation 19) <2003OL4795, 2005USP0239767>. 

Modified Peterson reaction. This reagent was used in an unusual application of the Peterson reaction. The a-trirtiethylsilyloxy aldehyde (1) was converted in 80% yield to the Ws-trimethylsilyl compound (2) by treatment at - 35" with 0.95 equiv. of trimethylsilyllithium in HMPT. Nucleophilic attack at the carbonyl carbon was followed by silicon migration to the secondary alkoxide. The reaction of 2 with 3 equiv. of lithium diisopropylamide in THE containing 5% HMPT at 23" gave the saturated aldehyde 3 in 80% yield. The reaction was used to convert a hindered >C=0 into >CHCH20H. 

A serious obstacle to the use of the Julia alkenation for the synthesis of trisubstituted alkenes is illustrated in Scheme 31. Addition of cyclohexanone to the lithiated sulfone (86) gave intermediate (87), which could not be acylated under the reaction conditions because of the sterically hindered tertiary alk-oxide. Owing to an unfavorable equilibrium, (87) reverted back to starting materials. However, by reversing the functionality of the fragments a stable adduct (88) was formed in which the less hindered secondary alkoxide was acylated and the resultant -benzoyloxy sulfone (89) reductively eliminated to the alkene (90) in 54% overall yield. Trisubstimted alkenes have been generated by reductive elimination of 3-hydroxy sulfones ° but, in general, retroaldol reactions compete. 

Hydrolysis studies of secondary and tertiary alkoxides (69) indicate that the degree of polymerization of secondary alkoxides in benzene is lower than for the normal alkoxides, whereas the teritary alkoxides are monomeric. Thus the hydrolysis data on tetraisopropoxide zirconium and tetra-sec-butoxide zirconium are consistent with the model (2) hypothesis, while the hydrolysis data of tetra-ter<-amyloxide fit the model (3) hypothesis. Additionally, crystal structure data on tetraisopropoxide... 

On nucleophilic attack by the secondary alkoxide ion, the tetrahedral intermediate (3) is formed in the rate-determining step. This is shown by the fact that the rate constants of a- or )8-cyclodextrin-accelerated cleavage of (4a) (1.5 X 10 or... 

There have been no examples of reactions proceeding via general acid catalysis alone by cyclodextrin. In the hydrolysis of trifluoroacetanilide, however, general acid catalysis enhances the cleavage of the tetrahedral intermediate (5) formed by nucleophilic attack by a secondary alkoxide ion. General acid catalysis serves to convert the leaving group from an extremely unstable anion of aniline to a stable neutral aniline molecule (Scheme 2) [14]. 

All of the above features show the specific character of the components of the Alfin reagent or catalyst. The method of preparing the reagent may be varied, but all three components must be present. These are as a rule an alkenylsodium compound, a secondary alkoxide, and a sodium halide. Of the first two salts the most effective have the shortest unbranched carbon chain. 

Substitution at the 3-positions (Fig. lb) in this imit has a much less adverse effect than at the 2-positions (Fig. Ic). As the data in Table I showed, a straight-chain olefin or a long-chain secondary alkoxide did not destroy Alfin activity. Substitution at the 2-positions, however, was possible only with a methyl group. An ethyl or lai er group could not be used successfully. For instance, i-butoxide permitted some Alfin activity, whereas <-pen-toxide caused none. Isobutenylsodium was somewhat effective, whereas... 

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