Ethers, methyl nucleophilic addition reactions

The introduction of umpoled synthons 177 into aldehydes or prochiral ketones leads to the formation of a new stereogenic center. In contrast to the pendant of a-bromo-a-lithio alkenes, an efficient chiral a-lithiated vinyl ether has not been developed so far. Nevertheless, substantial diastereoselectivity is observed in the addition of lithiated vinyl ethers to several chiral carbonyl compounds, in particular cyclic ketones. In these cases, stereocontrol is exhibited by the chirality of the aldehyde or ketone in the sense of substrate-induced stereoselectivity. This is illustrated by the reaction of 1-methoxy-l-lithio ethene 56 with estrone methyl ether, which is attacked by the nucleophilic carbenoid exclusively from the a-face —the typical stereochemical outcome of the nucleophilic addition to H-ketosteroids . Representative examples of various acyclic and cyclic a-lithiated vinyl ethers, generated by deprotonation, and their reactions with electrophiles are given in Table 6. 

An alternative method for dialkyl peroxide synthesis is the nucleophilic addition of an alkyl hydroperoxide to an alkene under acid catalysis reported by Davies and coworkers (Scheme 31, path B) ". A similar reaction is the nucleophilic addition of alkylhy-droperoxides to vinyl ethers under acid catalysis, producing perketals. Perketals can be deprotected under mild conditions (THF/water/acetic acid) and this hydroperoxide protection-deprotection sequence has been used by Dussault and Porter as a means for the resolution of racemic hydroperoxides (see also Section II.A.2) . In this respect more detailed studies were carried out with the perketals 75, which were prepared via reaction of alkyl hydroperoxides with vinyl ethers (Scheme 33). Weissermel and Lederer reported that in the presence of teri-butyl hypochlorite, a-chlorodialkyl peroxides can be formed in yields between 12% and 45% (Scheme 31, path C)". a-Alkoxydialkyl peroxides and diperoxyacetals were prepared by Rieche and coworkers via acid catalyzed reaction of one or two equivalents of alkyl hydroperoxides with acetals, ketals or aldehydes (Scheme 31, path D)" or by methylation of the corresponding a-alkoxy hydroperoxides with diazomethane (yields 11%, 27%)" . The diperoxyacetals 76 were isolated in yields ranging from 39 to 77%. 

A study of the photo-sensitized ring-opening reactions of the radical cations (76) of arylcyclopropanes (75) with methanol, water, and cyanide nucleophiles suggests a three-electron 5k2 mechanism (Scheme 11).185 The isolated products are methyl propyl ethers, derived from nucleophilic attack of methanol on the radical cation (76). They were detected by UV-VIS spectroscopy and shown to react with nucleophiles by transient kinetic methods. The benzyl radical (77) reacts with the DCB radical anion to afford monoaromatic ether (78) by oxidation and protonation or the disubstituted ether (79) by addition of DCB. Regio- and stereo-selectivity of the substitution were complete regiochemistry and rate constant were profoundly effected by the electronic nature of the aryl substituents.186 Elsewhere, a combined ab initio and CIDNP study... 

Examples of benzylic alkylation, aromatic ring deprotonation, and nucleophilic addition to a -position were used in a synthesis of (+)-20-methoxy-serrulat-14-en-7,8-diol. Deprotonation of the optically active complex (54) followed by reaction with chloromethyl methyl ether affords (55)... 

Tandem Carbon-Carbon Bond Formation via Brook Rearrangement Takeda et al. have reported that the reactions of benzoyl- and crotonylsilanes with hthium enolates of methyl ketones produce 1,2-cyclopropanediol monosilyl ethers via the Brook rearrangement of the initial 1,2-adduct 158 and the subsequent internal nucleophilic addition (Scheme 10.225) [587]. No formation of the corresponding cyclopropanes with alkanoylsilanes implies fhat fhe Brook rearrangement is accelerated by the phenyl or vinyl group. 

Singlet photosensitized polar addition of methanol to (A )-(>)-limonene (102) in nonpolar solvents afforded a mixture of the diastereomeric ethers 103 and 104 and the rearrangement product 105 (Scheme 6.42).677 The diastereomeric excess (de) of the photoadduct was optimized by varying the solvent polarity, reaction temperature and nature of the sensitizer. The first step of the reaction is the Z E photoisomerization (Section 6.1.1) of 102 to a highly strained /i-isomer, followed by protonation and methanol addition. The initial formation of a carbocation via the protonation step has been excluded under those reaction conditions. The Markovnikov-oriented methanol attack on the less-hindered (Rp)-(E)-102 compared with that of (Sp)-(E)-U)2 explains why 103 can be obtained in up to 96% de upon sensitization with methyl benzoate in a methanol solution. The hypothesis that Z E isomerization of the cyclohexene moiety affords a strained (reactive) alkene, whereas isomerization of the exocyclic double bond does not, was supported by the observation of an exclusive nucleophilic addition to the cyclohexene double bond. 

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