Oxiranes 2-alkyl-3-methyl

Synonyms Alkyl (C12-C14) glycidyl ether Dodecyl glycidyl ether n-Dodecyl glycidyl ether ((Dodecyloxy) methyl) oxirane Ether, dodecyl 2,3-epoxypropyl Oxirane, ((dodecyloxy) methyl)- Propane, 1-(dodecy I oxy)-2,3-epoxy-Empiricai C15H30O2... 

The reaction involving the alkylation of P-hydroxyalkyl selenides to give -hydroxyalkylselenonium salts which are then cyclized with a base is by far the most general. It allows the synthesis of a large variety of epoxides such as terminal, a,a- and a,3-disubstituted, tri- and tetra-substituted, as well as oxaspiro[2.0./i]-hexanes, -heptanes and -octanes (Scheme 161, g Scheme 162, d Scheme 164, d Scheme 165, b) - and vinyl oxiranes (Schemes 166 and i81) - from both p-hydroxy-alkyl methyl and phenyl selenides. ... 

O-Alkylation of 4-hydroxy-3-morpholino-l,2,5-thiadiazole 132 has been achieved with the chiral cyclic chloro-methyl sulfite 133 which subsequently suffers ring opening on treatment with simple alcohols <2001RCB436> or alkylamines <2002RJ0213> to afford the timolol analogues 134 with very little racemization (Scheme 20). This indicated an almost exclusive attack of the oxy anion on the exocyclic carbon atom and is a significant improvement on the previous oxirane method, which suffers from racemization. An alternative biocatalytic asymmetric synthesis of (A)- and (R)-timolol has also appeared <2004S1625>. 

The beneficial effect of added phosphine on the chemo- and stereoselectivity of the Sn2 substitution of propargyl oxiranes is demonstrated in the reaction of substrate 27 with lithium dimethylcyanocuprate in diethyl ether (Scheme 2.9). In the absence of the phosphine ligand, reduction of the substrate prevailed and attempts to shift the product ratio in favor of 29 by addition of methyl iodide (which should alkylate the presumable intermediate 24 [8k]) had almost no effect. In contrast, the desired substitution product 29 was formed with good chemo- and anti-stereoselectivity when tri-n-butylphosphine was present in the reaction mixture [25, 31]. Interestingly, this effect is strongly solvent dependent, since a complex product mixture was formed when THF was used instead of diethyl ether. With sulfur-containing copper sources such as copper bromide-dimethyl sulfide complex or copper 2-thiophenecarboxylate, however, addition of the phosphine caused the opposite effect, i.e. exclusive formation of the reduced allene 28. Hence the course and outcome of the SN2 substitution show a rather complex dependence on the reaction partners and conditions, which needs to be further elucidated. 

Thus, 2-furfuryl vinyl ether 6a is extremely sensitive to cationic activation (16) because of its very pronounced nucleophilic character, but the polymerization is accompanied by some gel formation due to abundant alkylation of the furan rings pendant to the macromolecules. This structural anomaly is not encountered with the 5-methylated monomer 6b (16) precisely because electrophilic substitutions take place predominantly at C5 and are therefore impossible with this monomer. A similar difference of phenomenolo was observed with the 2-fiiryl oxiranes 4a and 4b (17). 

The asymmetric induction also depends on the nature of the electrophile. Thus, iodomethane gave lower selectivities than the less reactive methyl sulfate or 4-methylbenzenesulfonate2. Higher alkyl 4-mcthylbenzenesulfonates or sulfates, however, react too slowly (yields 10-20%) at the low temperatures required in order to achieve a high enantiomeric excess in the alkylation reaction15. Furthermore, oxirane and alkyl chlorides did not react at all at these temperatures2-20. 

The original racemic patents described the use of resolution to give a chiral oxirane, such as 25, as an intermediate or the use of a chiral auxiliary (20) to produce the salmeterol enantiomers. Alkylation of chiral amine 20 with 2-benzyloxy-5-(2-bromo-acetyl)-benzoic acid methyl ester, followed by diastereoselective reduction of the ketone with lithium borohydride furnished intermediate 21 after chromatographic separation of the diasteromers. Removal of the benzyl group and the chiral auxiliary was... 

Carbon-13 shift values of parent heterocycloalkanes [408] collected in Table 4.61 are essentally determined by the heteroatom electronegativity, in analogy to the behavior of open-chain ethers, acetals, thioethers, thioacetals, secondary and tertiary amines. Similarly to cyclopropanes, three-membered heterocycloalkanes (oxirane, thiirane, and azirane derivatives) display outstandingly small carbon-13 shift values due to their particular bonding state. Empirical increment systems based on eq. (4.1) permit shift predictions of alkyl- and phenyl-substituted oxiranes [409] and of methyl-substituted tetrahydropyrans, tetrahydrothiapyrans, piperidines, 1,3-dithianes, and 1,3-oxathianes [408], respectively. Methyl increments of these heterocycloalkanes are closely related to those derived for cyclohexane (Table 4.7) due to common structural features of six-membered rings. 

Alkyl thiol anions displace halogens from halocodides to give corresponding alkylthiocodides. 192 Dihydrocodeinone (78) has been reported 200 to react with sodium dimethyloxosulfonium methylide (dimsyl sodium), giving the 6-oxirane (91), which opened under reducing conditions to the methyl carbinol, 92, an analgesic similar in potency to codeine. 

The reaction of lithium 1-propynyltributylborate with oxirane in dichloromethane affords, after protolysis, (Z)-3-methyl-3-octen-l-ol (27) as the major product, whereas the predominant product is the (E)-isomer (22) when THE is used as a solvent (Eq. 49) Consequently, great care should be taken in the alkylation of such 1-alkynyltrialkylborates, although they are versatile as synthetic reactions. 

Benzyl-1 -(3-hydroxy-propyl)- E16a, 487 (R2N —NO —Red.) 2-(2-Hydroxy-butyl)-l-phenyl- El6a, 601 (R-NH-NH2 + Oxiran) 2-(2-Hydroxy-2-methyl-propyl)- 3 -phenyl- E16a, 601 (R-NH-NH2 + Oxiran) (4-Isopropyloxy-benzyl)- E16a, 432 (Hydrazin-Alkyl.) (4-Propyloxy-benzyl)- E16a, 432 (Hydrazin-Alkyl.)... 

Product II may contain sufficient information in its structure to provide leads to at least one feasible mechanism. First, it displays a C-0 bond, now part of an oxirane, at the tertiary angular carbon where the angular methyl of I used to be. At the same time, this displaced methyl appears on that carbon atom where the nitrogen in I was located (C-1). This atom and group reorganization seems to follow the well established lines of a 1,2-alkyl migration, which in turn requires at some point the development of a low electron density center, evidently on the C-1 carbon. 

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