Enol ethers, acetaldehyde-derived

An additional indication of the mildness of the cyclization is provided by the synthesis of the chiral tetrahydroisoquinoline-3-carboxylic acid (294) (72HCA15) in the presence of hydrogen and palladium-on-charcoal the jV-methyl derivative was obtained. Acetaldehyde gave a mixture of diastereoisomers in which the cis isomer (295) predominated (95 5). Unstable aldehydes can sometimes be generated in situ, as when the phenylglycidate (296) replaces the much less stable phenylacetaldehyde (66T(S8)129) acetals, enol ethers and chloromethyl methyl ethers have also been used. The mild conditions also allow the isolation of 4-hydroxytetrahydroisoquinolines (297) (75H(3)311). A review is available listing syntheses of 4-oxytetrahydroisoquinolines (73AHC(15)99). 

The silatropic ene pathway, that is, direct silyl transfer from an silyl enol ether to an aldehyde, may be involved as a possible mechanism in the Mukaiyama aldol-type reaction. Indeed, ab initio calculations show that the silatropic ene pathway involving the cyclic (boat and chair) transition states for the BH3-promoted aldol reaction of the trihydrosilyl enol ether derived from acetaldehyde with formaldehyde is favored [60], Recently, we have reported the possible intervention of a silatropic ene pathway in the catalytic asymmetric aldol-type reaction of silyl enol ethers of thioesters [61 ]. Chlorine- and amine-containing products thus obtained are useful intermediates for the synthesis of carnitine and GABOB (Scheme 8C.26) [62],... 

The nucleophilic character of the intermediate was demonstrated by a Hammett plot for relative rates of oxidation of a series of sulfoxides substituted on the phenyl group. Jefford et al. [176,177] have extended their work on the trapping of intermediates derived from enol ethers. Photooxidation in acetaldehyde as solvent results in the formation of 1,2,4-trioxanes which have been proposed to arise via the sequence summarized in Eq. (58)... 

The enol ether (230) has features in common with (223) in that they both encompass part of the artemisinin skeleton. Rose bengal-sensitized photooxygenation of (230) in THF containing acetaldehyde is reported to give the pair of (35) 3-methyl trioxanes (231) (35% yield) which are epimeric at C5 (Equation (34)) <88CC372>. Paradoxically, when photooxygenation is carried out in methanol followed by acid hydrolysis, the secoartemisinin derivative (232) (15% yield) is formed in which the C(3) methyl substituent has the 3R configuration (Equation (35)). The structures of the 35,55 epimer of (231), and (232) are established by x-ray. 

Scheme 9.48. The use of a (Z)-silyl enol ether derivative of ethyl phenyl ketone in the aldol condensation reaction with ethanal (acetaldehyde, CH3CHO) in the presence of a Lewis acid (MXn). The Miikaiyama aldol reaction.

Table 2 Aldolization of acetaldehyde-derived enol ethers ...

Denmark SE, Bui T (2005) Lewis base-catalyzed enantioselective aldol addition of acetaldehyde-derived silyl enol ether to aldehydes. J Org Chem 70 10190-10193... 

Modified Ghugaev reaction. The Li-salt of (l-phenylcyclohexyl)methoxymethyl-carbinol, prepared from the carbinol with phenyllithium in ether according to J. Weinstock and F. G. Bordwell, Am. Soc. 77, 6706 (1955), allowed to react with GS2 then with methyl iodide, and the resulting crude S-methyl xanthate heated 4.5 hrs. at 190-195°crude 1-phenylcyclohexylacetaldehyde enol methyl ether. Y 64%.—This is one step in a multistep conversion of acids with a-quaternary G-atoms into j -subst. acetaldehyde derivatives. F. e. s. J. W. Wilt and B.H. Philip, J. Org. Ghem. 24, 616 (1959). 

TABLE 43 Catalytic Intermolecular [2+2] Cycloaddition of Acetaldehyde-Derived Silyl Enol Ether... 

The mechanism of the Horner-Wadsworth-Emmons reaction of the lithium enolate derived from trimethyl phosphonoacetate with acetaldehyde has been investigated by ab initio calculations. Oxaphosphetane formation is rate determining, both in the gas phase and with one ether moleeule solvating. The transition state leading to trans-alkene is more stable than that giving the cis form. 

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