Acetals from enol esters

Spirophostins 9, which have been prepared as conformationally restricted analogues of adenophostins, and some spiro-acetals obtained from enol esters are covered in Chapter 2. 

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

Enol esters are distinct from other esters not because of a particular stability or lability toward hydrolases, but due to their hydrolysis releasing a ghost alcohol (an enol), which may immediately tautomerize to the corresponding aldehyde or ketone. A well-studied example is that of vinyl acetate (CH3-C0-0-CH=CH2), a xenobiotic of great industrial importance that, upon hydrolysis, liberates acetic acid (CH3-CO-OH) and acetaldehyde (CH3-CHO), the stable tautomer of vinyl alcohol [25], The results of two studies are compiled in Table 7.1, and demonstrate that vinyl acetate is a very good substrate of carboxylesterase (EC 3.1.1.1) but not of acetylcholinesterase (EC 3.1.1.7) or cholinesterase (EC 3.1.1.8). The presence of carboxylesterase in rat plasma but not in human plasma explains the difference between these two preparations, although the different experimental conditions in the two studies make further interpretation difficult. 

Extensive investigations have been directed toward the development of chiral ester enolates that might exhibit practical levels of aldol asymmetric induction. Much of the early work in this area has been reviewed (111). In general, metal enolates derived from chiral acetate and propionate esters exhibit low levels of aldol asymmetric induction that rarely exceed 50% enantiomeric excess. The added problems associated with the low levels of aldol diastereoselection found with most substituted ester enolates (cf. Table 11) further detract from their utility as effective chiral enolates for the aldol process. Recent studies have examined the potential applications of the chiral propionates 121 to 125 in the aldol condensation (eq. [94]), and the observed erythro-threo diastereoselection and diastere-oface selection for these enolates are summarized in Table 31. For the six lithium enolates the threo diastereoselection was found to be... 

Camell, A.J., Barkely, J. and Singh, A., Desymmetrisation of prochiral ketones by catal3ftic enantioselective hydrolysis of their enol esters using enzymes. Tetrahedron Lett., 1997, 38, 7781-7784 Allan, G.R., Carnell, A.J. and Kroutil, W., One-pot deracemisation of an enol acetate derived from a prochiral cyclohexanone. Tetrahedron Lett., 2001, 42, 5959-5962. 

Again, the exclusive formation of six-membered rings indicates that the cyclization takes place by the electrophilic attack of a cationic center, generated from the enol ester moiety to the olefinic double bond. The eventually conceivable oxidation of the terminal double bond seems to be negligible under the reaction conditions since the halve-wave oxidation potentials E1/2 of enol acetates are + 1.44 to - - 2.09 V vs. SCE in acetonitrile while those of 1-alkenes are + 2.70 to -1- 2.90 V vs. Ag/0.01 N AgC104 in acetonitrile and the cyclization reactions are carried out at anodic potentials of mainly 1.8 to 2.0 V vs. SCE. 

Further investigation with various silyl ketene acetals is summarized in Table 6. Silyl ketene acetals derived from various esters were reacted with /V-benzyloxy-carbonylamino sulfones 1 in the presence of 0.5-1 mol% Bi(0Tf)3-4H20. The corresponding (3-amino esters 24 were obtained in moderate to good yields (Table 6). Silyl enolates derived from esters as well as thioesters reacted smoothly to give the adducts. The /V - be n z v I o x v c ar bo n v I a m i n o sulfone derived from n-butvraldehyde lp led to moderate yields of (3-amino esters when reacted with (thio)acetate-derived silyl ketene acetals (Table 6, entries 1 and 2). A very good yield was obtained when the same sulfone was subjected to a tetrasubstituted silyl ketene acetal (Table 6, entry 3). The latter afforded moderate to good yields of (3-amino esters 24 with phenylacetaldehyde, / -tolu aldehyde, and o-tolualdehyde-derived sulfones (Table 6, entries 4-6). 

Group transfer polymerization offers another route to LAP of (meth)acrylates without resorting to low temperatures [Hertler, 1994, 1996 Muller, 1990 Quirk et al., 1993 Reetz, 1988 Schubert and Bandermann, 1989, Sogah et al., 1987, 1990 Webster, 1987, 1992, 2000]. The initiator is a silyl ketene acetal (XXIV) that is synthesized from an ester enolate ... 

In contrast to titanium(IV) tetrachloride, which causes polymerization of a,3-unsaturated esters, aluminum triflate88 or aluminum-impregnated montmorillonite87b are excellent promoters of silyl ketene acetal additions to a,(3-unsaturated esters (Scheme 35). Similarly, the addition of silyl ketene acetals and enol silyl ethers to nitroalkenes, followed by Nef-type work-up, affords y-keto esters (216) and y-di-ketones (218), respectively (Scheme 35).89a>89b Mechanistically, the y-diketones (218) arise from Nef-type hydrolysis of an initial nitronate ester (217).89e 89d Mukaiyama reports that SbCls-Sn(OTf)2 catalyzes diastereoselective anti additions of silyl ketene acetals, silyl thioketene acetals and enol silyl ethers to a,(3-unsaturated thioesters (219).90... 

The synthesis of this starting material 73 X = SMe also uses interesting strategy. The first step was a Diels-Alder reaction between a cyelopentadiene 77 and the dienophile 62 used by Nicolaou in his taxol synthesis. The diene was made from the anion of cyclopentadiene 74 and ethyl formate,18 and the enolate 76 transformed into the enol acetate 77. Diels-Alder addition of 62 and hydrolysis of the enol ester gave the adduct19 78. 

Silyl ketene acetals from esters.1 Ireland has examined various factors in the enolization and silylation of ethyl propionate (1) as a model system. As expected from previous work (6, 276-277), use of LDA (1 equiv.) in THF at —78 -+ 25° results mainly in (E)-2, formed from the (Z)-enolate. The stereoselectivity is markedly affected by the solvent. Addition of TMEDA results in a 60 40 ratio of (Z)- and (E)-2 and lowers the yield significantly. Use of THF/23% HMPA provides (Z)- and (E)-2 in the ratio of 85 15 with no decrease in yield. This system has been widely used for (E)-selective lithium enolate formation from esters and ketones. Highest stereoselectivity is observed by addition of DMPU, recently introduced as a noncar-... 

The enol ester from Figure 10.47 and one equivalent of Me2CuLi react to give the methyl-cyclohexenone A. Presumably, the enolate B is formed first in this reaction—according to one of the two mechanisms shown in Figure 10.46. An acetate ion is eliminated from this enolate as in the second step of an Elcb elimination. As an alternative, the enol ester of Figure 10.47 can also react with two equivalents of Me2CuLi. The second equivalent adds to the enone A, which is formed as before, and converts it into 3,3-dimethylcyclohexanone. 

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