Enolization of methyl acetate

The addition of the lithium enolates of methyl acetate and methyl (trimelhylsilyl)acetate to ( + )-(S)-2-(4-methylphenylsulfinyl)-2-cycloalkenones gives, after desulfurization, (/ -substituted cycloalkenones. A higher level of selectivity is observed with the a-silyl ester enolate and in the cyclohexenone series13. The stereochemical outcome is rationalized by assuming attack on a ground-state conformation analogous to that in Section 1.5.3.2.1. 

Various kinds of chiral acyclic nitrones have been devised, and they have been used extensively in 1,3-dipolar cycloaddition reactions, which are documented in recent reviews.63 Typical chiral acyclic nitrones that have been used in asymmetric cycloadditions are illustrated in Scheme 8.15. Several recent applications of these chiral nitrones to organic synthesis are presented here. For example, the addition of the sodium enolate of methyl acetate to IV-benzyl nitrone derived from D-glyceraldehyde affords the 3-substituted isoxazolin-5-one with a high syn selectivity. Further elaboration leads to the preparation of the isoxazolidine nucleoside analog in enantiomerically pure form (Eq. 8.52).78... 

Table 2 shows the results of the addition of silicon and lithium enolates of methyl acetate to 2b and 2c (Eq. 3). Under the Fe-Mont catalysis, the t-butyldimethylsi 1yl ketene acetal of 6 is far less reactive than the trimethyl si 1 yl ketene acetal of 1, requiring higher reaction temperature moreover, it caused exclusive 1,2-addition to 2b in a good yield, but was inactive to 2c. Satisfactory yields of the expected products could not be... 

Etiolates. Asymmetric addition of enolates to enantiopure sulfinimines is an important method for the preparation of P-amino esters.21,84,85 For example, treatment of (Ss)-sulfinimine 47 with the sodium enolate of methyl acetate in ether afforded P-amino ester 149 in 84-85% yield and in >98% de.86,87 After removal of the N-sulfinyl group, P-amino esters 150 were obtained in >90% yield.84 The P-amino esters were further elaborated into the Taxol C-13 side chain 151a,21 its fluoro analogue 151b,85 (+)-2-phenylpiperidine (152a), and (+)-dihydropinidine (152b).87... 

Enantiopure bis-P-amino acids can be prepared from chiral bis-sulfinimines.37 Bis-sulfinimine (Ss,Ss)-160 and the sodium enolate of methyl acetate react to give 161 as a diastereomeric mixture. The major isomer (5s,/ ,Ss,/ )-161 can be isolated by preparative reverse-phase HPLC in 46% yield. Hydrolysis of (Ss,/ ,Ss,/ )-161 gave bis-P-amino ester (/ ,/ )-162 in >97% ee and 86% yield.37... 

Nucleophilic addition of ester enolates to enantiopure nitrones, followed by cyclization of the resulting hydro-xylamine, is a general approach to isoxazolidin-5-ones and can be applied to the stereoselective synthesis of these heterocycles <2005CRC775>. In some cases, the cyclization occurs spontaneously under the reaction conditions. For example, the addition of the sodium enolate of methyl acetate to chiral nitrone 551 gave directly the isoxazolidin-5-ones 552 in quantitative yield and high ty -diastereoselectivity (Equation 91) <1998CC493>. 

A two step synthesis of the first p-aminophosphotyrosyl mimetic (360) was carried out. Addition of (—)(R)-tert-butanesulfinylamide to 4-phosphonome-thyl benzaldehyde (361) gave chiral aldimine (362) which under treatment with the titanium enolate of methyl acetate produced the target compound with high diastereoselectivity (Figure 60). ... 

The total synthesis of the immunosuppressant (-)-pironetin (PA48153C) was accomplished by G.E. Keck and co-workers. The six-membered a,(3-unsaturated lactone moiety was installed using a lactone annulation reaction by reacting the advanced aldehyde intermediate with the lithium enolate of methyl acetate. The aldehyde was prepared by the Ley oxidation of the corresponding primary alcohol and was used without purification in the subsequent annulation step. 

Although addition of the trichlorosilyl enolate of methyl acetate to aldehydes is accelerated by a Lewis base catalyst, poor enantioselectivity is observed for the asymmetric version using 79, because of competition by the uncatalyzed achiral process (Scheme 10.30 in Section 10.2.1.4) [95]. Denmark et al. recently demonstrated that reactive silyl enolates are valuable for asymmetric addition to ketones (Scheme 10.67) [174]. The use of bis-N-oxide 80 as catalyst achieves high enantioselectivity in the reaction with aromatic ketones. 

A precursor 6.112 of carbapenems [1294] is selectively obtained by the reaction of 6.111 (R = 4-MeOCgH4) with the lithium enolate of methyl acetate, followed by treatment of the product with Ce(N03)g(NH4)2 and then with Na/NHj (Figure 6.92). 

The Mukaiyama reaction provides a good synthetic route to statine. L-Leucine methyl ester (6.104) was converted to the N-isopropylcarbamate aldehyde (6.105). Mukaiyama reaction with the trimethylsilyl enolate of methyl acetate, catalyzed by... 

Silyl Ketene Acetals. The lithium enolates of esters may be trapped with TBDMSCl to prepare the corresponding ketene silyl acetals. The resulting TBDMS ketene acetals are more stable than the corresponding TMS ketene acetals and have a greater preference for O- vs. C-silylation products. When TMSCl was used to trap the enolate of methyl acetate, a 65 35 ratio of O- to C-silated products was obtained. In addition, O-(TMS) sUyl ketene acetals are thermally and hydrolytically unstable. However, similar treatment of lithium enolates with TBDMSCl provided the corresponding O-(TBDMS) silyl ketene acetals exclusively (eq 3). The 0-TBDMS ketene acetals generally survive extraction from cold aqueous acid, lithium diisopropylamide was found to be satisfactory for the preparation of the ester enolates. The lower reactivity of TBDMSCl requires that the enol silation be performed at 0 °C with added HMPA. ... 

---