Enolate Additions

Instead of the pure organometal (cuprate and organolithium) sjiecies resonance-stabilized carbanions of the enolate-type can also be used for inter- and intramolecular 1,4-additions [90]. 

in the addition of ketene acetal 270 to cyclopentanone 269 the use of mercury diiodide as the Lewis acid leads to the cis-diastereomer 271, whereas TASF generates the trans-isomer 272, both with high selectivity. This result may be interpreted in terms of Hg-chelation leading to cis-induction, whereas the enolate follows a purely steric effect, which prefers the anti attack. However, the complexation with mercury may be overruled if the steric demand of the ketene acetal 273 is increased. Now only the trans-isomer 275 is found in both cases. 

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Other methods for the regioselective SN2-opening of vinyloxiranes include intramolecular enolate addition for formation of cyclohexane systems [135, 136] and Friedel-Crafts alkylations [49, 137, 138]. 

Other Enolate Additions Leading to Cyclic Amines... 

Auxiliary-Induced Diastereoselection I.4.3.3.I. Auxiliary Croup in the Enolate Addition to Imines or Iminium Salts... 

Although the methodology described so far produces <5-oxo esters via diastereoselective enolate additions to enones, the same product may be obtained via an alternate sequence, i.e., addition of ketone or aldehyde enolates to a,j3-unsaturated esters or amides. Enolates of ketones are known to react with a,/ -unsaturated esters to give the Michael adducts50, however, the study of simple diastcrcoselectivity has, so far, been limited to special cases (MIMIRC reactions, Section 1.5.2.4.4.). 

Closely related to enolate additions to enones is the diastereoselective 1,4-addition of lithium enolates of esters, thioesters and amides to a,/ -unsaturated esters. These reactions provide syn-or ar /-2,3-disubstituted glutarates (pentanedioates). 

I.5.2.4.I.2.3. Glutamic Acid Derivatives via Enolate Additions to a,/l-Unsaturated Esters... 

Although Baldwin s rules can be applied to ketone enolates, additional rules were added to make the terminology more specific. The orientation of the orbital as it approaches the reactive center must be considered for determining the correct angle of approach. Diagrams that illustrate the enolate rules are... 

The C(9)—C(16) subunit was synthesized from the same starting material. The chain was extended by a boron enolate addition to 2-methylpropenal (Step D-2). After introduction of a double bond by selenoxide elimination in Step E-4, a Claisen rearrangement was used to generate an eight-membered lactone ring (Step E-6). 

Lithium ester enolate addition to imines has been used for the construction of optically active p-lactams, e.g. 64 and the lithium enolates have been found to be superior to other metal derivatives for both yields and diastereoselectivity in some cases <00H(53)1479>. Immobilized lithium ester enolates have been utilized for the first time <00OL907> and soluble polymer supported imines were used to obtain N-unsubstituted azetidin-2-ones under mild conditions <00CEJ193>. Both lithium and titanium enolates have been employed to obtain cholesterol absorption inhibitors <99TA4841>. Lithium ynolates 65 add to imines to provide P-lactams in good to excellent yield <00TL5943>. 

Moreover, stereoselective titanium enolate additions to different iV-sulfinyl imines113 114 or in situ-prepared iV-arylimines (three-component reaction) have been carried out to afford the corresponding sulfinyl amides or valuable /3-amino acid precursors.115... 

Michael additions of ketone enolates. The stereochemistry of Michael additions of lithium enolates of ketones to a,(3-enones is controlled by the geometry of the enolate. Addition of (Z)-enolates results in anti-products with high diaster-eoselectivity, which is not changed by addition of HMPT. Reaction of (E)-enolates is less stereoselective but tends to favor syn-selectivity, which can be enhanced by addition of HMPT. 

Chiral a-sulfinyl alcohols have proved useful in enantioselective protonation of enolates.Addition of lithium bromide enhances the ee in a number of cases, apparently via simultaneous coordination of lithium to the enolate and to the sulflnyl alcohol. 

As shown in previous sections, NHCs promote acyl transfer in transesterification reactions. In a similar manner, O C acyl transfer can be achieved with substrates such as 351 in the presence of 0.9 mol% of triazolium pre-catalyst 353 and KHMDS (Scheme 53). Moderate yields are obtained by varying substitution of the oxazole from R = Me, Ph, t-Bu, and t-Pr [171], Deprotonation of the triazolium salt followed by nucleophilic addition to the carbonate moiety of the oxazole results in enolate intermediate LXXXIII and activated carboxylate LXXXIV. Enolate addition and regeneration of the active catalyst provides quaternary stereocenters 352. 

In this study, benzaldehyde and benzaldehyde-methyllithium adduct were fully optimized at HF/6-31G and their vibrational frequencies were calculated. The authors used MeLi instead of lithium pinacolone enolate, since it was assumed that the equilibrium IBs are not much different for the MeLi addition and lithium enolate addition. Dehalogena-tion and enone-isomerization probe experiments detected no evidence of a single electron transfer to occur during the course of the reaction. The primary carbonyl carbon kinetic isotope effects and chemical probe experiments led them to conclude that the reaction of lithium pinacolone enolate with benzaldehyde proceeds via a polar mechanism. 

The disulfide dimers of 2-aminothiophenols have also been used in the syntheses of benzothiazines. In this case, nitrogen acts as a nucleophile and sulfur as an electrophile. Reagents that have nucleophilic carbons adjacent to an electrophilic carbon can be reacted with these disulfides. Examples include a,(3-unsaturated esters that undergo conjugate addition followed by enolate addition to sulfur (Equation 86) <1983J(P1)567>, and 1,3-dicarbonyl compounds such as ethyl acetoacetate <2005AXEo2716> and dimethyl malonate <2006ARK(xv)68> (Scheme 63). 

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