Lithium enolates vinylogous

The Claisen-type condensation reaction of cyclic vinylogous carboxylic acid triflates with lithium enolates and their analogues has provided acyclic alkynes bearing a 1,3-diketone-type moiety.19 The reaction mechanism has been proposed to proceed via a 1,2-addition of the enolate to the vinylogous acyl triflate, followed by fragmentation of the aldolate intermediate (Scheme 2). 

Oxidation of the dienolate of (17) with (+)-( ) affords a-hydroxy ester (18), a key intermediate in the enantioselective synthesis of the antibiotic echinosporin (eq 19) whereas oxidation of enolates derived from 1,3-dioxin vinylogous ester (19) gives rise to both a - and y-hydroxylation depending on the reaction conditions (eq 20). With (+)-( ) the lithium enolate of (19) gives primarily the a -hydroxylation product (20), while the sodium enolate gives )/-hydroxylation product (21). Only low levels of asymmetric induction (ca. 16% ee) are found in these oxidations. Birch reduction products are also asymmetrically hydroxylated in situ by (+)-( ) (eq 21). ... 

The lithium enolates from tetronic acid-derived vinylogous urethanes have been generated and their reactivity investigated with a variety of electrophiles (eq 5). The reactions proceed with excellent regio- and diastereoselectivity and a variety of alkylating agents can be utilized. 

Two lithium enolates (174) and (175) derived from the vinylogous urethanes (176) and (177) have been crystallized and subjected to X-ray diffraction analysis.Although the individual enolate units combine to form different aggregates, they are very nearly identical in conformation, i.e. s-trans around the 2,3-bond however, both the aggregation state and the diastereoselectivity of the enolates differ. The enolate (175) is obtained from benzene solution as a tetramer and (174) is obtained from THF solution as a dimer. The origin of the diastereoselectivity shown by these enolates is subtle. 

A vinylogous Mukaiyama reaction, similar to that utilized in our synthesis, was employed to introduce the C-, stereocenter in Nicolaou s synthesis and also in the synthesis of preswinholide A reported by the Nakata group I53k One notable reaction in Nakata s synthesis of preswinholide A was the auxiliary-controlled aldol reaction shown in Scheme 9-31. Here the Evans auxiliary is used to couple two relatively complex fragments 91 and 92 to give 93. Unusually, this reaction was best performed using the lithium enolate of imide 91. 

VinylogoHS aldols and polyenonesf The lithium enolate (2) of (1), prepared with LDA, reacts with a ketone (e.g., /S-ionone, 3) to form the vinylogous aldol (4). The aldol can be converted into the polyenone (6) by reduction with sodium... 

Sodium and Potassium.—Although Li bases, because of their solubility, availability, or ease of preparation, are most popular for formation of reactive anions, occassions arise when basic Na or K compounds have advantages. For example, the reaction depicted in Scheme 8 occurs in 80% yield using the potassium enolate of ethyl cyanoacetate, but proceeds further to give unwanted products with the lithium enolate. Also, potassium enolates of vinylogous carboxylic acid derivatives are alkylated to give y-alkyl products more efficiently than the lithium enolates. ... 

Vinylogous amides undergo reduction with lithium aluminum hydride, by Michael addition of hydride and formation of an enolate, which can resist further reduction. Thus -aminoketones are usually produced (309, 563,564). However, the alternative selective reduction of the carbonyl group has also been claimed (555). 

When the enolate of an ,) - or a /j,y-unsatunited amide is used, it can react in an a or in a y fashion with a,/i-unsaturated esters, however, in most cases only a-selectivity is observed. Using l-(l-oxo-2-butenyl)pyrrolidine and lithium diisopropylamide at — 78 °C in a THF/HM-I A mixture (1 1), high. syn-selective formation of 3-alkyl-5-oxo-5-(l-pyrrolidinyl)-4-vinylpen-tanoates is achieved78,381 382. Related syn- or anti-selective additions of a vinylogous urethane also are known79. 

A correlation between rate acceleration and the electron-donating ability of the MO group of enolates 2 shows the potassium enolatc to be superior to the lithium, sodium or trimethylsilyl derivative84. The rate enhancement, in this case, lias been attributed to a vinylogous weakening effect of the oxyanion on the 0-3 C-4, oxygen-carbon bond, similar to effects that have been encountered in anionic oxy-Cope rearrangements119. 

---