Imine enolates

Spectroscopic investigation of enamines conjugated with ketone, ester and nitrile groups established the prevalence of enamine rather than imine-enol tautomers in examples of secondary amines (206-212). Similar studies have been made with enamines of acylpyridines and acetophenones (213,214). 

In this section, we will look at alkene, imine, enol ether and alkyne protons. It s convenient to consider the first three at this stage as they usually absorb in the 8-5 delta region and the alkyne is included here for convenience. 

Keywords Mannich reaction, p-Amino carbonyl compounds, Imine, Enolate... 

Fig. 10 The three-dimensional potential energy surface describing the motion of protons between N6(A) and 04(T) and between N3(T) and N1(A) shows two critical points in the ground state. The deeper minimum corresponds to the amine/keto structure of AT and a shallow one to the imine/enol structure (A T ). Upon absorption of a UV photon the initaly delocalized excitonic states (1) undergo a rapid localization on f 10 ps timescale for single bases and 100 ps timescale for stacked base pairs to form a charge transfer (CT) states. The subsequent CT states passing through a conical intersection are carried back to the ground state.

In some extreme cases, such stabilization in the biological systems may have significant consequences. For example, the tautomeric imine-enol form of thymine enables it to form H-bonding with guanine (26, dR = deoxyribose) instead of the normal adenine pair (27), wherein the enol is stabilized via H-bonding with the keto group on guanine which causes mismatch in the structure of the DNA double helix. 

Imine enolates can be prepared without self-condensation, yet they will add rapidly to carbonyl compounds. This circumvents the low reactivity of ketones toward carban-ions derived from nonactivated methylene compounds and permits addition of aldehyde enolate equivalents to ketones. 

Since nitrogen is less electronegative than oxygen, imines are less reactive toward carbanions than ketones or aldehydes are. Therefore imine enolate anions can be prepared without self- condensation, yet they will rapidly add to carbonyl compounds [9]. This amounts to a directed cross aldol condensation and can even be used to add aldehyde enolate equivalents to ketones. 

The first step is treatment of 201 with an excess of KH. Both the OH and the NH lose their protons and cyanide is eliminated 204 to give the starting material for the aza-Cope 205. The product is initially formed in a twisted conformation 206 that opens out to give the simple d.v-fuscd imine enolate 206a. Trapping the enolate with ClC02Me also converts the imine into the acylated enamine 207 and the enol ester is easily hydrolysed to give the ketone 202. 

Enantioselective methylation of imine enolates of aminoesters 5.41 by diace-toneglucose 1.48 methyl sulfate has been carried out by Duhamel and coworkers [154, 358], After hydrolysis, nonracemic a-alkyl alanines are obtained with enantiomeric excesses up to 76% (Figure 5.28). 

Amlno-keto Imine-keto Imine-enol... 

Quinazolinone annelation of the 0-protected chiral pyrolidinone 74 (derived from L-aspartic acid) forms pyrrolo[2,l-fc]quinazohn-9(lH)-one 75 subsequent desilylation affords (S)-(-)-vasicinone 10, which is identical with the natural /-product (Scheme 16) [212,213]. Asymmetric oxidation of de-oxyvasicinone 11 (via the imine enolate) with either (R)- or (S)-Davis ox-aziridine reagent (lO-camphorsulfonyloxaziridine) [214,215] provides a convenient route to both enantiomers, thus confirming the recently revised stereochemistry of natural vasicinone (Scheme 16) [212,213]. Recently another approaches to optically active pyrrolo[2,l-fo]quinazolinones 10 have been reported by Kamal et al. (lipase-catalyzed resolution) [56], and Argade et aL (asymmetric synthesis from (S)-acetoxysuccinic anhydride) [216]. One-pot synthesis of 11, and related alkaloids has been also developed by utilizing microwave irradiation by Liu et al. [217]. Biogenetically patterned short-step synthesis of pyrroloquinazolinone alkaloids is well established by On-aka [218], and for many other synthesis, see the references cited in these papers. 

Topping and co-workers [19] have shown that lithium battery membranes fabricated from a bistrifluorovinyletherarylamide have excellent electromechanical stability at high electric potentials, making them potential candidates for use in battery membranes. Preliminary molecular modelling studies indicated that lithium imine enolates may play a useful role in lithium ion transport along with the crown ether linkage. 

Aldehyde enolates present another problem. They tend to give selfcondensation before an electrophile can be added. This may be solved again by use of imine enolates or A,A-dimethylhydrazones, which are themselves of low electrophihcity and allow good crossed aldol condensations and alkylations. For example, the terf-butyl imine of propanal was converted to the enolate with LDA and used in a crossed aldol condensation (Eq. 7.16) [30]. 

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