Enolates lactam

Nakamura, E., New acyl anion equivalent. A short route to the enol lactam intermediate in cytochalasin synthesis. Tetrahedron Lett., 22, 663, 1981. 

The enol-lactam (30), which has occupied a central role in the synthesis of Erythrina alkaloids, has been converted in an unprecedented reaction into the dimeric isomers [31 C(6)-a-0] and [31 C(6)-/ -OJ.15 This reaction may be effected in benzene, pyridine, or acetic acid solution in the presence of lead tetra-acetate. The structures of the products were elucidated by spectral and chemical means. As enol ethers, these compounds were found to exhibit surprising stability to mineral acids. However, catalytic reduction of [31 C(6)-a-OJ under neutral conditions gave the starting enol-lactam (30) and the 7/Miydroxylactam (32 RJ = OH, R2 = R3 = H). The dimer [3 l C(6)-/i-0] yielded only compound (32 R1 = OH, R2 = R3 = H). Similarly, sodium borohydride reduction of the dimer mixture in hot isopropanol led to cleavage products (32 R1 = OH, R2 = R3 = H)and(32 RJ = R3 = H, R2 = OH). Besides the dimeric products, compound (32 R1 + R2 = O, R3 = OAc) was also isolated from the lead tetraacetate oxidation in low yields. Attempts to discover conditions for the formation of preparative amounts of (32 R1 + R2 = O, R3 = OAc), a compound of more potential usefulness for alkaloid synthesis, were fruitless. The other question of interest, whether or not the trans-dimer [31 C(6)-/i-0] could be converted into a monomeric trans-erythrinane system, remains to be answered. 

A new short route to the enol lactam (165) used in the Columbia synthesis... 

A) Keto or lactam form. (B) Enol or lactim form. 

The coupling of the enol triflate 703 with the vinylstannane 704[397] has been applied to the synthesis of glycinoeclepin[576]. The introduction of a (Z)-propenyl group in the / -lactam derivative 705 proceeds by use of tri-2-furylphosphine[577]. However, later a smooth reaction to give the propenyl-iactam in 82% yield was achieved simply by treating with Pd(OAc)2 in NMP or CH2CI2 for 3-5 min without addition of LiCI and the phosphine ligand[578]. 

The aromaticity of the pyrimidine and purine ring systems and the electron-rich nature of their —OH and —NHg substituents endow them with the capacity to undergo keto-enol tautomeric shifts. That is, pyrimidines and purines exist as tautomeric pairs, as shown in Figure 11.6 for uracil. The keto tautomer is called a lactam, whereas the enol form is a lactim. The lactam form vastly predominates at neutral pH. In other words, pA) values for ring nitrogen atoms 1 and 3 in uracil are greater than 8 (the pAl, value for N-3 is 9.5) (Table 11.1). 

Methylations—lactams, thiolactams, amino compounds, and enols. 

The methylation of 4-hydroxyquinol-2-one (71) is interesting. This compound is both an enol and a lactam it forms 80 of 4-methoxyquinol-2-one (70) and 20% of 2,4-dimethoxyquinoline (73). The dimethoxy compound must be formed from 2-methoxyquinol-4-one (72) because 4-methoxyquinol-2-one (70) does not react with diazomethane. 4-Hydroxy l-methylquinol-2-one (75) yields a mixture of the 4-methoxy analog (74) and 2-methoxy-l-methylquinol-4-one (76) the proportions of the products show kinetic dependence on the concentration of the diazomethane. 

A chiral sulfoxide can be used as a leaving group for the asymmetric inducdon via addidon-eliminadonprocess. 5-Lactam enolates are converted into the corresponding nitroalkenes subsdnited with lactams fEq. 4.101. ... 

When 2-lithio-2-(trimethylsilyl)-l,3-dithiane,9 formed by deprotonation of 9 with an alkyllithium base, is combined with iodide 8, the desired carbon-carbon bond forming reaction takes place smoothly and gives intermediate 7 in 70-80% yield (Scheme 2). Treatment of 7 with lithium diisopropylamide (LDA) results in the formation of a lactam enolate which is subsequently employed in an intermolecular aldol condensation with acetaldehyde (6). The union of intermediates 6 and 7 in this manner provides a 1 1 mixture of diastereomeric trans aldol adducts 16 and 17, epimeric at C-8, in 97 % total yield. Although stereochemical assignments could be made for both aldol isomers, the development of an alternative, more stereoselective route for the synthesis of the desired aldol adduct (16) was pursued. Thus, enolization of /Mactam 7 with LDA, as before, followed by acylation of the lactam enolate carbon atom with A-acetylimidazole, provides intermediate 18 in 82% yield. Alternatively, intermediate 18 could be prepared in 88% yield, through oxidation of the 1 1 mixture of diastereomeric aldol adducts 16 and 17 with trifluoroacetic anhydride (TFAA) in... 

In 1997, Lindstrom and Somfai reported aza-[3,3]-Claisen enolate rearrangements of vinylaziridines (Scheme 2.45) [70]. Treatment of l-acyl-2-vinylaziridines 179 with LHMDS resulted in the stereoselective formation of seven-membered lactams 181, presumably through a boat-like transition state 180. 

The oxidation of /(-amino-substituted iron acyl complexes which are prepared via condensation reactions of iron-acyl enolates and imines or iminium ions26,5 -47-54 generates /(-lactams 32,33,61. Brief treatment with bromine in dichloromethane at low temperature is the usual procedure. 

Since /1-lactams can be prepared via reactions of ester enolates with imines, these reactions are of great interest for synthetic and medicinal chemists. The synthesis of naturally occurring antibiotics and other physiologically active //-lactams is an objective of much current work. Though the stereocenters in those reactions are often established by addition of enolates to imines, they are discussed in Section D.1.6.1.3. In this section, only some basic results concerning //-lactams are presented. 

The Lewis acid induced reaction of silyl enol ethers and silyl ketene (thio)acetals with 4-acetoxyazetidinones is often used for introduction of a carbon substituent in the 4-position of the jS-lactam ring. Numerous examples are known, both with and without substituents at nitrogen, some of which are shown. 

Trimethylsilyl enol ethers, 94,133 Trimethylsilyl ketene acetals, 112-113 3-Trimethylsilyl -lactam, 71 Trimethylsilyl lithium, 51-2... 

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