Enol ring closure with

The second type of cyclodehydration to be presented is the formation of cyclic enol ethers and cyclic enamines. Here, an alcohol or amino group reacts with an enol, resulting in ring closure with loss of H20. Such reactions... 

The required 1-oxa-l,3-diene precursor was synthesized according to the synthesis design (Scheme 8). Cycloadditon with enol ether furnished exclusively the endo-isomer. Raney nickel treatment in refluxing ethanol yielded in one step the desired tetrahydropyran derivative in a favorable 6 1 cis/trans ratio. Transformation into the lactone and ring closure with potassium tert.-butoxide afforded (+)-ramulosin. 

The enolate of an a,p-ester cyclizes preferentially to an alkyl ester enolate, ring closure occurring at the a-carbon. Treatment of (70) with either sodium methoxide or potassium r-butoxide gives (71), via the enolate of the a,p-unsaturated ester. Similarly, (72) cyclizes to (73) with potassium r-butoxide. Cycli-zation of (74) occurs, however, from the saturated rather than unsaturated enolate to give (75). This may reflect the stabilizing effect of sulfur on the enolate or the greater stability of the enolate of (75) relative to that of the alternative product (Scheme 30). 

Ring closure with enol acetates Bicyclo[2.2.1]heptan-2-ones... 

Ring closure with enol phosphates N-Condensed 2-pyridone ring... 

P,Y-ethylene-Y-lactones 30 Enol phosphates -, ring closure with - 31,745 Enols (s. a. Ethylenehydroxy...)... 

Ring closure with enol sulfonates Thianaphthenes... 

This synthetic feat relies on an asymmetric Michael/Michael/Henry tandem sequence, resulting in a formal [24-24-2] cycloaddition. The generation of a chiral copper enolate, which undergoes two successive Michael additions on two nitroalkenes followed by ring closure with a Henry reaction, generates the expected adduct in a highly enantio- and diastereoselective manner (Scheme 7.14). 

The reaction of a cyclic ketone—e.g. cyclohexanone 1—with methyl vinyl ketone 2 resulting in a ring closure to yield a bicyclic a ,/3-unsaturated ketone 4, is called the Robinson annulation This reaction has found wide application in the synthesis of terpenes, and especially of steroids. Mechanistically the Robinson annulation consists of two consecutive reactions, a Michael addition followed by an Aldol reaction. Initially, upon treatment with a base, the cyclic ketone 1 is deprotonated to give an enolate, which undergoes a conjugate addition to the methyl vinyl ketone, i.e. a Michael addition, to give a 1,5-diketone 3 ... 

Using 3-substituted cyclohexanones the /rans-diastereoselective synthesis of decalones and octahydro-1 //-indenones may be achieved 164 169. This method has been applied, for instance, in the synthesis of 19-norsteroids. In a related Michael addition the lithium enolate of (R)-5-trimethylsilyl-2-cyclohexenone reacts with methyl 2-propenoate selectively tram to the trimethylsilyl substituent. Subsequent intramolecular ring closure provides a single enantiomer of the bicyclo[2.2.2]octane170 (see also Section 1.5.2.4.4.). 

Michael additions followed by further Michael additions have become popular reactions and are usually referred to as Michael Michael Induced Ring Closure (MIM1RC) reactions. A three component Michael-Michael-aldol reaction of ketone enolates with acrylates can be achieved, resulting in the formation of six-membered ring compounds with good efficiency and high diastereoselectivites319. 

Optically active, a-branched lactams 30 have been built by means of Meyers chiral auxiliaries [ 10]. The key step included the diastereoselective a-alkylations of the initially formed co-i -sulfonamido oxazolines 26. The R or S configuration in the product 27 was obtained reacting the appropriately configured intermediate aza enolates with alkyl halides, high diastereoselectivities have been reported. Several attempts to achieve a complete ring closure to the lactams 30 (via 29) by an acidic cleavage of the oxazolines 27 failed. Varying mixtures of... 

A useful method to synthesize ten and fourteen-membered ring imides 346 involved an initial condensation of macrocyclic -ketoestes 343 with alkyl or aryl isocyanates and carbodiimides, respectively, in the presence of a base [68]. After a nucleophilic attack of the enolate on the isocyanate C, the resultant amide N anion 344 induced a ring closure by addition to the keto group. Then, the intermediately formed four-membered ring 345 underwent a fragmentation... 

This reaction is extended to the intramolecular ring closure of the intermediate radical 224 with olefinic or trimethylsilylacetylenic side chains [121]. Cu(BF4)2 is also effective as an oxidant (Scheme 89) [122]. Conjugate addition of Grignard reagents to 2-eyclopenten-l-one followed by cyclopropanation of the resulting silyl enol ethers gives the substituted cyclopropyl silyl ethers, which are oxidized to 4-substituted-2-cyclohexen-l-ones according to the above-mentioned method [123]. (Scheme 88 and 89)... 

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