Cycloalkanones enamines

A particular use of aryllead triacetate is reported74 by which cycloalkanone enamines are arylated at the /f-carbon atom, giving sometimes acetoxylated compounds as by-products, by a mechanism analogous to that proposed for thallium triacetate75. 

In fact, treatment of cycloalkanone enamines with thallium triacetate, followed by rapid treatment with sodium hydroxide afforded /r[Pg.947]

Cycloalkanone enamines react with ethyl / -nitroacrylate to form adducts which yield y-lactones on treatment with sodium borohydride. Base-induced elimination of the elements of nitrous acid gives oe-methylenebutyrolactones 23 (equation 16)35. 

A novel reaction that probably involves tr-allyl intermediates is the reaction of allylic compounds with cycloalkanone enamines (208) ... 

When a large flexible cycloalkanone enamine 150 is used, MVK gives fused and bridged annulation products , and the relatively unreactive 3-quinuclidinone enamine 151 gives the quinolone 152 with methyl 2-propenyl ketone (Scheme 136). The use of 1-acetylcyclohexene as an MVK equivalent gives tricyclic systems (Scheme 137). 

Cycloaddition of aroyl isocyanates and trimethylsilyl ketene generates 4-trimethylsilyloxy-l,3-oxazin-6-ones 29 in situ, which smoothly react with cycloalkanone enamines to give 3,4-cycloalkeno-2-pyridones 30 [87] ... 

The vinylogous 3,5-hexadien-2-one (16) adds in a 1,4 cycloaddition with zl -dehydroquinolizidine (17) to form compound 18 (26). A similar 1,4-cycloaddition reaction takes place between pyrylium salts and the pyrrolidine or morpholine enamines of cycloalkanones (26a). 

A novel ring closure was discovered by Stork (6) in which the pyrrolidine enamine of a cycloalkanone reacts with acrolein. The scheme illustrates the sequence in the case of 1-pyrrolidino-l-cyclohexene, and the cyclopentane compound was found to undergo the reaction analogously. The procedure details the preparation of the bicyclo adduct and its cleavage to 4-cyclooctenecarboxylic acid. 

The Michael additions of chiral cycloalkanone imines or enamines, derived from (FV l-l-phcnyl-ethanamine or (5)-2-(methoxymethyl)pyrrolidine, are highly diastereofacially selective reactions providing excellent routes to 2-substituted cycloalkanones. This is illustrated by the addition of the enamine of (S)-2-(methoxymethyl)pyrrolidine and cyclohexanone to 2-(aryl-methylene)-l,3-propanedioates to give, after hydrolysis, the (2 5,a.S )-oxodicstcrs in 35-76% yield with d.r. (2 S,aS)/(2 S,a/ ) 94 6- > 97 3 and 80-95% ee214. 

Trimethylsilylketene and acyl isocyanates generate 4-trimethylsiloxy-l,3-oxazin-6-ones 12 in situ, which smoothly react with the enamines of cycloalkanones to give bicyclic 2-pyridones 13 <96TL(37)4977>. The heterocycles 12 also undergo the Diels-Alder reaction with dimethyl acetylenedicarboxylate or methyl propiolate to furnish substituted 2-pyridones <96TL(37)4973>. 

This topological rule readily explained the reaction product 211 (>90% stereoselectivity) of open-chain nitroolefins 209 with open-chain enamines 210. Seebach and Golinski have further pointed out that several condensation reactions can also be rationalized by using this approach (a) cyclopropane formation from olefin and carbene, (b) Wittig reaction with aldehydes yielding cis olefins, (c) trans-dialkyl oxirane from alkylidene triphenylarsane and aldehydes, (d) ketenes and cyclopentadiene 2+2-addition, le) (E)-silyl-nitronate and aldehydes, (f) syn and anti-Li and B-enolates of ketones, esters, amides and aldehydes, (g) Z-allylboranes and aldehydes, (h) E-alkyl-borane or E-allylchromium derivatives and aldehydes, (i) enamine from cyclohexanone and cinnamic aldehyde, (j) E-enamines and E-nitroolefins and finally, (k) enamines from cycloalkanones and styryl sulfone. 

Scheme IV/10. The enamine cycloalkanone reaction with acetylenecarboxylate [24], a) [2+2] Cycloaddition b) cycloreversion.

It has been observed8,27 that enamines of cycloalkanones can successively lose several H atoms. This tendency is greatly accentuated at higher temperature of the inlet system 8. For example, 27 loses 2, 3, 4 and up to 5 hydrogens with relative abundances of the corresponding ion-products 17, 17, 40 and 51%, respectively8. The most probable aromatized structure of the [M — 5] + ion is represented in Scheme 27. This phenomenon is worthy of mention although it is not a simple El phenomenon 8. 

The reductive coupling of carbonyl compounds with formation of C-C double bonds was developed in the early seventies and is now known as McMurry reaction [38, 39]. The active metal in these reactions is titanium in a low-valent oxidation state. The reactive Ti species is usually generated from Ti(IV) or Ti(III) substrates by reduction with Zn, a Zn-Cu couple, or lithium aluminum hydride. A broad variety of dicarbonyl compounds can be cyclized by means of this reaction, unfunctionalized cycloalkenes can be synthesized from diketones, enolethers from ketone-ester substrates, enamines from ketone-amide substrates [40-42], Cycloalkanones can be synthesized from external keto esters (X = OR ) by subsequent hydrolysis of the primary formed enol ethers (Scheme 9). 

A further example of the reactivity of (1) with carbonyl-activated methylene compounds is the reaction of (1) with cycloallcanones.4 Thus (1) reacts with cycloalkanones (9) in refluxing chloroform to give immonium chlorides (10), which on hydrolysis give amides (11) in overall yields of about 70-85%. The reagent (1) reacts with enamines... 

Earlier it was observed that the treatment of pyrylium salts (14) with enamines of cycloalkanones (15) in boiling acetonitrile results in the formation of substituted cycloalkenobenzophenones (17) if the pyrrolidino residue in (15) is used33. However, with enamines of morpholine preferentially the cycloalkenobenzenes (18) could be isolated. The heptatrienones (16), although not isolated, were supposed to be intermediates consistently with our experience, and a disrotatory ring-closure with c/s-elimination of the corresponding benzamide was proposed for the formation of (iS)33 (Table 4). 

Allylations. Allylation of enamines with 1-allylbenzotriazoles is accomplished in the presence of Pd(OAc)2-Ph3P and ZnBr2. The stepwise twofold allylation of cycloalkanones leading to bridged ring systems uses 2-methylene-1,3-propylene diacetate. Allylation of active methylene compounds with allylic alcohols is promoted by triethylborane. ... 

The 4-(chloromethyl)isoxazole 13, which is readily accessible from 3,5-dimethyloxazole, serves as a C4-building-block in annulations to cycloalkanones (isoxazole annelation according to Stork). The primary step is alkylation leading to product 14, a masked triketone. On hydrogenation, the isoxazole ring is reductively opened and cyclization via the enaminone 15 leads to the enamine 16. On treatment with sodium hydroxide, this is converted into the bicycloenone 17 by hydrolysis, acid fission of the y dicarbonyl system and an intramolecular aldol condensation (analogous to a Robinson annu-lation) ... 

Bicych[4.n.l]enones. These substances (3) can be obtained by cyclodialkylation of pyrrolidine enamines of cycloalkanones (1) with l,4-dichloro-2-butene (2) in the presence of potassium iodide, DMF, and this hindered amine. Yields of (3) are about 40% when n = 2 and 3, but only about 10% when n = 5. The reaction with the enamine of 4-methylcyclohexanone is improved by addition of HMPT. 

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