S unsaturated

Reagents with carbonyl type groupings exhibit a or (if n. S-unsaturated) a properties. In the presence of acidic or basic catalysts they may react as enol type electron donors (d or d reagents). This reactivity pattern is considered as normal . It allows, for example, syntheses of 1,3- and 1,5-difunctionaI systems via aldol type (a -H d or Michael type (a + d additions. 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

Selective oxidation of secondary alcohols to ketones is usually performed with CrOj/HjSO, I I in acetone (Jones reagent) or with CrOjPyj (Collin s reagent) in the presence of acid-sensitive groups (H.G. Bosche, 1975 C. Djerassi, 1956 W.S. Allen, 1954). As mentioned above, a,)S-unsaturated secondary alcohols are selectively oxidized by MnOj (D.G. Lee, 1969 D. Arndt, 1975) or by DDQ (D. Walker, 1967 H.H. Stechl, 1975). 

CLAISEN - IRELAND Rearrangment Rearrangement ol allyl phenyl ethers to o (or p-)allylphenols or of allyl vinyl ethers to y.S-unsaturated aldehydes or ketones (Claisen) Rearrangement ol allyl esters as enolale anions to y.S-unsaturated acids (Ireland)... 

As is clear from the preceding examples, there are a variety of overall reactions that can be initiated by photolysis of ketones. The course of photochemical reactions of ketones is veiy dependent on the structure of the reactant. Despite the variety of overall processes that can be observed, the number of individual steps involved is limited. For ketones, the most important are inter- and intramolecular hydrogen abstraction, cleavage a to the carbonyl group, and substituent migration to the -carbon atom of a,/S-unsaturated ketones. Reexamination of the mechanisms illustrated in this section will reveal that most of the reactions of carbonyl compounds that have been described involve combinations of these fundamental processes. The final products usually result from rebonding of reactive intermediates generated by these steps. 

It is possible to monitor the reaction and determine the end point by the absence of an a,/S-unsaturated ketone absorption in the UV or by the determination of the consumption of ca. one molar equivalent of hydrogen peroxide by permanganate titration. 

The configuration of the amine was retained, except in the case of amino acid derivatives, which racemized at the stage of the pyridinium salt product. Control experiments showed that, while the starting amino acid was configurationally stable under the reaction conditions, the pyridinium salt readily underwent deuterium exchange at the rz-position in D2O. In another early example, optically active amino alcohol 73 and amino acetate 74 provided chiral 1,4-dihydronicotinamide precursors 75 and 76, respectively, upon reaction with Zincke salt 8 (Scheme 8.4.24). The 1,4-dihydro forms of 75 and 76 were used in studies on the asymmetric reduction of rz,>S-unsaturated iminium salts. 

Halogenated- ,/S-unsaturated ketones or aldehydes are reacted with methyl thioglycolate and cyclized with alkali alcoholate/ Thus jS-bromobenzalacetone (75) gives methyl 3-methyl-5-phenyl-2-thio-phenecarboxylate (76) and from a-methyl-j5-chlorocrotonaldehyde (77), 4,5-dimethyl-2-thiophenecarboxylate (78) is obtained. 

The behavior of such activated halides as alkylating agents under Friedel-Crafts conditions expands the scope of the synthesis. Aluminum chloride enhances the electrophilic character of the a,/S-unsaturated carbonyl system and permits the nucleophilic attachment of the aromatic addendum (Y ) to the carbon bearing the positive charge, with displacement of halogen [Eq. (5)]. Thus,... 

In contrast to the saturated azlactones, the Friedel-Crafts reaction of 2-substituted-4-arylidene-5-oxazolones is quite complex and may follow several different courses, often concurrently, depending on both reaction conditions and structural variations in the arylidene ring. This behavior is readily interpreted in terms of the a,)S-unsaturated carbonyl moiety and the cross-conjugated system containing nitrogen, both of which provide potential reaction sites in addition to the lactone carbonyl group. The reaction has been investigated " ... 

A solution of 0.1 mole of the a,/S-unsaturated ketone dissolved in 15 ml of anhydrous ether is added dropwise, whereupon the solution is rapidly decolorized. The stirring is continued for 4 hours during which time it slowly becomes blue or green. 

The reduction of ,/S-unsaturated y-diketones can conveniently be done with zinc in acetic acid. The following procedure is applicable to the reduction of the Diels-Alder adduct of quinone and butadiene (Chapter 8, Section II). 

The ionic liquid process has a number of advantages over traditional cationic polymerization processes such as the Cosden process, which employs a liquid-phase aluminium(III) chloride catalyst to polymerize butene feedstocks [30]. The separation and removal of the product from the ionic liquid phase as the reaction proceeds allows the polymer to be obtained simply and in a highly pure state. Indeed, the polymer contains so little of the ionic liquid that an aqueous wash step can be dispensed with. This separation also means that further reaction (e.g., isomerization) of the polymer s unsaturated ot-terminus is minimized. In addition to the ease of isolation of the desired product, the ionic liquid is not destroyed by any aqueous washing procedure and so can be reused in subsequent polymerization reactions, resulting in a reduction of operating costs. The ionic liquid technology does not require massive capital investment and is reported to be easily retrofitted to existing Cosden process plants. 

Both primary and secondary amines add to a /S-unsaturated aldehydes and ketones to yield /3-amino aldehydes and ketones rather than the alternative imines. Under typical reaction conditions, both modes of addition occur rapidly. But because the reactions are reversible, they generally proceed with thermodynamic control rather than kinetic control (Section 14.3), so the more stable conjugate addition product is often obtained to the complete exclusion of the less stable direct addition product. 

Water can add reversibly to o ,/3-unsalurated aldehydes and ketones to yield /3-hydroxy aldehydes and ketones, although the position of the equilibrium generally favors unsaturated reactant rather than saturated adduct. A related addition to an c /S-unsaturated carboxylic acid occurs in numerous biological pathways, such as the citric acid cycle of food metabolism where ds-aconitate is converted into isocitrate by conjugate addition of water to a double bond. 

Conjugate addition of an alkyl group to an c /S-unsaturated ketone (but not aldehyde) is one of the more useful 1,4-addition reactions, just as direct addition of a Grignard reagent is one of the more useful 1,2-additions. 

The wide variety of methods available for the synthesis of orga-noselenides,36 and the observation that the carbon-selenium bond can be easily cleaved homolytically to give a carbon-centered radical creates interesting possibilities in organic synthesis. For example, Burke and coworkers have shown that phenylselenolactone 86 (see Scheme 16), produced by phenylselenolactonization of y,S-unsaturated acid 85, can be converted to free radical intermediate 87 with triphenyltin hydride. In the presence of excess methyl acrylate, 87 is trapped stereoselectively, affording compound 88 in 70% yield 37 it is noteworthy that the intramolecular carbon-carbon bond forming event takes place on the less hindered convex face of bicyclic radical 87. 

Schemes 28 and 29 illustrate Curran s synthesis of ( )-hirsutene [( )-1]. Luche reduction58 of 2-methylcyclopentenone (137), followed by acetylation of the resulting allylic alcohol, furnishes allylic acetate 138. Although only one allylic acetate stereoisomer is illustrated in Scheme 28, compound 138 is, of course, produced in racemic form. By way of the powerful Ireland ester enolate Clai-sen rearrangement,59 compound 138 can be transformed to y,S-unsaturated tm-butyldimethylsilyl ester 140 via the silyl ketene acetal intermediate 139. In 140, the silyl ester function and the methyl-substituted ring double bond occupy neighboring regions of space, a circumstance that favors a phenylselenolactonization reac-...

The diastereoselective addition of [(S)-3-alkoxy-l-octenyl]lithium to an enantiomerically pure cyclic y-(rer/-butyldimethylsilyloxy)-o(,/S-unsaturated sulfone was employed in the synthesis of ( )-prostaglandin E219, with addition occurring exclusively anti to the sterically demand-... 

Double intramolecular /zcfcro-Diels-Alder reaction of 1,3-diynil-bis-a,)S-unsaturated hydrazones 139 and 140 is a good example of a thermal multiple Diels-Alder reaction and is a particularly attractive route to annelated pyridines [123]. The initial cycloadduct readily aromatizes by the loss of dimethylamine (Scheme 2.52) under thermal reaction conditions. 

Transition-metal-based Lewis acids such as molybdenum and tungsten nitro-syl complexes have been found to be active catalysts [49]. The ruthenium-based catalyst 50 (Figure 3.6) is very effective for cycloadditions with aldehyde- and ketone-bearing dienophiles but is ineffective for a,)S-unsaturated esters [50]. It can be handled without special precautions since it is stable in air, does not require dry solvents and does not cause polymerization of the substrates. Nitromethane was the most convenient organic solvent the reaction can also be carried out in water. 

Supported Lewis acids are an interesting class of catalysts because of their operational simplicity, filterability and reusability. The polymer-bound iron Lewis-acid 53 (Figure 3.8) has been found [52] to be active in the cycloadditions of a, S-unsaturated aldehydes with several dienes. It has been prepared from (ri -vinylcyclopentadienyl)dicarbonylmethyliron which was copolymerized with divinylbenzene and then treated with trimethylsilyltriflate followed by THF. Some results of the Diels-Alder reactions of acrolein and crotonaldehyde with isoprene (2) and 2,3-dimethylbutadiene (4) are summarized in Equation 3.13. 

The effectiveness of LP-NM with respect to LP-DE has also been proven by the cycloaddition of ketals of a,)S-unsaturated ketones with open-chain and cycloaliphatic dienes [46]. In 4.0m LP-NM the Diels-Alder reaction occurs with good yields and selectivities without using CSA, which is absolutely necessary when the reaction is performed in LP-DE (Section 6.2.1). Some examples are illustrated in Scheme 6.25. 

The most important of these three types of target innlecule is the a, S-unsaturated carbonyl compound. Disconnect TMs (10) and (11) and provide starting materials. 

The a,a -dianions of a-ketomethyl sulphoxides 476 react with esters exclusively at the a -position (equation 287). With a,/S-unsaturated esters these anions afford substituted 3-oxothian-1-oxides 477 the products of annelation " (equation 288). 

An illustrative example of the Michael reaction is that of the thiirene dioxide 19b with either hydroxylamine or hydrazine to give desoxybenzoin oxime (87) and desoxybenzoin azine ( ), respectively, in good yields (see equation 29). The results were interpreted in terms of an initial nucleophilic addition to the a, )S-unsaturated sulfone system, followed by loss of sulfur dioxide and tautomerization. Interestingly, the treatment of the corresponding thiirene oxide (18a) with hydroxylamine also afforded 86 (as well as the dioxime of benzoin), albeit in a lower yield, but apparently via the same mechanistic pathway . 

Thus, like a, )S-unsaturated ketones and sulfones, both thiirene dioxides and thiirene oxides are preferentially attacked by the less basic nucleophiles on the vinylic carbon atom. This would lead to formally 1,4 Michael-type adducts and/or other products resulting from further transformations following the initial formation of the a-sulfonyl and a-sulfoxy carbanions. 

In the base-catalyzed condensation of diethyl ethylsulfonylmethylphosphate with aldehydes or ketones, the corresponding a, )S-unsaturated sulfones were obtained in good yields - s . 

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