Vinyl sulfones, Michael reactions

Base-induced eliminative ring fission, in which both the double bond and the sulfone function take part, has been observed in thiete dioxides253. The reaction can be rationalized in terms of initial Michael-type addition to the double bond of the ring vinyl sulfone, followed by a reverse aldol condensation with ring opening. The isolation of the ether 270c in the treatment of 6c with potassium ethoxide (since the transformation 267 -> 268 is not possible in this case) is in agreement with the reaction mechanism outlined in equation 101253. 

Also known as Morita-Baylis-Hillman reaction, and occasionally known as Rauhut-Currier reaction. It is a carbon—carbon bond-forming transformation of an electron-poor alkene with a carbon electrophile. Electron-poor alkenes include acrylic esters, acrylonitriles, vinyl ketones, vinyl sulfones, and acroleins. On the other hand, carbon electrophiles may be aldehydes, a-alkoxycarbonyl ketones, aldimines, and Michael acceptors. 

Nitrones can be generated by Michael reaction of oximes with appropriate conjugated substrates.25 If a generated nitrone has a built-in dipolarophile, cyclization can ensue (Scheme 15). There are three synthetic variations on this theme.25a,b First, the oxime may contain the dipolarophile as in (56). Reaction of (56) with phenyl vinyl sulfone provided a quantitative yield of the tandem product as one stereoisomer. Alternatively, die dipolarophile can reside in the Michael substrate as in (57). Reaction of (57) with cyclohexanone oxime produced two isoxazolidines from competitive cyclization of the intermediate nitrone through six- and seven-membered carbocyclic transition states. It is also possible to carry out an intramolecular Michael addition followed by an intramolecular nitrone cyclization as in thermolysis of (58) to produce a tricyclic isoxazolidine. Very recently several examples of a tandem Diels-Alder, Michael addition, nitrone cyclization sequence have been reported.250... 

Acceptor-substituted alkenes that are employed as substrates in Michael additions include a./l-unsaturated ketones (for example, see Figure 10.59), a,/3-unsaturated esters (Figure 10.60), and a,/3-unsaturatcd nitriles (Figure 10.61). The corresponding reaction products are bifunctional compounds with C=0 and/or C=N bonds in positions 1 and 5. Analogous reaction conditions allow Michael additions to vinyl sulfones or nitroalkenes. These reactions lead to sulfones and nitro compounds that carry a C=0 and/or a O N bond at the C4 carbon. 

Michael addition is a facile reaction between nucleophiles and activated olefins and alkynes in which the nucleophile adds across a carbon-carbon multiple bond [25], For the preparation of hydrogels, the hydroxyl, thiol or amine functionalities have been reacted with vinyl sulfones [26-28], acrylates [29-31], acrylamides [32], and maleimides [33, 34] (Scheme 2). 

As electron-rich olefins are more reactive, vinyl-sulfones are the most reactive species and are capable of reacting with thiols, amines, and even with small nucleophilic alcohol groups. Less reactive are acrylamides and acrylates, which are reactive towards amines and thiols. Maleimides are the least reactive of the mentioned species and allow selective addition of thiols in the presence of amines in the pH range 6.5-7.5. However, hydrolysis of the imide, especially at elevated pH values [35], may be a concern for certain applications. The mentioned Michael addition reactions do not require organic solvents and can be carried out at physiological temperature and pH [36], In acidic conditions, the reaction is either very slow or does not proceed because protonation removes the nucleophilic form in the case of amines, and the thiolate anion is usually the active species in Michael additions involving thiols [25],... 

Another frequent use of (1) and its enantiomer is the stereospecific conjugate addition of carbonyl compounds to a,p-unsaturated systems. Most published examples contain chiral imine derivatives of cyclic ketones, which add to a,p-unsaturated esters and ketones in a highly stereoselective manner (eq 13 and eq 14). When the ketone is not symmetrically substituted, reaction usually occurs at the most substituted a-position, including those cases where the ketone is a-substituted by oxygen (eq 15). High stereoselectivity can also be achieved when the Michael acceptor is other than an unsaturated ketone or ester, such as a vinyl sulfone (eq 16). Intramolecular variations of this transformation have also been described (eq 17). ... 

Vinyl sulfone-modifled carbohydrates, such as 111, can be subjected to Michael addition reaction with primary or secondary amines to constmct 112 bearing amino groups at the C-2 carbon... 

Recent investigations into the chemistry of vinyl sulfones have revealed that they are versatile synthetic intermediates, serving either as dienophiles or Michael acceptors. Methods for the preparation of vinyl sulfones from unactivated olefins have customarily involved the catalyzed (boron trifluoride or benzoyl peroxide) addition of PhS02X (X Cl, Br, I, or SePh), followed by elimination of HX. However, when phenylsulfonyl halides are employed, yields are variable, reactions are frequently incomplete, and the Lewis acid or free-radical catalyst employed can potentially interfere... 

The Michael addition of enolates to vinyl sulfones allows one-pot tandem reactions to be devised to achieve cyclisations as illustrated in Scheme 55. In the first reaction, the enolate (131) is transformed into the cyclic p-hydroxy sulfone (132) in good yield. In the second reaction, the enolate (133) yields the tricyclic compound (134) as a result of a double Michael reaction followed by intramolecular elimination of the benzenesulfonyl group. 

Very recently, Lu and coworkers successfully applied aminocatalysis via the enamine intermediate to the Michael addition of cyclic ketones to vinyl sulfones 181 [56]. In the presence of the cinchonidine-derived primary amine salt 179, the Michael reactions between vinyl sulfones 181 and cyclic ketones 180 proceeded smoothly, affording the desired adduct 182 in very high yield and with excellent enantioselectivity (up to 97% ee) (Scheme 9.63). They also successfully applied this methodology to the synthesis of sodium cyclamate. However, this protocol gave poor yields and ee values for acyclic ketones. 

The reaction of a,/ -unsaturated sulfones with chloroform, carried out under base/phase-trans-fer catalyst conditions, depends on the type of substituent on the sulfonyl group. Thus, phenyl vinyl sulfone underwent the Michael reaction with trichloromethyl anion to give 1, while ethyl vinyl sulfone underwent addition of dichlorocarbene to give cyclopropane 2. °... 

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