Addition-elimination reactions Michael-type

Additions of the Michael type of nucleophiles to the carbon-carbon double bond of thiete 1,1-dioxides to give 3-substituted thietane 1,1-dioxides occur readily. The addition of hydrogen has been discussed in Section A. Nucleophiles include cyanide, the anion of nitroethane, the lithium salt of r-butyl o-tolyl sulfone, dimethylamine, cyclohexylamine, ethoxide, and hydrogen sulfide. The reaction is exemplified by the synthesis of 278. Additions to 3-chloro-2H-thiete 1,1-dioxide most likely proceed by an addition-elimination mechanism an example is shown for the addition of the anion of dimethylmalonate to give 279. The replacement of a 3-morpholinyl group by a 3-A methyl-A-phenylamino group in thiete 1,1-dioxide is another example of addition-elimination. An addition of ethoxide with elimination of p-nitrophenyl anion may occur with 268 (Ar = / -N02C6H4). " Addition of bromine via N-bromo-succinimide to the double bond of 4-phenyl-2H-thiete 1,1-dioxide occurs only in 1.5% yield. ... 

In the reaction of Q,/3-unsaturated ketones and esters, sometimes simple Michael-type addition (insertion and hydrogenolysis, or hydroarylation, and hydroalkenylation) of alkenes is observed[53,54]. For example, a simple addition product 56 to methyl vinyl ketone was obtained by the reaction of the heteroaromatic iodide 55[S5]. The corresponding bromide affords the usual insertion-elimination product. Saturated ketones are obtained cleanly by hydroarylation of o,/3l-unsaturated ketones with aryl halides in the presence of sodium formate, which hydrogenolyses the R—Pd—I intermediate to R— Pd—H[56]. Intramolecular hydroarylation is a useful reaction. The diiodide 57 reacts smoothly with sodium formate to give a model compound for the afla-toxin 58. (see Section 1.1.6)[57]. Use of triethylammonium formate and BU4NCI gives better results. 

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. 

Additionally, uracil 6-iminophosphorane, isocyanate, and o-methyl-e-caprolactim ether join to form the intensely yellow pyrimido[4 5 4,5] pyrimido[6,l-n]azepine (360), as shown in Scheme 130. Upon ring closure, methanol is spontaneously eliminated. Diethyl azodicarboxylate affords with the other components pyrimido[4,5-e][l,2,4]triazoline (361), which is closely related to the alkaloid isofervenuline. The imidazo[5, -/][ ,2,4]tria-zine (362) results in a known Michael-type rearrangement sequence by treatment with diethyl acetylenedicarboxylate (86JOC149, 86JOC2787) in this latter case, the Michael-type addition occurs much faster than the expected three-component reaction [93H(35)1055]. 

The exceptional nucleofugality of the phenyliodonio group has been determined in an alkenyl salt and it is about 106 times greater than that of triflate [30]. This remarkable property makes alkenyl iodonium salts excellent vinyl cation equivalents in nucleophilic substitutions. The chemistry of alkenyl iodonium salts is dominated by the transfer of their aliphatic moiety to a variety of nucleophiles other important reactions involve Michael-type addition and alkylidenecarbene generation, along with elimination to alkynes which is actually an undesirable side-reaction. 

Treatment of 206 with cesium fluoride in DMF clearly promoted an intramolecular nitro-aldol reaction furnishing, after acetylation, nitrocyclitol 207 as an a, 3-anomeric mixture. Exposure of 207 to liquid ammonia in THF resulted in formation of kinetically favoured a-acetamido derivative 208, probably from a Michael-type addition of ammonia to a nitroolefin intermediate. Reductive elimination of nitro-group in 208 and subsequent deprotection gave validamine 202, in a global 6% yield from glucuronolactone 205. 

Simple double aza-Michael reaction of divinyl ketones with primary amines was utilized to generate TV-substituted 3-phenyl-4-piperidones in good yields <07EJO4376>. In a somewhat similar mode, the diastereoselective synthesis of cyclic (3-amino esters by an Sn2 substitution-cyclization of an iodo-a,(3-unsaturated ester with (.Sj-u-mcthy 1 benzylamine was described <07OBC3614>. A combination intramolecular Michael-type addition followed by retro-Michael elimination was exploited in the generation of a phosphoryl dihydropyridone intermediate in the synthesis of /m .v-2,6-disubstitutcd 1,2,5,6-tetrahydropyridines <07JOC2046>. 

It has also been demonstrated that ketimines may participate in reactions with nitrostyrenes providing fused pyrroles, as shown by the preparation of the system 311. The series of events leading to this outcome were suggested to involve a Michael-type addition of the enamine tautomer of the substrate 312 to the olefin, followed by annulation with concomitant elimination of the nitro functionality (Equation 92) <1999TL4177>. In addition, solid-state reactions of enamine esters or ketones with ( )-l,2-dibenzoylethene induced by milling gave excellent yields of pyrroles <1999AGE2896>. 

The analogue of 1 hydroxylated at C-6, e.g. 3-deoxyrabelomycin (20), was synthesized by Kraus and Wu using the excellent Michael acceptor properties of the extremely electron-deficient 3-acetyl-5-methoxy-1,4-naphthoquinone (17) [31, 32] (for related reactions of Eugster et al. compare [33]). The addition of 5-methyl-l,3-cyclohexadione (18) proceeded at 20-25 C without catalyst to afford adduct 19 after methylation. The subsequent intramolecular Michael-type reaction followed by elimination of methanol afforded more drastic conditions (NaOH, MeOH, 140 °C) and gave relatively low yields (27%) of a tetracyclic intermediate which was demethylated in the usual manner with AICI3 to yield 3-deoxyrabelomycin (20, Scheme 6). 

The intermediate of the ElcB mechanism is a carbanion, and thus any factors that stabilise such an ion should favour this mechanism. We have already noted above that on the face of it, elimination reactions are the reverse of addition reactions. However, we also noted that the actual mechanistic pathways involved in elimination reactions were more similar to substitution reactions than addition reactions. This is because normally elimination reactions proceed via a carbonium ion or in a single step that has certain similarities to an SN2 substitution reaction. However, there are also addition reactions that proceed via a carbanion intermediate, for example the Michael-type reaction, in which a carbanion adds to an a,(3-unsaturated carbonyl compound. Indicate the Michael-type addition between the anion formed from the diester of propandioic acid (or malonic acid) and 2-butenal. 

Eliminations. Based on an addition-elimination sequence initiated by Michael reaction between MeONHR and electron-deficient alkenes, functionalized enamines are synthesized. f-BuOK is an excellent base to promote such reactions. - a-Azido carbonyl compounds also undergo elimination to give a different type of enamines. ... 

The first prominent catalytic asymmetric Michael-type addition reaction of an organolithium reagent was shown by the reaction of 1-naphthy[lithium with 1-fluoro-2-naphthylaldehyde imine in the presence of 6 to afford the binaphthyls in high ee. Only catalytic amounts of 6 (0.05 mol%) effects the reaction to give 82% ee, in which an enantioselective Michael-type addition-elimination mechanism is operative (Eq. (12.12)) [31],... 

Allyl vinyl ethers have also been obtained by elimination reactions, e.g., intramolecular bromo-etherification/base-catalyzed hydrogen bromide elimination164 166( 0r the phenylseleno etherifi-cation/selenoxide elimination reaction158 167. Tertiary allylic alcohols have been vinylated by a Michael-type addition to a vinyl sulfoxide followed by elimination of benzenesulfenic acid168. 

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