Sulfones activated methylenes

Other Applications. Hydroxylamine-O-sulfonic acid [2950-43-8] h.2is many applications in the area of organic synthesis. The use of this material for organic transformations has been thoroughly reviewed (125,126). The preparation of the acid involves the reaction of hydroxjlamine [5470-11-1] with oleum in the presence of ammonium sulfate [7783-20-2] (127). The acid has found appHcation in the preparation of hydra2ines from amines, aUphatic amines from activated methylene compounds, aromatic amines from activated aromatic compounds, amides from esters, and oximes. It is also an important reagent in reductive deamination and specialty nitrile production. 

The organic chemistry of sulfuryl chloride involves its use in chlorination and sulfonation (172,175,196,197). As a chlorinating agent, sulfuryl chloride is often mote selective than elemental chlorine. The use of sulfuryl chloride as a chlorinating agent often allows mote convenient handling and measurement as well as better temperature control because of the lower heat of reaction as compared with chlorine. Sulfuryl chloride sometimes affords better selectivity than chlorine in chlorination of active methylene compounds (198—200) ... 

Another important reaction in synthetic chemistry leading to C-C bond formation is the Michael addition. The reaction typically involves a conjugate or nucleophilic 1,4-addition of carbanions to a,/l-unsaturated aldehydes, ketones, esters, nitriles, or sulfones 157) (Scheme 21). A base is used to form the carbanion by abstracting a proton from an activated methylene precursor (donor), which attacks the alkene (acceptor). Strong bases are usually used in this reaction, leading to the formation of byproducts arising from side reactions such as condensations, dimerizations, or rearrangements. 

Other Applications. Hydroxylainine-O-sulfonic acid has many applications in the area of organic synthesis. The acid has found application in the preparation of hydrazines from amines, aliphatic amines from activated methylene compounds, aromatic amines from activated aromatic compounds, amides from esters, and oximes. 

Alternatively, active methylene groups in the starting materials would facilitate sulfonation by ... 

The synthetic utility of this base (1) was demonstrated in the preparation of vinyl iodides in high yields from simple ketohydrazones and iodine (Table), a process that normally gives mixtures of vinyl iodides and geminal diiodides if less hindered bases are employed.6 This base has also been used in the elimination of sulfonic acids from the corresponding sulfonates, the alkylation of compounds containing active methylene groups, the conversion of hydrazones to vinyl selenides, and the preparation of esters from sterically hindered acids.4 5... 

Reactions [99] of active methylene nucleophiles other than aldehydes and ketones with carbonyl compounds are also used for cyclizations. An example is the coupling reaction between sulfone and carbonyl. A sulfonyl group is easy to introduce and easy to remove. Yoshii and coworkers [100] used a sulfone-mediated macrocycliza-tion in the synthesis of ( )-0(26)-methyl-28,29-bisnor-kijanolide 171), the aglycone of the antitumor antibiotic kijanimicin. As shown in Scheme 56, treatment of the linear precursor 169 with 1 equiv of sodium r-amylate at room temperature for 10 min. afforded the macrocycle 170 in 82% yield. On the other hand, a diastereoisomer of 169 with opposite configuration at all the stereocenters in the octalin system resisted cyclization under the same conditions. This failure comes from a severe steric hindrance in the transation state of cyclization. Once again, stereochemistry is also an important factor for macrocyclization (cf. Section 2.10). 

This loses one of the carboxylates on heating in the presence of toluene-sulfonic acid to afford the (B-ketoester (82). Reaction of this intermediate with ethylorthoformate then adds a carbon atom to the activated methylene. Heating that compound with cyclopropylamine in effect exchanges the ethoxy group with the amine to afford enamine (84). Treatment 84 with sodium fluoride leads to displacement of one of the ring fluoro groups by the basic nitrogen on the side chain. This step concludes the formation... 

Nitriles have also been obtained recently from active methylene compounds of type 1 by a two-step process. Treatment with the aminal ester 2 (5, 71-73) leads to an enamine (3), which reacts with hydroxylamine-O-sulfonic acid in an aqueous medium to give a nitrile (4). This reaction docs not proceed through an aldehyde,... 

Similarly, mixtures of diastereomers of a-silylalkanesulfonates 5 are obtained by silylation of the active methylene group in sulfonates bearing optically active monoterpene substituents26. 

The halogenopurines react with many other nucleophiles including hydrazines, hydrox-ylamine and alkoxyamines, sulfonic acids and thiocyanates, and compounds with active methylene groups such as diethyl malonate furnish appropriate purine derivatives which offer valuable routes to alkyl and substituted alkyl derivatives. Also aryl groups have been substituted for halogen using aryllithiums (63N224). 

Knorrpyrrole synthesis. The reagent reacts with some active methylene compiounds to give products of C-amination. Thus 2,4-dimethyl-3,5-dicarhethoxypyrrole (2) can be prepared in one step by the reaction of hydroxylamine-O-sulfonic acid with ethyl acetoacctate (1). ... 

This self-proclaimed simple elegant method for the preparation of 2-hydroxy-substituted aromatic phenyl ethyl sulfones, a family of compounds with insecticidal activity, is actually the unexpected result of an attempted synthesis of sulfonyl chromenes of type IV (see Scheme 18.1). These dihydropyranyl derivatives have been prepared by the reaction of ot-hydroxybenzylamines with active methylene compounds such as malonic, cyanoacetic, and acetoacetic esters as well as 1,3-diketones, under alkaline conditions. ... 

In most cases, treatment of allylic halides containing one ASG with a nucleophile does not result in formation of electrophilic cyclopropanes (MIRC product) instead, other reaction pathways are followed, e.g. addition, substitution, rearrangement and elimination reactions.However, with certain alkenes or nucleophiles or under the appropriate conditions a conjugate addition-nucleophilic substitution pathway is favored, resulting in cyclopropanes substituted with one ASG. Representative examples are compiled in Tables 20 and 21 where organometallic compounds or active methylene compounds are used as the nucleophilic species in combination with allyl bromides containing an ester or a sulfone as ASG. 

The most widely explored method is the formation of tri- and tetrasubstituted cyclopropanes by reaction of vinylsulfonium salts with methylene compounds activated by ester, ketone, nitrile, or sulfone substituents. A series of examples is collected in Table 25. A variant of this method, where cyclopropanedicarboxylates cis-1 were actually obtained by intramolecular cyclization of the sulfonium salt Cj building block is also shown.Alkylthiocyclopropane derivatives 8 were obtained by the reaction of a ketene dithioacetal monosulfonium salt with carbanions derived from doubly activated methylene compounds. ... 

Obtained from active methylene compounds, such as malonic esters, -0x0 esters and jS-oxo sulfones, iodonium ylides serve as precursors of the corresponding carbenes. Their decomposition by a catalytic amount of a copper salt in the presence of a C-C double bond has been used for inter- and intramolecular cyclopropanation reactions. Thus, reaction of cyclohexene with bis(methoxycarbonyl)methylene(phenyl)iodine(III) under the catalytic action of bis(acetylacetonato)copper(II) yielded dimethyl bicyclo[4.1.0]heptane-7,7-dicarboxylate (1) (38%, mp 91-93°C) in addition to tetrakis(methoxycarbonyl)ethene (41%). ... 

The commonly encountered acidic functional groups in organic compounds include carboxylic acids, phenols, ammonium ions, alcohols, and thiols. To a lesser extent, sulfonic acids and active methylene compounds (those containing the —CO—CH2—CO— structural moiety) are also encountered. 

A related example of an organocatalytic asymmetric Mannich reaction that makes use of an aqueous biphasic system (aq. K2CO3/toluene) was reported by Ricci et al. Catalysts 19 derive from quinine and act as typical phase-transfer reagents. Active methylene compounds are used as donors, and 7V-Boc and A-Cbz protected a-amido sulfones as precursors of TV-prolcclcd imines (Scheme 1.9). ... 

The direct functionalisation of ketones is not limited to simple sulfonates. The a-(+)-10-camphorsulfonyloxy group has been also introduced into various types of ketones or carbonyl compounds bearing an active methylene group by using the HTIB analog, [a-(+)-10-camphorsulfonyl-oxy]hydroxyiodobenzene (147).250... 

The condensation of aromatic and aliphatic aldehydes with sulfoxide-activated methylenes like phenylsulfmylacetonitriles and phenylsulfmylacetates selectively forms a-sulfinyl-a,3-unsaturated carbonyl compounds (144) with the alkyl or aryl group trans to the sulfinyl group (see Section 1.11.2.5). 2 Oxidations of (144) with m-chloroperbenzoic acid yield the unsaturated ( )-sulfones... 

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