Sulfonylimines

In the initial report by Corey and Chaykovsky, dimethylsulfonium methylide (2) reacted smoothly with benzalaniline to provide an entry to 1,2-diphenylaziridine 67. Franzen and Driesen reported the same reaction with 81% yield for 67. In another example, benzylidene-phenylamine reacted with 2 to produce l-(p-methoxyphenyl)-2-phenylaziridine in 71% yield. The same reaction was also carried out using phase-transfer catalysis conditions.Thus aziridine 68 could be generated consistently in good yield (80-94%). Recently, more complex sulfur ylides have been employed to make more functionalized aziridines, as depicted by the reaction between A -sulfonylimine 69 with diphenylsulfonium 3-(trimethylsilyl)propargylide (70) to afford aziridine 71, along with desilylated aziridine 72. ... 

A-Sulfonylimines as useful synthons in stereoselective synthesis of heterocycles 97MI40. 

Scheme 2.8 Reactions between N-sulfonylimines and allylic ylides.

Bode and co-workers have used NHCs to form y-butyrolactams 34 from enals 27 and saccharin-derived cyclic sulfonylimines 32. A range of [3-alkyl and [3-aryl substituted enals, and a variety of substituted imines, are tolerated in this reaction,... 

Bode and co-workers have demonstrated the application of such substrates in a number of reactions, including cyclopentene ring formation and y-lactamisation [15]. For example, y-lactamisation to give 56 with saccharin-derived sulfonylimines 54 was achieved from a-hydroxyenone 53 with moderate to excellent stereocontrol (Scheme 12.10). 

Bode and co-workers have extended the synthetic ntility of homoenolates to the formation of enantiomerically enriched IV-protected y-butyrolactams 169 from saccharin-derived cyclic sulfonylimines 167. While racemic products have been prepared from a range of P-alkyl and P-aryl substitnted enals and substitnted imi-nes, only a single example of an asymmetric variant has been shown, affording the lactam prodnct 169 with good levels of enantioselectivity and diastereoselectivity (Scheme 12.36) [71], As noted in the racemic series (see Section 12.2.2), two mechanisms have been proposed for this type of transformation, either by addition of a homoenolate to the imine or via an ene-type mechanism. 

A mechanistic rationale for the observed cw-selectivity has been proposed based on preorganisation of the Breslow-type intermediate and imine through hydrogen bonding 253, with an aza-benzoin oxy-Cope process proposed. Reaction via a boat transition state delivers the observed cw-stereochemistry of the product (Scheme 12.57). Related work by Nair and co-workers (using enones 42 in place of a,P-unsaturated sulfonylimines 251, see Section 12.2.2) generates P-lactones 43 with fran -ring substituents, while the P-lactam products 252 possess a cw-stereo-chemical relationship. 

Scheme 10.17 Additions of ZnEtz to A-sulfonylimines with binaphthylthiopho-sphoramide ligand.

Scheme 10.19 Additions of ZnEt2 to A-sulfonylimines with (17 ,27 )-cyclohex-anediamine-derived thiophosphoramide ligand.

Clerici and Porta reported that phenyl, acetyl and methyl radicals add to the Ca atom of the iminium ion, PhN+Me=CHMe, formed in situ by the titanium-catalyzed condensation of /V-methylanilinc with acetaldehyde to give PhNMeCHMePh, PhNMeCHMeAc, and PhNMeCHMe2 in 80% overall yield.83 Recently, Miyabe and co-workers studied the addition of various alkyl radicals to imine derivatives. Alkyl radicals generated from alkyl iodide and triethylborane were added to imine derivatives such as oxime ethers, hydrazones, and nitrones in an aqueous medium.84 The reaction also proceeds on solid support.85 A-sulfonylimines are also effective under such reaction conditions.86 Indium is also effective as the mediator (Eq. 11.49).87 A tandem radical addition-cyclization reaction of oxime ether and hydrazone was also developed (Eq. 11.50).88 Li and co-workers reported the synthesis of a-amino acid derivatives and amines via the addition of simple alkyl halides to imines and enamides mediated by zinc in water (Eq. 11.51).89 The zinc-mediated radical reaction of the hydrazone bearing a chiral camphorsultam provided the corresponding alkylated products with good diastereoselectivities that can be converted into enantiomerically pure a-amino acids (Eq. 11.52).90... 

A large specific microwave effect was observed in the solvent-free synthesis of N-sulfonylimines, a similar type of reaction [64] (Eq. 12). 

The preparation of imines, enamines, nitroalkenes and N-sulfonylimines proceeds via the azeotropic removal of water from the intermediate in reactions that are normally catalyzed by p-toluenesulfonic acid, titanium(IV) chloride, or montmorillonite K 10 clay. A Dean-Stark apparatus is traditionally used which requires a large excess of aromatic hydrocarbons such as benzene or toluene for azeotropic water elimination. 

Expeditious preparation of N-sulfonylimines has been optimized for one-pot solventless operation that involves microwave thermolysis of aldehydes and sulfonamides in presence of relatively benign reagents, calcium carbonate and montmoril-lonite K 10 clay (Scheme 6.23) [76],... 

An improved synthesis of a COX-2 inhibitor based on ring system 72 involves the cyclization of an imine intermediate formed between a 1-aminopyridazine salt and a benzyl ketone <2007TL911>. A tetrahydro derivative of ring system 73 has been prepared by dipolar cycloaddition of an iV-sulfonylimine to a diazafulvenium methide <2007JOC4406>. 

The sulfonylimine 72 reacts with cyclopentadiene in benzene at 0°C to afford solely the exo-adduct 73 in 84% yield (equation 48)42. The unstable inline 75, formed from the phosphorus compound 74 and ethyl glyoxylate by an aza-Witig reaction, adds to dienes... 

Aside from aldehydes, imines can be considered to be suitable substrates for the addition of reagents with umpoled carbonyl reactivity because useful building blocks and important compounds like a-amino acid and aldehydes will result from this conversion (Scheme 21). The S -configurated carbenoid 41 has been found to add to mesitylene-sulfonylimines 154, available from the corresponding aldehydes with predominant attack... 

Use of an alkyl hydrazine as the nucleophile followed the expected course of addition. The resulting product (33), however, opened to an N-sulfonylimine (34) which rearranged to a thia-triazoleoxide (35) in 65% yield (Scheme 7) <86H(24)ii93>. 

A sulfonylimine that is formed in situ as a reactive intermediate by interaction of the corresponding aminosulfonyl chloride and triethylamine has proved to be a popular cycloaddition reagent in the synthesis of 1,1-thiazetidines. 

In contrast to the sulfinylimines, the sulfonylimines are used only at a low temperature. Nagai et have studied the reaction of a sulfonylimine with enamines that do not have any reactive hydrogen atoms in the molecule ( Type C enamine). The cyclic product may be produced via a two-step mechanism in which a zwitterionic intermediate (168) occurs (Eq. 34). The Me... 

Oxaziridination of bridged bicyclic A -sulfonylimine 97 with OT-chloroperbenzoic acid (MCPBA), in the presence of K2CO3, affords OTr/o-compound 98 in high yields and 60% de (Equation 8) <1997JOC3625>. 

This work has been extended from aryl and alkyl substituted systems (42) (R = aryl, alkyl) to analogues where R is an amino group, so giving access to synthetic equivalents of the nonstabilized amino nitrile ylides (45). Adducts were obtained in good-to-moderate yield with A-methyhnaleimide (NMMA), DMAD, electron-deficient alkenes and aromatic aldehydes (27,28), and with sulfonylimines and diethyl azodicarboxylate (29). Similarly the A-[(trimethylsilyl)methyl]-thiocarbamates (46) undergo selective S-methylation with methyl triflate and subsequent fluorodesilylation in a one-pot process at room temperature to generate the azomethine ylides 47. 

Diazo(trimethylsilyl)methane reacts with A-sulfonylimines derived from aldehydes to give 2-(trimethylsilyl)aziridines in good yield and with high cis-stereo-... 

When we entered the field, Tomioka et al. had just introduced the dialkylzinc addition to N-sulfonylimines in the presence of chiral amidophosphine-copper(II) complexes, producing high levels of enantioselectivity (up to 94% ee) [27]. At the... 

Several types of cyclocondensation have been used to prepare imidazoles on insoluble supports (Figure 15.7). These include the condensation of 1,2-dicarbonyl compounds with aldehydes and amines, the 1,3-dipolar cycloaddition of iV-sulfonylimines to miinchnones, and the condensation of /V-acylated a-amino ketones with ammonia (Table 15.11). 

Polystyrene-bound o-quinodimethanes, which are formed upon thermolysis of ben-zocyclobutanes, can be converted into 1,2,3,4-tetrahydroisoquinoline derivatives by reaction with /V-sulfonylimines. Reaction of o-quinodimethanes with electron-poor nitriles leads to the formation of 1,4-dihydroisoquinolines, which undergo elimination with simultaneous release of isoquinolines into solution (Entry 7, Table 15.25). 

The submitters employed a toluene solution of crude imine prepared in part B and obtained somewhat higher yields (90-95%). However, the checkers obtained yields in this range on one half the scale using isolated sulfonylimine. 

Quite recently, there has been significant expansion and development in the alkylation of imines with organozinc reagents using chiral Lewis acid catalysts. In 2000, Tomioka and co-workers reported a copper(II)-chiral amidophos-phine 4-catalyzed asymmetric process for the addition of diethylzinc to N-sul-fonylimines (Scheme 2) [8]. Excellent enantioselectivities (90-94%) and yields (83-99%) were obtained in reactions of N-sulfonylimines derived from arylal-dehydes. 

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