N-Tosyl imine

Solladie-Cavallo has recently reported a two-step asymmetric synthesis of dis-ubstituted N-tosylaziridines from (R,R,R,Ss)-(-)-sulfonium salt 2 (derived from Eliel s oxathiane see Section 1.2.1.1) and N-tosyl imines with use of phosphazine base (EtP2) to generate the ylide (Scheme 1.42) [67], Although the diastereoselectiv-ity was highly substrate-dependent, the enantioselectivities obtained were very high (98.7-99.9%). The chiral auxiliary, although used in stoichiometric quantities, could be isolated and reused, but the practicality and scope of this procedure is limited by the use of the strong - as well as expensive and sensitive - phospha-zene base. 

Ye and co-workers have shown that NHC 67 can catalyse the aza-Morita-Bay-lis-Hillman reaction of enones 66 and N-tosyl imines 63, presumably via initial NHC conjugate addition to the enone to generate an azolium enolate 68 [18]. A related conjugate addition approach has been exploited by Fu and co-workers, with tautomerisation of the initial enolate 72 derived from NHC conjugate addition to 70 giving 73, with subsequent cyclisation resulting in the umpolung of Michael acceptors (Scheme 12.13) [19]. 

New electrophilic substitution reaction methods for the preparation of dipyrromethanes have been reported. The condensation of IV-methylpyrrole with benzaldehyde leading to the corresponding dipyrromethane was promoted by the addition of the organic catalyst, pyrrolidinium tetrafluoroborate <06T12375>. The reaction between pyrrole and N-tosyl imines promoted by metal triflates gave dipyrromethanes whereas tripyrromethane byproducts were not observed <06T10130>. 

In related work, Sasai developed several bifunctional BINOL-derived catalysts for the aza-Morita-Baylis-Hillman (aza-MBH) reaction [111]. In early studies, careful optimization of the catalyst structure regarding the location of the Lewis base unit revealed 41 as an optimal catalyst for the aza-MBH reaction between acyclic a,P-unsaturated ketones and N-tosyl imines. Systematic protection or modification of each basic and acidic moiety of 41 revealed that all four heterofunctionalities were necessary to maintain both chemical and optical yields. As seen in Scheme 5.58, MO calculations suggest that one hydroxyl groups forms a... 

Table 1.4 Catalytic asymmetric addition to N tosyl imines R sZn...

As mentioned, in most copper and zirconium catalyzed alkylations of imines, the addition of less reactive dimethylzinc (relative to diethylzinc) usually requires a large excess of the organometallic reagent. Hayashi reported that the methylation of N tosyl imines could be achieved using only 1.5 equiv of dimethylzinc in the presence of a chiral rhodium complex that is coordinated with chiral diene 54 [86]... 

Scheme 1.21). This catalyst provides the addition product derived from the N tosyl imines of aryl substituted aldehydes in high yield and enantiocontrol. It is believed that the addition proceeds via the formation of a methylrhodium species obtained by the reaction between the rhodium catalyst and dimethylzinc. 

Catalytic Asymmetric Nucleophilic Addition to Achiral Imines 37 Table 1.18 Addition of a lboronic adds to N tosyl imines. 

Rhodium Diene-Catalyzed Arylation of Imines Hayashi has shown that the asymmetric synthesis of diarylmethylamines could be realized with high enantio control by the rhodium catalyzed arylboronic acid addition to N tosyl imines [119]. Ihe rhodium catalyst bears the C2 symmetrical bicyclo 2.2.1]heptadicne ligand 54. 

Scheme 6.11 Asymmetric hydrogenation of N tosylated imines by a palladium/diphosphine catalyst.

Meanwhile, Leitner and coworkers monitored the aza MBH reaction of methyl vinyl ketone (MVK) with N tosylated imine in the presence of P Ph 3 in TH F dg at room temperature by NMR spectroscopy [10]. The rate law was derived by analyzing the initial rates as a function of concentration for the individual components. The broken order of 0.5 in imine indicated that the rate determining step was partially influenced by proton transfer. A variety of Bronsted acidic additives with different p/<., values were examined with 3,5 bis(CF3)phenol at pKa 8 corresponding to a 14 fold rate enhancement as compared to the reaction without additive. Examination of the kinetics in the presence of phenol as prototypical additive revealed that the rate law of the reaction changed in the presence of the Bronsted acid, showing first order dependence on imine. Thus, the elimination step was not involved in the... 

Sasai and coworkers reported that a chiral BINOL derived amine 16a catalyzed asymmetric aza MBH reaction of N tosyl imines with acrolein and alkyl vinyl ketones [22]. The corresponding aza MBH adducts were obtained in good to excellent yields with high enantiomeric excesses (Table 13.4). Replacing the tPr group with other substituents in amine 16a provided less effective catalysts regarding yield or enantioselectivity [23]. 

Boger and Corbett have also recently described a convenient modification of the original Hudson methodology [20]. Their procedure is based upon the known [21] propensity of methanesulfonyl- and toluenesulfonyl cyanide to rearrange to the corresponding sulfinyl cyanate (cf. 8, Scheme 4). Thus, treatment of an oxime with commercially available tosyl cyanide (7) generates 8 in situ, which leads to the O-sulfinylated oxime 9 and then to the N-tosyl imine. This methodology avoids the use of reactive, often unstable sulfinyl chlorides. 

This supposition raises an interesting point with regard to the site of Lewis acid complexation of N-sulfonyl imines. Weinreb and Sisko [38] have observed that H and 13C NMR spectra of alkyl N-tosyl imines in the presence and absence of a Lewis acid are virtually identical. It would be anticipated that if Lewis acid complexation in fact occurred at nitrogen, one should observe a significant downfield shift [39] of the imino proton or carbon. Therefore, it may be that in general Lewis acids prefer to coordinate at the sulfonyl group of this type of imine, although additional work is necessary to verify the exact position of Lewis acid complexation. 

An interesting and highly stereoselective reaction of dimethoxy cyclopropane derivative 81 with some aromatic N-tosyl imines was recently described by Saigo and coworkers [41] (Scheme 16). In the presence of TiCl4, compound 81 condenses with N-sulfonyl imines to stereoselectively produce lactams 84 and 85, with the cis isomer being the predominant product. It is likely that the dimethoxy cyclopropane initially opens to zwitterionic ester enolate 82, which adds to the imine to yield intermediate 83. The rationale presented for the stereoselectivity in condensation of enolate 82 with the imines is similar to that described for the reactions in Schemes 14 and 15, cf. Fig. (1). 

Table 1 Reactions of in situ Generated N-Tosyl Imines with Allyl Silanes...

Despite a considerable amount of recent work on reactions of vinyl silanes with various kinds of imines [48,49], scant attention has been paid to N-sulfonyl imi-nes in this area. A single study of a vinyl silane/N-sulfonyl imine reaction has been published by McIntosh and Weinreb in the context of an approach to the total synthesis of [1, 3]-dioxolophenanthrene structural types of Amaryllida-ceae alkaloids such as narciclasine (137), lycoricidine (138) and pancratistatin (139) [50]. The substrate used in this approach was vinyl silane aldehyde 140, prepared enantiomerically pure in a straightforward manner from L-arabinose (Scheme 26). The N-tosyl imine derived from this aldehyde could be generated in two different ways. The first involved combination of 140 with N-sulfinyl-p-toluenesulfonamide at 80 °C, followed by exposure of the imine to BF3 etherate at 0°C, leading to a single cyclization product 142 in 36% yield. The second procedure was to simply react aldehyde 140 with p-toluenesulfonamide and BF3 etherate (-78°C -rt) to afford a 9.5 1 mixture of 142 144 in -80% yield. It was pro-... 

Weinreb and coworkers have also developed a simple one-pot procedure for reductive sulfonamidation of both aromatic and aliphatic aldehydes [14], Again using the Kresze methodology an aldehyde could be converted to a Lewis acid-complexed N-tosyl imine which in the presence of triethylsilane was reduced to a sulfonamide in good yields [Eq. (29)]. 

In a recent report [77], Furukawa et al. found a novel method for generation of N-tosyl imines which have been trapped as [4+2]-cycloadducts. 1,8-Naphthalene dithiol can be converted in two steps into sulfilimines 210 [Eq. 

This heterocycle rearranges in the presence of BF3 etherate into 211, which then leads to N-tosyl imine 212. This species can subsequently be used in Diels-Alder reactions to produce cycloadducts in moderate yields. 

When the N-tosyl imine prepared from ethyl glyoxylate was treated with E-2-butene at 150°C, a 9 1 mixture of adducts 239 and 241 was produced (Scheme 42). It was rationalized that the reaction in fact proceeds via a concerted pericyclic mechanism [86] and formation of the major isomer 239 involves an endo ene transition state 238, while the minor product 241 is formed from the... 

It has also been demonstrated that it is possible to metalate camphor-derived N-tosyl imine 276 and to dichlorinate it to produce 277 [92] [Eq. (64)]. 

Glass and Hoy have reported that treating an N-tosyl imine derived from an aromatic aldehyde with cyanide in HMPT leads to aryl nitriles in generally good yields [96]. It was proposed that this transformation might involve intermediates shown in Eq. (68). Alternatively, a dianion corresponding to the mono anions shown could be involved here. 

Cycloadditions. It was found recently that N-tosyl imines of a variety of aldehydes react with alkynyl sulfides in the presence of a Lewis acid catalyst to afford a, /J- unsaturated thioimidates [100]. Thus alkynyl sulfide 291 combines with an N-sulfonyl imine in the presence of a catalyst such as BF3 etherate, Yb(OTf)3, Sc(OTf)3 or Ln(OTf)3to give an imidate 293 [Eq. (70)]. It is believed that this transformation occurs through an initial [2 + 2]-cycloaddition of the reactants to form an azetine 292. Other types of N-substituted imines were found to react with alkynyl sulfides under these conditions to provide different sorts of products and not a, /3-unsaturated imidates like 293. 

For X-ray studies on the bis-N-tosyl imine of p-benzoquinone, see Shuets AE, Mishnev AF, Vleidelis YY (1978) Zh Strukt Khim 19 544... 

The imine and iminium functional groupings are, of course, the nitrogen equivalents of carbonyl and O-protonated carbonyl groups, and their reactivity is analogous. The Mannich reaction of pyrrole produces dialkylaminomethyl derivatives, the iminium electrophile being generated in situ from formaldehyde, dialkylamine and acetic acid. There are only a few examples of the reactions of imines themselves with pyrroles the condensation of 1-pyrroline with pyrrole as reactant and solvent is one such example. N-Tosyl-imines react with pyrrole with Cu(OTf>2 as catalyst. ... 

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