Chloromethyl imines

The chloromethyl imines lOa-lOi were employed as representatives of derivatives with a potentially reactive group in the side chain. Their reduction afforded the corresponding amines in >90% ee (Table 4.6, entries 1 9). The resulting amino chlorides were then cyclized to the corresponding aziridines on treatment with t BuO K with retention of the stereochemical integrity [ 12d]. It is pertinent to note that the preparation ofthe sensitive chloro imines lOa-lOi from the a chloro ketones was not entirely free of problems while the electron neutral and electron poor imines lOa-lOc were synthesized and isolated as individual substances, their electron rich counterparts lOg and lOh could not be obtained as pure compounds, since the reaction did not proceed to completion. Therefore, in the latter instances, the imines were generated in situ [12d]. 

The only 5//-1,3,6-triazonine system which has been reported and is fully supported by spectral data and elemental analysis is obtained by reaction of the imine 1 with chloroacetic acid and polyphosphoric acid.22 From a mixture of products, 2-chloro-6-(chloromethyl)-13-phenyl-dibenzo[e/, h [, 3,6]triazonine (2) was separated by silica-gel flash chromatography in poor yield. 

TABLE 3 Chloromethyl Alkylnitrosamines synthesized by Addition of NOCl to Imines... 

Alkylation of x-(.S )-A/-(2-phcnyl-l -propylidene)- -(methoxymethyl)benzeneethanamine with 4-chloromethyl-3,5-dimethylisoxazole proceeded with 12% ee by addition of the imine to the LDA solution at 0°C, whereas under inverse conditions (addition of LDA to imine) an enantiomeric excess of 70% was achieved (see Tabic 5)26. 

Similarly, (/ ,i )-f-binaphthane 103 and (7 ,i )-binaphthane 104 were obtained in one step directly from 2,2 -bis(chloromethyl)-1,1 -binaphthyl 101 and corresponding phosphines. These molecules were shown to be highly efficient chiral auxiliaries in the enantioselective hydrogenation of acyclic imines <2001AGE3425, 19990L1679>. 

The addition of halomethyl metal reagents provides another Darzens-like route to aziridines <06JOC9373>. Reaction of ICHjCl with MeLi generates a chloromethyllithium reagent, which then adds to the imine 74. A subsequent intramolecular A -alkylation provides the aziridine 75. The isolation of a chloromethyl ketone byproduct demonstrated that the chloromethyllithium reagent is operative as opposed to a carbene. 

More recently, Yamamoto and coworkers [36] have developed a new acyl anion equivalent based upon the ethoxyethyl-protected a-hydroxymalonodini-trile derivative shown in Scheme 13 and have applied it in the area of N-sulfonyl imine chemistry. Thus, the carbanion derived from the dinitrile was added to imine 60 to afford adduct 61 which was rather unstable. However, N-alkylation of 61 with chloromethyl methyl ether yielded the stable product 62. Removal of... 

Reactions of carbonyl compounds and imines. The salt 4 obtained from reaction of cinchonine with m-xylylene dibromide is shown to promote enantioselective transfer of the trifluoromethyl group from Me3SiCF3 to aryl ketones Also obtained from quinidine the salt containing a trifluorobenzyl group (5) promotes the condensation of chloromethyl phenyl sulfones with ArCFlO to give benzenesulfonyl epoxides ... 

The non-classical system (182) has been synthesized, starting from 4,5-bis(chloromethyl)-l,2,5-thiadiazole, and characterized by the isolation of its dimer and adducts. The more complex but stable non-classical thiophens (183)—(185) have been prepared, starting from azomethine imine ylides, generated in situ from 1-aminopyridinium, 1-aminoquinolinium, or... 

The use of chloromethyl phenyl sulfone as a carbon nucleophile in the VNS reaction of 17 and 18 allowed one to obtain substitution products 27 and 28. In this case, the undesirable para-substituted regioisomer of 27 was formed in only 4% yield. Reduction of the nitro group in sulfones 27, 28 provided corresponding anilines 29 and 30, which gave good yields of imines 31, 32 with both electron-acceptor and electron-donor benzalde-hydes. Further cychzation under basic conditions provided access to 2-aryl substituted 5(6)-SF5-indoles 33 and 34 (Scheme 7). 

Sc(OTf)3 was widely used as a Lewis acid catalyst in Friedel-Crafts acylation [38-40], amination [41], chloromethylation [42], and nitration of aromatic compounds [43]. It also exhibited a superior catalytic activity for one-pot three-component phenol-imine Friedel-Crafts reactions to give the corresponding amino acid derivatives. Among various Lewis acids including La(OTf)3, Yb(OTf)3, YbCl3, InCl3, SnCU, and TiCU, Sc(OTf)3gave the best results (Scheme 12.21) [44]. 

The AMEBA linker " was installed upon NaH-mediated alkylation of Merrifield resin with 4-hydroxy-2-methoxy-benzaldehyde in DMF at 120°C for 5 min under microwave irradiation (Scheme 8.20). The authors then chose to attach 4-methyl-3-nitroaniline to the linker through a previously established two-step reductive amination protocol, involving the imine formation mediated by Ti(0 Pr)4 followed by reduction of the imine using NaBH (OAc)3 (Scheme 8.20). The free amino group was then acylated with 4-(chloromethyl) benzoyl chloride using DIPEA in DMF to form the corresponding amide. 

Oxazolinylaziridines have been prepared by addition of (chloromethyl)oxazolines to imines. °... 

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