Isopropyl-substituted imine

Some recent work has been directed towards the use of organocatalysts, in particular Lewis basic pipecolinic formamides, in the asymmetric hydrosilylation of N-arylimines. These catalysts function by activating the silane and exhibit broad substrate scope. For example formamide (3.186) effects enantioselective hydrosilylation of aryl-derived ketimines along with isopropyl-substituted imine (3.187) and a,P-unsaturated imine (3.188). 

The acyclic version of Larock s heteroannulation was successfully applied to the synthesis of highly substituted pyridines [166]. The annulation of rert-butylimine 210 with phenyl propargyl alcohol produced pyridine 211 regioselectively in excellent yield. The regiochemistry obtained was governed by steric effects. Furthermore, the choice of imines was crucial to the success of the heteroannulations. terr-Butylimine was the substrate of choice, since all other imines including methyl, isopropyl, allyl and benzyl imines failed completely to produce the desired heterocyclic products. 

Tridentate ligands for cobalt and iron catalysts. The catalysts discussed earlier in the section on ethene oligomerisation can also be used for making polymers, provided that they are suitably substituted. In Figure 10.30 we have depicted such a catalyst, substituted with isopropyl groups at the aryl substituents on the imine group, as in Brookhart s catalysts [49], The initiation is now carried out by the addition of MAO to a salt of the cobalt or iron complexes. The catalysts obtained are extremely active, but they cannot be used for polar substrates. 

A RhCp complex (S,S)-6 (Cp =pentamethylcyclopentadienyl), which is iso-lobal with Ru(rj6-arene) complex (S,S)-5 (Scheme 13), effected the transfer hydrogenation of a cyclic imine substituted by an isopropyl group with an S/C of 200 in the presence of a 5 2 mixture of formic acid and triethylamine to give the R amine in 99% ee (Scheme 13) [31]. When the reaction was performed with an S/C of 1,000, the optical yield decreased to 93%. The methyl imine was reduced with a 91% optical yield. Reduction of a cyclic sulfonimide resulted in the R sul-tam in 81% ee. 

Treatment with BuLi generates chemoselectively the lithium enolate of the less substituted lactim and electrophiles attack the face opposite the branched isopropyl group. Selectivity is good the purified diastereoisomers can be isolated in over 80% yield and hydrolysis requires only dilute aqueous acid as these are easily protonated imines. These examples show a benzylic and an allylic halide. The first 50a is unnatural (R) -phenylalanine and the second 50b is an unnatural amino acid. 

Arylideneanilines are converted into fused pyridines by heating with an alkyne and an oxidizing agent such as di-isopropyl peroxydicarbonate (DP) when the aniline is unsymmetrically substituted, a mixture of isomers may be formed [3173]. a-Halo ketones (and, less efficiently, simple aliphatic ketones [2639]) react with imines to give fused pyridines in variable yields [2715]. An imine formed by reaction of a 6-aminopyrimidinedione with DMFDMA undergoes cycloaddition with an electron-deficient alkene the first product is dehydrogenated in hot nitrobenzene [3620]. 

Some examples of combined syn-anti and diastereofacial selectivity employing /V-n-propyl- and N-isopropyl-aldimines, derived from a-phenylpropionaldehyde, and crotyl-9-BBN, -magnesium and -zirconium reagents have been reported by Yamamoto et al. Cram selectivity, which is observed in the analogous reactions of these chiral imines with allyl organometallics (see Section 4.3.2.1.2i), is preserved as ratios of Cram anti-Cram products are consistently about 8 1. Anti selectivity is also observed but the ratios do not exceed 7 3. The weak anti selectivity parallels that observed in reactions of crotyl-9-BBN with branched a-alkylaldimines. Since syn-anti selectivity is influenced more by the a-substituent than by the A-substituent of the aldimine, more synthetically useful levels of combined syn-anti and diastereofacial selectivity might be expected in other series of a-substituted aldimines. 

Dimethoxy-3,6-dihydropyrazine (109), prepared by methylation of 2,5-piperazinedione with trimethyloxonium tetrafluoroborate, is susceptible to lithiation because the protons at C-3 and C-6 are activated by adjacent imine moieties. The lithium salt of this bislactim ether reacts with the 2-chloro-l-phenylsulfonyl alkene (110) to give the 3-substituted pyrazine (111) (Scheme 25) <89JCS(P1)453>. The bislactim ether from piperazinedione cyclo(L-Val—Gly) is lithiated with butyl-lithium and then treated with ketones, alkyl halides, or others to form, nearly stereospecifically, ran5-3-isopropyl-6-substituted piperazinediones due to the steric influence of the isopropyl group <828866, 838673). Similar stereoselective syntheses have been achieved in reactions starting from cyclo(L-Val—D,L-Ala) <828864, 918939). Acid hydrolysis of these products affords chiral a-amino acids. 

This reaction usually works for nonenolizable imines (e.g., A -aryl aldimines) and has the features of readily accessible starting materials, and simple preparation of 3-substituted or unsubstituted 2-azetidinones (i.e., 3-lactams) with direct control of stereoselectivities. It has been reported that the yield of this reaction depends on the activation and the type of zinc. The stereochemistry of /3-lactams depends on the a-substituent of bromoacetates, the solvent, and the alkyl portion of the esters. For example, when the a-substituent is an alkyl group (e.g.. Me, Et, /-Pr, cyclohexyl, r-Bu), the major product has cis geometry, such a trend is especially prevailing for the reaction of acetate with a branched a-substituent (e.g., j-Pr, cyclohexyl, r-Bu) in THF. s For comparison, the reaction of isopropyl acetate in toluene tends to form jS-lactams of trans geometry. In addition, phenyl acetates favor the trans isomers regardless of the solvents. ... 

Bis(imino)pyridine]bis(dinitrogen)iron complexes such as [( PDI)Fe(N2)]2(p2-N2) are active catalysts for the hydrogenation of a,P-unsaturated esters (Scheme 4-334). The efficiency of the catalyst can be adjusted by the substitution pattern of the aryl moiety. The dimethylaiyl substituent shown is superior to the corresponding ethyl or isopropyl derivatives. Bis(imino)pyridines with phenyl substituents in the imine backbone exhibit a much reduced activity to alkene hydrogenation as they are prone to carbonyl coordination. ... 

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