Imines selectivity

If the imine formation is conducted in a flow tube, residence times of 4 to 10 seconds can be used to suppress secondary reactions such as the polymerization of ethylenimine. The imine selectivity then increases to 80% to 85% (based on MEA)46. 

The reduction of 2-imino ketones is performed with Bu2SnClH-HMPA to give 2-amino ketones where no reduction of the carbonyl group takes place.84 The reductive amination of carbonyl compounds is one of the most convenient routes to various secondary amines. The high imine selectivity of Bu2SnClH-HMPA can be applied to... 

Table 13.3 imines. Selected examples for the enantioselective aza MBH reaction of aromatic and aliphatic... 

As mentioned, Matsumura published the first asymmetric reduction of ketimines with a proline formamide activator A 1 and trichlorosilane. The yield and selectivities were only moderate, but it paved the way for further developments. They showed that it was possible to reduce imines selectively in the presence of ketones without affecting the latter. Additionally, a transition state explaining the stereoinduction was hypothesized (Figure 32.6). Transition state TS 1 is preferred over TS 2 because of the steric phenyl-phenyl repulsion of the activator and the substrate. This explains the need of aryl imines for successfid stereoinduction. 

The nucleophilicity of amine nitrogens is also differentiated by their environments. In 2,4,5,6-tetraaminopyrimidine the most basic 3-amino group can be selectively converted to a Schiff base. It is meta to both pyrimidine nitrogens and does not form a tautomeric imine as do the ortho- and /xira-amino groups. This factor is the basis of the commercial synthesis of triamterene. 

Aromatization of indolines is important in completing synthetic sequences in which the directive effects of the indoline ring have been used to achieve selective carbocyclic substitution[l]. Several methods for aromatization have been developed and some of these are illustrated in Table 15.2. A range of reagents is represented. One type of procedure represents use of oxidants which are known to convert amines to imines. Aromatization then provides the indole. Such reagents must not subsequently oxidize the indole. Mereuric acetate (Entry 1) is known to oxidize other types of amines and presumably reacts by an oxidative deprotonation ot- to the complexed nitrogen. 

Under conditions similar to those already outlined, stable aziridin imine derivatives, e.g. (422) and (423), can be prepared in excellent yields (70-80%) by treating the appropriate a-bromoamidines (easily accessible from the amide precursor) with potassium t-butoxide in ether <70AG(E)38l). At low temperatures the elimination proceeds with high regio- and stereo-selectivity at -40 °C (421) yields predominantly (422). 

FORSTER - DECKER Amine Synthesis Selective monoalkylation of primary amines via imines An altemativa method is the reaction ol 1 and 2 in the preserve of NaCNBH4 or tnaceloxyborohydride (Borch reduction)/... 

In a manner analogous to classic nitrile iinines, the additions of trifluoro-methylacetonitrile phenylimine occur regiospecifically with activated terminal alkenes but less selectively with alkynes [39], The nitnle imine reacts with both dimethyl fumarate and dimethyl maleate m moderate yields to give exclusively the trans product, presumably via epimenzation of the labile H at position 4 [40] (equation 42) The nitrile imine exhibits exo selectivities in its reactions with norbornene and norbornadiene, which are similar to those seen for the nitrile oxide [37], and even greater reactivity with enolates than that of the nitnle oxide [38, 41], Reactions of trifluoroacetomtrile phenyl imine with isocyanates, isothiocyanates, and carbodiimides are also reported [42]... 

The alkylation of imines by an alkyl halide to give an iminium salt will be illustrated by selected reactions over a period of years. A more complete survey is available (88). Decker and Becker (89) prepared a number of iminium salts (91, for example) by mixing methyl iodide and aromatic imines in benzene. 2,5-Dimethyl-2-pyrroline (92) has been alkylated and the... 

Analogous to the selectivity observed for the conversion of 48 into 50, pyridyl 51 formed enamine 52 which underwent cyclization to give 4-pyridyl-substituted quinoline 53. Again, imine formation first occurs on the less hindered ketone and subsequent cyclization on the more reactive carbonyl occurred in high yield. ... 

Evans et al. reported that the bis(imine)-copper (II) complex 25, prepared from chiral bis(imine) ligand and Cu(OTf)2, is also an effective chiral Lewis acid catalyst [34] (Scheme 1.44, Table 1.18). By tuning the aryl imine moiety, the bis(2,6-dichlor-ophenylimine) derivative was found to be suitable. Although the endojexo selectivity for 3-alkenoyloxazolidinones is low, significant improvement is achieved with the thiazolidine-2-thione analogs, for which both dienophile reactivity and endojexo selectivity are enhanced. 

Other advances include the construction of seven- and nine-membered rings via the analogous [4-1-3] and [6-1-3] cycloadditions with dienes and trienes respectively. Heterocycles, such as tetrahydrofurans and pyrrolidines, are accessible using carbonyl compounds and imines as substrates. The following discussion is organized around these recent discoveries. It serves to illustrate the versatility and the high degree of selectivity which are some of the distinctive features of the Pd-TMM chemistry. 

The assumed transition state of this reaction is shown in Scheme 5.3. Yb(OTf)3, (J )-(-h)-BINOL, and DBU form a complex with two hydrogen bonds, and the axial chirality of (J )-(-h)-BINOL is transferred via the hydrogen bonds to the amine parts. The additive would interact with the phenolic hydrogen of the imine, which is fixed by bidentate coordination to Yb(III). Because the top face of the imine is shielded by the amine, the dienophiles approach from the bottom face to achieve high levels of selectivity. 

The assumed transition state for this reaction is shown in Scheme 5.5. The two bulky t-butoxy groups are expected to locate at the two apical positions. One of the 3,3 -phenyl groups would effectively shield one face of an imine, and consequently, a diene attacks from the opposite side. Judging from this model, similar selectivities were expected in the Mannich-type reactions of imines with silyl eno-lates. Actually, when ligand 10 was used in the reaction of imine la with S-ethyl-thio-l-trimethylsiloxyethene, the corresponding / -amino thioester was obtained in 84% ee (Scheme 5.6). As expected, the sense of the chiral induction in this case was the reverse of that observed when using catalyst 6 [12, 25]. 

Polymer-supported BINOLs thus prepared were treated with Zr(Ot-Bu)4 to form polymer-supported zirconium 20. In the presence of 20 mol% of various zirconium 20, the model aza Diels-Alder reactions of imine Id with Danishefsky s diene (7a) were performed results from selected examples are shown in Table 5.8. Whereas the 4-t-butylphenyl group resulted in lower enantiomeric excess (ee), higher ee were obtained when 3,5-xylyl, 4-biphenyl, 4-fluorophenyl, and 3-tri-... 

For imines, a-imino esters with an N-p-methoxyphenyl substituent (21b) also reacted with Danishefsky s diene in the presence of 10 mol% of CUCIO4-T0I-BINAP to give the corresponding adduct in high yield with good enantiomeric excess (Scheme 5.10). Remarkably, reverse enantioselectivity was observed when the a-imino esters 21a and 21b were used. This notable selectivity was explained by as-... 

Irradiation of the dimers 1 of quinoline 1-imines 2 gives stable 1H-1,2-benzodiazepines. Selected examples are given.122... 

The action of phosgene or carbon disulfide on the l-(2-aminophenyl)imidazolidin-2-imines 5 gives benzotriazepinones 6a-d or benzotriazepinethiones 6e j, respectively. Selected examples are given.378... 

Saito has recently reported high yields and enantioselectivities in aziridine synthesis through reactions between aryl- or vinyl-substituted N-sulfonyl imines and aryl bromides in the presence of base and mediated by a chiral sulfide 122 (Scheme 1.41) [66]. Aryl substituents with electron-withdrawing and -donating groups gave modest transxis selectivities (around 3 1) with high enantioselectiv-... 

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