Imines crowded

The preparation of thiiranes is most conveniently performed in solution. However, there are also protocols reported for reaction in the gas and solid phase. By using diazo and thiocarbonyl compounds in ether as solvent, both alkyl and aryl substituted thiiranes are accessible. As indicated earlier, aryl substituents destabilize the initially formed 2,5-dihydro-1,3,4-thiadiazole ring and, in general, thiiranes are readily obtained at low temperature (13,15,35). On the other hand, alkyl substituents, especially bulky ones, enhance the stability of the initial cycloadduct, and the formation of thiiranes requires elevated temperatures (36 1,88). Some examples of sterically crowded thiiranes prepared from thioketones and a macro-cyclic diazo compound have been published by Atzmiiller and Vbgtle (106). Diphenyldiazomethane reacts with (arylsulfonyl)isothiocyanates and this is followed by spontaneous N2 elimination to give thiirane-2-imines (60) (107,108). Under similar conditions, acyl-substituted isothiocyanates afforded 2 1-adducts 61 (109) (Scheme 5.23). It seems likely that the formation of 61 involves a thiirane intermediate analogous to 60, which subsequently reacts with a second equivalent... 

Like many other 1,3-dipoles (e.g., nitrile ylides, imines, and oxides) (7), thiocarbonyl ylides undergo head-to-head dimerization to give sterically crowded 1,4-dithianes. The first reported example involves the formation of 2,2,3,3-tetraphenyl-l,4-dithiane (18) from thiobenzophenone (5)-methylide (16) (17,28) (cf. Scheme 5.3). Other (5)-methylides are known to form analogous 1,4-dithianes (e.g., thiofluorenone (5)-methylide yields 172) (17). The (5)-methylides of 4,4-dimethyl-2-phenyl-l,3-thiazole-5(4//)-thione (105) and methyl dithiobenzoate (60,104) dimerize to give compounds 173 and 174, respectively. 

This transformation is in contrast to the corresponding more sterically crowded [Mo N (Bu )Ar 3] which does not exhibit this type of behaviour. Initially it was assumed that the cyclometallated structure would inhibit the type of reactions (e.g. with N2 or N2O) shown by the t-Bu substituted tris-amido complex. Investigation of the chemistry, however, showed that this is not the case and the imine-hydrido product behaves as an effective source of [Mo N(Pr )Ar 3] which, because of its less sterically encumbered nature, exhibits reactivity not observed for its more hindered [Mo N(Bu )Ar 3] counterpart. A simple example is provided by complex formation with benzophenone to give [Mo N(Pr )Ar 3(r 2-OCPh2)], whereas the Bu analogue did not react with this reagent. ... 

The dithiazolidine ring is of moderate stability, depending on its substitution. Some dithiazolidine derivatives, obtained by 1,3-dipolar cycloaddition of the thionc-.S -imide 113 and thiones 114, are indefinitely stable at room temperature as compounds 115 (R1, R2 = Ar). Others decomposed during recrystallization affording the corresponding imines 118, and some, such as the sterically crowded 115 (R1, R2 = 2-adamantyl), are so unstable that they spontaneously decompose, affording hexafluorothioacetone 116 and finally the more stable compound 117 (Scheme 16) <1998EJ0459>. 

If the imine is stable enough to be isolated,5 as with diaryl imines 32 or crowded aliphatic amines such as 35, then NaBH4 can be used for the reduction as there is no competition with unreacted aldehyde. 

The Mannich adducts are readily transformed to optically active a-amino-y-lac-tones via a one-pot diastereoselective reduction and lactonization sequence and the tosyl group exchanged for a Boc group via a two-step procedure. The cop-per(II) ion is crucial for the success of this reaction [21]. It has the properties necessary both to generate the enol species in situ and, in combination with the C2-symmetric ligand, coordinate it as well as the imine in a bidentate fashion. The reaction proceeds via a cyclohexane-like transition state with the R substituent of the enol in the less sterically crowded equatorial position, which is required to obtain the observed diastereoselectivity (Fig. 5). 

Rhodopsin is a light-sensitive compound located in the membrane of the rod cells in the retina of the eye. Rhodopsin contains the protein opsin bonded to 11-c/s-retinai via an imine iinkage. When light strikes this molecule, the crowded 11-cis double bond isomerizes to the 11 -trans isomer, and a nerve impulse is transmitted to the brain by the optic nerve. 

With addition of a large excess of C6FsSi(CH3)3 (lb), the mono-CsFs-substituted compound can react with lb by two possible routes, A and B. Because the mono-C6F5-substituted olefin 2b has two bulky substituents (CeFs and CF3) on the active site of the C=C double bond, the excess lb reacts on the / ara-position of CeFs group to provide the nonafluorobiphenyl olefin 4 (route B). On the other hand, the double bond of the mono-CsFs-substituted imine 6b is not so crowded that the excess lb can react on the C=N double bond to provide the bis-CeFs-substituted imine 7b (route A). 

As far as S-apip and S-ahaz are concerned, products with less crowded ketones such as MVK, HBO, MNPK, or HPO have, without exception, the amine-imine linkage formed between primary and secondary amines. Hence, the products are either A or B, or sometimes both of them, as in the case of S-apip-MNPK and S-ahaz-MVK. Further, the yields are not so bad. Therefore it is very probable that linkage formation takes place, almost exclusively, on the five-coordinated structure of copper(II), as expected above. Such selectivity due to the coordination mode about copper(II) ion will not work well in the case of the S-ampr complex, because of its structure, so that a small amount of type C is obtained. 

In the L-proline-catalyzed intermolecular Mannich reaction [9], the stereoselectivity is opposite that of the aldol reaction the si face of the imine is preferentially attacked, and the major Mannich adducts have a syn relative configuration. Computational investigations by Bahmanyar and Houk [26] show that the more stable trans-imine acceptor is placed so as to accommodate proton transfer to the nitrogen lone pair which is in a c/s relationship with the imine C-substituent this forces this substituent to occupy a more crowded pseudoaxial position (Figure 2.8). The anti-re Mannich transition state was calculated (in a model compound) to be 3 kcal/mol less stable than the anti-si one. It is worth noting that this model also accounts for the fact that, contrary to aldol reactions, best enantioselectivities are obtained when the C-imine substituent R is a relatively unhindered planar aryl group. 

The half-unit E of salen is not accessible. Even the reaction of salicylaldehyde with a 20-fold excess of ethylenediamine at low temperatures yields only the symmetric salen. Thus, the key step in the synthesis of a triplesalen ligand C is the preparation of a half-unit, either E or G. Several methods for the preparation and isolation of derivatives of the parent salen half-unit E are described in the literature [155-159]. We applied several of these methods for the synthesis of a triplesalen ligand and obtained various new compounds [160]. However, the successful synthesis of a triplesalen ligand is based on an observation of Elias and coworkers [158]. They reported that the slightly modified diamine I (Scheme 4.4) reacts with its sterically more crowded amine function not with ketones to form ketimines, but only with aldehydes to form aldimines. On the other hand, the less crowded amine function does react with aldehydes as well with ketones to form imines. Thus, the reaction of the diamine I with the triketone H affords chemoselectively the triple ketimine J, which corresponds to the triplesalen halfunit G. In a second step, the triple ketimine J can be reacted with a simple salicylaldehyde (corresponding to F) to yield the desired triplesalen (Scheme 4.4). 

Extremely crowded imines have been prepared using a rhodium-catalyzed process (Scheme 3.127) [139]. The key to the catalyst system was the use of an iminopyridine... 

The hydrophosphonylation of imines bearing a variety of organic fragments has been reported under a range of conditions. Even crowded substrates are typically responsive to the addition reaction. As an example of this, an anthracene bearing imine has been successfully functionalized using secondary phosphites (Scheme 4.87) [160]. Simply refluxing the reaction mixture for 14h afforded moderate yields of the a-aminophosphonates. 

In a non-coordinating medium like THF, die intramolecular coordination between the sulfonyl oxygen atom of the imine 5 and the positively charged iodine (III) of the ylide 2 should be possible. This would lead to more tightened transition states during the nucleophilic addition step that could be represented as 15 and 16. Undoubtely 15 is considerably less crowded than 16 and hence should be preferentially formed, finally leading to ds-aziridines 6 as major reaction products (Scheme 31.8). 

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