Z/E isomerism

The spectroscopic properties of the /V-nitrosamines, especially the nmr and mass spectra, vary widely depending on the substituents on the amine nitrogen (44—47). The nmr spectra are affected by the E—Z isomerism around the N—N partial double bond and by the axial—equatorial geometry resulting from conformational isomerism in the heterocycles (44,45). Some general spectral characteristics for typical dialkylnitrosamines and simple heterocycHc nitrosamines are given in Table 1. 

Asano and co-workers have reported die kinetic effects of pressure, solvent, and substituent on geometric isomerization about die carbon-nitrogen double bond for pyrazol-3-one azomethines 406 (R = H), 406 (R = NO2) and 407, (Scheme 93). The results demonstrate the versatility of die inversion mechanism. The rotation mechanism has been invalidated. First-wder rate constants and activating volumes for diermal E-Z isomerization for 406 (R = H) and 406 (R = NO2) are given at 25°C in benzene and methanol (89JOC379). 

Cyclocondensation of 2-iminopiperidine hydrochloride with an E Z isomeric mixture of ethyl 2-cyano-3-methylsulfanyl-3-( 1,2,4,5-tetrahydro-3/f-benzo[r/ azepin-3-yl)acrylate in DMF in the presence of DBU at 100°C gave 2-substituted 6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-carbo-nitrile (01EUP1074549). 

In the coupling with vinyl groups, the olefin geometry is usually retained E/Z-isomerization is only rarely observed. 

In Ghosh s enantioselective total synthesis of the cytotoxic marine macrolide (+)-amphidinolide T1 (318) [143], the C1-C10 fragment 317 was constructed by CM of subunits 315 and 316 (Scheme 62). The reaction mediated by catalyst C (5 mol%) afforded in the first cycle an inconsequential 1 1 mixture of (E/Z)-isomeric CM products 317 in 60% yield, along with the homodimers of 315 and 316. The self-coupling products were separated by chromatography and exposed to a second metathesis reaction to provide olefins 317 in additional 36% yield [144]. 

Isomerization of ( /Z) isomers is another important transformation. Isomerization of ( ) and (Z-) conjugated amides is effected photochemically " (photo-isomerization " ). There is a rather high energy barrier for the excited state required for (E/Z) isomerization. Isomerization of the C=C units in dienes is also induced photochemically. " Isomerization of cyclic alkenes is more difficult but cyclooctene is isomerized photochemically. " Conjugated aldehydes have been isomerized... 

The reactions are accelerated by bromide salts, which are thought to exchange for acetate in the ir-allylic complex. The reactions of acyclic compounds occur with minimal E Z isomerization. This result implies that the TT-allyl intermediate is captured by carbonylation faster than E Z isomerization occurs. 

The reaction conditions were optimized to afford clean coupling of enol tosylate 32 using only a slight excess of amide 24 (1.05equiv) at 100 °C, 5mol% Pd2(dba)3/ dppb catalyst, and a toluene/tert-amyl alcohol solvent system. Even under the harsh reaction conditions required for complete conversion of the tosylate (100 °C, 20 h) no detectable E/Z isomerization was seen, providing further proof that the hindered nature of the enamide aids stability to isomerization. Treatment of the mixture with activated carbon (Darco KB-B) at the end of the reaction followed by isolation of the product by crystallization, afforded enamide 22 in 92% isolated yield. 

Information on the E-Z isomerization of the disilenes sheds light on the nature of the chemical bonding of the silicon-silicon double bond. Kinetic parameters, which have been reported for cis-trans isomerization of five disilenes, are listed in Table IV. 

One important aspect of the photochemistry of aikenes 301,302) is the E—Z isomerization around the C—C double bond 303). This is also valid for cycloalkenes with the obvious exception of cyclopropenes304a,b) which exhibit a distinct photochemical behaviour, and cyclobutenes and cyclo-pentenes where the ring is to rigid to allow sufficient twisting of the double bond. 

Also, an intramolecular version of E-Z isomerization seems possible (Scheme 2.75) (304). 

Table 3 Asymmetric hydrogenation of a-phenylenamide and E/Z isomeric mixture of / -methyl-a-phenylenamide...

In general, the same sense of chiral induction is obtained with either geometrical stereoisomer, which facilitates the use of (E/Z)-isomeric mixtures. An exception to this was recently reported by Heller and Bomer [56d]. Remarkably, hydrogenation of methyl (Z)-/3-acetylamino pentenoate with [(S,S)-Et-DuPhosRh (COD)]BF4 at 1 bar gave the (R)-enantiomer of product in 31% ee, whereas the same reaction at 30 bar resulted in an inversion of configuration and the (S)-product in 77% ee. 

Rh-catalyzed hydrogenation of simple enamides has attracted much attention recently. With the development of increasingly efficient chiral phosphorus ligands, extremely high ee-values can be obtained in the Rh-catalyzed hydrogenation of a-aryl enamides. E/Z-isomeric mixtures of -substituted enamides can also be hydrogenated, with excellent ee-values. Some efficient examples (>95% ee) of hydrogenation of a-phenylenamide and E/Z-isomeric mixtures of / -methyl-a-phenylenamide are listed in Table 26.3. 

The hydrogenation of a series of E/Z-isomeric mixtures of a-arylenamides with a MOM-protected /1-hydroxyl group catalyzed by a Rh-complex of 1,4-dipho-sphane T-Phos with a rigid 1,4-dioxane backbone led to chiral / -amino alcohol derivatives in excellent enantioselectivities (Scheme 26.4) [55]. DIOP -Rh is also effective for this transformation [51b]. 

One problem for the asymmetric hydrogenation of imine is (E)/(Z) isomerism of the substrate, which may have a significant effect on the enantioselectivity of the reaction. This problem was difficult to address because of the rapid interconversion of the E and Z isomers of the imines under reaction conditions (Fig. 6-8). 

When the C=N bond is fixed in a ring system in which no (E)/(Z) isomerization can take place, the asymmetric hydrogenation of the C=N bond can be highly enantioselective. Oppolzer et al." found that cyclic sulfonimide was hydrogenated with an Ru(BINAP) catalyst to give a product with essentially quantitative optical yield (Scheme 6-45). 

Scheme 5.—Photochemical, E-Z Isomerization of Groups Attached to a Double...

Several other types of photochemical reactions involving unsaturated carbohydrates have been reported. One of these is38 photochemical, E -Z isomerization of the groups attached to a double bond (see Scheme 5). A second is the internal cycloaddition between two double bonds connected by a carbohydrate chain.39-41 Although the carbohydrate portion of the molecule is not directly involved in this cycloaddition, its presence induces optical activity in the cyclobutane derivatives produced photochemically. Finally, a group of acid-catalyzed addition-reactions has been observed for which the catalyst appears to arise from photochemical decomposition of a noncarbohydrate reactant.42-44... 

In the last 5 years, catalytic antibodies have been generated for several reaction types, including the various types of hydrolysis, transesterification, amide bond formation, /3-elimination, cycloreversion, transacylation, redox reactions, E-Z isomerization, epoxidation, and Diels-Alder reactions. For more information on these and other recent developments, such as semi-synthetic antibodies, site-directed mutagenesis, and the bait-and-switch strategy, the reader should consult the appropriate authorities (Schultz, 1988, 1989a,b Benkovic et al., 1990 Janda et al., 1990, 1991 Janjic and Tramontano, 1990 Lerner et al., 1991). 

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