Alkenes template reactions

A final example used a chiral, nonracemic amino aldehyde as a chiral template. Reaction of 5.139 with vinyl Grignard led to amino alcohol 5.140 as a 6 1 (syn anti) mixture of diastereomers.62 Reaction with 1-ethoxy-ethanol protected the alcohol and oxidative cleavage of the alkene led to 3-(N-Boc amino)-2-(l-ethoxyethoxy)-3-phenylpropanoic acid, 5.141. 

In an alternative application of this DNA-based technology, a novel palladium-catalysed allgtne-alkene macrocyclization reaction was identified (Scheme 11.38). Optimization of this reaction for metal catalyst system, solvent, temperature and time was also enabled by using the DNA-template methodology, which led to a highly efficient ring closure of 277 to 278 in excellent yield. 

Nickel(O) reacts with the olefin to form a nickel(0)-olefin complex, which can also coordinate the alkyl aluminum compound via a multicenter bond between the nickel, the aluminum and the a carbon atom of the trialkylaluminum. In a concerted reaction the aluminum and the hydride are transferred to the olefin. In this mechanistic hypothesis the nickel thus mostly serves as a template to bring the olefin and the aluminum compound into close proximity. No free Al-H or Ni-H species is ever formed in the course of the reaction. The adduct of an amine-stabihzed dimethylaluminum hydride and (cyclododecatriene)nickel, whose structure was determined by X-ray crystallography, was considered to serve as a model for this type of mechanism since it shows the hydride bridging the aluminum and alkene-coordinated nickel center [31]. 

Ratios of turnover frequencies (TOFs) corresponding to the degree of enhancement of the reaction rates by the imprinting revealed that the imprinted Rh-dimer catalyst (10) showed size and shape selectivities for the alkenes as shown in Figure 8.10. Selectivity for the alkene hydrogenation on the Rh2imp catalyst (10) depends on the size and shape of the template cavity as reaction site in... 

The use of chiral azomethine imines in asymmetric 1,3-dipolar cycloadditions with alkenes is limited. In the first example of this reaction, chiral azomethine imines were applied for the stereoselective synthesis of C-nucleosides (100-102). Recent work by Hus son and co-workers (103) showed the application of the chiral template 66 for the formation of a new enantiopure azomethine imine (Scheme 12.23). This template is very similar to the azomethine ylide precursor 52 described in Scheme 12.19. In the presence of benzaldehyde at elevated temperature, the azomethine imine 67 is formed. 1,3-Dipole 67 was subjected to reactions with a series of electron-deficient alkenes and alkynes and the reactions proceeded in several cases with very high selectivities. Most interestingly, it was also demonstrated that the azomethine imine underwent reaction with the electronically neutral 1-octene as shown in Scheme 12.23. Although a long reaction time was required, compound 68 was obtained as the only detectable regio- and diastereomer in 50% yield. This pioneering work demonstrates that there are several opportunities for the development of new highly selective reactions of azomethine imines (103). 

The rhodium(II) catalysts and the chelated copper catalysts are considered to coordinate only to the carbenoid, while copper triflate and tetrafluoioborate coordinate to both the carbenoid and alkene and thus enhance cyclopropanation reactions through a template effect.14 Palladium-based catalysts, such as palladium(II) acetate and bis(benzonitrile)palladium(II) chloride,l6e are also believed to be able to coordinate with the alkene. Some chiral complexes based on cobalt have also been developed,21 but these have not been extensively used. 

Cycloadditions are useful for the preparation of cyclic ompounds. Several thermal and photoactivated cycloadditions, typically [4+2] (Diels-Alder reaction), are known. They proceed with functionalized electronically activated dienes and monenes. However, various cycloaddition reactions of alkenes and alkynes without their electronical activation, either mediated or catalysed by transition metal complexes under milder conditions, are known, offering a useful synthetic route to various cyclic compounds in one step. Transition metal complexes are regarded as templates and the reactions proceed with or without forming metallacycles [49]. 

Although epoxidation reactions are treated in detail elsewhere in these volumes, it should be mentioned here that a template ester attached to a steroid alkene can direct epoxidation to remote double bonds using the general concepts of remote functionalization. Steroidal diene (5) underwent the epoxidation shown (Scheme 13) with excellent regiochemical and stereochemical control. The product was formed in quantitative yield, although the reaction was carried through to only 25% conversion. 

As a striking exanqrle, photo-initiated chlorination (Scheme 21) of 3 mM (19) with 1.5 equiv. PhICb led to the 9-chloro derivative (20) in >98% yield with Ag this was converted to the A -alkene. Again the template-directed reaction overcomes the normal reactivity of the substrate, but at 21 mM (19) undirected reactions start to compete and some 6-chloro steroid is also formed. A pyridine A(-oxide template, that can use three-electron bonding to complex a chlorine to the oxygen atom, seems to be almost as effective. Furthermore, an imidazole template in compound (21) directs chlorination at C-9 with similar efficiency to the templates previously examined, and (21) is particularly easily prepared using caibonyldiimidazole. 

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