Ylide compounds azomethine ylides

Type (b) 1, 3-dipoles with non-bonding pair of electrons on central atoms. For examples nitrones, ozone, azoxy compounds, azomethine ylides etc. 

Interesting structures can be formed by combinations of ring and side-chain substituents in special relative orientations. As indicated above, structures (28) contain the elements of azomethine or carbonyl ylides, which are 1,3-dipoles. Charge-separated species formed by attachment of an anionic group to an azonia-nitrogen also are 1,3-dipoles pyridine 1-oxide (32) is perhaps the simplest example of these the ylide (33) is another. More complex combinations lead to 1,4-dipoles , for instance the pyrimidine derivative (34), and the cross-conjugated ylide (35). Compounds of this type have been reviewed by Ramsden (80AHCl26)l). 

Dehydrogenation has been used as a method for azomethine ylide formation. Treatment of compound 206 with iV-methylmaleimide in the presence of palladium black gives a 1 1 mixture of the endo- and f .tf-diastereomcrs 207 and 208, in 65% combined yield <1989J(P1)198> (Equation 24). 

The 1,3-dipolar cycloaddition reactions to unsaturated carbon-carbon bonds have been known for quite some time and have become an important part of strategies for organic synthesis of many compounds (Smith and March, 2007). The 1,3-dipolar compounds that participate in this reaction include many of those that can be drawn having charged resonance hybrid structures, such as azides, diazoalkanes, nitriles, azomethine ylides, and aziridines, among others. The heterocyclic ring structures formed as the result of this reaction typically are triazoline, triazole, or pyrrolidine derivatives. In all cases, the product is a 5-membered heterocycle that contains components of both reactants and occurs with a reduction in the total bond unsaturation. In addition, this type of cycloaddition reaction can be done using carbon-carbon double bonds or triple bonds (alkynes). 

Highly stereoselective intramolecular cycloadditions of unsaturated N-substituted azomethine ylides have been conducted under microwave irradiation. Oritani reported that a mixture of the aldehyde 137 and N-methyl- or N-benzylglycine ethyl ester (138) on the surface of silica gel, irradiated under microwaves for 15 min, generated azomethine ylides 139 that subsequently underwent in situ intramolecular cycloadditions to afford the corresponding tricyclic compounds 140 in 79 and 81% yield, respectively (Scheme 9.42) [93],... 

Compounds of the general formula 69 are prepared by cycloaddition of N-methyl- or A(-arylmaleimides with arylidene imines of AAs and in the presence of an aromatic aldehyde. Stabilized azomethine ylides are formed as intermediates, which then afford the cycloadducts. Several isomers are formed, and the influence of various metal salts and solvents was investigated (87BCJ4067 88T557). Similar transformations have been performed with A-ailyl glycine esters (91TL1359). 

Alternatively, 2,3-dihydro-1,2,4-oxadiazoles are prepared by cycloaddition of nitroso compounds to azomethine ylides (223) (Scheme 96) <87T2223>. 

Similarly, Hosomi and co-workers (15) reported isothioureas as azomethine ylide equivalents. Both A-substituted and A-unsubstituted A-(trimethylsilylmethyl)-isothiourea precursors underwent cycloaddition reactions with carbonyl compounds, when treated with stoichiometric CsF to deliver a range of 2-iminooxazolidine derivatives. Typically, 63 (R = CN, R = H) furnished adduct... 

Pyridones, as exemplified by ABT-719 (154, Figure 3.8), represent a new class of DNA gyrase inhibitors possessing a broad spectmm of antibacterial activity and, in studies toward such compounds, it was revealed that the C(8) functionality was an important part of the DNA binding action. Azomethine ylide cycloadditions were employed to give a range of proline-type derivatives in order to study stmcture-activity relationships (39). 

As previously described, thermolysis of aziridines is one of the standard methods for the generation of azomethine ylides. A diastereomeric mixture of the aziridines 199 possessing an enantiomerically pure N-substituent underwent ylide formation at 280 °C and subsequent cycloaddition to vinylidine carbonate to form a mixture of four separable compounds (d-200, l-201, d-202, l-203) in a 3 3 1 1 ratio (55). Subsequent LiAlH4 reduction and hydrogenolytic N-benzyl cleavage led to all... 

One of the most novel uses of azomethine ylides was reported in the synthesis of fulleroproline compounds that have been shown to exhibit interaction with the... 

Only a few examples of the [3 + 2] cycloaddition of thiocarbonyl ylides with C=N compounds have been reported so far. By comparison with aldehydes, imines are poor dipolarophiles. For example, Al-benzylidene methylamine and adamanta-nethione (5)-methylide (52) produce 1,3-thiazolidine (129) in only 13% yield (163). An alternative and efficient approach to 1,3-thiazohdines involves the [3 + 2] cycloaddition of azomethine ylides with thiocarbonyl compounds [cf. (169)]. 

N-Metalated azomethine ylides generated from a-(alkylideneamino) esters can exist as tautomeric forms of the chelated ester enolate (Scheme 11.8). On the basis of the reliable stereochemical and regiochemical selectivities described below, it is clear that the N-metalated tautomeric contributor of these azomethine ylides is important. Simple extension of the above irreversible lithiation method to a-(alkylideneamino) esters is not very effective, and cycloadditions of the resulting lithiated ylides to a,(3-unsaturated carbonyl compounds are not always clean reactions. When the a-(alkylideneamino) esters bear a less bulky methyl ester moiety, or when a,(3-unsaturated carbonyl compounds are sterically less hindered, these species suffer from nucleophihc attack by the organometalhcs, or the metalated cycloadducts undergo further condensation reactions (81-85). 

One problem in the anti-selective Michael additions of A-metalated azomethine ylides is ready epimerization after the stereoselective carbon-carbon bond formation. The use of the camphor imines of ot-amino esters should work effectively because camphor is a readily available bulky chiral ketone. With the camphor auxiliary, high asymmetric induction as well as complete inhibition of the undesired epimerization is expected. The lithium enolates derived from the camphor imines of ot-amino esters have been used by McIntosh s group for asymmetric alkylations (106-109). Their Michael additions to some a, p-unsaturated carbonyl compounds have now been examined, but no diastereoselectivity has been observed (108). It is also known that the A-pinanylidene-substituted a-amino esters function as excellent Michael donors in asymmetric Michael additions (110). Lithiation of the camphor... 

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). 

---