Olefins azomethine ylide generation

The azomethine ylide was generated by treatment of A -benzyl-Af-(methoxy-methyl)-trimethylsilylmethylamine (155) with TFA and underwent the required cycloaddition step with chiral dipolarophile 156, stereocontrol being induced by Evan s auxiliary. The ot, p-unsaturated acid dipolarophile was tethered to a chiral oxazoladine in two easy, high-yielding steps. The auxiliary served three purposes to give asymmetric control to the reaction, to allow for separation of the reaction products by generating column separable diastereoisomers, and hnally to activate the olefin in the cycloaddition step (Scheme 3.45). 

To use 1,3 dipolar cycloadditions in a retrosynthetic sense, it is necessary to know what 1,3 dipoles are available. The list on pages 319-320 is representative of die more common and useful examples, although many others have been reported. Azides, diazo compounds, and nitrones are normally isolable compounds which can be added to a solution of an olefin. Other 1,3 dipolar species such as nitrile oxides and azomethine ylides are not stable molecules they must be generated in the reaction mixture in the presence of the olefin. As might be expected, many different ways to generate 1,3 dipoles have been developed. 

A similar treatment of stable keteneiminium triflate 72 with sodium bis(trimethylsilyl)amide generates azomethine ylide 73, together with a small amount of the demethylated product of 72. Ylide 73 undergoes readily dimerizes, leading to l,4-diethyl-2,5-bis[2,2-dimethyl-l-(t-butyl)propyridene]-piperazine when no dipolarophile is present. The trapping of ylide 73 with electron-deficient olefins is completely unsuccessful because these activated olefins cannot withstand such strongly basic conditions. The only dipolar-... 

Deprotonation of N-methylpiperidine Al-oxide with LDA in THF at — 78°C takes place regioselectively on the least crowded methyl carbon to generate azomethine ylide 122 (8SJOC2910). Ylide 122 is again highly reactive toward nonactivated olefins such as ethene, cyclopentene, styrene, (E)- and (Z)-stilbene, and ( )-)S-methoxystyrene. 

An increased reactivity of such ylides to nonactivated olefins is shown in the following intramolecular ylide trapping. The highly stabilized azomethine ylides 157, which are thermally generated by heating 4-isoxazolines 156... 

There are some examples known for the cycloaddition of azomethine ylides with nonactivated olefins such as aryl-substituted olefins, strained olefins, acyclic or cyclic olefins, and electron-rich olefins. Stabilized ylide 79 (R = H, R = Et, R = Me), bearing an ester moiety as the only C substituent, can be successfully trapped with styrene when generated by the deprotonation route (Section II,D) from ethyl sarcocinate and paraformaldehyde under reflux in toluene, to give 194 as a mixture of two regioisomers (86CL973). 

This cycloaddition methodology utilizing N-lithiated azomethine ylides has some advantages. (1) The ylides can be generated in situ concurrently with or prior to cycloaddition. (2) The ylides are highly reactive toward a number of carbonyl-activated olefins. (3) Wide structural modification of ylides is possible. (4) The cycloadditions are perfectly diastereoselective. (5) No demetallation procedure is necessary. (6) No critical epimerization occurs even in the reactions of cyano-stabilized ylides 144. 

A reaction of trimethylamine JV-oxide with a large excess of lithium diiso-propylamide (LDA) in tetrahydrofuran at — 78°C generates C-unsubstituted azomethine ylide 121. The ylide intermediate 121 is reactive so as to undergo smooth cycloadditions to nonactivated olefinic dipolarophiles, such as... 

---