Cycloaddition reactions Lithium diisopropylamide

The conversion of the polystyrene-supported selenyl bromide 289 into the corresponding acid 290 allowed dicyclohexylcarbodiimide (DCC)-mediated coupling with an amidoxime to give the 1,2,4-oxadiazolyl-substituted selenium resin 291 (Scheme 48). Reaction with lithium diisopropylamide (LDA) and allylation gave the a-sub-stituted selenium resin 292, which was then used as an alkene substrate for 1,3-dipolar cycloaddition with nitrile oxides. Cleavage of heterocycles 293 from the resin was executed in an elegant manner via selenoxide syn-elimination from the resin <2005JC0726>. 

Azomethine ylides such as 64 can be generated from tertiary amine A-oxides (63) by reaction with lithium diisopropylamide (EDA) (Scheme 12.22) (97). Several different chiral A -substituted azomethine ylides were prepared in this manner. The best results were obtained when using 64 in 1,3-dipolar cycloaddition with alkenes, but the de values obtained of the product 65 were <60%. 

In a different type of procedure, 2 + 3 cycloadditions are performed with ally lie anions. Such reactions are called 1,3-anionic cycloadditions.915 For example, a-methylstyrene adds to stilbene on treatment with the strong base lithium diisopropylamide.916... 

An interesting Darzens-like formal cycloaddition of azirines has also been reported <2004EJ02421>. While this is not a true cycloaddition reaction, two bonds are formed in the same reaction sequence. Reaction of sulfone 114 with lithium diisopropylamide (LDA) generates a carbanion which then adds to the azirine to generate intermediate 115. Cyclization of this intermediate with the allyl halide provides the product aziridine 116. This reaction proceeds in only 13% yield but is nonetheless an interesting route to fused-ring aziridines (Equation 27). 

Asymmetric Dieh-Alder Reactions. The commercial availability of either enantiomer of camphorsulfonic acid has made it quite useful in asymmetric Diels-Alder reactions. Reaction of the sultone (generated from CS A) with Lithium Diisopropylamide followed by esterification and (3-elimination yields the crystalline acrylate (eq 14). The Lewis acid-catalyzed [4 + 2] cycloaddition of 1,3-dienes with this acrylate affords the corresponding scalemic adduct which can be reduced with Lithium Aluminum Hydride to yield an enantiomerically pure alcohol (eq 15). ... 

Aryl triflates 35, generated from the corresponding phenols, react with lithium diisopropylamide (EDA) in diisopropylamine (DIA) to give 36 in good yield. The reaction was demonstrated (via substitution pattern in the products) to proceed via an aryne intermediate. The choice of LDA as the base is critical BuLi, NaNH2, sodium acetylide and 2-lithiofuran all failed to generate an aryne from 35 (R = p- h). Application of the method to other nucleophiles than DIA, or to cycloadditions, has not yet been demonstrated. 

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