Electrophilic reactions aldehyde trapping

This enolate can then react with a plethora of electrophiles, setting a new stereocenter by a diastereoface-selective reaction. The simplest electrophile to trap enolate 71 is H" ", which can, for example, originate from methanol [89] or diphenyl acetaldehyde (as a readily enolizable aldehyde) [90] leading to the acy-lated catalyst species (Fig. 38). The free catalyst is regenerated by acyl-group transfer to methanol(ate) or the aldehyde-derived enolate, producing methyl or enolesters 72/73 in good yields and enantioselectivities. 

If the alkenes and acetylenes that are subjected to the reaction mediated by 1 have a leaving group at an appropriate position, as already described in Eq. 9.16, the resulting titanacycles undergo an elimination (path A) as shown in Eq. 9.58 [36], As the resulting vinyltitaniums can be trapped by electrophiles such as aldehydes, this reaction can be viewed as an alternative to stoichiometric metallo-ene reactions via allylic lithium, magnesium, or zinc complexes (path B). Preparations of optically active N-heterocycles [103], which enabled the synthesis of (—)-a-kainic acid (Eq. 9.59) [104,105], of cross-conjugated trienes useful for the diene-transmissive Diels—Alder reaction [106], and of exocyclic bis(allene)s and cyclobutene derivatives [107] have all been reported based on this method. 

Beak and coworkers found the (—)-sparteine-complex of iV-Boc-Af-(p-methoxyphe-nyl)benzyllithium 244, obtained from 243 by deprotonation with n-BuLi/(—)-sparteine (11) in toluene, to be configurationally stable (equation 57) . On trapping 244 with different electrophiles, the substitution products 245 are formed with high ee. Efficient addition reactions with imines and aldehydes have also been reported. The p-methoxyphenyl residue is conveniently removed by treatment with cerinm ammoninm nitrate (CAN). 

The lithiooxirane can also be stabilized by a remote functionality in the molecule. The deprotonation of the two isomeric terminal oxiranes 113 and 114 (Scheme 53) affords the two remote carbonyl stabilized lithiooxiranes 115 and 116 which, due to this stabilization, could be trapped by various electrophiles. Deprotonation occurs stereoselectively cis to the ester moiety. The reaction with aldehydes gives the corresponding epoxylactones in good yields and excellent stereoselectivities . 

These lithiooxiranes can be trapped by various electrophiles with retention of the configuration. The addition to aldehydes occurs with a low diastereoselectivity [but this can be enhanced by adding ClTi(OPr-/)3]. The reaction with enones occurs in a 1,2 fashion only. Intramolecular 1,4-silicon shift has also been reported. The reaction of the enantiomerically pure TMS-stabilized lithiooxirane 189 (Scheme 80) with an aldehyde has been used in a total synthesis of (-l-)-cerulenine. It must be noted that protodesi-lylation using TBAF (tetrabutylammonium fluoride) occurs with conservation of the oxirane stereochemistry. 

O-Substituted oxime derivatives are synthetically useful in a wide variety of transformations. Hoffman and Butani have observed that reaction of a series of aldehydes and ketones with the potassium salt of Af,0-bis(trimethylsilyl)hydroxylamine 4a or 4b (a rapid equilibrium between 4a and its Af,N-bis(silylated) isomer 4b probably exists in solution) gave high yields of the corresponding oximate anion 5, formed via the Peterson-type reaction, together with the silyl ether 6. Anion 5 could be protonated to the oxime 7 or trapped in situ with a variety of electrophiles to give 0-substituted oxime derivatives (Scheme 6). 

Evidence for this mechanism is (1) two equivalents of RLi are required (2) the hydrogen in the product comes from the water and not from the adjacent carbon, as shown by deuterium labeling 209 and (3) the intermediates 31-33 have been trapped.210 This reaction, when performed in tetramethylenediamine, can be a synthetically useful method211 of generating vinylic lithium compounds (33), which can be trapped by various electrophiles such as D20 (to give deuterated alkenes), C02 (to give a, 3-unsaturated carboxylic acids—6-34), or DMF (to give a, 3-unsaturated aldehydes—0-105). 

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