Imine additions Michael reaction

Protected glycine derivatives have been used as the nucleophilic partner in enantioselective syntheses of amino acid derivatives by chiral PTC (Scheme 10.9). Loupy and co-workers have reported the addition of diethyl acetylaminomalonate to chalcone without solvent with enan-tioselectivity up to 82% ee [44]. The recent report from the Corey group, with catalyst 8a used in conjunction with the benzophenone imine of glycine t-butyl ester 35, discussed earlier, results in highly enantioselective reactions (91-99% ee) with various Michael acceptors (2-cyclo-hexenone, methyl acrylate, and ethyl vinyl ketone) to yield products 71-73 [21], Other Michael reactions resulting in amino acid products are noted [45]. 

Finally, a fascinating development in the field of lanthanum-BINOL complexes remains to be mentioned [25]. These compounds so far have proved to catalyze enantioselectively hydrophos-phonylations of imines [26], nitroaldol reactions [27], Michael additions [28] and cpoxidations of... 

A 1-phenylethylamino moiety is used for diastereomeric control not only in addition of nucleophiles to A-(l-phenylethyl)imines but also in diasteroselective Michael addition to a,P-unsaturated esters. Thus, lithium A-(l-phenylethyl)-A-benzylamide 148 is employed for a one-pot tandem Michael addition-fluorination reaction (see Scheme 9.32) [58]. The reaction provides a/i/f-3-amino-2-fluoroesters 149 exclusively, whose diastereoselectivi-ties (64-66% de) to the chiral carbon of the 1-phenylethyl-group are good enough. 

The thiazolium-catalyzed addition of an aldehyde-derived acyl anion with a Michael acceptor (Stetter reaction) is a well-known synthetic tool leading to the synthesis of highly funtionalized products. Recent developments in this area include the thiazolylalanine-derived catalyst 191 for asymmetric intramolecular Stetter reaction of a,P-unsaturated esters <05CC195>. However, these cyclizations proceed only in moderate enantioselectivities and yields even under optimized conditions. Thiazolium salt 191 has been used successfully for enantioselective intermolecular aldehyde-imine cross coupling reactions <05JA1654>. Treatment of tosylamides 194 with aryl aldehydes in the presence of 15 mol% of 191 and 2... 

Alkyl phosphonates are prepared smoothly by TMG (1) catalysed aldol-type addition of dialkyl phosphites to ketones and imines under mild conditions [28] (Scheme 4.9). Dialkyl phosphites can also serve as good nucleophiles for Michael addition (phospha-Michael Reaction). 

Asymmetric Michael reactions via enamines. Imines (via the tautomeric enam-ines) undergo conjugate addition to electrophilic alkenes, but the first asymmetric reaction of this type was accomplished in 1985 using chiral imines derived from (+)- or (—)-l (equation I). Of a large number of chiral amines examined as the chiral auxiliary, the... 

The first example of the application of pincer complex catalysts for selective synthesis involves aldol type of reactions involving imines and isocyanoacetates. In aldol [13-27] and Michael addition [13, 28-34] reactions, palladium pincer complexes have usually been employed as Lewis acid catalysts, for the first time by Richards and coworkers [13, 28]. This also means that the palladium(II) atom in these processes is not involved in redox reactions, and therefore reduction to palladium(O) does not happen. The aldol and the Michael reactions are useful C-C bond-forming reactions. In these processes, new stereocenters are generated, and therefore the processes can be used for stereoselective synthesis. A typical example is the reaction of suUbnimines (2) with isocyanoacetate (3) to form imidazohne (4) derivatives. The imidazolines can be easily hydrolyzed to diamino acid derivatives in a one-pot process (Figure 4.2) [24]. 

A broad range of enantiomericaUy pure 4,5-dihydrobenzo[r [l,3]diox-epines 177 have been prepared via a four-component Mannich reaction and subsequent intramolecular oxo-Michael reaction (14CC2196). The reactions proceeded with both high enantio- and diasteroselectivity, utilizing a dual catalytic system of Rh2(OAc)4 and a chiral phosphoric acid 178. The rhodium catalyst forms the protic oxonium ylide 174 from a diazo compound 171 and this subsequently adds to imine 175, formed in situ. The resulting enantiomericaUy enriched intermediate 176 then undergoes an intramolecular and diastereoselective oxo-Michael addition to form the final product 177. 

The aza-Morita-Baylis-HiUman reaction is known to be a useful and atom-economical C-C bond-forming reaction of electron-deficient alkenes with imines usually catalyzed by Lewis bases [202]. It formally involves a sequence of reactions including a Michael addition, a Mannich reaction, a proton transfer, and a retro-Michael reaction ( -elimination). Although there are many reports in the field of the enantioselective aza-Morita-Baylis-Hilhnan reaction, only rare examples of asymmetric domino reactions initiated by this reaction have been reported. In 2010, Sasai et al. [203] developed the first organocatalyzed asymmetric domino aza-Morita-Baylis-Hillman/aza-Michael reaction of a,p-unsaturated carbonyl compounds with N-tosylimines, allowing an easy access to chiral cis-1,3-disubstituted isoindolines as single diastereomers. The process was induced by a Hg-BINOL-derived catalyst and provided these products in high yields and enantioselectivities, as shown in Scheme 10.18. 

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