Mukaiyama aldol reaction cleavage

The synthesis of the carboxylic acid 9a commenced with silylation of known alcohol 16 followed by reductive removal of the chiral auxiliary to give the aldehyde 17 (Scheme 3). Vinylogous Mukaiyama aldol reaction" " of 17 with Chan s diene 18" afforded the alcohol 19 in 95% yield with 10 1 diastereoselectivity. Treatment of 19 with PPTS in MeOH resulted in cleavage of the silyl ether and spontaneous methyl acetalization to provide the methyl acetal 20. Protection of the hydroxyl group of 20 by using MPM trichloroacetimidate in the presence of La(OTf >3" gave the MPM ether 21. Hydrolysis of the methyl ester of 21 afforded the carboxylic acid 9a. 

Numerous in-depth mechanistic studies have been performed on the Mukaiyama aldol reaction. " Although various mechanisms exist in the literature that take into account the various roles of the numerous catalysts used for the enantio- and diastereoselective Mukaiyama aldol reaction, the commonly accepted mechanism accounting for bond formation is shown below.The reaction begins with the coordination of a Lewis acid with aldehyde 4 to form complex 5. Due to its enhanced electrophilicity, complex 5 is attacked by the 7t-bond of the enol silane 6, giving rise to resonance stabilized cation 7. At this point, either intermolecular silyl cleavage upon hydrolysis or intramolecular silyl transfer to the product hydroxyl group occurs to give products such as 8 or 9. 

While the order of silyl transfer or cleavage is inconsequential to bond formation, it is one of the more important and hotly debated aspects of the mechanism owing to its importance in the development of catalytic enantioselective variants of the Mukaiyama aldol reaction. Intramolecular silyl transfer, as shown in the formation of 10, would regenerate the chiral,... 

Alternatively, a Friedel-Crafts mechanism has been proposed to account for bond formation via the Mukaiyama aldol reaction. As stated, attack of the enol silane 11 on the activated aldehyde 12 provides carbocation 13. Prior to silyl group transfer or outright silyl cleavage seen in the mechanism above, removal of the a-hydrogen regenerates the enol silane 14. While highly dependent on specific reaction conditions, the isolation of 15 leads to the suggestion of 14 as a potential intermediate in the Mukaiyama aldol reaction. 

In the Mukaiyama variation of the aldol reaction, 3-benzoyloxy-2-trimethylsiloxy-l-butene adds to 2-methylpropanal in a stereoselective manner. Best results are obtained in the presence of titanium(IV) chloride, giving the adducts 9/10 in a diastereomeric ratio of 92 8. Hydrolysis of the benzoyl group and subsequent oxidative cleavage of the 1,2-diol moiety liberates / -hy-droxycarboxylic acids593. 

Mukaiyama-aldol [45] (8.3) and Diels-Alder [46] (8.4) reactions. Lectka and coworkers [47] reported an efficient catalytic enantioselective imino-ene reaction using a copper catalyst in BTF (8.5), which gave better results in BTF compared to traditional solvents like THF or dichloromethane. They suggested that the aromatic character of BTF has a favorable influence for the enantiosel-ectivity. Trimethylaluminum and dimethylaluminum-perfluorophenolate were successfully used for the cleavage of acetals derived from C2-symmetric diols... 

Acyl-1,3-thiazolidines-2-ones 1.123 (X = S, R = COOMe), obtained from cysteine methyl ether [261], have been introduced by Mukaiyama and coworkers for use in asymmetric aldol reactions [261, 433, 434, 435], In reactions of related //-acyl-1,3-oxazolidines-2-thiones 1.123 (X = O, R = COOMe), each enantiomer can be obtained either from L- or D-serine [434] and the auxiliaries can easily be recovered by methanolysis. Similarly, //-acyl derivatives of 1.121 (X = S) have been used in asymmetric aldol reactions [429, 436], and //-acyl- 1,3-thiazo-lidinethiones 1.123 (X = S, R = r -Pr) are useful in asymmetric acylation [437] and aldol and related reactions [437, 438], Cleavage of the chiral auxiliary is accomplished by aminolysis with O-benzylhydroxylamine or by reduction with LiAlH.,. ... 

The Mukaiyama aldolization of a-sulfc A related reaction is the opening of 0-n involving C-N bond cleavage, trapping wit... 

Aliphatic nitro compounds are versatile building blocks and intermediates in organic synthesis,14 15 cf. the overview given in the Organic Syntheses preparation of nitroacetaldehyde diethyl acetal.16 For example, Henry and Michael additions, respectively, lead to 1,2- and 1,4-difunctionalized derivatives.14 18 1,3-Difunctional compounds, such as amino alcohols or aldols are accessible from primary nitroalkanes by dehydration/1,3-dipolar nitrile oxide cycloaddition with olefins (Mukaiyama reaction),19 followed by ring cleavage of intermediate isoxazolines by reduction or reduction/hydrolysis.20 21... 

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