Crossed Mukaiyama

The crossed aldol reaction of silyl enol ethers with carbonyl compounds (Mukaiyama-aldol) was studied by Lubineau and co-workers... 

As described above, our synthetic strategy involves the convergent construction of the central cyclopentanone ring with a carbonylative cross-coupling reaction and a photo-Nazarov cyclization reaction (Chart 2.2). The electrophilic coupling component 51 was synthesized by an intramolecular Diels-Alder reaction [34] and the nucleophilic coupling component 52 by a vinyiogous Mukaiyama aldol reaction [35]. 

An exceptionally mild procedure for the cross-condensation of aldimines and enolsilanes has been described (eq. [67]) (80). This titanium tetrachloride-mediated reaction is predicated on the previous analogies provided by Mukaiyama for related aldol condensations (73a). Depending on aldimine structure and reaction time, either -lactams or their penultimate amino esters may be isolated from the reaction. The authors postulate that these reactions are proceeding via titanium enolates derived from ligand exchange by... 

In the Mukaiyama cross-aldol reaction, an aldehyde and a ketene silyl acetal [e.g. (43)] react via Lewis acid catalysis to give a jS-silyloxy ester (44). The reaction... 

The aldehyde-aldehyde aldol reactions were first nsed in a natural product synthesis setting by Pihko and Erkkila, who prepared prelactone B in only three operations starting from isobutyraldehyde and propionaldehyde (Scheme 40). Crossed aldol reaction under proline catalysis, followed by TBS protection, afforded protected aldehyde 244 in >99% ee. A highly diastereoselective Mukaiyama aldol reaction and ring closure with aqueous HE completed the synthesis [112]. 

Analysis of the Mukaiyama-type aldol coupling (Eq. 2) and the well-known hydrosilyla-tion of a,/l-unsaturated carbonyl compounds 11 in the presence of a rhodium catalyst, indicate that both can be explained by the intervention of the rhodium enolate 13. This line of reasoning provided the impetus to develop a new crossed aldol coupling using a hydrosilane, an a,yS-unsaturated ketone 11, and an aldehyde to form 15 (Scheme 6.4). 

Fig. 13). The cross-linked scandium-modified dendrimer was tested in a number of Lewis acid-catalyzed reactions, including Mukaiyama aldol additions to aldehydes and aldimines, Diels-Alder reactions, and Friedel-Crafts acylations. The dendritic catalyst was recovered by a simple filtration. The Mukaiyama aldol... 

In the Mukaiyama aldol additions of trimethyl-(l-phenyl-propenyloxy)-silane to give benzaldehyde and cinnamaldehyde catalyzed by 7 mol% supported scandium catalyst, a 1 1 mixture of diastereomers was obtained. Again, the dendritic catalyst could be recycled easily without any loss in performance. The scandium cross-linked dendritic material appeared to be an efficient catalyst for the Diels-Alder reaction between methyl vinyl ketone and cyclopentadiene. The Diels-Alder adduct was formed in dichloromethane at 0°C in 79% yield with an endo/exo ratio of 85 15. The material was also used as a Friedel-Crafts acylation catalyst (contain-ing7mol% scandium) for the formation of / -methoxyacetophenone (in a 73% yield) from anisole, acetic acid anhydride, and lithium perchlorate at 50°C in nitromethane. 

UMukaiyama Hayashi Chem. Lett. 1974,15 Mukaiyama Kobayashi Murakami Chem. Lett. 1984,1759 Murata Suzuki Noyori Tetrahedron 1988, 44, 4259. For a review of cross-coupling reactions of acetals, sec Mukaiyama Murakami Synthesis 1987, 1043-1054. 

The Mukaiyama reaction is a versatile crossed-aldol reaction that uses a silyl enol ether of an aldehyde, ketone, or ester as the carbon nucleophile and an aldehyde or ketone activated by a Lewis acid as the carbon electrophile. The product is a /1-hydroxy carbonyl compound typical of an aldol condensation. The advantages to this approach are that it is carried out under acidic conditions and elimination does not usually occur. 

S)-Proline-catalyzed cross-aldol reaction of aldehydes followed by Mukaiyama aldol reaction sequence was used for the synthesis of prelactone B [27]. The products of the aldol reactions of O-protected a-oxyaldehydes are protected carbohydrates, and were also transformed to highly enantiomerically enriched hexose derivatives, again through a second Mukaiyama aldol reaction (Scheme 2.5) [28]. The products of the aldol reactions of N-protected a-aminoaldehyde donor were easily converted to the corresponding highly enantiomerically enriched /Miydroxy-a-amino acids and their derivatives (Scheme 2.6) [24]. (For experimental details see Chapter 14.1.1). 

Cross-Coupling Reactions Based on Acetals, Mukaiyama, T Murakami, M. Synthesis 1987, 1043. 

A very elegant asymmetric synthesis of D-ribose from achiral starting materials has been presented by Mukaiyama and coworkers [36]. It is based on the cross-aldolization of crotonaldehyde and enoxysilane 74 in the presence of an enantiomerically pure diamine 75, the chiral inducer (Scheme 13.33). High diastereoselectivity anti syn > 98 2) and high... 

Mukaiyama and coworkers [37] (Scheme 13.72) have prepared 4-C-methyl-D-ribose via their asymmetric cross-aldolization between a-methylacrolein and enoxysilane 74 (Scheme 13.33). 

Importantly, with a-silyloxy acetaldehyde, the syn aldol is the major dimer (threose derivative). Thus, applying Mukaiyama condensations with 27 (see O Scheme 23), hexoses such as idose, gulose, and galactose can be prepared. A highly stereoselective protocol for the cross coupling of aldehydes and ketones with a-thioacetal aldehydes has been developed... 

An enantioselective synthesis of 3-deoxypentoses from (—)-myrtenal has been proposed by Franck-Neumann and co-workers (O Scheme 54) [251], It features the Mukaiyama cross-aldolization of benzyloxyacetaldehyde and the tricarbonyliron complex 124 derived from the condensation of (—)-myrtenal with acetone. The diastereomeric aldols 125 andl26 are separated and converted (O Scheme 54) into 3-deox) entoses 127 and 128 [251]. 

The Mukaiyama Reaction —Lewis Acid-Catalyzed Crossed Aldol Reactions... 

Mukaiyama, T., Banno, K., Narasaka, K. New cross-aldol reactions. Reactions of silyl enol ethers with carbonyl compounds activated by titanium tetrachloride. J. Am. Chem. Soc. 1974, 96, 7503-7509. 

Ellis, W. W., Bosnich, B. Mechanisms of the catalyzed Mukaiyama cross-aldol reaction. Organic Synthesis via Organometallics, Proceedings of the Symposium, 5th, Heidelberg, Sept. 26-28, 19961997, 209-227. 

Mukaiyama, T., Murakami, M. Cross-coupling reactions based on acetals. Synthesis 1987, 1043-1054. 

LLC networks containing catalytic headgroups have also been shown to be useful for heterogeneous Lewis acid catalysis. The Sc(III)-exchanged cross-linked Hu phase of a taper-shaped sulfonate-functionalized LLC monomer has been shown to be able to catalyze the Mukaiyama aldol and Mannich reactions [115] with enhanced diastereoselectivity. This Sc(III)-functionalized Hu network affords condensation products with syn-to-anti diastereoselectivity ratios of 2-to-l, whereas Sc(III) catalysts in solution or supported on amorphous polymers show no reaction diastereoselectivity at all. 

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