Mukaiyama reaction with

Scheme 2.3. Examples of Aldol and Mukaiyama Reactions with Stereoselectivity Based... 

The Mukaiyama reaction with the dimethoxy acetal of azidoacetaldehyde gives 2,3-disubstituted pyrroles (Scheme 50) (90AG(E)777). 

Silyl enol ethers of acyl silanes have been used in Lewis acid-mediated Mukaiyama reactions with acetals. Treatment of the resulting /1-alkoxy acyl silanes with tetrabutylammonium hydroxide or tetrabutylammonium fluoride gave the corresponding a,/J-unsaturated aldehydes (Scheme 99)210. 

Carbonyl activation and deactivation.1 Aldehydes, but not ketones, undergo aldol condensation with silyl enol ethers at —78° in the presence of dibutyltin bistriflate. In contrast, the dimethyl acetals of ketones, but not of aldehydes, can undergo this condensation (Mukaiyama reaction) with silyl enol ethers at -78° with almost complete discrimination, which is not observed with the usual Lewis-acid catalysts. Thus dibutyltin bistriflate activates aldehydes, but deactivates acetals of... 

The Mukaiyama reaction provides a good synthetic route to statine. L-Leucine methyl ester (6.104) was converted to the N-isopropylcarbamate aldehyde (6.105). Mukaiyama reaction with the trimethylsilyl enolate of methyl acetate, catalyzed by... 

A series of chiral boron catalysts prepared from, e.g., N-sulfonyl a-amino acids has also been developed and used in a variety of cycloaddition reactions [18]. Corey et al. have applied the chiral (S)-tryptophan-derived oxazaborolidine-boron catalyst 11 and used it for the conversion of, e.g., benzaldehyde la to the cycloaddition product 3a by reaction with Danishefsky s diene 2a [18h]. This reaction la affords mainly the Mukaiyama aldol product 10, which, after isolation, was converted to 3a by treatment with TFA (Scheme 4.11). It was observed that no cycloaddition product was produced in the initial step, providing evidence for the two-step process. 

For a review of reactions with this and related methods, see Mukaiyama, T. Angew. Chem. Int. Ed. Engl., 1979, 18, 707. 

For some other aldol reactions with preformed enol derivatives, see Mukaiyama, T. Isr. J. Chem., 1984, 24, 162 Caine, D. in Augustine, Ref 564, p. 264. 

Danshefsky s diene [19] is the 1,3-butadiene with amethoxy group at the 1-position and a trimethylsiloxy group at the 3-position (Scheme 18). This diene and Lewis acids extended the scope of hetereo-Diels-Alder reactions with aldehydes [20], This diene reacts with virtually any aldehyde in the presence of Lewis acids whereas dienes usually react with only selected aldehydes bearing strongly electron accepting a-substituents. There are two (Diels-Alder and Mukaiyama aldol) reaction pathways (Scheme 18) identified for the Lewis acids catalyzed reactions of Danishefsky diene with aldehydes [21, 22]. The two pathways suggest that these reactions occur on the boundary between the delocahzation band (the pericyclic... 

Another SBU with open metal sites is the tri-p-oxo carboxylate cluster (see Section 4.2.2 and Figure 4.2). The tri-p-oxo Fe " clusters in MIL-100 are able to catalyze Friedel-Crafts benzylation reactions [44]. The tri-p-oxo Cr " clusters of MIL-101 are active for the cyanosilylation of benzaldehyde. This reaction is a popular test reaction in the MOF Hterature as a probe for catalytic activity an example has already been given above for [Cu3(BTC)2] [15]. In fact, the very first demonstration of the catalytic potential of MOFs had aheady been given in 1994 for a two-dimensional Cd bipyridine lattice that catalyzes the cyanosilylation of aldehydes [56]. A continuation of this work in 2004 for reactions with imines showed that the hydrophobic surroundings of the framework enhance the reaction in comparison with homogeneous Cd(pyridine) complexes [57]. The activity of MIL-lOl(Cr) is much higher than that of the Cd lattices, but in subsequent reaction rans the activity decreases [58]. A MOF with two different types of open Mn sites with pores of 7 and 10 A catalyzes the cyanosilylation of aromatic aldehydes and ketones with a remarkable reactant shape selectivity. This MOF also catalyzes the more demanding Mukaiyama-aldol reaction [59]. 

Scheme 10.24 Cu-catalysed Mukaiyama-type aldol reactions with Ci-symmetric benzene-bridged aminosulfoximine ligands.

Scheme 10.26 Sn-catalysed Mukaiyama aldol reaction with S/N ligands.

Scheme 10.27 Yb-catalysed Mukaiyama aldol reactions with sulfonamide ligand.

Scheme 2.2 illustrates several examples of the Mukaiyama aldol reaction. Entries 1 to 3 are cases of addition reactions with silyl enol ethers as the nucleophile and TiCl4 as the Lewis acid. Entry 2 demonstrates steric approach control with respect to the silyl enol ether, but in this case the relative configuration of the hydroxyl group was not assigned. Entry 4 shows a fully substituted silyl enol ether. The favored product places the larger C(2) substituent syn to the hydroxy group. Entry 5 uses a silyl ketene thioacetal. This reaction proceeds through an open TS and favors the anti product. 

Mukaiyama reactions of a-methyl aldehydes proceed through an open TS and show a preference for the 3,4-syn stereoisomer, which is consistent with a Felkin TS.80... 

In the synthesis shown in Scheme 13.15, racemates of both erythro- and threo-juvabione were synthesized by parallel routes. The isomeric intermediates were obtained in greater than 10 1 selectivity by choice of the E- or Z-silanes used for conjugate addition to cyclohexenone (Michael-Mukaiyama reaction). Further optimization of the stereoselectivity was achieved by the choice of the silyl substituents. The observed stereoselectivity is consistent with synclinal TSs for the addition of the crotyl silane reagents. 

An enantiospecific synthesis of longifolene was done starting with camphor, a natural product available in enantiomerically pure form (Scheme 13.31) The tricyclic ring was formed in Step C by an intramolecular Mukaiyama reaction. The dimethyl Multistep Syntheses substituents were formed in Step E-l by hydrogenolysis of the cyclopropane ring. 

On the other hand, Li and Wang recently developed a highly efficient asymmetric Mukaiyama reaction by using chiral gallium catalysts with Trost s chiral semicrown ligands (Eq. 8.106).287 Such a system can achieve high enantioselectivity even in pure water. The combination... 

Using a cyclic enone 2-29b and an ester-TMS enolate 2-30 in the presence of catalytic amounts of SmI2(THF)2, the Michael addition and the Mukaiyama/aldol reaction with the added aldehyde 2-32 led to the diastereomeric adducts 2-33 and 2-34 via 2-31 with a dr =80 20 to 98 2 and 70-77% yield (Scheme 2.7) [13]. The major product is the trans-l,2-disubstituted cycloalkanone. 

The stereochemical outcome of the Mukaiyama reaction can be controlled by the type of Lewis acid used. With bidentate Lewis acids the aldol reaction led to the anti products through a Cram chelate control [366]. Alternatively, the use of a monoden-tate Lewis acid in this reaction led to the syn product through an open Felkin-Anh... 

Mukaiyama reaction (Lewis acid-catalyzed Michael reaction) with electron-poor olefins, ketals and acetals, and enones 32... 

Recent developments of aldol-type reactions with titanium enolates include the a- and /3-C-glycosidation of glycals73 and the diastereoselective addition to 2-acetoxytetrahydrofurans.74 Mukaiyama and co-workers have developed a one-pot procedure for the preparation of unsymmetrical double aldols.75... 

The first demonstration of fluorous synthesis was in the preparation of small (8-12 members) isoxazo-line and isoxazole libraries by the three-step procedure outlined in Figure 8.1461 All reactions were purified by three-phase liquid-liquid extraction. The starting substrates were simple allylic alcohols which were tagged with the fluorous silyl halide 5 to make substrates 6 for an ensuing dipolar cycloaddition. This was conducted by the Mukaiyama method with a large excess of nitro compound and... 

The salt 18 was explored in the Mukaiyama aldol reaction with acetophenone, and a yield of 96% was obtained after 1 h at -78 °C (Scheme 11). When MejSiOTf was used as a catalyst, a yield of 0% was observed. Me3SiNTf3 and Et3SiNTf3 resulted in 12% and 8% yield, respectively. 

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