Mukaiyama aldol reaction catalyzed

Table 9.2 Asymmetric Mukaiyama aldol reactions catalyzed by chiral quaternary ammonium fluorides4b with various methods of preparation.

Combining the D-erythrose derivative 26 obtained by L-proline-catalyzed dimerization of (t-Bu)Ph2SiOCH2CHO with enoxysilane 27 in Mukaiyama aldol reactions catalyzed by various Lewis acid, MacMillan and co-workers have realized efficient, two-step syntheses of semi-protected D-glucose (28G), L-mannose (28M) and L-allose (28A) (O Scheme 23) [148]. Using D-proline to generate tetrose 29 and its condensation with 27b, the semi-protected D-glucose derivative 30 was obtained in two steps [149]. 

Enones. The hydroxy ketones obtained from Mukaiyama aldol reaction catalyzed by bis(3,4,5-trifluorophenyl)borinic acid undergo dehydration by the stronger borinic acid. 

Mukaiyama aldol reactions catalyzed by the pybox-copper complex 65 lead to high enantiocontrol with a range of nucleophiles adding to benzyloxy acetaldehyde [44]. As shown in Scheme 9-22, catalyst 66 also led to high enantioselectiv-ities (up to 99% ee) on addition to various pyruvate esters to generate adducts 67 [45]. 

The synthesis of another Ci-Ce ketone 210 used an asymmetric Mukaiyama aldol reaction catalyzed by oxazaborolidine 135 (Scheme 9-58) [78]. This concise synthesis is reminiscent of an earlier approach to the bryostatins (see Scheme 9-42) and can also be compared with the chromium-mediated addition of a-bromoimide 211 to simple aldehyde 212 to give 213, which proceeded with excellent stereo-control (>99 1) [76]. 

Displayed here is a general Mukaiyama aldol reaction catalyzed by Lewis acid TiCU. 

Scheme 1.28 Enantioselective vinylogous Mukaiyama aldol reactions catalyzed by TADDOL (22a).

Scheme 10.2 Enantioselective vinylogous Mukaiyama aldol reaction catalyzed by taddol 1.

Chiral salen chromium and cobalt complexes have been shown by Jacobsen et al. to catalyze an enantioselective cycloaddition reaction of carbonyl compounds with dienes [22]. The cycloaddition reaction of different aldehydes 1 containing aromatic, aliphatic, and conjugated substituents with Danishefsky s diene 2a catalyzed by the chiral salen-chromium(III) complexes 14a,b proceeds in up to 98% yield and with moderate to high ee (Scheme 4.14). It was found that the presence of oven-dried powdered 4 A molecular sieves led to increased yield and enantioselectivity. The lowest ee (62% ee, catalyst 14b) was obtained for hexanal and the highest (93% ee, catalyst 14a) was obtained for cyclohexyl aldehyde. The mechanism of the cycloaddition reaction was investigated in terms of a traditional cycloaddition, or formation of the cycloaddition product via a Mukaiyama aldol-reaction path. In the presence of the chiral salen-chromium(III) catalyst system NMR spectroscopy of the crude reaction mixture of the reaction of benzaldehyde with Danishefsky s diene revealed the exclusive presence of the cycloaddition-pathway product. The Mukaiyama aldol condensation product was prepared independently and subjected to the conditions of the chiral salen-chromium(III)-catalyzed reactions. No detectable cycloaddition product could be observed. These results point towards a [2-i-4]-cydoaddition mechanism. 

For example in the so-called Mukaiyama aldol reaction of an aldehyde R -CHO and a trimethylsilyl enol ether 8, which is catalyzed by Lewis acids, the required asymmetric environment in the carbon-carbon bond forming step can be created by employing an asymmetric Lewis acid L in catalytic amounts. 

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]. 

The Mukaiyama aldol reaction refers to Lewis acid-catalyzed aldol addition reactions of silyl enol ethers, silyl ketene acetals, and similar enolate equivalents,48 Silyl enol ethers are not sufficiently nucleophilic to react directly with aldehydes or ketones. However, Lewis acids cause reaction to occur by coordination at the carbonyl oxygen, activating the carbonyl group to nucleophilic attack. 

Quite a number of other Lewis acids can catalyze the Mukaiyama aldol reaction, including Bu2Sn(03SCF3)2,51 Bu3SnC104,52 Sn(03SCF3)2,53 Zn(03SCF3)2,54 and... 

Dipole-dipole interactions may also be important in determining the stereoselectivity of Mukaiyama aldol reactions proceeding through an open TS. A BF3-catalyzed reaction was found to be 3,5-anti selective for several (3-substituted 5-phenylpentanals. This result can be rationalized by a TS that avoids an unfavorable alignment of the C=0 and C-X dipoles.97... 

Asymmetric Lewis-Acid Catalyzed. Another important advance in aqueous Mukaiyama aldol reaction is the recent success of asymmetric catalysis.283 In aqueous ethanol, Kobayashi and co-workers achieved asymmetric inductions by using Cu(OTf)2/chiral >A(oxazoline) ligand,284 Pb(OTf)2/chiral crown ether,285 and Ln(OTf)3/chiral Mv-pyridino-18-crown-6 (Eq. 8.105).286... 

Scheme 2.7. Domino Mukaiyama/Michael/aldol reactions catalyzed by Sml2(THF)2.

Mukaiyama aldol reactions of aldehydes with silyl enol ethers are amongst the most widely used Lewis-acid-mediated or -catalyzed reactions. However, trimethylsilyl triflate is not active enough to promote these reactions,66 and more active silicon-based Lewis acids have been developed. One example is the species generated by mixing trimethylsilyl triflate (or chloride) and B(OTf)3,319,320 for which the formulation R3Si + [B(OTf)4] is suggested by NMR experiments. Only a catalytic amount of this was needed to complete Mukaiyama aldol reactions of... 

A Lewis acid-catalyzed vinylogous Mukaiyama aldol reaction between 2-trialkylsilyloxyfurans and a-substituted ketones proceeded diastereoselectively... 

Pro-chiral pyridine A-oxides have also been used as substrates in asymmetric processes. Jprgensen and co-workers explored the catalytic asymmetric Mukaiyama aldol reaction between ketene silyl acetals 61 and pyridine A-oxide carboxaldehydes 62 <06CEJ3472>. The process is catalyzed by a copper(II)-bis(oxazoline) complex 63 which gave good yields and diastereoselectivities with up to 99% enantiomeric excess. 

The isomerization of an O-silyl ketene acetal to a C-silyl ester is catalyzed by a cationic zirconocene—alkoxide complex [92], This catalysis was observed as a side reaction in the zirconocene-catalyzed Mukaiyama aldol reactions and has not yet found synthetic use. The solvent-free bis(triflate) [Cp2Zr(OTf)2] also catalyzes the reaction in nitromethane (no reaction in dichloromethane), but in this case there may be competitive catalysis by TMSOTf (cf. the above discussion of the catalysis of the Mukaiyama aldol reaction) [91] (Scheme 8.51). 

Scheme 25 Vinylogous Mukaiyama aldol reaction of aldehyde 53 and ketene acetal 54 catalyzed by different Lewis acids...

Scheme 54 Salt 52 catalyzed Mukaiyama aldol reaction...

In order to enhance the catalytic activity of a carbocationic center, the novel Lewis acid 54 was designed by Mukaiyama [149-152]. The 1-oxoisoindolium-based carbenium salt 54 [149], possessing a weak coordinating borate counter anion, proved to be a very active catalyst in the aldoUzation (Scheme 58) [150]. The Mukaiyama aldol reaction was catalyzed by 1 mol% of salt 54 and proceeded in up to 97% yield in 30 min. 

Lewis acids are quite often used as catalysts in organic synthesis. Although most Lewis acids decompose in water, it was found that rare earth triflates such as Sc(OTf)3, Yb(OTf)3, etc. can be used as Lewis acid catalysts in water or water-containing solvents (water-compatible Lewis acids) [6-9]. For example, the Mukaiyama aldol reactions of aldehydes with silyl enol ethers were catalyzed by Yb(OTf)3 in water-THF (1 4) to give the corresponding aldol adducts in high yields [10, 11]. Interestingly, when the reactions were carried out in dry THF (without water), the yield of the aldol adducts was very low (ca. 10%). Thus, this catalyst is not only compatible with water but also is activated by water, probably due to dissociation of the counteranions from the Lewis acidic metal. Furthermore, the catalyst can be easily recovered and reused. 

Bismuth-Catalyzed Mukaiyama Aldol Reaction of Silyloxyfurans. 102... 

Table 16 Vinylogous Bi(OTf)3-catalyzed Mukaiyama aldol reactions involving benzaldehyde and 2-(trimethylsilyloxy)furan...

Table 19 Bi(OTf)3-catalyzed vinylogous Mukaiyama aldol reaction of benzaldehyde...

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