Michael addition Mukaiyama

L2909>. An organocatalytic addition of 2-trimethylsilyloxyfuran to aldehydes using 10 mol% of l,3-bis(3-(trifluoromethyl)phenyl)urea provided adducts with modest threo selectivity <06TL8507>. A syn-selective, enantioselective, organocatalytic vinylogous Mukaiyama-Michael addition of 2-trimethylsilyloxyfuran to (E)-3-... 

Silylketene acetals and enolsilanes can also undergo conjugate addition to a,/ -unsaturated carbonyl derivatives. This reaction is referred to as the Mukaiyama-Michael addition and can also be used as a mild and versatile method for C-C bond formation. As shown in Scheme 8-34, in the presence of C2-symmetric Cu(II) Lewis acid 94, asymmetric conjugate addition proceeds readily, giving product with high yield and enantioselectivity.75... 

The elfectiveness of imidazolidinone of type 11 was confirmed by successful application to a broad range of chemical transformations, including cycloadditions, conjugate additions, Friedel-Crafts alkylations, Mukaiyama-Michael additions, hydrogenations, cyclopropanations, and epoxidations. A summary of these enantio-selective iminium catalyzed processes is provided by reaction subclass. 

MacMillan reported a short and effective synthesis of spiculisporic acid which elegantly exemplified his Mukaiyama-Michael addition of silyloxyfurans to a,P-unsatu-rated aldehydes [88], Robichaud and Tremblay augmented this in a formal synthesis of compactin [224], Within this report it was shown that low enantioselectivities were obtained in the conjugate addition to aCTolein. Use of p-silyl acrolein 177 circumvented this and gave butenohde 178 in 95% yield and 82% ee. Conversion of adduct 178 to the decaUn (179) in eight steps resulted in a formal synthesis (Scheme 71). 

Figure 9.73. Enantioselective Mukaiyama-Michael addition of enolsilanes. TABLE 9.39. CYCLOPROPANATIONS WITH SULEUR YLIDES"...

Mukaiyama-Michael addition of a chiral ketene acetal to nonprochiral vinyl ketones gives products of 72-75% ee.145 A chirally modified glycine derivative (Schiff-base) adds to vinylic phosphorus compounds to yield, after hydrolysis, products with 54-85% ee.146 Another chiral glycine equivalent was used for the preparation of homochiral proline derivatives via diastereoselective addition to a,3-unsatu-rated aldehydes and ketones.147-148... 

A highly enantioselective Mukaiyama-Michael addition of silyl ethers, CH2= C(OSiMe3)R1, to a,/9-unsaturated aldehydes, R2CH=CHCHO, catalysed by MacMillan s chiral imidazolidinone (150), in the presence of 2,4-(N02)2C6H3C02H as an acid... 

The use of simple silyl enol ethers for the asymmetric organocatalyzed Mukaiyama-Michael addition was recently reported. For reference, see W. Wang, H. Li, J. Wang, Org. Lett. 

A ry -selective, organocatalytic, enantioselective vinylogous Mukaiyama-Michael addition of 2-trimethylsilyloxyfuran to a,/ -unsaturated aldehydes to produce 7-butenolides was achieved by using a chiral amine catalyst... 

Vinylogous Mukaiyama-Michael additions of 2-trimethylsilyloxyfuran to 3-alkenoyl-2-oxazolidinones to provide 7-butenolides were shown to be /7-selective. The reaction could be rendered enantioselective in the presence of a (T symmetric copper-bisoxazoline complex <1997T17015, 1997SL568> or a l,T-binaphthyl-2,2 -diamine-nickel(ii) complex as catalyst, as depicted in Equation (16) <2004CC1414>. 

Trimethylsilyloxyfuran reacted stereoselectively with chiral tungsten carbene complexes in a Mukaiyama-Michael addition fashion to provide -products, as shown in Equation (18) <2005AGE6583>. The metal carbene in the butenolide product serves as a useful functional group for further transformations. 

C6F5)2SnBr2 [53, 54a] are efficient catalysts of fhe Mukaiyama-Michael addition. 

The Mukaiyama-Michael addition of silyl enolates to a, -unsaturated thioesters is promoted by an SbCl5-Sn(OTf)2 binary catalyst to afford d-keto thioesters with high anti selectivity (Scheme 14.23) [60]. The successive treatment of lactones with a ketene silyl acetal and silyl nucleophiles in the presence of an SbCl5-Me3SiCl-Snl2 ternary catalyst yields a-mono- and a/ -disubstituted cyclic ethers (Scheme 14.24) [61]. SbFs promotes the condensation of a,y5-unsaturated aldehydes and ketones with a-diazo-carbonyl compounds to give cyclopropane derivatives in high isomeric purity [62]. 

BiX mediates the Mukaiyama-Michael addition of a./i-urisaluraled carbonyl compounds (Scheme 14.87) [171, 172 b, c]. The BiCb-catalyzed Michael addition of 1,3-dicarbonyl compounds to methyl vinyl ketone and benzal acetophenone proceeds efficiently under microwave irradiation [179]. The Knovenagel condensation of aldehydes with active methylene compounds can also be promoted by BiCl3 (Scheme 14.88) [180]. 

Michael addition/enamine chlorination reaction <05JA15051>. 2-Trimethylsilyloxyfuran reacted readily with chiral tungsten carbene complexes in a Mukaiyama-Michael addition manner to give the anti products selectively, as depicted in the example below <05AGa)6583>. 

As will be shown, the stereochemistry of Mukaiyama-Michael additions is in many instances insensitive to the stereochemistry of the silyl enol ether used. This method is potentially advantageous relative to the direct conjugate addition of ketone enolates when it is impossible to obtain the enolate or silyl enol ethers in a stereoisomerically pure form. 

The geometry of the silyl enol ether has only a slight influence on the stereochemistry of the Mukaiyama-Michael addition. For example, the Z silyl enol ether in entry 5 (Table 10) provides a 35 65 (syn/anti) mixture of diastereomers. With the corresponding E silyl enol ether (entry 25), a 23 77 (syn/anti) mixture of diastereomers results. 

In all instances, the Mukaiyama-Michael addition of silyl enol ethers is anti selective. For the most part, however, the selectivity is only modest. A... 

In some instances, particularly when a dependence of the stereochemistry on the double-bond geometry of either the acceptor or donor is observed, it appears likely that the stereochemistry-determining step is the initial conjugate addition. The stereochemical consequences of Lewis-acid-mediated additions of silyl enol ethers (116) and allylsilanes (117,118) have frequently been rationalized by open-extended transition states. Similar pathways seem likely with the Mukaiyama-Michael addition (vide infra) (77,79). 

Mukaiyama-Michael addition is the method of choice for providing a specific stereochemistry. 

Mechanistically, enamine and Lewis-acid-mediated conjugate additions are complex. The opportunity exists for the product-determining step to occur at a number of points and, without further study, the precise nature of the manifold is not entirely clear. In some enamine cases where the stereoselectivity likely results from the conjugate addition, a synclinal type transition state seems to be involved. With the Mukaiyama-Michael addition, some processes implicate an open-extended pathway. Despite the mechanistic uncertainties that remain, sufficient data are now available so that the stereochemistry in many cases can be anticipated by extrapolation. 

Mukaiyama-Michael addition. The reaction of silyl ketene acetals with enones is catalyzed with a species formed from P4O10 and MeCN. 

Mukaiyama-Michael Addition, Mukaiyama-Michael Conjugate... 

This reaction was first reported by Mukaiyama et al. in 1974. It is a Lewis acid-catalyzed Michael conjugate addition of silyl enol ether to o ,/3-unsaturated compounds. Therefore, it is generally referred to as the Mukaiyama-Michael reaction. Because this reaction is essentially a conjugate addition, it is also known as the Mukaiyama-Michael addition or Mukaiyama-Michael conjugate addition. This reaction is a mechanistic complement for the base-catalyzed Michael addition, j and often occurs at much milder conditions and affords superior regioselectivity. s Besides silyl enol ether, silyl ketene acetals are also suitable nucleophiles in this reaction.For the hindered ketene silyl acetals, the Lewis acid actually mediates the electron transfer from the nucleophiles to o ,/3-unsaturated carbonyl molecules.On the other hand, the Q ,j8-unsaturated compounds, such as 3-crotonoyl-2-oxazolidinone, alkylidene malonates, and a-acyl-a,/3-unsaturated phosphonates are often applied as the Michael acceptors. It has been found that the enantioselectivity is very sensitive to the reactant structures —for example, Q -acyl-Q ,j8-unsaturated phosphonates especially prefers the unique syn- vs anft-diastereoselectivity in this reaction. In addition,... 

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