Silyl ethers Mukaiyama-Michael

Methyl 1-phenylthiovinyl ketones can also be used as enones in kinetically controlled Robinson annulation reactions, as illustrated by Entry 6. Entry 7 shows a annulation using silyl enol ether as the enolate equivalent. These reactions are called Mukaiyama-Michael reactions (see Section 2.6.3). 

Conditions for effecting conjugate addition of neutral enolate equivalents such as silyl enol ethers in the presence of Lewis acids have been developed and are called Mukaiyama-Michael reactions. Trimethylsilyl enol ethers can be caused to react with electrophilic alkenes by use of TiCl4. These reactions proceed rapidly even at -78° C.308... 

Initial stereochemical studies suggested that the Mukaiyama-Michael reaction proceeds through an open TS, since there was a tendency to favor anti diastereoselec-tivity, regardless of the silyl enol ether configuration.312... 

The titanium(IV) chloride-catalyzed conjugate addition of enol silyl ethers (182) to (184) and (189 Scheme 30), and silyl ketene acetals, (191) to (194), to ot, 3-enones is die key feature in various synthetic strategies (Mukaiyama-Michael) (Scheme 31).78 79 In contrast to the earlier described enolate addition... 

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... 

Mukaiyama-Michael reaction1 (13, 339-340 14, 344-345). The conjugate addition of enol silyl ethers of optically active ketones to a,(i-enones catalyzed by trityl perchlorate can proceed with high diastereoselectivity. Thus the (Z)-enol silyl ether (2) of the ketone (R)-l reacts with enone 3 to give the 1,5-ketone 4 with high... 

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. 

Stereoselective Mukaiyama-Michael reactions, Heathcock et alJ have investigated the syn anti stereoselectivity in the reaction of twelve silyl enol ethers with a variety of acyclic and cyclic enones catalyzed by TiCh or SnCh. Preliminary results suggest that the stereoselectivity is independent of the geometry of the silyl enol ether, and that silyl enol ethers derived from aliphatic ketones show a preference for (2n /-addition ranging from 1.5 1 to 10 1. The preference for a/ift-addition is even higher in the case of (Z)-silyl enol ethers of aromatic ketones (10 1 to >20 1). However, high 5y/i-selectivity is observed with acyclic -butyl enones. 

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]. 

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). 

The chiral acyloxyborane 7 (CAB) has also been found to be an excellent catalyst for asymmetric Mukaiyama-Michael type aldol reaction between silyl enol ethers and aldehydes (Scheme 8). Yamamoto et al. [27] have used 20 mol % of CAB in propionitrile at -78 °C as a highly efficient catalyst for the condensation of several E and Z silyl enol ethers and ketene acetals with a variety of aldehydes (yields 49-97 %, 80-97 % ee). 

The catalytic asymmetric Michael reaction using silyl enol esters (Mukaiyama-Michael reaction) as the pronucleophiles has been reported using a titanium/BINOL catalyst (in up to 90% ee). Considering furan (11.36) as a silyl enol ether, this has been shown to undergo nucleophilic addition to the Michael acceptor (11.37). The product (11.38) canbe obtained with excellent diastereocon-trol with the scandium complex of hgand (11.39), or with excellent enantiocontrol... 

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,... 

Alternatively, the iminium-activation strategy has also been apphed to the Mukaiyama-Michael reaction, which involves the use of silyl enol ethers as nucleophiles. In this context, imidazolidinone 50a was identified as an excellent chiral catalyst for the enantioselective conjugate addition of silyloxyfuran to a,p-unsaturated aldehydes, providing a direct and efficient route to the y-butenolide architecture (Scheme 3.15). This is a clear example of the chemical complementarity between organocatalysis and transition-metal catalysis, with the latter usually furnishing the 1,2-addition product (Mukaiyama aldol) while the former proceeds via 1,4-addition when ambident electrophiles such as a,p-unsaturated aldehydes are employed. This reaction needed the incorporation of 2,4-dinitrobenzoic acid (DNBA) as a Bronsted acid co-catalyst assisting the formation of the intermediate iminium ion, and also two equivalents of water had to be included as additive for the reaction to proceed to completion, which... 

Dihydropyran derivatives can be synthesized facilely by a smooth oxidative Mukaiyama-Michael addition followed by a cyclization with silyl enol ethers in the presence of Dess Martin periodinane (DMP) and pyridine under mild reaction conditions from MBH adducts in a one-pot process (Scheme 4.95). Notably, these dihydropyrans were obtained exclusively as cw-isomers in good yields. Moreover, all the reactions worked very well, irrespective of whether MBH adducts were derived from aliphatic or aromatic aldehydes, and silyl enol ethers were derived from acetophenone, cyclohexanone or cyclopentanone. 

Scheme 2.50 PTC Mukaiyama-Michael addition of silyl enol ethers to chtJcones...

Maruoka et al. have developed and used A-spiro C2-symmetric chiral quaternary ammonium bifluorides [151] 102, 103, and more recently 104, to promote the regio- and anti-selective Mukaiyama-Michael addition of silyl nitronates to a, 3-unsaturated aldehydes [152], cyclic a,P-unsaturated ketones [153], and nitroalk-enes [154] with good yields and enantioselectivities (Scheme 2.52). Final chiral silyl enol ethers are easily hydrolyzed to the corresponding carbonyl compounds or functionalized at the a-position by reaction with electrophiles. 

In some cases, using the silyl enol ethers form of nucleophiles in the asymmetric Michael reactions is necessary for ensuring high reactivity and selectivity. MacMillan and co-workers [113] developed the first enantioselective organocata-lytic Mukaiyama-Michael reaction for the synthesis of enantioenriched 7-butenolide architecture in 2003. In the presence of chiral imidazolidinone catalyst 120 with acid additive, the reactions of silyloxy furan 118 with simple a,(3-unsaturated aldehydes... 

Using the silyl enol ethers 120 as nucleophiles, the Mukaiyama-Michael reactions with a,(3-unsaturated aldehydes and chalcones proved to be powerful tools for the preparation of synthetically useful 1,5-dicarbonyl compounds [114] (Scheme 5.56). 

SCHEME 5.56. Mukaiyama-Michael reaction of silyl enol ethers. 

The Yamamoto group developed tethered bis(8-quinolinolato)-Al complex 26-catalysed asymmetric Mukaiyama-Michael additions of silyl enol ethers to ot,p-unsaturated acyl phosphonates (Scheme 19.30). A range of tetra-substituted trimethylsilyl enol ethers reacted well and formed the adducts with all-carbon quaternary stereocentres in 80-99% enantiomeric excess. 

Scheme 19.30 A mmetric Mukaiyama-Michael additions of silyl enol ethers to a,p-unsaturated atyl phosphonate catalysed by bis(8-quinolinolato)-Al complex.

Keywords Baylis-Hillman adducts, silyl enol ethers, Dess-Martin periodinane (DMP), pyridine, dichloromethane, room temperature, oxidative Mukaiyama-Michael addition, diaster-eoselective cyclization, c -fused dihydrpyrans... 

Kobayashi et al. disclosed the effectiveness of lanthanides triflates as Lewis acid fear Mukaiyama-Michael reactions of a,p-unsaturated ketones and enol silyl ethers [llj. Virtually all of the lanthanide triflates except for Ce(OTf)3 and Tb(OTf)3 worked well and could be reused. By using 10mol% of Yb(OTf)3, the reaction proceeded smoothly with both cyclic and acyclic a,p-unsaturated ketones to afford 1,5-dicarbonyl compounds in high yield (Scheme 13.3). Remarkably, the recovered catalyst exhibited comparable catalytic performance in the second runs. 

The highly electrophilic cationic bis(8-quinolinolato)aluminum complex 407 enabled Yamamoto and coworkers to perform Mukaiyama-Michael additions of silyl enol ethers to crotonylphosphonates 406. The procedure was not only applicable to enol silanes derived from aryl methyl and alkyl methyl ketones (a-unsubstituted silicon enolates) but also to several cycfic a-disubstituted silyl enol ethers, as illustrated for the derivatives of a-methyl tetralone and indanone 405 in Scheme 5.105. Despite the steric demand of that substitution pattern, the reaction occurred in relatively high chemical yield with varying diastereoselectivity and excellent enantiomeric excess of the major diastereomer. The phosphonate residue was replaced in the course of the workup procedure to give the methyl esters 408. The protocol was extended inter alia to the silyl enol ether of 2,6,6-tetramethylcyclohexanone. The relative and absolute configuration of the products 408 was not elucidated [200]. 

Jung and coworkers reported AlBr3/Me3Al system as an effective mixed Lewis acid system for Diels-Alder reaction of sterically hindered dienophiles and dienes (Scheme 6.126) [150]. It was proposed that this reaction proceeds via Mukaiyama-Michael addition of silyl enol ether moiety to cyclohexenone followed by intramolecular Michael like process. 

Conjugate addition of nitroalkanes to a,P-unsaturated aldehydes in the presence of imidazolyl-imidazolidin-4-ones was described by Arvidsson and coworkers [92], In addition, silyl enol ethers of substituted acetophenones [93] or thioesters [94] react with a,P-unsaturated aldehydes under iminium-catalysis conditions in the sense of a Mukaiyama-Michael reaction (Scheme 4.24). Applications of this transformation can be found in the total syntheses of compactin [95] and homocitric acid lactone and its homolog [96]. 

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