Enantioselective reactions Mukaiyama Michael addition

The enantioselective vinylogous Mukaiyama—Michael addition of 2-silyloxyfurans to cyclic unsaturated oxo esters afforded a variety of compounds bearing a y-butenolide or y-lactone connected to a cycloalkane or cycloalkene moiety (13JOC2289). The reaction of siloxyfurans with aromatic aldimines could be catalyzed efficiently by silver(I) complexes of the Ar-BlNMOL-derived chiral monophosphine (13T8777). 

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... 

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>. 

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,... 

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. 

The first report of an enantioselective organocatalytic Mukaiyama-Michael reaction involves the use of an amine catalyst during the 1,4-addition of TMSOF to the electron deficient olefin ( )-but-2-enal. The cafalyst is employed as its dinitroben-zoic acid (DNBA) salt (eq 35). Several other substituted TMSOFs are used in this reaction with similar levels of success. A formal enantioselective synthesis of (+)-compactin incorporates this method. ... 

A catalytic asymmetric amination reaction has been developed using Cu(2+) catalysts (246). The azodicarboxylate derivative 392 reacts with enolsilanes in the presence of catalyst 269c to provide the adducts in high enantioselectivity, Eq. 213. As observed in the Mukaiyama Michael reactions, alcoholic addends proved competent in increasing the rate of this reaction. Indeed, in the presence of tri-fluoroethanol as additive, the reaction time decreases from 24 to 3 h. 

In 1988, Mukaiyama et al. reported the Sn(OTf)2-50d-catalyzed asymmetric Michael reaction of a trimethylsilyl enethiolate, CH2=C(SMe)SSiMej (up to 70% ee) [243]. It was proposed that the catalytic reaction proceeded via an Sn(II) enethiolate. They also demonstrated that a BINOL-derived oxotitaniurn catalyzes the Michael addition of ketene silyl thioacetals to a-enone with high enantioselectivity (up to 90% ee) [244]. After this pioneering work other research groups developed new reaction systems for enantioselective Mukaiyama-Michael reactions. 

The utihty of Cu(II)-box complex 96 for asymmetric Mukaiyama-Michael reaction has been intensively studied by Evans et al. (Scheme 10.91) ]248]. In the presence of HFIP fhe 96-catalyzed reaction of S-t-butyl thioacetate TMS enolate with alkylidene malonates provides fhe Michael adducts in high chemical and optical yield. HFIP plays a crucial role in inducing catalyst turnover. Slow addition of the silyl enolate to a solution of 96, alkylidene malonates, and HFIP is important in achieving high yields, because fhe enolate is susceptible to protonolysis with HFIP in fhe presence of 96. The glutarate ester products are readily decarboxylated to provide chiral 1,5-dicarbonyl synthons. Quite recenfly, Sibi et al. reported enantioselective synthesis of t -amino acid derivatives by Cu( 11)-box-catalyzed conjugate addition of silyl enolates to aminomefhylenemalonates ]249]. 

During the last decade, use of oxazaborolidines and dioxaborolidines in enantioselective catalysis has gained importance. [1, 2] One of the earliest examples of oxazaborolidines as an enantioselective catalyst in the reduction of ketones/ketoxime ethers to secondary alco-hols/amines was reported by Itsuno et al. [3] in which (5 )-valinol was used as a chiral ligand. Since then, a number of other oxazaborolidines and dioxaborolidines have been investigated as enantioselective catalysts in a number of organic transformations viz a) reduction of ketones to alcohols, b) addition of dialkyl zinc to aldehydes, c) asymmetric allylation of aldehydes, d) Diels-Alder cycloaddition reactions, e) Mukaiyama Michael type of aldol condensations, f) cyclopropana-tion reaction of olefins. 

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... 

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... 

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