Mukaiyama-type reactions promoted

The TMSOTf-promoted Mukaiyama-type reaction of trimethylsilyloxyfuran 54 with the nitrone of lactaldehyde 55 affords hydroxylated piperidines after reduction of the isoxazolidine intermediates (Scheme 15) <970PP485>. 

The silatropic ene pathway, that is, direct silyl transfer from an silyl enol ether to an aldehyde, may be involved as a possible mechanism in the Mukaiyama aldol-type reaction. Indeed, ab initio calculations show that the silatropic ene pathway involving the cyclic (boat and chair) transition states for the BH3-promoted aldol reaction of the trihydrosilyl enol ether derived from acetaldehyde with formaldehyde is favored [60], Recently, we have reported the possible intervention of a silatropic ene pathway in the catalytic asymmetric aldol-type reaction of silyl enol ethers of thioesters [61 ]. Chlorine- and amine-containing products thus obtained are useful intermediates for the synthesis of carnitine and GABOB (Scheme 8C.26) [62],... 

The third part of this chapter reviews previously described catalytic asymmetric reactions that can be promoted by chiral lanthanoid complexes. Transformations such as Diels-Alder reactions, Mukaiyama aldol reactions, several types of reductions, Michael addition reactions, hydrosilylations, and hydroaminations proceed under asymmetric catalysis in the presence of chiral lanthanoid complexes. 

As discussed in Section III J, in general, catalytic asymmetric aldol reactions have been studied using enol silyl ethers, enol methyl ethers, or ketene silyl acetals as a starting material. So far several types of chiral catalysis have been reported.75-85 The chiral lanthanoid complex prepared from Ln(OTf)3 and a chiral sulfonamide ligand was effective in promoting an asymmetric Mukaiyama aldol reaction with a ketene silyl acetal.86 The preparation of the catalyst and a representative reaction are shown in Figure 45. 

Bis(pentafluorophenyl) tin dibromide effects the Mukaiyama aldol reaction of ketene silyl acetal with ketones, but promotes no reaction with acetals under the same conditions. On the other hand, reaction of silyl enol ether derived from acetophenone leads to the opposite outcome, giving acetal aldolate exclusively. This protocol can be applied to a bifunctional substrate (Equation (105)). Keto acetal is exposed to a mixture of different types of enol silyl ethers, in which each nucleophile reacts chemoselectively to give a sole product.271... 

The Mukaiyama aldol reaction of carbonyl substrates with silyl enol ethers is the most widely accepted of Lewis acid-promoted reactions. Many Lewis acids for the reaction have been developed and used enantioselectively and diastereoselectively. In 1980, catalytic amounts of la were found by Noyori et al. to effect aldol-type condensation between acetals and a variety of silyl enol ethers with high stereoselectivity [2c,20]. Unfortunately, la has poor Lewis acidity for activation of aldehydes in Mukaiyama s original aldol reaction [21]. Hanaoka et al. showed the scope and limitation of 11-cat-alyzed Mukaiyama aldol reaction, by varying the alkyl groups on the silicon atom of silyl enol ethers [22]. Several efforts have been since been made to increase the reactivity and/or the Lewis acidity of silicon. One way to enhance the catalyst activity is to use an additional Lewis acid. 

The activation of the carbonyl group by Lewis acids was another leap made in the 1960s as typified by Mukaiyama-aldol reaction. In sharp contrast to the conventional carbonyl addition reactions that had been run under basic conditions, this new method allowed the addition of various nucleophiles under acidic conditions with high chemo- and stereocontrol and, consequently, the scope of the carbonyl addition reaction was extensively expanded. The Lewis acid-promoted ally-lation with allylmetals and ene reaction also received as much attention as the aldol-type reaction. It should be further pointed out that the catalytic versions of asymmetric reactions, which represent one of the most exciting topics in recent synthetic chemistry, owe their development strongly to the Lewis acid activation protocol. The design of a variety of chiral ligands for metals has produced luxuriant fruits in this field. 

As described in the sections above, it is well established that reactions of Lewis acid-activated aldehydes and ketones with silyl enolates afford -hydroxy or /7-sil-oxy carbonyl compounds (Mukaiyama aldol reactions). Occasionally, however, ene-type adducts, that is /-siloxy homoallyl alcohols, are the main products. The first example of the carbonyl-ene reaction of silyl enolates was reported by Snider et al. in 1983 [176]. They found that the formaldehyde-MesAl complex reacted smoothly with ketone TMS enolates to give y-trimethylsiloxy homoallyl alcohols in good yield. Yamamoto et al. reported a similar reaction of formaldehyde complexed with methylaluminum bis(2,6-diphenylphenoxide) [177]. After these early reports, Kuwajima et al. have demonstrated that the aluminum Lewis acid-promoted system is valuable for the ene reactions of several aldehydes [178] and for-maldimine [179] with silyl enolates bearing a bulky silyl group. A stepwise mechanism including nucleophihc addition via an acyclic transition structure has been proposed for the Lewis acid-promoted ene reactions. 

The titanium(IV) chloride-promoted reactions of enol silyl ethers with aldehydes, ketones, and acetals, known as Mukaiyama reaction, are useful as aldol type reactions which proceed under acidic conditions (eq (23)) [20], Enol silyl ethers also undergo the Michael type reactions with enones or p.y-unsaturated acetals (eq (24)) [21]. Under similar reaction conditions, enol silyl ethers are alkylated with reactive alkyl halides such as tertiary halides or chloromethyl sulfides (eq (25)) [22], and acylated with acid halides to give 1,3-diketones (eq (26)) [23]. 

The Mukaiyama reaction is an aldol-type reaction between a silyl enol ether and an aldehyde in the presence of a stoichiometric amount of titanium chloride. The reaction, which displays a negative volume of activation, could be performed without acidic promoter under high pressure [58]. In this case, the major product is the syn hydroxy ketone, not as for the TiCl4-promoted reactions which lead mostly to the anti addition product. Since the syn or anti selectivity is the result of two transition states with different activation volumes (AV n < AVfnti), it was of great interest to investigate the aldol reaction in water. Indeed, the reaction of the silyl enol ether of cyclohexanone with benzaldehyde in aqueous medium was shown to proceed without any catalyst and under atmospheric pressure, with the same syn... 

In analogous to the bisoxazoline ligands promoted asymmetric aldol reaction, Cl symmetric aminosulfoximines and oxazolinyl sulfoximines are a new class of electron-rich aryl-bridged sulfoximine ligands with excellent levels of enantioinduction in the copper-catalyzed Mukaiyama-type aldol reaction (Scheme 13) (90-92). 

The authors found that the addition of TMEDA before oxidation was necessary to increase both reproducibility and yields of this sequential process, presumably due to the inhibition of the oxidative dimerization [98], a side reaction known in the chemistry of organocopper compounds. Alkynes with electron-withdrawing groups directly bound to the sp carbon were also employed in the stereoselective carbocupration [99]. For example, the carbocupration of alkynoates 341 promoted by Lewis acids, such as trimethylsilyl triflate, leads to the isomeric TMS-allenoate compounds, which on hydrolysis or a Mukaiyama-type aldol reaction produce the corresponding di- and trisubstituted acrylates 342 (Scheme 10.116) [100]. 

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