Carbonyl compounds Lewis base catalyzed

Many noticeable examples of chiral Lewis base catalyzed allylation of carbonyl compounds have also appeared. Iseki and coworkers published a full paper on enantioselective addition of allyl- and crotyltrichlorosilanes to aliphatic aldehydes catalyzed by a chiral formamide 28 in the presence of HMPA as an additive [41]. This method was further applied to asymmetric allenylation of aliphatic aldehydes with propargyltrichlorosilane [40]. Nakajima and Hashi-moto have demonstrated the effectiveness of (S)-3,3 -dimethyl-2,2 -biquinoline N,AT-dioxide (29) as a chiral Lewis base catalyst for the allylation of aldehydes [42]. In the reaction of (fs)-enriched crotyltrichlorosilane (54 , E Z=97 3) with benzaldehyde (48), y-allylated anfi-homoallylic alcohol 55 was obtained exclusively with high ee while the corresponding syn-adduct was formed from its Z isomer 54Z (fs Z= 1 99) (Scheme 6). Catalytic amounts of chiral urea 30 also promote the asymmetric reaction in the presence of a silver(I) salt, although the enantioselectivity is low [43]. 

The first example of chiral Lewis base-catalyzed allylation of carbonyl compounds was shown by Denmark et al. [35]. They surveyed a variety of achiral and chiral Lewis bases as stoichiometric reagents to promote the addition of al-lyltrichlorosilane to benzaldehyde and found that the chiral phosphoramide 14 was a superior chiral promoter. When crotyltrichlorosilane was employed, the diastereoselectivity anti/syn) of the product was dependent on the geometry of the crotylsilane. Based on the stereochemical outcome, the reaction was proposed to proceed via closed transition structures involving hexacoordinate siH-conates. The potential for catalysis was proved using a 25 mol % of 14 at -78 °C and a moderate enantiomeric excess was obtained (Scheme 13). 

Transition metal-free hydrosilylation of carbonyl compounds can be realized with the use of Brpnsted or Lewis acids as well as Lewis bases. Alkali or ammonium fiuorides (CsF, KF, TBAF, and TSAF) are highly effective catalysts for the reduction of aldehydes, ketones, esters, and carboxylic acids with H2SiPh2 or PMHS. Lithium methoxide promotes reduction of esters and ketones with trimethoxysilane. A generally accepted mechanism of Lewis base-catalyzed hydrosilylation of carbonyl compovmds involves the coordination of the nucleophile to the silicon atom to give a more reactive pentacoordinate species that is attacked by the carbonyl compound giving hexacoordinate silicon intermediates (or transition states), in which the hydride transfer takes place (Scheme 30) (235). 

New challenges were then made to develop useful Lewis base-catalyzed aldol reactions of trimethylsilyl enolates, simple and the most popular silicon enolates. It has recently been found that aldol reactions of trimethylsilyl enolates with aldehydes proceed smoothly under the action of a catalytic amount of lithium diphenylamide or lithium 2-pyrrilidone in DMF or pyridine (Eq. (38)) [57]. This Lewis base-catalyzed aldol reaction of trimethylsilyl enolates [58] has an advantage over acid-catalyzed reactions in that aldol reaction of carbonyl compounds with highly-coordinative functional groups with Lewis acid catalysts are smoothly catalyzed by Lewis bases to afford the desired aldol adducts in high yields. 

Silyl enol ethers and silyl ketene acetals also offer both enhanced reactivity and a favorable termination step. Electrophilic attack is followed by desilylation to give an a-substituted carbonyl compound. The carbocations can be generated from tertiary chlorides and a Lewis acid, such as TiCl4. This reaction provides a method for introducing tertiary alkyl groups a to a carbonyl, a transformation that cannot be achieved by base-catalyzed alkylation because of the strong tendency for tertiary halides to undergo elimination. 

Ethers, sulfides, amines, carbonyl compounds, and imines are among the frequently encountered Lewis bases in the ylide formation from such metal carbene complex. The metal carbene in the ylide formation can be divided into stable Fisher carbene complex and unstable reactive metal carbene intermediates. The reaction of the former is thus stoichiometric and the latter is usually a transition metal complex-catalyzed reaction of a-diazocarbonyl compounds. The decomposition of a-diazocarbonyl compounds with catalytic transition metal complex has been the most widely used approach to generate reactive metal carbenes. For compressive reviews, see Refs 1,1a. 

The mechanism for the addition of dialkylzincs to aldehydes has been studied. Without any activation, addition of dialkylzincs to aldehydes scarcely proceeds. Thus, how to activate dialkylzinc and/or aldehyde should be considered. There are two ways of catalyzing the addition of diorganozinc to carbonyl compounds. One is activation by Lewis base catalyst (equation 1). 

Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cycloaddition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-catalyzed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41-43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cycloadditions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

The asymmetric aldol reaction is one of the most important topics in modern catalytic synthesis [54]. The products, namely />-hydroxy carbonyl compounds, have a broad range of applications and play a key role in the production of pharmaceuticals [55], Since the discovery of the catalytic asymmetric aldol reaction with enolsi-lanes by Mukaiyama et al. [56], steady improvements of the metal-catalyzed asymmetric aldol reaction have been made by many groups [57]. For this type of aldol reaction a series of chiral metal catalysts which act as Lewis acids activating the aldol acceptor have been shown to be quite efficient. It was recently shown by the Shibasaki group that the asymmetric metal-catalyzed aldol reaction can be also performed with unmodified ketones [57a], During the last few years, several new concepts have been developed which are based on use of organocatalysts [58], Enolates and unmodified ketones can be used as aldol donors. 

On the other hand, rare-earth trifluoromethanesulfonates (rare earth triflate, RE(OTf)3) have been found to work efficiently as Lewis acids even in aqueous media or in the presence of amines [4], A catalytic amount of RE(OTf)3 enables several synthetically useful reactions, for example aldol, Michael, allylation, Mannich, Diels-Alder reactions, etc., to proceed. It has also been demonstrated that a small amount of RE(OTf)3 is enough to complete the reactions and that RE(OTf)3 can easily be recovered from the reaction mixture and can be reused. A key to accomplishing the catalytic processes was assumed to be the equilibrium between Lewis acids and Lewis bases, for example water, carbonyl compounds, and amines, etc. A similar equilibrium was expected between Lewis adds and aromatic ketones, and, thus, RE(OTf)3-catalyzed Friedel-Crafts acylation was investigated [5]. 

The reaction of -halo carbonyl compounds with primary amides is appropriate for oxazoles containing one or more aryl groups . Ureas form 2-aminooxazoles. Formamide can be used resulting in a free 2-position in the oxazole. A convenient synthesis of 5-substituted-4-cyanooxazoles 223 is based on the condensation of -hydroxy—cyanoenamines 222 with trimethyl orthoformate (Scheme 109). The cyanoenamine intermediates 222 are derived from Lewis acid-catalyzed Passerini reactions between /-butyl isonitrile and aldehydes <2002S1969>. 

A polymeric binaphthyl zinc complex has been used for related epoxidation reactions <1999JOC8149>.A bimetallic samarium-based Lewis acid complex catalyzes the nucleophilic epoxidation of unsaturated carbonyl compounds very efficiently <2002JA14544>. The use of amino acids has organocatalysts for asymmetric epoxidations of enones and enals has been investigated <2005OL2579, 2005JA6964>. 

Silylated cyanohydrins have found considerable utility in the regioselective protection of p-qui-nones, as intermediates for the preparation of 3-amino alcohols and as precursors to acyl anion equivalents. Such compounds are typicdly prepared in high yield by either thermal or Lewis acid catalyzed addition of TMS-CN across the carbonyl group. This cyanosilylation has a variety of disadvantages and modified one-pot cyanosilylation procedures have been reported. - The carbonyl group can be regenerated by treatment with acid, silver fluoride or triethylaluminum hydrofluoride followed by base. ... 

Keto-enol tautomerism of carbonyl compounds is catalyzed by both acids and bases. Acid catalysis occurs by protonation of the carbonyl oxygen atom (a Lewis base) to give an intermediate cation that can lose H from its a carbon to yield a neutral enol (Figure 22.1, p. 904). This proton loss from the cation intermediate is similar to what occurs during an El reaction when a carbocation loses H" to form an alkene (Section 11.14). 

Protic-acid-catalyzed Michael additions (59) are subject to most of the limitations of base-catalyzed Michael additions (regioselectivity and stereoselectivity of enol generation, polyaddition, etc.), and hence, the stereochemistry has been little studied (60). At low temperatures silyl and stannyl enol ethers,+ ketene acetals, and allyl species are unreactive to all but the most reactive activated olefins. However, it was discovered by Mukaiyama and co-workers that enol ethers and ketene acetals react with a,/f-unsaturated carbonyl compounds in the presence of certain Lewis acids (4,61,62). Sakurai, Hosomi, and co-workers found that allylsilanes behave similarly (5,63,64). 

The second chapter, by David A. Oare and Clayton H. Heathcock, deals with the stereochemistry of uncatalyzed Michael reactions of enamines and of Lewis acid catalyzed reactions of enol ethers with a,/ -unsaturated carbonyl compounds. It is effectively a continuation of their definitive review of base-promoted Michael addition reaction stereochemistry that appeared in the preceding volume of the series. 

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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