Enol silyl ethers chemoselectivity

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... 

Imines and their derivatives could be used in an analogous way to aldehydes, ketones, or their derivatives this subject has been reviewed [79]. A competition experiment between an aldimine and the corresponding aldehyde in the addition to an enol silyl ether under titanium catalysis revealed that the former is less reactive than the latter (Eq. 14) [80]. In other words, TiCU works as a selective aldehyde activator, enabling chemoselective aldol reaction in the presence of the corresponding imine. (A,0)-Acetals could be considered as the equivalent of imines, because they react with enol silyl ethers in the presence of a titanium salt to give /5-amino carbonyl compounds, as shown in Eqs (15) [81] and (16) [79,82]. 

Enol siiyl ethers undergo Pd-catalyzed coupling with aromatic bromides in the presence of tributyltin fluoride, which converts the enol silyl ethers into the stannyl ethers or a-stannyl ketones regarded as real active species chemoselective a-arylation of terminal ketones is possible (equation 110). ... 

A new concept was introduced in which the bidentate coordination of type E2 facilitated the chemoselective conversion of carbonyl functions [67], Distinct from the above results obtained with the typical tin-Lewis acids, this by 8 doubly activating system is suited even for the selective aldolization of aldehydes with enol silyl ethers. KSA and allylstannane reagents showed similar bias of preferential transformation of aldehydic carbonyls (Table 2-8). 

Aldol-type condensation of enol silyl ethers and acetals or orthoesters can be accontplished by the use of trimethylsilyl trifluoromethanesulfonate (TMSOTf). In these reactions, TMSOTf acts as a true catalyst and is required in 1-S ntol %. The reactions show interesting chemoselectivity in that acetals are highly reactive receptors of enol silyl ethers but the parent aldehydes and ketones do not react under these conditions (Scheme 37). Similarly, trityl perchlorate is found to be an efficient catalyst to promote the reaction between enol silyl ethers and acetals. 

The synthesis of the non-racemic cyclopentanone (+)-93 is outlined in Scheme 15. Starting with 2-methyl-cyclopent-2-enone (90), sequential cuprate addition and enolate alkylation afforded the racemic cyclopentanone rac-92 as a single diastereomer. The double bond was cleaved by ozonolysis, the resulting aldehyde chemoselectively reduced in the presence of the keto function and the primary hydroxyl function was subsequently protected as a silyl ether to provide racemic rac-93. This sequence has been applied fre-... 

There were two related questions of chemoselectivity to be answered here would the amino groups in 238 be too reactive to survive the oxidation with mCPBA and would the rather stable silyl enol ether of the p-ketoester be reactive enough to be epoxidised Langlois decided to conduct a trial experiment with the simple amino-P-ketoester 239 that contains all these features. If this is successful, there will still be the question of stereoselectivity. The silyl enol ether 240 was duly formed in the most stable position between the two carbonyl groups and epoxidation with an excess of mCPBA gave a good yield of the required a-hydroxyester 243 via the epoxide 241 and the silyl ether 242 which was desilylated in aqueous base without isolation. 

The aldol reaction and related processes have been of considerable importance in organic synthesis. The control of syn/anti diastereoselectivity, enantioselectivity and chemoselectivity has now reached impressive levels. The use of catalysts is a relatively recent addition to the story of the aldol reaction. One of the most common approaches to the development of a catalytic asymmetric aldol reaction is based on the use of enantiomerically pure Lewis acids in the reaction of silyl enol ethers with aldehydes and ketones (the Mukaiyama reaction) and variants of this process have been developed for the synthesis of both syn and anti aldol adducts. A typical catalytic cycle is represented in Figure 7.1, where aldehyde (7.01) coordinates to the catalytic Lewis acid, which encourages addition of the silyl enol ether (7.02). Release of the Lewis acid affords the aldol product, often as the silyl ether (7.03). 

Trimethylsilyloxy-substituted alkenes are by far the most widely used enol ethers because of their straightforward preparation from the corresponding ketones (equation 20)78-82 -pjjg electron-rich character of silyl enol ethers allows for highly chemoselective cyclopropanations in the presence of additional double bonds (eqnation 21). ... 

The combinations of chlorotrimethylsilane-hexamethylphosphoramide (HMPA) or chlorotrimethylsi-lane-4-(dimethylamino)pyridine (DMAP) are also powerful accelerants for copper(I)-catalyzed Grignard conjugate additions,33 and stoichiometric organocopper and homocuprate additions (Scheme 21 ).36 However, these reactions must be performed in tetrahydrofuran instead of ether.37 These procedures are noted for their high yields with stoichiometric quantities of Grignard reagents, excellent chemoselectivity and efficiency with a,3-unsaturated amides and esters and enals.58 Typically, additions to enals proceed via the S-trans conformers to afford stereo-defined silyl enol ethers for example, enals (122) and (124) give the ( )-silyl enol ether (123) and (Z)-silyl enol ether (125), respectively. 

Krapcho decarbomethoxylation of diester 216 provided monoester 217 (06SL1691). Chemoselective Swern oxidation of 3-(3-hydroxypropyl)-1,2,3,4,11, 1 lrt-hexahydro-6/T-pyrazino[l,2-fr]isoquinolin-4-ones 203 followed by silyl enol ether formation with TIPSOTf and Et3N in Et20 for 12 h at room temperature gave compounds 218 as a single isomer in excellent yields (08JA7148,09JOC2046). 

However, all attempts to activate the a-position of the cyclohexanone ring in order to facilitate a subsequent diazotization, which was to be followed by rhodium carbenoid-mediated aryl C-H insertion onto C-4 [21], were unsatisfactory [22], One of the approaches was based on the generation of the silyl enol ether 35, but attempts to achieve its a-acylation led only to the formation of Paal-Knorr-type cyclization products 36. Chemoselective formylation of 34 to 37 was possible by reaction with ethyl formate in the presence of a large excess of sodium ethoxide, but in situ oxidation of the desired compound 37 to 38, which was the major isolated product, made the reaction impractical (Scheme 6). 

In contrast, the related silyl enol ethers are available by mild selective transformations from carbonyl compounds or other precursors 55). Their stability and that of products derived from these alkenes can easily be regulated by choosing suitable substituents at silicon. Selective cleavage of a Si—O-bond is possible with fluoride reagents under very mild conditions, and this is why cyclopropane ring opening can now be performed with high chemoselectivity. 

First, chemoselective (Chapter 24) conjugate addition of the silyl ketene acetal on the enone is preferred to direct aldol reaction with the aldehyde. Then an aldol reaction of the intermediate silyl enol ether on the benzaldehyde follows. The stereoselectivity results, firstly, from attack of benzalde-hyde on the less hindered face of the intermediate silyl enol ether, which sets the two side chains trans on the cyclohexanone, and, secondly, from the intrinsic diastereoselectivity of the aldol reaction (this is treated in some detail in Chapter 34). This is a summary mechanism. 

A keto group was extensively used in olefinations, providing a convenient access to natural-type oxonine products. Chemoselective formation of silyl enol ether of oxonine 171 (Scheme 34) followed by Wittig olefination, deprotection, and diastereoselective methylation afforded acetate 172 in good yield <2004JA1642>. 

Kobayashi et al. also reported interesting chemoselectivity of aldehydes and imines in the Yb(OTf)3-catalyzed addition reactions of silyl enol ether, allylstannane or trimethylsilyl cyanide [12]. In the competitive reactions between aldehydes and imines, the imines reacted faster than the aldehydes (Tables 4-6). This tendency is not unique to Yb as catalyst selectivity is similar for other Ln(OTf)3. Nuclear magnetic resonance (NMR) studies revealed selective formation of an imine-Yb(OTf)3 complex in the presence of an aldehyde. This preference was reversed when conventional Lewis acids (SnCE, TiCU, TMSOTf, and BF3 OEt2) were used. 

We find that we need a crossed aldol condensation between two ketones so tve chemoselectivity. We also need to make one enol(ate) from an unsymmetrical ketone so v. r regioselectivity too. The obvious solutions are a lithium enolate, a silyl enol ether, or a come with an extra ester group. 

The Eu-catalyst Eu(dppm)3 provides a remarkable level of chemoselectivity but is only effective for the Mukaiyama-aldol reaction of aldehydes with several ketene silyl acetals (KSA) (Table 2-3) [55]. When ketones and aldehydes are treated, respectively, with KSA and ketone-derived silyl enol ethers, no reaction results. The rate enhancement by chelation control (entry 4, Table 2-3) is intriguing. This is a feature common to other Lewis acids such as TiC [56] or LiC104 [57],... 

While selective reaction of aldehydes takes place with the typical Lewis acids TiCL, SnCl4, TMSOTf, etc., lanthanide triflates [Ln(OTf)3] are unique Lewis acids that change the reaction course dramatically aldimine reacts selectively in the coexistence of aldehydes [70]. Among a series of Ln(OTf)3 tested, Yb(OTf)3 exhibited the most prominent chemoselectivity in addition to high chemical yields. The silyl enol ethers of ketones, allyltributylstannane and Me3SiCN are all applicable as chemoselective nucleophiles (Table 2-9). Preferential formation of Yb(OTf)3-aldimine complexes was postulated by C NMR spectral analysis in the presence of PhCHO and Y-benzylideneaniline. 

We shall discuss further aspects of the aldol reaction in the next two chapters where we shall see how to control the enolisation of unsymmetrical ketones, and how to control the stereochemistry of aldol products such as 121. We shall return to a more comprehensive survey of specific enol equivalents in chapter 10. In this chapter we are concerned to establish that chemoselective enolisation of esters, acids, aldehydes, and symmetrical ketones can be accomplished with lithium enolates, enamines, or silyl enol ethers, and we shall be using all these intermediates extensively in the rest of the book. 

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