Acetals Lewis acid promotion

Lewis acid promoted condensation of silyl ketene acetals (ester enolate equiv.) with aldehydes proceeds via "open" transition state to give anti aldols starting from either E- or Z- enolates. 

Mukaiyarna-Johnson AJdoJ- Lewis acid promoted condensation of silyl enol ethers with acetals ... 

Ketene acetals prepared from fluorinated esters by trimethylsilylation undergo Lewis acid-promoted aldol condensations giving satisfactory yields but low diastereoselectivity [27] (equation 22). 

Our group has exploited 4-phenylthio-l,3-dioxanes as convenient precursors to 4-lithio-l,3-dioxanes [45,65-69]. 4-Phenylthio-l,3-dioxanes 184 were originally prepared from -silyloxy aldehydes 183 [65] (Eq. 28). Lewis acid-promoted addition of phenylthiotrimethylsilane gave an unstable thioacetal intermediate, which could be converted in situ to the corresponding 1,3-dioxane. Yields for this process are variable, as the product is unstable under the conditions of its formation. The reaction slowly evolves to a mixture of the desired product, the phenylthio acetal of 183, the phenylthio acetal of acetone, and a variety of other unidentified products. 

Bu2Sn(03SCF3)2.68 The Lewis acids promote ionization of the acetal to an oxonium ion that acts as the electrophile. The products are (J-alkoxy ketones. 

The simplest nitroalkene, nitroethene, undergoes Lewis acid-promoted [4+2] cycloaddition with chiral vinyl ethers to give cyclic nitronates with high diastereoselectivity. The resulting cyclic nitronates react with deficient alkenes to effect a face-selective [3+2] cycloaddition. A remote acetal center controls the stereochemistry of [3+2] cycloaddition. This strategy is applied to synthesis of the pyrrolizidine alkaloids (+)-macronecine and (+)-petasinecine (Scheme 8.33).165... 

Representative Procedure for Lewis Acid Promoted Clycosylation with Glycosyl Acetate Donors Using SnCI4 [198]... 

Suitably protected glycosyl halides or acetates, upon Lewis-acid promoted SN1 heterolysis, generate glycosyl cation intermediates that can react with electron-rich arenes, heteroarenes, Me3SiCN, enoxysilanes, enamines, allyl silanes and stannanes, acetylenyl silanes and stannanes affording C-glycosyl compounds. 

Lewis-acid promoted C-allylations of furanose acetates 101 with allyl-(trimethyl)silane are a-selective and the selectivity is governed by the alkoxy group at C-3. The lowest energy conformers bear the 3-alkoxy group in a pseudoaxial orientation (Scheme 35). To a lesser extent, the 2-substituent... 

The mechanism of the Lewis acid promoted reaction of acetals has been investigated extensively. For example, Denmark demonstrated the presence of... 

The alkoxycarbenium ions generated by the cation pool method react with various carbon nucleophiles such as substituted allylsilanes and enol silyl ethers to give the corresponding coupling products in good yields. It should be noted that the reactions of alkoxycarbenium ion pools with such nucleophiles are much faster than the Lewis acid promoted reactions of acetals with similar nucleophiles. A higher concentration of the cationic species in the cation pool method seems to be responsible. 

Our preliminary experiments have provided the first example of Lewis acid promoted C-C bond heterolysis of epoxides and productive cycloaddition (eq 7). Under the influence of TiCl4-(THF)2 (2 equiv), epoxide 26 reacts with methyl pyruvate to provide acetal 27 (52% isolated yield), along with C-O cleavage product 28 (23 °C, 3 h). The diaste-reoselectivity for formation of 27 is 2.3 1. We have performed the analogous reaction in the absence of a Lewis acid the thermal reaction requires several days at 110 °C and gives a diastereomer ratio (dr) of ca. 1.3 1... Although not optimized from the standpoint of chemoselectivity, these results are promising because of the relatively low reaction temperature and potential for enhanced diastereocontrol. 

The established activity of ethereal a-C-H bonds toward carbene and nitrene insertion has evoked new applications for sulfamate oxidation [76-78] In principle, a C-H center to which an alkoxy group is attached should be a preferred site for amination irrespec-hve of the addihonal functionality on the sulfamate ester backbone (Scheme 17.20). Such a group can thus be used to control the regiochemistry of product formation. The N,0-acetal products generated are iminium ion surrogates, which may be coupled to nucleophiles under Lewis acid-promoted conditions [79]. This strategy makes available substituted oxathiazinanes that are otherwise difficult to prepare in acceptable yields through direct C-H amination methods [80]. 

Further versatility of this approach has been realized with contrasting Lewis acid promoted additions of silyl ketene acetals, (191) to (194), to ethyl propynoate (Scheme 42). In fact, the tandem 1,4-conjugate addition-electrophile trapping protocol is feasible when titanium(IV) tetrachloride is employed. In situ functionalization of the intermediate titanate enoate (259), with select electrophiles, affords a-substituted enoates (260) to (262). On the other hand, the zinc iodide and zirconium(IV) tetrachloride protocols afford directly -y-alkoxycarbonyl-a-trimethylsilylenoates (263) and [2 + 2] adducts (264), respectively.100... 

Cyclization to a morpholinolactone (59) occurs in the hydrolysis reaction of the di-A-hydroxylethylated compound (60). Compound (59) is rapidly hydrolysed by water to (61) but in file presence of equimolar amounts of amines (RNH2) or ammo acid derivatives (62) forms.56 A novel reaction of cyclic 2-diazo-l,3-dicarbonyl compounds (63) with lactones (64) affords the products (65) in the presence of rhodium acetate, Rh2(OAc)4.57 Lewis acid-promoted intramolecular additions of allylsilanes to lilac tones gave substituted cyclopentanes.58 A proposed transition state guided efforts to improve the stereoselectivity of the reaction. The reaction of a series of /1-lactone derivatives, such as (66)-(68), has been studied and they have been ling cleaved the reaction outcome is both Lewis acid and structure dependent.59... 

Significantly higher stereoselectivities were observed in the Lewis acid-promoted 1,4-additions. Kinetically controlled deprotonation/silylation of esters 33 followed by treatment of the resulting crude ketene silyl acetals 35 with TiCl4/Ti(Oi-Pr)4 (2 1) and DTBAD (1.25 equiv.) at -78 °C, gave the adducts 34 in good yields and excellent diastereoselectivities (Scheme 15 Table 3.2). 

Use of allylsilanes as 1,2-dipole equivalents is valuable also for the construction of six-membered rings. f3-Oxyaldehydes undergo Lewis acid-promoted cycloadditions with allylsilanes to provide substituted tetrahydropyrans (Equation (52)). 3 A similar [4 + 2]-cycloaddition of /V-/-butoxycarbonyl-0,Ar-acetals is available for the synthesis... 

Protected 1,3-an/i-diols 14 are accessible by the highly stereoselective Lewis acid promoted addition of dialkylzinc compounds to 4-acet-oxy-1,3-dioxanes 13 (Scheme 3) [5]. The two d, -orientated alkyl substituents at C2 and C6 fix the carboxonium ion 15 in the half-chair conformation, which undergoes preferential axial attack by the dialkylzinc under stereoelec-tronic control. The 4-acetoxy-1,3-dioxanes 13 may be synthesized from the Seebach 1,3-diox-an-4-ones 12 by reduction with diisobutylalumi-num hydride (DIBAH) and acetylation. Since dialkylzinc compounds are now readily available and are compatible with many functional groups, this... 

The 7] -osmium complexes of a-unsubstituted thiophenes undergo Lewis acid-promoted addition with acetals at C-2 to give the thiophenium complexes in good yields <19990M2988>. These can be deprotonated to give the 2-substituted thiophene complexes. The electrophile attacks the substrate on the rivn-face (Scheme 83). 

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