Acetals with aldehydes

Protective Groups for Diols. Diols represent a special case in terms of applicable protecting groups. 1,2- and 1,3-diols easily form cyclic acetals with aldehydes and ketones, unless cyclization is precluded by molecular geometry. The isopropylidene derivatives (also called acetonides) formed by reaction with acetone are a common example. 

TABLE 3-4. Reaction of Silyl Ketene Acetals with Aldehydes... 

Resin-bound diols, amino alcohols, and dithiols, which reversibly form cyclic acetals with aldehydes and ketones, have been successfully used as linkers for carbonyl compounds (Entries 5-11, Table 3.40). Acetal formation on insoluble supports can be achieved by azeotropic removal of water (C6H6, TsOH, reflux [720]), whereas dithio-acetals can be prepared by acid-catalysis alone (BF3 OEt2 or TMSC1 CHCI3,0 °C, 2 h [721]). /V-Acylaminals such as R-CFI(OMe)NFI-CO-Pol have been prepared by treatment of resin-bound amides H2NCO-Pol with aldehydes in the presence of HC(OMe)3 and TFA [722],... 

Scheme 8.8 Mukaiyama aldol reactions of silyl ketene acetals with aldehydes.

Allyl complexes of some other transition metals, such as Ru, Fe, Cr and Ti, are also used for synthetic purposes. Reaction of allylic acetates with aldehydes catalyzed by a Ru complex in the presence of Et3N and CO gives the alcohol 39. It seems likely that the reaction itself is stoichiometric. But a high-valent Ru complex, formed by the reaction with the electrophile, is reduced to a lower valences with Et3N or CO, making whole reaction catalytic [2,13],... 

Table 11 Reaction of O-silacyclobutyl A/.O-ketene acetals with aldehydes...

Griesbeck, A.G. and Bondock, S. (2001) Paterno-Biichi reactions of allylic alcohols and acetates with aldehydes hydrogen-bond interaction in the excited singlet and triplet states Journal of the American Chemical Society, 123 (25), 6191-6192. 

Aldol reactions of various silyl enol ethers or ketone silyl acetals with aldehydes and imines proceed smoothly in the presence of catalytic amount of 516 or 519 (Equations (242) and (243)).1034-1037 B(G6F5)3 516 catalyzed the... 

Mukaiyama aldol reactions of various silyl enol ethers or ketene silyl acetals with aldehydes or other electrophiles proceed smoothly in the presence of 2 mol % B(CgF5)3 [151a,c]. The following characteristic features should be noted (i) the products can be isolated as j8-trimethylsilyloxy ketones when crude adducts are worked-up without exposure to acid (ii) this reaction can be conducted in aqueous media, so that the reaction of the silyl enol ether derived from propiophenone with a commercial aqueous solution of formaldehyde does not present any problems (iii) the rate of an aldol reaction is markedly increased by use of an anhydrous solution of B(C6Fs)3 in toluene under an argon atmosphere and (iv) silyl enol ethers can be reacted with chloromethyl methyl ether or trimethylorthoformate hydroxymethyl, methoxy-methyl, or dimethoxymethyl Cl groups can be introduced at the position a to the carbonyl group. These aldol-type reactions do not proceed when triphenylborane is used (Eq. 92). 

This reaction of silyl ketene acetals with aldehydes, using 29 as a stoichiometric chiral reagent (Eq. 46), was reported by Reetz et al. [42]. The aldol addition of l-(trimethyl-siloxy)-l-methoxy-2-methyl-l-propene and 3-methylbutanal provides the aldol in only 57 % yield, but with 90 % ee. 

Table 2. Aldol reactions of ketene silyl acetals with aldehydes, ketones, and acetals.

Starting from a copolymer of vinyl acetate and silicone made by radical polymerization in solution, the saponification leads to a silicone-modified polyvinyl alcohol. This modified polyvinyl alcohol is dissolved in water and then acetalized with aldehydes (butyr- or acetaldehyde)... 

Table 6 Reaction of Unsaturated Dialkyl Acetals with Aldehydes using CrCl2 S-I (equation 58) ...

Diols Both cis- and tran5-l,3-diols form cyclic acetals with aldehydes in the presence of an acid catalyst to furnish the corresponding benzylidene and ethylidene derivatives, respectively. 

Mixed substituted orthoesters, e.g. (383 equation 180), can be obtained by addition of alcohols to ketene 0,0-acetals. With the aid of phosphoranes containing a ketene O,(7-acetal structure, various orthoesters, e.g. (384) and (385) (Scheme 70) were prepared. " Cyclic orthoesters (386)-(390) (Scheme 71) are formed in cycloaddition reactions of ketene 0,0-acetals with aldehydes, ketones, 7.848 gj.yj cyanides, oxiranes, a-keto esters, o-diketones or ketones (with irradiation), a,3-unsaturated aldehydes and ketones (under pressure or catalyzed by ZnCh), diazoaceto-phenone, 7 diazoacetone and azodicarboxylate. ... 

Boeckman, R. K., Jr., Hudack, R. A. A Variant of the Takai-Utimoto Reaction of Acrolein Acetals with Aldehydes Catalytic in Chromium A Highly Stereoselective Route to Anti Diol Derivatives. J. Org. Chem. 1998, 63, 3524-3525. 

Condensations. The reaction of silyl ketene acetals with aldehydes favors enals over saturated aldehydes, when promoted by BUjSnClO. The catalyst is obtained from reaction of trityl perchlorate and tributyltin hydride. 

Lanthanide(lII) chlorides or some organolanthanide compounds catalyzed aldol reactions of ketene silyl acetals with aldehydes were reported, (a) Takai, K. Heathcock, C. H. J. Org. Chem. 1985, 50, 3247. (b) Vougioukas, A.E. Kagan, H.B. Tetrahedron Lett. 1987, 28, 5513. (c) Gong,... 

Ethanol can - like any alcohol - form acetals with aldehydes (Fig. 5.24). The formation of acetal is reversible. With an acid pH value ethanol and aldehyde are released again. In foods containing ethanol with a pH of 7, part of the aldehyde is bound as acetal. 

Reetz, M.T., Peter, R., and von Itzstein, M., Titanium-mediated stereoselective Knoevenagel condensation of ethyl (diethoxyphosphoryl)acetate with aldehydes, Chem. Ber., 120, 121, 1987. 

Spectacular results were reported by Mukaiyama and coworkers in the field of chiral Lewis acids. Reaction of thiol ester derived silylketene acetals with aldehydes promoted by the combined use of a chiral diamine coordinated with tin(II) triflate and tributyltin fluoride gave excellent yields of aldol products in very high enantiomeric excess (Scheme 19). 

Aldol-type reaction. The low-temperature-catalyzed condensation of O-silyl ketene acetals with aldehydes leads to /3-hydroxy esters. The same catalyst also mediates allylation of aldehydes. 

Catalyzed Mukaiyama-type aldol reactions of silyl enol ethers or silyl ketene acetals with aldehydes lead to the same products. For recent advances see a) G. E. Keck, D. Krishnamurthy, J. Am. Chem. Soc. 1995, 117, 2363 b) M. Sato, S. Sunami, Y. Sugita, C. Kaneko, Heterocycles 1995, 41, 1435, and references therein. 

The reaction of lithiated S,S-acetals with aldehydes and ketones is a well-established reaction and needs no exemplification by an experimental procedure. The reactions with most of the aldehydes and ketones are extremely rapid, even at temperatures in the region of — 80 °C. A number of examples have been mentioned in the reviews of Seebach [1,2]. 

The use of TMSOTf in aldol reactions of silyl enol ethers and ketene acetals with aldehydes is ubiquitous. Many refinements of the basic reaction have appeared. An example is shown in eq 16. ... 

Formation of p-hydroxy ketones via reaction of silyl enol ethers or ketene silyl acetals with aldehydes in presence of a Lewis acid, such as titanium tetrachloride, tin tetrachloride or boron trifluoride etherate ... 

Reports of the use of chiral aluminum Lewis acids in the asymmetric aldol reaction are quite limited. The first enantioselective aluminum-catalyzed Mukaiyama aldol reaction was reported about 10 years ago (158). In this asymmetric version, /5-hydroxy ester was formed in high enantiomeric excess by the ketene silyl acetal with aldehyde in the presence of a chiral Lewis acid prepared from diethylaluminum chloride (Et2AlCl) and chiral diol derived from... 

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