P-alkoxy carbonyl compounds

Angew Int 23 556 (1984) (chelation and non-chelation control in addition reactions of chiral a- and p-alkoxy carbonyl compounds) 30 49 (1991) (enantioselectivity)... 

The relative energies of the intermediates and transition structures along the reaction coordinates are subject to the influence of solvation, which may alter relative stabilities and rates. This may explain the solvent effects discussed earlier (c/. Table 4.3, entries 1, 3 and 4). The energetic features outlined above may also explain the lack of selectivity in the nucleophilic additions to P-alkoxy carbonyl compounds. It is possible that even though 6-membered chelates are formed, their rates of formation are slower than addition via the nonchelated path, or that they are less reactive than a 5-membered chelate. Either of these circumstances (or a combination of both) would raise the transition state energy for the chelate path and the primary addition mode could be shifted to the less selective nonchelated mechanism. ... 

Ethyl tetrahydrofuran-2-carboxylates. p-Alkoxy carbonyl compounds in which the alkoxy group is readily detached in the presence of a Lewis acid undergo condensation with ethyl diazoacetate. Tin(IV) chloride is a suitable catalyst for P-alkoxy aldehydes, but it requires zirconium(IV) chloride to effect a reaction with P-alkoxy ketones. 

CHELATION CONTROLLED ADDITIONS TO a AND P ALKOXY CARBONYL COMPOUNDS... 

M. T. Reetz, Angew. Chem., 96, 542 (1984). Chelat- oder Nicht-Chelat-Kontrolle bei Addi-tionsreaktionen von chiralen a- und p-Alkoxy Carbonyl-Verbindungen. Angew. Chem., Int. Ed. Engl., 23, 556 (1984). Chelation or Non-Chelation Control in Addition Reactions of Chiral a- and p- Alkoxy Carbonyl Compounds. 

The Lewis acid-promoted reaction of acetals with trimethylsilyl (TMS) enolates is valuable for the synthesis of p-alkoxy carbonyl compounds, that is, O-alkylated aldols [44]. This aldol-type reaction is effectively catalyzed by (la) [7d, 43], trimethylsilyl iodide (MesSil) [45] and trimethylsilyl bis(fluorosulfonyl)amide (Me3SiN(S02P)2) [46]. Recently, bis (trifluoromethanesulfonyl) amine (HNTf2) has been found to catalyze the aldol-type reaction. A comparison of HNTf2 with Me3SiNTf2 (lb) in catalytic activity suggests that an initial protodesilylation of TMS enolates with HNTf2 forms (lb) as the actual catalyst [47] (Scheme 9.8). 

Alcohols add to conjugated ketones with a PMe3 catalyst to give the p-alkoxy ketone.The conjugate addition of peroxide anions (HOO and ROO ) to cx,p-unsaturated carbonyl compounds is discussed in 15-48. 

Usefiil levels of stereoselectivity were obtained in intermolecular addition reactions of C(3)-sub-stituted allylsilanes to chiral aldehydes. Lewis acids that are citable of chelating to heteroatoms have been used to direct the stereochemical course of allylsilane additions to a-alkoxy and a,p-dialkoxy carbonyl compounds. The allylation of a-benzyloxy iddehyde (94) in the presence of TiG4 and SnOt furnished products with high levels of syn stereoselection (syn-9. In contrast, under nonchelation-controlled reaction conditions (BF3-OEt2) allyltrimethylsilane reacted to form predonunantly the anti-1,2-diol product (anti-95), as shown in Scheme 45. 

The opposite polarity in the organotin reagent R3Sn5+X5 can be exploited in, for example, the reaction of a tin alkoxide with an vinyl ester,83 the addition of an alkoxy- or amino-tin compound to a ketene,84 the reaction of a silyl enolate with a tin chloride,85 or the addition of an alkyltin hydride under non-radical conditions to an a,P-unsaturated carbonyl compound.86... 

Hydroxybenziodoxole 104 can be readily converted into its acetoxy derivative, l-acetoxy-1,2-benziodoxole-3(l//)-one (88, 2X = O, Y = OAc), by heating 104 with acetic anhydride and the acetoxy derivative can be further converted into the alkoxy derivatives by treatment with an appropriate alcohol [280], The tetrabutylanmionium salt of hydroxybenziodoxole 104 has been prepared by the reaction of hydroxybenziodoxole with tetrabutylammonium fluoride in THF it is a mild oxidant that is useful for the preparation of epoxides from a,p-unsaturated carbonyl compounds [281], l-Hydroxy-l,2-benziodoxole-3(l//)-one and l-acetoxy-l,2-benziodoxole-3(l//)-one have found wide application as starting compounds for the synthesis of various benziodoxole-based hypervalent iodine reagents by ligand exchange on iodine [239]. 

Miscellaneous Other interesting Fe-catalyzed MCRs that have been described in the last years are the alkoxy allylation of activated double bonds [190], one-pot synthesis of p-acetamido carbonyl compounds [191], and Ritter and Strecker reactions [192]. 

Nucleophilic Additions. MgBr2 has been shown to form discrete bidentate chelates with various species, particularly a-and/or a,3-alkoxy carbonyl compounds, and thus functions as a diastereofacial control element in many nucleophilic addition reactions. In many cases, its inclusion completely reverses the nonchelation-controlled stereochemistry observed with nonchelating Lewis acids such as Boron Trifluoride Etherate. Highest diastereoselectivity is observed with a-substituted aldehydes (eq 1). High selectivities are observed for p-alkoxy aldehydes as well, including cases where three contiguous chiral centers are defined during the reaction (eq 2). ... 

Ceric ions react rapidly with 1,2-diols. There is evidence for chelation of cerium and these complexes are likely intermediates in radical generation10 106 The overall chemistry may be understood in terms of an intermediate alkoxy radical which undergoes p-scission to give a carbonyl compound and a hydroxyalkyl radical (Scheme 3.59). However, it is also possible that there is concerted electron transfer and bond-cleavage. There is little direct data on the chemical nature of the radical in termediates. 

Heterosubstituted cyclopropanes can be synthesized from appropriate olefins and car-benes. Since cyclopropane resembles olefins in its reactivity and is thus an electron-rich car bo-cycle (p. 76ft). it forms complexes with Lewis acids, e.g. TiCL, and is thereby destabilized This effect is even more pronounced in cydopropanone ketals. If one of the alcohols forming the ketal is a silanol, the ketal is stable and distillable. The O—Si-bond is cleaved by TiCl4 and a d3-reagent is formed. This reacts with a -reagents, e.g. aldehydes or ketals. Various 4-substituted carboxylic esters are available from 1-alkoxy-l-siloxycyclopropanes in this way (E. Nakamura, 1977). If one starts with l-bromo-2-methoxycyclopropanes, the bromine can be selectively substituted by lithium. Subsequent treatment of this reagent with carbonyl compounds yields (2-methoxycyclopropyl)methanols, which can be transformed to /7,y-unsaturated aldehydes (E.J. Corey, 1975B). 

Hetero-Diels-Alder reaction with inverted electron demand between a,p-unsatu-rated carbonyl compounds (l-oxa-l,3-butadienes U Scheme 6) and enol ethers provides an access to 6-alkoxy-3,4-dihydro-2i/-pyrans 12 [31,32]. These heterocycles are also useful... 

A high degree of stereoselectivity can be realized under chelation control, where an oxygen atom of an ether function (or more generally a Lewis base) in the a-, P- or possibly y-position of carbonyl compounds can serve as an anchor for the metal center of a Lewis acid. Since Cram s pioneering work on chelation control in Grignard-type addition to chiral alkoxy carbonyl substrates [30], a number of studies on related subjects have appeared [31], and related transition state structures have been calculated [32], Chelation control involves Cram s cyclic model and requires a Lewis acid bearing two coordination sites (usually transition metal-centered Lewis acids). 

The carbenoid reaction between alkyl diazoacetates and enol ethers, enol acetates and silyl enol ethers furnishes P-oxycyclopropane carboxylates (see Tables 2, 4, 5, 6, 7 and Scheme 5). The recently recognized synthetic versatility of these donor/acceptor-substituted cyclopropanes i 2,io3) (precursors of 1,4-dicarbonyl and P, 7-unsaturated carbonyl compounds, 4-oxocarboxylic acids and esters, among others) gave rise to the synthesis of a large number of such systems with a broad variation of substituents p-acetoxycyclopropanecarboxylates , p-alkoxy- or p-aryloxysubstituted cyclopropanecarboxylates 2-alkoxy-1-methyl-1-cy-... 

Peterson aikenation of carbonyl compounds with trimethylsilylmethoxymethyl carbanion (14) can also give enol ethers. An example is the reaction of (14) with adamantanone. Another method of alkene synthesis is the elimination of CO2 and H2O from a P-hydroxycarboxylic acid. If the carboxylic acid is substituted by an a-alkoxy group, the reaction can be used for the synthesis of enol ethers, as illustrated in Scheme 4. ... 

Other classes of radicals have also been examined with TRIR methods. The rate constant for P-scission of alkoxy radicals (Scheme 2.6) was found to be enhanced in polar solvents by monitoring the rate of production of the product carbonyl compound [74]. The decarboxlyation of peroxyesters [75], the reactivity of azidyl radicals [76], and chlorine atom abstraction reactions [77] have also been investigated. 

A competing reaction is p-cleavage of the alkoxy radical to form a carbonyl compound and a carbon radical (4.28). The extent of this reaction varies with the structure of the substrate and will predominate if 1,5-hydrogen atom abstraction is unfavourable. 

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