Ether Auxiliaries

Radical 37 adds to methyl acrylate in good yield with a selectivity of 11 1 at -78 °C. The addition of 37 to more reactive radical traps such as 2-nitropropene gives product with lower selectivity, however, 5 1 at —78°C. Garner suggests that the reason for poorer selectivity of 37 in reactions with the more reactive alkene is that an earlier transition state makes substituents at the C-6 position less effective as a stereoscreening element. In support of this notion, a 6-fcrt-butyltetrahydropyran-substituted radical provides selectivities of 35 1 in reactions with 2-nitropropene carried out at -78 °C. A model for the early transition state in reactions with 2-nitropropene is presented in Fig. 7 [39]. 

The carbohydrate-based ether auxiliaries have been used to develop a radical-based asymmetric aldol reaction. Glycoside radicals such as 37 are generated from Barton ester precursors 39 [40], and the addition of these radicals to 2-nitropropene gives a thiopyridyl adduct 40 that can be converted to an aldol product [41]. The yield for the conversion is moderate to good and the diastereoselectivity ranges from 5 1 to 8 1, depending on R and temperature. 

New innovations incorporated in the sequences shown in Eqs. (25) and (26) are an improved method for Barton ester formation by the use of a thiouronium derivative of Barton s reagent 42 [41] and new auxiliary groups 43 bearing a tertiary C-6 substituent, which can be prepared in either enantiomeric form. These new auxiliaries give product as a mixture of diastereomers in a ratio of 7 1 to 10 1. The fact that both enantiomers of 43 are available permits one to dial in the configuration of each stereogenic center produced in a complex product. 

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Selenski investigated the use of chiral enol ether auxiliaries in order to adapt method F-H for enantioselective syntheses. After surveying a variety of substituted and unsubstituted enol ethers derived from a vast assortment of readily available chiral alcohols, she chose to employ enol ethers derived from trans-1,2-phenylcyclohexanol such as 73 and 74 (Fig. 4.37). These derivatives were found to undergo highly diastereoselective cycloadditions resulting in the formation of 75 and 76 in respective... 

Table 39. Additions of a y-oxygenated allylic stannane bearing a chiral ether auxiliary to achiral aldehydes. OH OH...

Chips, semiconductor Chiral additives Chiral-AGP Chiral auxiliaries Chiral crown ethers Chiral hydrogenation Chirality... 

Ironically, auxiliary-induced control via the alkene failed to generate synthetically useful selectivities, but direct substrate-induced control did. In particular, chiral silyl enol ethers with stereocenters in the y-position allowed the synthesis of enantiomerically... 

As well as the disubstituted C2-symmelrie pyrrolidines E and F, the monosubstituted (f> )-2-(mcthoxymethyl)pyrrolidine G can be used as chiral auxiliary for the diastereoselecti ve addition of organomctallic reagents to a-oxo amides16. As with the phenylglyoxylic acid derivatives derived from amines E and F. methyllithium or methylmagnesium bromide in diethyl ether preferentially attack the (,S)-mms-conformer 11 (R = ( 6H5), leading to predominant formation of the (2 S)-diastercomer by Re-side attack. 

Acyclic Oxime Ethers 1.4.1.5.1.1. Auxiliary-Induced Diastereoselection Stereogenic Center at Carbon... 

Amidoalkylation of silyl enol ethers with /V-acyliiiiiiiium ions containing camphanoyl-derived acyl functions (see Appendix) as the chiral auxiliary leads to optically active 2-substituted piperidine derivatives with moderate to high diastereoselectivity, depending on the chiral auxiliary and the cnol ether82 99. The auxiliary is removed by hydrolysis with base or acid. 

One of the longest known synthetically prepared surfactants are the fatty alcohol sulfates, which were prepared on technical scale before 1940. Along with their ethoxylated counterparts, the fatty alcohol ether sulfates, which appeared on the stage shortly after, their use in toiletries is very popular but they can also be found in products for textile industry and auxiliaries in emulsion polymerization. With the exception of soaps, the mentioned anionic surfactants all have a sulfur-containing functional group. Denying the differences between these, their skin irritancy potential is remarkably high. 

Mukaiyama aldol reactions have been reported, usually using chiral additives although chiral auxiliaries have also been used. This reaction can also be run with the aldehyde or ketone in the form of its acetal R R C(OR )2> in which case the product is the ether R COCHR2CR R OR instead of 27. Enol acetates and enol ethers also give this product when treated with acetals and TiCLi or a similar catalyst. When the catalyst is dibutyltin bis(triflate), Bu2Sn(OTf)2, aldehydes react, but not their acetals, while acetals of ketones react, but not the ketones themselves. 

Simple 1,2,4-triazole derivatives played a key role in both the synthesis of functionalized triazoles and in asymmetric synthesis. l-(a-Aminomethyl)-1,2,4-triazoles 4 could be converted into 5 by treatment with enol ethers <96SC357>. The novel C2-symmetric triazole-containing chiral auxiliary (S,S)-4-amino-3,5-bis(l-hydroxyethyl)-l,2,4-triazole, SAT, (6) was prepared firmn (S)-lactic acid and hydrazine hydrate <96TA1621>. This chiral auxiliary was employed to mediate the diastereoselective 1,2-addition of Grignard reagents to the C=N bond of hydrazones. The diastereoselective-alkylation of enolates derived from ethyl ester 7 was mediated by a related auxiliary <96TA1631>. 

The enolates of other carbonyl compounds can be used in mixed aldol reactions. Extensive use has been made of the enolates of esters, thiol esters, amides, and imides, including several that serve as chiral auxiliaries. The methods for formation of these enolates are similar to those for ketones. Lithium, boron, titanium, and tin derivatives have all been widely used. The silyl ethers of ester enolates, which are called silyl ketene acetals, show reactivity that is analogous to silyl enol ethers and are covalent equivalents of ester enolates. The silyl thioketene acetal derivatives of thiol esters are also useful. The reactions of these enolate equivalents are discussed in Section 2.1.4. 

The potential of crown ethers for use as auxiliaries in textile coloration processes does not appear to have been evaluated recently, although their potential to complex with alkaline-... 

The titanated bislactim ethers of cyclo(L-Val-Gly-) are added to nitroalkenes with high diastereo-selectivity (Eq. 4.60).SOa Michael addition of lactam bearing (S)-2-( 1-ethyl-1-methoxypropyl) pyrrolidine as auxiliary on the lactam nitrogen to nitroalkenes proceeds with high selectivity (de >96%, ee >96%).80b... 

Another useful method for the asymmetric oxidation of enol derivatives is osmium-mediated dihydroxylation using cinchona alkaloid as the chiral auxiliary. The oxidation of enol ethers and enol silyl ethers proceeds with enantioselectivity as high as that of the corresponding dihydroxylation of olefins (vide infra) (Scheme 30).139 It is noteworthy that the oxidation of E- and Z-enol ethers gives the same product, and the E/Z ratio of the substrates does not strongly affect the... 

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