Auxiliary, Sultam-based chiral

Sultam-based chiral auxiliaries mediate the stereoselectivity of Diels-Alder reactions, and the reaction of various substituted furans with benzyne provided an insight into the... 

Oppolzer and colleagues performed pioneering work on the application of chiral sultam based dienophiles in asymmetric Diels-Alder reactions. The bomanesultam based dienophiles provided excellent de values in the Lewis acid mediated Diels-Alder reactions with a wide variety of dienes179. The efficiency of the simpler toluene-2,a-sultam based dienophiles was also studied180. Chiral auxiliary 282 proved superior to 283 and 284 in the aluminum Lewis acid catalyzed Diels-Alder reactions of its A-acryloyl derivative with cyclopentadiene, 1,3-butadiene and isoprene, affording the adducts with >90% de. 

A potential method for the preparation of novel amino acids via the highly selective addition of radicals to the glyoxylic oxime derivative of Oppolzer s camphor sultam (88) has been reported.181 Both Lewis acid and non-Lewis acid-mediated reaction conditions for the addition of alkyl radicals generated from alkyl iodides and Et3B/Bu3SnH were examined. A new chiral auxiliary based upon (R,R)-2,5-diphenylpyiTolidine has been used in the addition of phenylthiyl radicals to unsaturated methacrylamides. The selectivity was found to be better than that reported for the structurally related 2,5-dimethylpyrrolidine derivative.182... 

Oppolzer et al. used (2M)-bornanc-10, 2-sultam as an effective chiral auxiliary to achieve a highly enantioselective syn-aldol reaction17 (Scheme 2.1p). Treatment of A-propionylsultam (46) with dibutylboron triflate and Hunig s base at -5°C in CH2CI2 followed by addition of aldehydes at -78° C provided, after a simple crystallization, the pure vyn-aldols 47a. It is noteworthy that no anti-aldol product was observed in the aldol reactions with any of the aldehydes. From the1 nuclear magnetic resonance (NMR) study, it was confirmed that the boron... 

The first enantioselective total synthesis of (-)-denticulatin A was accomplished by W. Oppolzer. The key step in their approach was based on enantiotopic group differentiation in a meso dialdehyde by an aldol reaction. In the aldol reaction they utilized a bornanesultam chiral auxiliary. The enolization of A/-propionylbornane-10,2-sultam provided the (Z)-borylenolate derivative, which underwent an aldol reaction with the meso dialdehyde to afford the product with high yield and enantiopurity. In the final stages of the synthesis they utilized a second, double-dlastereoditferentiating aldol reaction. Aldol reaction of the (Z)-titanium enolate gave the anf/-Felkin syn product. The stereochemical outcome of the reaction was determined by the a-chiral center in the aldehyde component. 

Aldol reactions using chiral auxiliaries are popular as the stereochemical outcome is usually highly predictable and, as such, they provide a reliable method for the incorporation of adjacent stereocenters. The oxazolidinone-based imides 36 and (ent)-36 are the most commonly employed, and these lead to syn aldol products with high levels of stereocontrol [20]. The reaction can be extended to include a variety of a-heteroatom functionality as in 37 (Scheme 9-13) [21]. Numerous examples of the use of these auxiliaries in the synthesis of polypropionate natural products have been reported. Many related auxiliaries are also available and the camphor-based sultam 38 is notable [22]. 

Oppolzer and coworkers [147, 454] have developed a class of reagents based on the enantiomeric bomane-2,10-sultam skeleton 1.133. These chiral auxiliaries are easily prepared from the enantiomeric 10-camphosulfonic adds [455]. Saturated or a,P-unsaturated TV-acylsultams 1.134, occasionally prepared from Af-silyl precursors [396], have been used very frequently. Asymmetric alkylations, animations and aldol reactions of enolates or enoxysilane derivatives of 1.134 (R = R CH2) [147, 404, 407, 456-460] are highly selective. The a,(3-unsaturated TV-acylsultams 1.134 (R = R R"C=CH) suffer highly stereoselective organocuprate 1,4-additions [147, 173], cyclopropanations [461], [4+2] and [3+2] cydoadditions [73,276,454,462], OSO4 promoted dihydroxylations [454,463] and radical addi-... 

Oppolzer et al. developed useful auxiliaries based on a camphor precursor,231 and one of the best was a sultam (277). When this sultam was converted to an acrylamide (278) and reacted with butadiene, cycloadduct 280 was produced (85% yield, 95 % ee).232 Selectivity in this Diels-Alder reaction is due to chelation of the amide oxygen and the sulfonyl group, as shown in 279. Oppolzer and co-workers applied this methodology to a chiral synthesis of the aglycone of loganin.233... 

Oppolzer s camphor-based sultams 92 proved itself as an efficient, robust auxiliary for enolate amination with 1-chloro-l-nitroso cyclohexane 486 as an electrophile. Thus, sultams 92 were first deprotonated with NaHMDS, and to the sodium enolates thus formed was added a solution of the blue nitrosochloride 486. Decolorization occurred immediately, and the mixture was quenched with hydrochloric acid to give hydroxylamines 487, in all cases as essentially pure diastereomers. The reductive cleavage of the nitrogen-oxygen bond was achieved with zinc dust to yield a-aminoacyl sultams 488. By mild hydrolysis with lithium hydroxide, the chiral auxiliary 91 was removed and recovered under concomitant formation of a-amino acids 490. Any racemization was avoided by applying this procedure, even in the case of the labile substrates with R equals a phenyl or / r -methoxyphenyl substituent. On the other hand, the auxiliary could be cleaved at the stage of hydroxylamines 487, so that not only a-amino acids 490 but also a-hydroxyamino acids 489 became available with excellent enantiomeric purity (Scheme 4.103) [232]. 

Two other alkylations were based on readily-available chiral auxiharies. PhUippe Karoyan of the Universite Pierre et Marie Curie observed Tetrahedron Lett. 2008, 49, 4704) that the acylated Oppolzer camphor sultam 20 condensed with the Mannich reagent 21 to give 22 as a single diastereomer. Andrew G. Myers of Harvard University developed the pseudoephedrine chiral auxiliary of 23 to direct the construction of ternary alkylated centers. He has now established J. Am. Chem. Soc. 2008,130, 13231) that further alkylation gave 24, having a quaternary alkylated center, in high diastereomeric excess. 

Derivatives of the Oppolzer sultam [32] may be employed in a general, chiral auxiliary-based approach to stereoselective synthesis of substituted cyclopropanes. In this context, Hacksell carried out a study in which unsaturated substrates such as 30 were converted into the corresponding cyclopro-... 

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