Oppolzer’s auxiliary

Cyclization of 1,6-dienes containing Oppolzer s auxiliary is promoted by permanganate affording fM-2,6-bis-hydroxyalky 1-te tra hydropyrans <2004TL7269>. 

Chiral ft-hydroxy esters The N-acetyl derivative 1 of Oppolzer s auxiliary can be converted into the 0-silyl-N,0-ketene acetal 2, which reacts with aldehydes in the presence of TiCU to afford aldols 3 or 4. These arc hydrolyzed to /3-hydroxy esters 5. The stereoselectivity depends upon the stcric demands of the aldehyde group R mainly, with... 

Oppolzer s auxiliary opened, in addition, an access to a/iti-configured aldol adducts 272 (Scheme 4.62). For this purpose, silyl ketene N,0-acetal 271 was prepared from propionic sultam 92, obtained as a single diastereomer, according to the NMR spectra of the crude product, and isolated as a crystalline compound it was characterized as a cis-silicon enolate by a crystal structure analysis. For the subsequent Mukaiyama aldol addition, titanium tetrachloride was found to be the optimum Lewis acid to yield the awti-diastereomers 272 in excellent diastereoselectivity. Their formation under attack of the enolate to the Re-face of the aldehyde is consistent with an open transition state 275, wherein the Lewis acid-coordinated aldehyde is located on the face opposite to the sulfonyl group (Scheme 4.62) [136b]. An alternative approach to the a fi-aldol adducts was also elaborated, based upon cA-boron enolates 267 when they are reacted with aldehydes in the presence of titanium tetrachloride, an ti-selective aldol addition occurs leading to the products 272 rather than to sy -aldols 268 that result in the absence of the Lewis acid [136c]. 

Evans and Oppolzer s auxiliaries are of comparable efficacy with regard to chemical yields and the stereoselectivities they induce in the a-alkylation process. In some cases Oppolzer s imide enolates are superior because they give slightly higher stereoselectivities, the resultant a-branched iV-acylsultams are often more easily purified by simple crystallization, and the auxiliary is easier and cleaner to remove. For both auxiliaries, the iV-acylated derivatives required for alkylation are readily accessible by treatment of the deprotonated auxiliaries with the respective acyl halides or mixed anhy-drides , generated in situ from the free acid (or the sodium salt) and pivaloyl chloride in... 

The easy accessibility of haloacetates labeled at Cl and/or C2 and aldehydes labeled at the carbonyl group makes it feasible to selectively prepare adducts labeled at any or all of three different positions, all using the same procedures. However, in carbon-14 chemistry, the synthetic potential of isotopically labeled haloacetates and haloaldol adducts has been exploited so far only for Oppolzer s auxiliaries, and only some of the potential options have been executed so far. The preparation of the bromo[ C ]acetyl (+) and ( )-bornane-10,2-sultams ((25)/(2/ )-[ " C ]BABS, n = l,2 1391 as depicted in Figure 11.83 is also described in Section 11.3.6. 

On the contrary, application of Oppolzer s chiral sultam 100 in Method 1 led to good diastereoselectivity (d.e. 60-70% after chromatography), and pure (4R)-diastereomers have been isolated by recrystallization. Moreover, the chiral auxiliary was cleaved successfully by reduction with LiAlH4.2-Aminopyran-5-carbinols 101 were produced without... 

Further examples of the endocychc nitrone route to spirocychc adducts are the total syntheses of (—)-histrionicotoxin (230) by Holmes and of cyhndricines by Weinreb. Histrionicotoxin is one of many spiropiperidine alkaloids isolated from the poison-arrow frog Dendrobates histrionicus and has been the subject of many attempted total syntheses by a nitrone cycloaddition strategy that failed to provide the desired regioisomer, possibly through unfavorable steric interactions (265-268). Unlike these reports, Holmes and co-workers (101) found that the intermolecular reaction of nitrone (231), prepared by the 1,3-APT of the corresponding alkynyl-hydroxylamine carrying Oppolzer s chiral sultam auxiliary, afforded the styrene... 

One of the most successful auxiliaries for ot,p-unsaturated carbonyl compounds for not only 1,3-dipolar but also other cycloadditions is Oppolzer s chiral sultam (276). In particular, the acrylate 165 of Oppolzer s chiral sultam is one of the most frequently used substrates for asymmetric 1,3-dipolar cycloadditions, as shown in Scheme 12.52. 

For most of reactions of different 1,3-dipoles with Oppolzer s chiral sultam shown in Scheme 12.52, it has been demonstrated that the auxiliary can be recovered. 

Other chiral auxiliaries like Oppolzer s bornanesultam 35 or chiral oxazolidinone 36 gave excellent results in stereocontrol and yield (Figure... 

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 s chiral auxiliary,6 (-)-2,10-camphorsultam, is useful in the asymmetric Diels-Aider reaction,3.4 and for the preparation of enantiomerically pure p-substituted carboxylic acids7 and diols,8 in the stereoselective synthesis of A2-isoxazolines,9 and in the preparation of N-fluoro (-)-2,10-camphorsultam, an enantioselective fluorinating reagent.10... 

Chiral auxiliaries can be attached to either the alkene or the alkyne in order to influence the reaction. They should be easily removed following the reaction to afford the stereochemically pure product. In 1997, Moyano, Pericas and co-workers used a phenylpropynoyl derivative of Oppolzer s bornane-10,2-sultam to bring about complete diastereoselectivity in the intermolecular PK reaction (29- 30 - Scheme ll).39... 

Scheme 11 Use of Oppolzer s bornane-10,2-sultam as a chiral auxiliary.

The chiral auxiliary approach. Poncas group has worked with chiral sulfur moieties like 10-methylthioisoborneol, Oppolzer s camphorsultam or chiral oxazolidinones which gave excellent results in stereo control and yields [95-100]. Recently they have reported that chiral alkynylthiols like 46 exhibit excellent diastereoselectivities in both inter- and intramolecular PKR, and have used this approach for the synthesis of 47, an intermediate in the synthesis of (+)-15-nor-pentelenene (48) (Scheme 15) [101,102]. 

Oppolzer s camphor sultam, a well known chiral auxiliary, has been applied to the asymmetric synthesis of chial fluorine-containing amino acids <07OL2513>. Photoinduced addition of perfluoroalkyl iodides 189 to /V-acyloylcamphorsultam 188 in the presence of an aqueous solution of sodium sulfite provides alkyl iodides 190 with moderate to good stereoselectivities. Azide displacement with the major diastereomer of 190 proceeds with inversion of configuration. Subsequent removal of the sultam auxiliary and hydrogenation of the azide afford the chiral fluorine-containing amino acid 192. 

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