Oppolzer s chiral auxiliary

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 a-halo esters (72a) and (72b) and a-halo imide (72c) have been prepared in high diastereomeric purity by the use of Oppolzer s chiral auxiliary (71a) and (71b) and Evans chiral auxiliary (71c), respectively. The reactions of (72a), (72b) and (72c) with azide ion proceeded with inversion of configuration (Scheme 30). In the latter reaction, the use of NaNs (DMF or DMSO, 0 C) has been reported to afford 2-5% epimerization. The azides thus prepared were transformed into the corresponding amino acids with high chemical and optical yields. 

Scheme 15.44 [2,3]-Stevens rearrangement with Oppolzer s chiral auxiliary.

In addition, Sato et al. developed an interesting enantioselective synthesis of bicyclic cyclopropanols 31 from A-acylcamphorsultam (the Oppolzer s chiral auxiliary) derivatives 30. ... 

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. 

Diels-Alder reactions with Oppolzer s chiral sultam Diels-Alder reactions with pantolactone as chiral auxiliary Chiral auxiliaries attached to the diene Improved Oxazolidinones SuperQuats Asymmetric Michael (Conjugate) Additions... 

Since conjugate (Michael) addition and Diels-Alder reactions use a,p-unsat united carbonyl compounds, asymmetric versions of these reactions could use the auxiliaries that we have seen in aldol reactions in the form of 118 and 119. Diels-Alder reactions work very well with these unsaturated amides and also with amides 121 derived from Oppolzer s chiral sultam14 120, prepared simply from camphorsulfonyl chloride. 

Optically pure sultams have been used by Oppolzer as chiral auxiliaries in various asymmetric transformations, including Diels-Alder reaction, aldoliza-tion, conjugate addition, his-hydroxylation, and catalytic hydrogenation [42,43]. In the literature, the most commonly used chiral sultam is derived from camphor (Oppolzer s sultam). The ready access to 80 and other chiral sultams from the Diels-Alder cycloadducts could further expand the scope of their use as chiral auxiliaries in asymmetric synthesis. 

Miscellaneous. lodomethoxylation of chiral o ,/8-unsaturated amides has been described to afford a highly regioselective addition of NIS and methanol across an alkene in moderate diastereos-electivity using both Oppolzer s chiral sultam (eq 35) and Evans chiral oxazoUdinone. Subsequent cleavage of the chiral auxiliary, conversion of the iodide to the azide, and reduction to the amine results in synthetically useful a -amino acids. 

Acylation Catalyst. iV-Trimethylsilyl derivatives of (-1-)-bornane-2,10-sultam (Oppolzer s chiral sultam) and chiral 2-oxazolidinones (the Evans chiral auxiliaries) are Al-acylated with a number of acyl chlorides including acryloyl chloride in refluxing benzene in the presence of CuCl2 The M-acylated products were... 

The phosphodiesterase (PDE) IV inhibitor (109, Scheme 2.17) has been identified by Merck Research Laboratories as a potential lead for the treatment of asthma. Although an early synthesis of 109 relied on the use of Oppolzer s chiral sultam auxiliary, a more economic approach was subsequently developed that exploited an aminoindanol auxiliary. In the revised synthesis, the car-boxyhc acid 103 (available in two steps from isovanillin) is coupled with (15,2/ )-cis -aminoindanol 12 and subsequently converted into the amide 104. After protection of the amino alcohol, reaction of the resulting Michael acceptor 106 with phenyllithium 107 and subsequent... 

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

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