Sultams Oppolzer

The reaction can be applied to imines. Recently, the preparation of chiral allylglycines was effected by addition of allyl groups to the C=N bond in glyoxylic acid oximes modified as chiral sultams (Oppolzer chiral induction methodology).55 The yields (> 88%) and the diastereoselectivity (d.e. > 80 20) are excellent. 

Solid-phase synthesis of substituted pyrazolones 550 from polymer-bound /3-keto esters 549 has been described (Scheme 68) <2001EJ01631>. Trisubstituted pyrazole carboxylic acids were prepared by reaction of polymer-bound arylidene- or alkylidene-/3-oxo esters with phenylhydrazines <1999S1961>. 2-(Pyrazol-l-yl)pyrimi-dine derivatives were prepared by cyclocondensation of ethyl acetoacetate and (6-methyl-4-oxo-3,4-dihydropyrimi-din-2-yl)hydrazine with aromatic aldehydes <2004RJC423>. Reactions of acylated diethyl malonates with hydrazine monohydrochloride in ethanol afforded 3,4-disubstituted-pyrazolin-5-ones <2002T3639>. Reactions of hydrazines with A -acetoacetyl derivatives of (45 )-4-benzyloxazolidin-2-one (Evans oxazolidinone) and (2R)-bornane-10,2-sultam (Oppolzer sultam) in very acidic media gave pyrazoles retaining the 3(5)-chiral moiety <1999S157>. 

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... 

From the Oppolzer sultam by exchange AllylOH, Ti(OR)4, 67-95% yield. 

The classical aza-Darzens reaction (between bromoenolates and imines) has been investigated by several groups in recent years, especially with respect to the design and execution of asymmetric variants. Both stoichiometric and catalytic methods have been studied thus, the reactions between N-Dpp imines and chiral ot-bromoenolates [49] (derived from Oppolzer s sultams Scheme 4.35) and between S-chiral sulfmylimines and achiral bromoenolates [50] (Scheme 4.36) have been reported. 

Kim B. H., Curran D. P. Asymmetric Thermal Reactions With Oppolzer s Camphor Sultam Tetrahedron 1992 49 293-318... 

Oligomers Oppolzer s camphor sultam (see also camphor derivatives) Organometallics Organosilicon Organosulfur Organozirconocenes Orthoquinodimethanes Oxabutadienes Oxanorbornadiene(s) Oxazinolactams Oxazinones Oxazoles... 

Indium-mediated allylation reactions of a-keto imides derived from Oppolzer s sultam proceeded in aqueous THF in good yields and excellent diastereoselectivity (Eq. 11.43).74 The indium-mediated allylation of the Oppolzer camphorsultam derivatives of glyoxylic oxime ether... 

In the former case, both antipodes of sultams were used and the initially formed cycloadducts (288a-e) were transformed into more stable isoxazolines (289a-e) and (289 a-c) with retention of configuration of the new stereocenter at C-5. For Oppolzer s sultam, (435-437) the yields of the target products were high and the ratio of diastereomers was close to 1 10. 

Acylsultam Systems. Oppolzer et al.53 developed a general route to enantiomerically pure crystalline a,a-disubstituted carboxylic acid derivatives by asymmetric alkylation of A -acylsul tarns. Acylsultam 50 can be readily prepared from the inexpensive chiral auxiliary sultam 53.5 4... 

For a review of sultam chemistry, interested readers can refer to Oppolzer s article57 on Camphor as a Natural Source of Chirality in Asymmetric Synthesis. ... 

Figure 4.7. Acylated Oppolzer s sultam 66 and proposed Zr-chelate intermediate 67.

Asymmetric cyclopropanol formation has been achieved with olefmic acylsulfonamides, which act like olefmic esters. Thus, their reaction with 1 provides a method for synthesizing cyclopropanols in an optically active form. As represented by Eq. 9.41, alkylation of Oppolzer s camphor sultam and reaction of the resulting unsaturated acylsulfonamides with 1 provides optically active bicyclic cyclopropanols having exclusively the structure shown in the equation [76],... 

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 series of cyanoacetic acid derivatives 96 (94TA1435, 95TA255) was used for the introduction of a chiral moiety into position 3 of a pyran ring Oppolzer s sultam (a), (—)-menthol (b), (IS)-endo-(-)-borneol (c), ethyl (S)-(—)-lactate (d), diisopropylidene-o-glucofuranose (e). Both Methods 1 and... 

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... 

Oppolzer sultam-like chiral auxiliary (e.g., Xc in 304) has been studied in Diels-Alder cycloaddition reactions (Scheme 43) <2003JP0700>. The TiCU-promoted reaction of dienophile 304 and 1,3-cyclopentadiene 305 in DCM is complete within 18h and excellent diastereoselectivity of product 306 is observed. The same reaction in the absence of Lewis acid provides product 306 in very low yield. However, switching to trifluoroethanol as the solvent, the cycloaddition reaction proceeds to completion, albeit with slightly diminished levels of diastereoselectivity for Diels-Alder adduct 306. Surprisingly, the use of hexane as the solvent affords the opposite (23, J 31-diastereomer of 306 as the major product. 

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... 

In synthetic efforts toward the DNA reactive alkaloid naphthyridinomycin (164), Gamer and Ho (41) reported a series of studies into the constmction of the diazobicyclo[3.2.1]octane section. Constmction of the five-membered ring, by the photolytic conversion of an aziridine to an azomethine ylide and subsequent alkene 1,3-dipolar cycloaddition, was deemed the best synthetic tactic. Initial studies with menthol- and isonorborneol- tethered chiral dipolarophiles gave no facial selectivity in the adducts formed (42). However, utilizing Oppolzer s sultam as the chiral controlling unit led to a dramatic improvement. Treatment of ylide precursor 165 with the chiral dipolarophile 166 under photochemical conditions led to formation of the desired cycloadducts (Scheme 3.47). The reaction proceeded with an exo/endo ratio of only 2.4 1 however, the facial selectivity was good at >25 1 in favor of the desired re products. The products derived from si attack of the ylide... 

The chiral dipolarophiles of Garners and Dogan, which were derived from Oppolzer s sultam, have been previously discussed in Section 3.2.1 and, in an extension to these results, the sultam moiety was used as the stereodirecting unit in enantiopure azomethine ylides (56). The ylides were generated either by thermo-lytic opening of N-substituted aziridines or by the condensation of the amine functionality with benzaldehyde followed by tautomerism. These precursors were derived from the known (+)-A-propenoylbornane-2,10-sultam. Subsequent trapping of the ylides with A-phenylmaleimide furnished the cycloaddition products shown in Schemes 3.60 and 3.61. 

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. 

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