Oppolzer s sultams

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. 

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. 

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

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... 

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. 

Wallace et al. (293) applied the boronic ester derivative 177 of Oppolzer s sultam acrylate for a special nitrile oxide cycloaddition (Scheme 12.53). This reaction has the advantage that it allows for the introduction of a hydroxy group in the 4-position of the isoxazoline product 178 after oxidative cleavage of the boronic... 

Garner et al. (90,320) used aziridines substituted with Oppolzer s sultam as azomethine ylide precursors. The azomethine ylide generated from 206 added to various electron-dehcient alkenes, such as dimethyl maleate, A-phenylmalei-mide, and methyl acrylate, giving the 1,3-dipolar cycloaddition product in good yields and up to 82% de (for A-phenylmaleimide). They also used familiar azomethine ylides formed by imine tautomerization (320). Aziridines such as 207 have also been used as precursors for the chiral azomethine ylides, but in reactions with vinylene carbonates, relatively low de values were obtained (Scheme 12.59) (92). 

A clean, high-yielding asymmetric Baylis-HiUman reaction has been reported employing Oppolzer s sultam,63ab it couples acrylates witii a variety of aldehydes at 0 °C, with >99% ee in all cases described.630 Another new, practical variant of the reaction employs a phosphine catalyst,64 and here the temperature effect is critical the rate increases in either direction from room temperature, with a dramatic improvement observed at 0 °C. This unusual observation is explained in tenns of a temperature-dependent equilibrium between efficient and inefficient intermediates. 

The double diastereoselection of cycloaddition of chiral nitrones with Oppolzer s sultam acrylamide was studied and the adducts were converted into 4-hydroxy-pyroglutamic acid derivatives <02TA167,02TA173>. 

Diastereoselective allylation of ct-keto imides derived from Oppolzer s sultam has been realized in aqueous THF (Equation (20)).181... 

This methodology which bases on Oppolzer s sultams has also been employed in the synthesis of 2,6-N,N-diacetyl-D-purpurosamidine C [475,476]. Hetero Diels-Alder reactions of carbonyl dienophiles are furthermore involved in the preparation of ( )-ketoheptulosic acid [477] and in the already mentioned asymmetric approach to the C-26-C-32 tetrahydropyran subunit of swinholide A [92]. 

A chiral enolate derived from a bromoacetyl camphor sultam [(52) in turn prepared from Oppolzer s sultam ] undergoes an aza-Darzens reaction with modified amines to produce aziridine derivatives in high deJ Cleavage yields aziridine carboxylates. 

Reaction of these N -protected amino acid derivatives with electrophiles have been shown to produce the desired compounds with superior stereoselectivity and in higher yields compared to the alkylations of A -benzylidene-protected derivatives.Best results were obtained with the Oppolzer s sultam-derived glycine equivalents 133 (Scheme 70). Dia-stereomeric ratios were usually better than 98 2, and yields were between 85-96%. Liberation of the unnatural amino acids is quantitative and the products are virtually en-antiomerically pure (>99.8% Good results have been further achieved with chiral... 

N-Arylated 1,3-propanesultams 236 (R =Ar, R = H) are efficiently prepared from a Pd-catalyzed cross-coupling reaction with different aryl bromides in the presence of Xantphos <2004TL3305>. N-Fluorinated (-l-)-camphorsultams 237 (X = H, Cl, OMe R = F) have been prepared the corresponding imine 16 and difluoro derivative 238 were formed as by-products. The use of 237 is reported in Section 4.05.12.1 <1998JOC9604>. The syntheses of Ar-(l-alkynyl)-Oppolzer s sultams are reported in Section 4.05.6.3.4. Many examples of acylated Oppolzer s sultams are reported in Section 4.05.12.1. 

Several dihydro- or tetrahydro-isothiazole derivatives are used mainly as chiral scaffolds in diastereoselective syntheses. Among these, Oppolzer s sultam 582 (R = H) has been the most frequently used when functionalized at nitrogen with different acyl residues. A method for the removal of this chiral auxiliary has been described <1998SL882>. 

An efficient synthetic procedure to dienes containing a chiral auxiliary is achieved by Heck condensation of acrylamide of 582 (R = COCH=CH2) and silyl enol ethers <2002EJO3646>. The synthesis of various 1,3,5-hexatrienes 583 (R = Oppolzer s sultam) and their subsequent brt-electrocyclization were studied... 

Palladium acetate was also recently used as catalyst in a multistep stereospecific synthesis of enantiomeric rigid tryptamine derivatives [13]. The chiral auxiliary is Oppolzer s sultam (e.q. (3)). 

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