Bornane-10,2-sultam

Asymmetric hefera-Diels-Alder addition of 1 -methoxybuta-1,3-diene to (2R)-N-pyruv-oyl-and (2R)-N-(phenylglyoxyloyl)bornane-10,2-sultam [69]... 

Amides prepared from both enantiomers of 10,10-dimethyl-4-aza-3-thiatricyclor5.2.1.01,5ldecane 3,3-dioxide (bornane-10,2-sultam) can be used in diastereoselective alkylation reactions to give high chemical yields and high diastereomeric ratios of monoalkylation products5,6,10,16-19. 

V-Acylbornane-l 0,2-sultams 2 are prepared from the bornane-10,2-sultam 1 via NH-deproto-nation with sodium hydride and subsequent acylation with a suitable acid chloride. 

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.

Recently, Oppolzer s group reported on the synthesis and use of a new sulfinylating agent,107 the /V-sulfinyl sultam 82, as part of a broad program on the use of the versatile bornane-10,2-sultam 81 in asymmetric synthesis.108 The condensation of p-TolSOCI with 81 in THF, using dimethylaminopyridine (DMAP) as catalyst, gave the /V-(p-tolylsulfinyl)bornane- 10,2-sultam as a 6.2 1 diastereomeric mixture. Crystallization of the mixture from E O/hexane afforded pure 82 in 77% yield. X-ray analysis showed the absolute configuration at the sulfinyl sulfur to be (/ ). The reaction has been shown to be kinetically controlled, in contrast to the results obtained when n-BuLi was used instead of DMAR In the latter case, the reaction was under thermodynamic control, in accord with the result obtained by Evans with iV-sulfinyl oxazolidinone (Scheme 25). 

Bornane[10,2]sultams have been exploited as chiral auxiliaries for stereoselective aziridination of attached 7V-enoyl substituents28. The alkene substitution pattern markedly affected the diastereoselectivity, which was excellent when the C — C double bond was unsubstituted in this case the configuration of the prevalent diastereomer 5 was established by X-ray crystallographic analysis. Thus, the addition occurred to the Re-face at the a-carbon. In the other cases the stereochemistry of the major diastereomers was tentatively assigned by analogy. Furthermore, the yield dropped drastically when an a-substituent was present. Removal of the auxiliary was achieved by titanium isopropoxide alcoholysis, but was not optimized. No epimerization occurred during the cleavage process. 

The nitroso urea 1, derived from D-bornane-10,2-sultam. has been shown to be useful in asymmetric hetero-Diels Alder cycloaddilions. It can be generated in situ by oxidizing the corresponding jV-hydroxyurea with tetraethylammonium periodate in dichloromethane at 20 °C. In the presence of a five-fold excess of 1,3-cycloalkadiene, the corresponding adducts 2 are obtained in good yield and complete facial stereoselectivity104. 

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>. 

Oppolzer s (2/ )-bornane-10,2-sultam 150 is a good auxiliary that transmits its chirality to the a-carbon of an amide. The reaction of lithium enolate of 151 with the corresponding... 

The isoxazoline is also obtained from other reactions with pyridinium nitrate and pyrrolidine <89JHC1569>. Silyl nitronate (259) (R = H, Me, Et, Ph) with Ar-acrylyl-(2/ )-bornane-10,2-sultam (260) yielded a mixture of adducts. Further treatment with p-toluene sulfonic acid afforded the diastereomeric isoxazoline (261) (Equation (45)) <91PHC166>. 

Since our catalytic approaches failed, we next attempted a chiral auxiliary approach. The glyoxyloyl function was incorporated into (2R)-bornane-10,2-sultam,... 

Similarly, using bornane [10,2] -sultam as a chiral auxiliary, provides, via the bromination of the intermediate boryl enolates, an alternative route to diastereoisomerically pure a-halo esters (ref. 10) (Fig. 5) ... 

Cycloaddition of Af,Ar-fumaroyldi[(2/ )-bornane-10,2-sultam] 32 to cyclopentadiene (2) proceeds with excellent diastereoselectivity affording adducts 33 and 34 with a d.r. [(55,65)/ (5f ,6i )] >98 2 and in very good yields (80-95 %). In contrast to ethyl (5)-lactate and (5)-pro-line fumarates the d.r. value is almost independent of the amount of equivalents of TiCl4 used... 

A diastereoselective Diels-Alder reaction of cyclopentadiene with a chiral dienophile, iV,iV -fumaroyldi[(2/ )-bornane-10,2-sultam], was carried out in scC02. The highest diastereoselectivity (65% conversion and 93% de) is obtained around the critical point (74 bar) at 33 C. Lanthanide triflate catalyzes the reaction of cyclopentadiene and 3-acryloyl-(4S)-isopropyloxazolidin-2-one 21 in SCCO2 to give the endo adduct endo exo = 10 30) with a higher diastereoselectivity (59% de) than in CH2CI2 (38-42% de) (Scheme 36). ... 

Oppolzer s bornane-10,2-sultams have been used by Josien et al. [56] in the synthesis of a series of conformationally restrained arylalanines [for example, (28), Scheme 5.13] as binding probes for the tachykinin NK-1 receptor. Highly diastereoselective alkylation of the chiral glycinate equivalent (29) was followed by sequential acid- and base-catalyzed hydrolysis reaction to yield the unprotected a-amino acid (28). 

Figure 6.34 Use of bromo[ C]acetyl bromide in N-acylation of amides, imides and sulfonamides preparation of (2S-N-bromo[ " C]acetyl)bornane-10,2-sultam...

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