Camphorsultam

Tsuehihashi, G.-I. Mitamura, S. Kitajima, K. Kobayashi, K. Tetrahedron Lett. 1982, 23,5427. 

P Neumann, D. Diimer, G. Helv. Chim. Acta 1989, 72,1753. Mori, K. Kisida, H. Justus Liebigs Ann. Chem./Liebigs Ann. Chem. 1989, 35. 

Berthet, M. Sonveaux, E. Chem. Commun./J. Chem. Soc., Chem. Commun. 1983, 10. 

Oppolzer, W. Poll, G. Starkemann, C. Bernardinelli, G. Tetrahedron Lett. 1988, 29, 3559. 

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The first diastereoselective synthesis of a tetrahydrothiophene derivative was reported by Karlsson and Hdgberg (32,95). The parent ylide la was added to a variety of C,C-dipolarophiles (79) bearing (—)-(15)-2,10-camphorsultam as the chiral auxiliary group to exclusively give trans-cycloadducts 80a,b with high diastereoselectivity [diastereomeric ratio (dr) 9 1], (Scheme 5.28). 

A practicable strategy to provide access to chiral pyrazolidine-3-carboxylic acid (16) makes use of asymmetric dipolar cycloaddition of diazoalkanes to u,p-unsaturated carboxylic acid derivatives. For this purpose a chiral auxiliary of the alkene component is used, e.g. Op-polzer s1166 1671 (lf )-2,10-camphorsultam.t164l As shown in Scheme 7, by reaction of (tri-methylsilyl)diazomethane (41) with /V-( aery I oy I )cam p h ors u 11 am (42), the AL(4,5-dihy-dropyrazoline-5-carbonyl)camphorsultam (43) is obtained. Reduction of 44 with sodium cyanoborohydride leads to A-(pyrazolidine-3-carbonyl)camphorsultam (45) as the 35-dia-stereoisomer (ee 9 1) in 65 to 80% yields.[164] The camphorsultam 45 is then converted into the methyl ester 46 by reaction with magnesium methylate without racemizationj1641... 

Camphorsultam. A dry, 2-L, three-necked, round-bottomed flask is equipped with a 1.5-in egg-shaped Teflon stirring bar, a 250-mL addition funnel, and a 300-mL Soxhlet extraction apparatus equipped with a mineral oil bubbler connected to an inert gas source. The flask is charged with 600 mL of dry tetrahydrofuran (THF) (Note 1) and 6.2 g (0.16 mol) of lithium aluminum hydride (Note 2). Into the 50-mL Soxhlet extraction thimble is placed 35.0 g (0.16 mol) of (-)-(camphorsulfonyl)imine (Note 3) and the reaction mixture is stirred and heated at reflux. After all of the (camphorsulfonyl)imine has been siphoned into the reaction flask (3-4 hr), the mixture is allowed to cool to room temperature. The unreacted lithium aluminum hydride is cautiously hydrolyzed by dropwise addition of 200 mL of 1 N hydrochloric acid via the addition funnel (Note 4). After the hydrolysis is complete the contents of the flask are transferred to a 1-L separatory funnel, the lower, silver-colored aqueous layer is separated, and the upper layer placed in a 1-L Erlenmeyer flask. The aqueous phase... 

Camphorsultam was first prepared by the catalytic hydrogenation of (-)-(camphorsulfonyl)imine over Raney nickel.2 Lithium aluminum hydride reduction was used by Oppolzer and co-workers in their synthesis of the sultam.3-4 However, because of the low solubility of the sultam in tetrahydrofuran, a large amount of solvent was required.4 In the procedure described here the amount of solvent is significantly reduced by using a Soxhlet extractor to convey the imine slowly into the reducing medium.5... 

Oppolzefs chiral auxiliary,6 (-)-2,10-camphorsultam, is useful in the asymmetric Diels-Alder 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... 

In addition to the synthesis of enantiomerically pure (camphorylsulfonyl)oxaziridine7 and its derivatives,8 the (camphorsulfonyl)imine has been used in the preparation of (-)-2,10-camphorsultam (Oppolzers auxiliary),6-9 (+)-(3-oxocamphorysulfonyl)oxaziridine10 and the N-fluoro-2,10-camphorsultam, an enantioselective fluorinating reagent.11... 

Michael C. Weismiller, James C. Towson, and Franklin A. Davis 154 SYNTHESIS OF (-)-D-2,10-CAMPHORSULTAM... 

A method of preparing either cis- or trans-aziridine carboxylates (39) from A-diphenylphosphinylimines (37) and the chiral enolate (36) derived from A-bromo-acetyl 25-2,10-camphorsultam (35) has been reported.54 When the arylimine is substituted in the ortho -position, the product is either a mixture of cis- and trans-aziridine or only the trans-isomer. When the ortho-substituent is H or NO2, only a cz s-aziridine is obtained. The suggested mechanism is partially shown in Scheme 18. Both steric and inductive effects of the ortho- substituent affect the stereochemistry of the addition complex (38) and the stereochemistry of the final aziridine. 

Fluorination of Ketone Enolates. (+)-lV-Fluoro-2,10-(3,3-dichlorocamphorsultam) (1) reacts with ketone enolates to give a-fluoro ketones. For example, reaction of the sodium enolate of propiophenone 2 gives a-fluoropropiophenone 3 in 41% isolated yield (eq 1). No enantioselectivity, however, is observed due to racemization of the product under the reaction conditions. When a tertiary substituted ketone such as a-methyltetralone (4) is employed, the desired a-fluorinated product (S)-(-)-S is obtained in 76% ee and 53% isolated yield (eq 2). In this reaction, (+)-l was found to be more reactive, affording higher yields and better enan-tioselectivities than its parent (-)-N-fluoro-2,10-camphorsultam i.e., 35% ee, < 5% yield. ... 

Related Reagents. (+)-N-fluoro-2,10-camphorsultam (—)-N-fluoro-2,10-(3,3-dimethoxycamphorsultam) (35)-(—)-lV-flu-oro-3-cyclohexyl-3-methyl-2,3-dihydrobenzo[ 1,2-[Pg.343]

The desired molecular tool, CSDP acid (-)-l, was synthesized by reacting (lS,2R,4R)-(-)-2,10-camphorsultam anion with 4,5-dichlorophthalic anhydride [(-)-l, mp 221 °C from EtOH [a]D ° -101.1 (c 1.375, MeOH) Fig. 9.2]. This carboxylic acid was condensed with alcohol in the presence of 1,3-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) [17]. 

Fig. 9.2 Design of a chiral molecular tool, CSDP and CSP acids containing the 2,10-camphorsultam moiety.

Camphorsultam, a frequently used chiral auxiliary in diastereoselective syntheses [101], has also been applied in radical reactions [99]. Heterocoupling reactions with 42, 43, and the coacids 33 and 35, afforded the products 44-48 (Eq. 7). The results demonstrate that the diastereoselectivity strongly increases with the steric bulk of the 2-substituent in the malonates 42 and 43, namely 79.5% de with R = tBu and 41.3% de with R = iPr. With increasing bulk of the substituents in the coacid, hydrogen abstraction of the auxiliary substituted radical becomes a major competing reaction leading to 47 and 48. 

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