Camphorsulfonamide

In the same area, Moreau et al. have developed new hydrophobic ionic liquids containing chiral camphorsulfonamide units and showed that they could be used as ligands for the Ti-catalysed addition of ZnEt2 to benzaldehyde. The ionic... 

Scheme 3.48 C2-S5mmetric bis(camphorsulfonamides) ligands for addition of ZnEt2 to benzaldehyde.

Hydroxypiperidine alkaloids have been synthesized via anodic methoxylation that allowed the regio- and stereoselective introduction of substituents [213]. A highly diastereoselective fluorination was achieved with chiral l,3-oxathiolan-5-ones derived from camphorsulfonamide. In dimethoxyethane containing Et4NF-4HF, the monofluorinated product (9) was obtained as a single diastereomer [214]. 

GC analysis of these diastereomeric sulfonamides and estimation of the absolute configuration is also possible. Usually the 5-configurated camphorsulfonamides of the analytes are eluted first. 

The camphorsulfonamide 24, when treated with LDA in tetrahydrofuran, yields the ( >enolate 25, which has been alkylated with 78-89% diastereoselectivity to give 26124-l25. 

On the other hand, in the presence of Lewis acid, addition of dialkylzinc to ketones occurs (equation 14)45. A stoichiometric amount of Ti(OPr-i)4 and a catalytic amount of camphorsulfonamide 33 enable an enantioselective addition of dialkylzincs to ketones46. Later, bis(sulfonamide) ligand 34 was found to be a more enantioselective catalyst in this... 

Chiral Zn(salen) catalyzed enantioselective alkynylation of ketones has been examined by Cozzi82 and by Saito and Katsuki83. Camphorsulfonamide/Cu(OTf)284, Ti(0-i-Pr)4/BINOL85 and Et3Al/cinchona alkaloid86 systems have also been reported. Chiral / -amino alcohols work as chiral catalysts without an additional Lewis acid component87. 

A. (+)-(1S)-10-Camphorsulfonamide. Into a 2-L, three-necked, round-bottomed flask equipped with mechanical stirrer, 65-mm Teflon stirring blade, and a 250 mL... 

S. (-)-(Camphorsulfonyl)imine. A 1 -L, round-bottomed flask is equipped with a two-inch egg-shaped magnetic stirring bar, a Dean-Stark water separator, and a double-walled condenser containing a mineral oil bubbler connected to an inert gas source. Into the flask are placed 5 g of Amberylst 15 ion exchange resin (Note 4) and 41.5 g of the crude (+)-(1 S)-camphorsulfonamide in 500 mL of toluene. The reaction mixture is heated at reflux for 4 hr. After the reaction flask is cooled, but while it is still warm (40-50°C), 200 mL of methylene chloride is slowly added to dissolve any (camphorsulfonyl)imine that crystallizes. The solution is filtered through a 150-mL sintered glass funnel of coarse porosity and the reaction flask and filter funnel are washed with an additional 75 mL of methylene chloride. 

Camphorsulfonyl)imine has been reported as a by-product of reactions involving the camphorsulfonamide.2 5 Reychler in 1898 isolated two isomeric camphorsulfonamides,2 one of which was shown to be the (camphorsulfonyl)imine by Armstrong and Lowry in 1902.3 Vandewalle, Van der Eycken, Oppolzer and Vullioud described the preparation of (camphorsulfonyl)imine in 74% overall yield from 0.42 mol of the camphorsulfonyl chloride.6 The advantage of the procedure described here is that, by using ammonium hydroxide, the camphorsulfonyl chloride is converted to the sulfonamide in >95% yield.7 The sulfonamide is of sufficient purity that it can be used directly in the cyclization step, which, under acidic conditions is quantitative in less than 4 hr. These modifications result in production of the (camphorsulfonyl)imine in 86% overall yield from the sulfonyl chloride. 

The pure isomers have been obtained by crystallization when Ar = 2-chloro-5-nitrophenyl. The configuration has been determined by X-ray analysis of the corresponding reagent prepared from d-a-bromo-Jt-camphorsulfonamide. 

Compared to the well-developed organozinc addition to aldehydes, the related addition to ketones has been far less studied. However, the first catalytic addition of diaUcylzinc to ketones has been achieved few years ago using camphorsulfonamide alcohols ligands and Ti(0-(-Pr)4 salt (equation 66). In the same year, it was also discovered that 15 mol % of (-l-)-DAIB catalyze the diphenylzinc addition to ketones to generate chiral (see Chiral) tertiary alcohols with up to 91% e.e. (equation 67). 

A general protocol for the HPLC separation of diastereomeric camphorsulfonamides derived from racemic ot-amino acids has been developed (eq 1). More complex amino acids, such as (8), were successfully analyzed by this procedure. ... 

A -Fluoro-dihydrobenzo[l,2-i isothiazole is an efficient agent for electrophilic asymmetric fluorination of enolates <1999JOG5708>. A -Fluoro-2,10-camphorsulfonamide 237 (see Section 4.05.6.4.2) is a good asymmetric reagent for a-fluorination of ketones <1998JOG9604>. 

Esters of a chiral trani-2-(2-naphthale with excellent diastereofacial (hence enami formed into chiral homologues via formata 10-camphorsulfonamide and subsequent alk ... 

Camphorsulfonyl chloride can be used as a resolving reagent for chiral amines, alcohols, and binaphthols. Derivatives of camphor-sulfonates and camphorsulfonamides are generally crystalline compounds and frequently form crystals suitable for X-ray analysis. For example, racemic 3,3,3-trifluoroalanine derivative 22 was resolved into optically pure sulfonamides 23a and 23b by deriva-tization with (15)-camphorsulfonyl chloride followed by HPLC separation (eq 11). Upon recrystallization from ethyl acetate-hexane (1 5), isomer 23a forms white needles and X-ray analysis established its configuration as R,S). 

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