cis-3-[N-(3,5-Dimethylphenyl)benzenesulfonamido]borneol1

(1R) (endo,endo)

[87360-02-9]  · C24H31NO3S  · cis-3-[N-(3,5-Dimethylphenyl)benzenesulfonamido]borneol  · (MW 413.63)

(chiral auxiliary; ester enolate derivatives undergo stereoselective alkylations2 and enantioselective anti-aldol reactions;3 enoate derivatives undergo stereoselective 1,4-conjugate additions of organocopper reagents4)

Alternate Name: N-(3,5-dimethylphenyl)-N-(3-hydroxy-4,7,7-trimethylbicyclo[2.2.1]hept-2-yl)benzenesulfonamide.

Physical Data: (1R) (endo,endo): mp 147-150 °C; [a]20D -26.0° (c = 4.0, CHCl3).

Handling, Storage, and Precautions: the auxiliary is stable indefinitely at ambient temperatures in a sealed container.

Introduction.

One of several auxiliaries that exploit the asymmetry of naturally occurring (+)-camphor, the 3-(N-(3,5-dimethylphenyl)benzenesulfonamido)borneol auxiliary has proven significant utility in the p-facial differentiation of ester enolates and enoate derivatives. The endo orientation of the C(2) and C(3) substituents places the reactive functionality within the concave pocket created by the bornane skeleton as well as the shielding ability of the N-arylbenzenesulfonamide.

Preparation of the Auxiliary.

A synthesis of the (1R) auxiliary has been reported starting from (+)-camphor (eq 1). Zinc reduction of the intermediate imine (2) followed by sulfonylation and ketone reduction with Ca(BH4)2 afforded the cis,endo product in 70-75% overall yield from camphorquinone (1).

Preparation of Derivatives.

Enoate derivatives were prepared by Horner-Wittig reactions between aldehydes and the ethyl phosphonate derived from the chloroacetyl ester of (3) in high (E) selectivity (97:3).4b Ester derivatives were obtained by treating alcohol (3) with the corresponding carboxylic acid chloride.5

a-Alkylation of Ester Derivatives.2

Alkylation of ester enolate derivatives, prepared by metalation with lithium cyclohexylisopropylamide (LICA), proceeds with high stereoselectivity. The configuration of the product is dependent on the solvent employed (eqs 2 and 3). When performed in THF with the addition of HMPA the product with the (S) configuration was formed preferentially; however, without HMPA the (R) configuration predominated. Silyl chloride trapping studies suggest that in the presence of HMPA the (E)-ester enolate is stereoselectively formed, as opposed to the (Z)-ester enolate in THF alone.2b The stereochemical outcome has been explained by alkylation of the corresponding enolate p-face opposite to the shielding 3,5-dimethylphenyl moiety. O-Benzylglycolates have also been employed in stereoselective alkylations, affording diastereomeric excesses of 88-95%.2c In this case the solvent-dependent stereochemical reversal does not occur and the (E)-ester enolate is stereoselectively formed in both cases.

Aldol Reactions of Ester Derivatives.3

The Titanium(IV) Chloride-catalyzed addition of aldehydes to O-silyl ketene acetals derived from acetate and propionate esters proceeds with high stereoselectivity. Formation of the silyl ketene acetal was found to be essential for high diastereoselectivity. Treatment of the silyl ketene acetal, derived from deprotonation of the acetate ester with LICA in THF and silyl trapping, with a corresponding aldehyde in the presence of TiCl4 (1.1 equiv) afforded the addition products in 93:7 diastereoselectivity and moderate yield (51-67%). Similarly, the propionate ester provides the anti-aldol product in high anti/syn selectivity (14:1) and facial selectivity (eq 4).

1,4-Conjugate Additions to Enoate Derivatives.4

High diastereoselectivity has been observed for Boron Trifluoride-promoted addition of alkyl and aryl organocopper reagents to enoate derivatives (eq 5).4b When the organocopper reagent was prepared from alkyl- or aryllithiums, diethyl ether was found to be the solvent of choice; however, with Grignard reagents, THF was superior. The addition of boron trifluoride exhibited little influence on reactivity of the copper reagent but did enhance the stereoselectivity of the addition. It is believed that the enoate adopts an s-trans conformation and the observed stereochemical preference results from approach of the organocopper reagent to the less sterically hindered face opposite the aryl moiety.

Nondestructive Removal of the Auxiliary.

Primary alcohols are obtained by Lithium Aluminum Hydride reduction of the corresponding chiral esters. Also, hydrolysis of the auxiliary under basic conditions, 2N KOH in methanol,4b provides the carboxylic acid and recovered alcohol (3).

Related Reagents.

3-Hydroxyisoborneol; (1R,2S)-N-Methylephedrine.


1. Oppolzer, W. T 1987, 43, 1969.
2. (a) Schmierer, R.; Grotemeier, G.; Helmchen, G.; Selim, A. AG(E) 1981, 20, 207. (b) Helmchen, G.; Selim, A.; Dorsch, D.; Taufer, I. TL 1983, 24, 3213. (c) Helmchen, G.; Wierzchowski, R. AG(E) 1984, 23, 60.
3. Helmchen, G.; Leifauf, U.; Taufer-Knöpfel, I. AG(E) 1985, 24, 874.
4. (a) Rossiter, B.; Swingle, N. M. CRV 1992, 92, 771. (b) Helmchen, G.; Wegner, G. TL 1985, 26, 6051.
5. Dorsch, D.; Kunz, E.; Helmchen, G. TL 1985, 26, 3319.

Mark E. Schnute

University of Illinois at Urbana-Champaign, IL, USA



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