(R,R)-1,2-Diphenyl-1,2-diaminoethane N,N-Bis[3,5-bis(trifluoromethyl)benzenesulfonamide]

(1; R = 3,5-(CF3)2C6H3)

[127445-51-6]  · C30H20F12N2O4S2  · (R,R)-1,2-Diphenyl-1,2-diaminoethane N,N-Bis[3,5-bis(trifluoromethyl)benzenesulfonamide]  · (MW 764.66) (2; R = CF3)

[121788-73-6]  · C16H14F6N2O4S2  · (R,R)-1,2-Diphenyl-1,2-diaminoethane N,N-Bis(trifluoromethanesulfonamide)  · (MW 476.46) (3; R = 4-MeC6H4)

[121758-19-8]  · C28H28N2O4S2  · (R,R)-1,2-Diphenyl-1,2-diaminoethane N,N-Bis(p-toluenesulfonamide)  · (MW 520.72) (4; R = 4-NO2C6H4)

[121809-00-5]  · C26H22N4O8S2  · (R,R)-1,2-Diphenyl-1,2-diaminoethane N,N-Bis(4-nitrobenzenesulfonamide)  · (MW 582.66)

(chiral controller group for enantioselective Diels-Alder reactions,1 aldol additions,2 Ireland-Claisen rearrangements,3 ester-Mannich additions,4 and carbonyl allylation5 and propargylation6)

Alternate Name: (R,R)-stilbenediamine N,N-bis-3,5-bis(trifluoromethyl)benzenesulfonamide.

Physical Data: (1) mp 155-156 °C; aD +83.7° (c = 1, CHCl3). (2) mp 213-214 °C; aD +6.6° (c = 1.4, CHCl3). (3) mp 213-214 °C; aD +43.9° (c = 1.74, CHCl3). (4) mp 243 °C (dec); aD 122° (c = 0.107, acetone).

Solubility: except for the nitro derivative, the sulfonamides are sol CH2Cl2.

Preparative Methods: the most convenient preparation of (R,R)-stilbenediamine is described in Organic Syntheses.7 Condensation of benzil and cyclohexanone in the presence of ammonium acetate and acetic acid (eq 1) produces a spirocyclic 2H-imidazole (mp 105-106 °C). Reduction with Lithium in THF/NH3 followed by an ethanol quench and hydrolysis with aqueous HCl (eq 2) affords the racemic diamine as a pale yellow solid (mp 81-82 °C). Resolution is achieved by multiple recrystallizations of the tartaric acid salts from water/ethanol. The sulfonamides are prepared by reaction of the enantiomerically pure diamine with the appropriate anhydride1b or sulfonyl chloride2a in CH2Cl2 in the presence of Triethylamine and a catalytic amount of 4-Dimethylaminopyridine (eq 3).

Handling, Storage, and Precautions: the sulfonamides are all stable, crystalline compounds that do not require any special precautions for storage or handling.

Diels-Alder Reactions.

Reaction of the bis(triflamide) (2) with Diisobutylaluminum Hydride or Trimethylaluminum affords chiral Lewis acids that catalyze Diels-Alder reactions of acryloyl or crotonoyl derivatives with cyclopentadienes (eq 4).1 The aluminum complex must be crystallized before use to remove traces of trimethylaluminum. High diastereo- and enantioselectivities are achieved with as little as 0.1 equiv of the Lewis acid, and the chiral sulfonamide is recoverable.

Asymmetric Aldol Reactions.

Reaction of (1) with Boron Tribromide in CH2Cl2 affords, after removal of solvent and HBr, a complex (5) useful for the preparation of chiral enolates (eq 5).1a Complex (5) is moisture sensitive and is generally prepared immediately before use. For propionate derivatives, either syn or, less selectively, anti aldol adducts may be obtained by selection of the appropriate ester derivative and conditions.2a Thus reaction of t-butyl propionate with (5) and triethylamine produces the corresponding E(O) enolate, leading to formation of anti aldol adducts upon addition to an aldehyde (eq 6). Selectivities may be enhanced by substitution of the t-butyl ester with the (+)-menthyl ester. Conversely, reaction of S-phenyl thiopropionate with (5) and Diisopropylethylamine affords the corresponding Z(O) enolates and syn aldol products (eq 7).2a,c

Products with low enantiomeric purity are obtained by direct application of this chemistry to unsubstituted acetate esters. However, aldol reactions of t-butyl bromoacetate mediated by (5) afford synthetically useful bromohydrins (6) with high selectivities (eq 8).2b These may be reductively dehalogenated or converted to a variety of compounds by way of the derived epoxides.

Asymmetric Ireland-Claisen Rearrangements.

Chiral enolates derived from the boron complex (5) and allyl esters rearrange with excellent selectivity upon warming to -20 °C for a period of 1-2 weeks (eqs 9 and 10).3 As discussed above, the geometry of the intermediate enolate can be controlled by appropriate choice of base and solvent, thus allowing access to either syn or anti configuration in the product. The reaction can be completed in 2-4 days with little erosion in selectivity when run at 4 °C.

Ester-Mannich Additions.

The E(O) enolate (7) reacts with N-allyl or N-benzyl aldimines to afford chiral b-amino esters (eq 11).4 As with the aldol reactions, best selectivities are achieved with imines derived from aromatic or unsaturated aldehydes. The method appears to have good potential for the synthesis of useful b-lactams if extended to other enolates.

Carbonyl Allylation and Propargylation.

Boron complex (8), derived from the bis(tosylamide) compound (3), transmetalates allylstannanes to form allylboranes (eq 12). The allylboranes can be combined without isolation with aldehydes at -78 °C to afford homoallylic alcohols with high enantioselectivity (eq 13).5 On the basis of a single reported example, reagent control might be expected to overcome substrate control in additions to aldehydes containing an adjacent asymmetric center. The sulfonamide can be recovered by precipitation with diethyl ether during aqueous workup. Ease of preparation and recovery of the chiral controller makes this method one of the more useful available for allylation reactions.

In the same way, reaction of (8) with allenyl- or propargylstannanes affords intermediate borane derivatives which, upon reaction with aldehydes, produce the expected adducts with high selectivities (eqs 14 and 15).6

Other Applications.

Other (R,R)-stilbenediamine derivatives have been used to direct the stereochemical course of alkene dihydroxylation8 (with stoichiometric quantities of Osmium Tetroxide and epoxidation of simple alkenes with Sodium Hypochlorite and manganese(III) complexes.9

Related Reagents.

B-Allyldiisopinocampheylborane; Chloro(h5-cyclopentadienyl)[(4R,trans)-2,2-dimethyl-a,a,a,a-tetraphenyl-1,3-dioxolane-4,5-dimethanolato(2-)-Oa,Oa]titanium; Chloro(cyclopentadienyl)bis[3-O-(1,2:5,6-di-O-isopropylidene-a-D-glucofuranosyl)]titanium; Diisopinocampheylboron Trifluoromethanesulfonate; Diisopropyl 2-Allyl-1,3,2-dioxaborolane-4,5-dicarboxylate; (4R,5R)-2,2-Dimethyl-4,5-bis(hydroxydiphenylmethyl)-1,3-dioxolane-Titanium(IV) Chloride; 2,2-Dimethyl-a,a,a,a-tetraphenyl-1,3-dioxolane-4,5-dimethanolatotitanium Diisopropoxide.

1. (a) Corey, E. J.; Imwinkelried, R.; Pikul, S.; Xiang, Y. B. JACS 1989, 111, 5493. (b) Pikul, S.; Corey, E. J. OS 1992, 71, 30.
2. (a) Corey, E. J.; Kim, S. S. JACS 1990, 112, 4976. (b) Corey, E. J.; Choi, S. TL 1991, 32, 2857. (c) Corey, E. J.; Lee, D.-H. TL 1993, 34, 1737.
3. Corey, E. J.; Lee, D.-H. JACS 1991, 113, 4026.
4. Corey, E. J.; Decicco, C. P.; Newbold, R. C. TL 1991, 32, 5287.
5. Corey, E. J.; Yu, C.-M.; Kim, S. S. JACS 1989, 111, 5495.
6. Corey, E. J.; Yu, C.-M.; Lee, D.-H. JACS 1990, 112, 878.
7. Pikul, S.; Corey, E. J. OS 1992, 71, 22.
8. Corey, E. J.; DaSilva Jardine, P.; Virgil, S.; Yuen, P.-W.; Connell, R. D. JACS 1989, 111, 9243.
9. Zhang, W.; Jacobsen, E. N. JOC 1991, 56, 2296.

James R. Gage

The Upjohn Company, Kalamazoo, MI, USA

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