Sc(OTf) 3 catalyzed carbon-carbon and carbon-heteroatom bond forming reactions: a review

In recent years scandium(III) trifluoromethanesulfonate [Sc(OTf) 3 ] has emerged as an efficient, mild, commercially available, inexpensive, water tolerant Lewis acidic catalyst in the formation of both carbon-carbon and carbon-heteroatom bonds, and thereby the formation of various biologically promising organic compounds. The present review summarizes the latest developments on Sc(OTf) 3 -catalyzed organic transformations especially carbon-carbon and carbon-heteroatom bond forming reactions reported during the last decade.


Introduction
2][3] Catalysts play an obvious role in such reactions and thus they find wide application.But the screening of suitable catalysts plays a crucial role among the other significant parameters during such chemical praxis.
The last decade has seen a great development in the use of triflate salts as catalysts for organic transformations. 4][7][8][9][10][11][12][13][14][15][16][17] The catalytic applicability of this mild catalyst is well documented in the literature, especially in cycloaddition reactions, 18 Diels-Alder, 19 Ugi, 20 and Michael reactions. 21Though the majority of the developed methods are based upon the ability of scandium to activate C=X π-bonds toward nucleophilic additions, more recently it has been found that scandium(III) can also activate C-X σ-bonds. 22n 1993, Kobayashi et al. 23 first demonstrated the use of Sc(OTf)3 as a promising Lewis acid catalyst in organic synthesis.Sc(OTf)3 is now commercially available and can be prepared easily from scandium oxide (Sc2O3) and aqueous trifluoromethanesulfonic acid (TfOH). 7In general, most of the traditional Lewis acids are deactivated in the presence of water, but Sc(OTf)3 is stable in an aqueous environment and can efficiently catalyze organic transformations in aqueous media.Moreover, Sc(OTf)3 is well tolerated and worked efficiently as a Lewis acid catalyst in several other organic solvents.As the size of the scandium (Sc 3+ ) ion is smaller than those of the rare-earth elements forming triflate salts, Sc(OTf)3 is a much more efficient Lewis acid catalyst than its congeners.Because of all these benefits the use of this unique catalyst has increased rapidly in organic synthesis especially in carbon-carbon and carbon-heteroatom bond forming reactions. 24he present communication focuses on the catalytic application of Sc(OTf) 3 as a mild Lewis acid in organic synthesis, leading to carbon-carbon and carbon-heteroatom bond forming reactions, with up-to-date literature reported on this subject during the last decade.
The following Sections describe the catalytic applicability of scandium(III) triflate in organic synthesis.

Synthesis of primary homoallylic alcohols
Sultana et al. 29 developed a simple protocol for the synthesis of primary homoallylic alcohols (15) from the reaction of alkenes (13) and paraformaldehyde ( 14) using scandium triflate as catalyst at room temperature (Scheme 5).

Synthesis of indolemethane derivatives
Kerr and his group 33 developed an expedient and efficient method for the synthesis of indolemethane derivatives (29) from the reaction of indolylmethyl Meldrum's acids (27) with a variety of nucleophiles (28) via the nucleophilic displacement of the Meldrum's acid moiety in the presence of catalytic scandium triflate at 50 o C in acetonitrile as solvent (Scheme 9).Scheme 9. Scandium(III) triflate catalyzed synthesis of indolemethane derivatives.

Synthesis of primary amides
Allam et al. 34 described a versatile microwave-assisted synthetic protocol for the one-pot synthesis of primary amides (31) from aldehydes (19) and hydroxylamine hydrochloride (30) using scandium(III) triflate as a catalyst in water (Scheme 10).

Synthesis of β-amino alcohols
Placzek et al. 36 reported a simple, straight forward, efficient method for the synthesis of β-amino alcohols (38, 39, 40) via ring opening of epoxides (36, 37) with amines (35) in the presence of a catalytic amount of Sc(OTf)3 at room temperature under solvent-free conditions (Scheme 12).

Synthesis of N-substituted pyrroles
Chen et al. 37 developed a simple and efficient method for the synthesis of N-substituted pyrroles (43) by the Paal-Knorr condensation of various amines (42) with 1,4-diketones (41) using a catalytic amount of Sc(OTf)3 under neat conditions at ambient temperature (Scheme 13).They also successfully recovered and reused the catalyst without significant loss in catalytic activity.

Synthesis of N-substituted 1,4-dihydropyridine derivatives
Kikuchi et al. 43 developed a facile and straight forward method for the synthesis of N-substituted 1,4dihydropyridine derivatives (59) from the reaction of imines (57) with ethyl propiolate (58) using catalytic amount of scandium(III) triflate in toluene or benzotrifluoride under reflux conditions (Scheme 19).

Synthesis of esters
Atkinson et al. 47 demonstrated a scandium(III) triflate catalyzed protocol for the synthesis of esters (66) from the reaction of various primary amides (31) and alcohols in n-heptane at 100 o C (Scheme 23).

Conclusions
The present review offers an up-to-date literature on the latest developments of Sc(OTf)3-catalyzed organic transformations specially carbon-carbon and carbon-heteroatom bond forming reactions reported during the last decade.Therefore the present review will surely make some impacts on the on-going developments of triflate salts catalyzed organic transformations as it is one of the thrusting areas for today's organic methodologists worldwide.

Synthesis of sugar fused pyranopyran derivatives
49with pent-4-ene-1,2-diol (67) in the presence of 5 mol% scandium triflate and 15 mol% ptoluenesulfonic acid in dichloroethane at 80 o C. Tandem ene-Prins cyclization between an aldehyde(19)and O-prenyl derivative of a sugar aldehyde (69) was successfully coupled by Reddy et al. (Scheme 25)49using a catalytic amount of scandium triflate (10 mol %) at ambient temperature in dichloromethane to produce a novel series of sugar fused pyranopyran derivatives (70) in good to excellent yields with high enantioselectivity.

Sulfur-Sulfur Bond-forming Reactions 7.1 Synthesis of thiosulfonates
55(OTf)3-catalyzed sulfenylation of sodium sulfinates (82) with N-(organothio)succinimides (83) ionic liquids and water as cosolvent was by Liang et al. (Scheme 31)55to afford thiosulfonates (84) in moderate to excellent yields at ambient temperature.They also successfully recovered and reused the ionic liquid containing Sc(OTf)3 for several reaction cycles without any significant loss of catalytic activity.

Other Reactions 8.1. Deprotection of tert-butyl aryl sulfonamides
56halingam et al.56developed a mild and high-yielding method for removal of a variety of tert-butyl protecting group from the N-substituted aryl sulfonamides (85) to form the corresponding sulfonamides (86) utilizing Sc(OTf)3 as catalyst in nitomethane at ambient temperature (Scheme 32).