Chiral sulfonamide alcohol, enantioselective

Enantioselective reduction of jS-keto nitriles to optically active 1,3-amino alcohols has been carried out in one step using an excess of borane-dimethyl sulfide complex as a reductant and a polymer-supported chiral sulfonamide as a catalyst with moderate to high enantioselectivity (Figure 3.11). The facile and enantioselective method to prepare optically active 1,3-amino alcohols has been used to prepare 3-aryloxy-3-arylpropylamine type antidepressant drugs, for example (l )-fluoxetine. 

Dosa and Fu reported the first catalytic enantioselective phenyl transfer reaction to ketones (equation 25)100. In the presence of 1.5 equivalents of MeOH, the chiral tertiary alcohol was produced in good yield and with high enantioselectivity. Walsh and workers recently reported the Ti(OE -i Vchiral dihydroxybis(sulfonamide) catalyst 34 system, whereby enones have been converted to enantioenriched allyl alcohols101. 

Surprisingly few studies have been directed towards the development of noncinchona alkaloid-based catalysts for the alcoholative ASD of meso-anhydrides, or indeed any of the enantioselective alcoholysis processes. Uozumi has reported a series of (2S, 4R)-4-hydroxyproline-derived 2-aryl-6-hydroxyhexahydro-lfi-pyr-rolo[l,2-c] imidazolones which mediate the methanolytic ASD of ds-hexa-hydrophthalic anhydride in up to 89% ee when employed at the 10 mol% level for 20 h at —25 °C in toluene [186]. Additionally, Nagao has described the use of a bifunctional chiral sulfonamide for the thiolytic ASD of meso-cyclic anhydrides in up to 98% ee when employed at the 5 mol% level for 20 h at rt in ether [187]. 

The excellent enantioselectivity and wide scope of the CBS reduction have motivated researchers to make new chiral auxiliaries [3]. Figure 1 depicts examples of in situ prepared and preformed catalyst systems reported since 1997. Most of these amino-alcohol-derived catalysts were used for the reduction of a-halogenated ketones and/or for the double reduction of diketones [16-28]. Sulfonamides [29,30], phosphinamides [31], phosphoramides [32], and amine oxides [33] derived from chiral amino alcohols were also applied. The reduction of aromatic ketones with a chiral 1,2-diamine [34] and an a-hydroxythiol [35] gave good optical yields. Acetophenone was reduced with borane-THF in the presence of a chiral phosphoramidite with an optical yield of 96% [36]. 

Several catalytic systems have been reported for the enantioselective Simmons Smith cyclopropanation reaction and, among these, only a few could be used in catalytic amounts. Chiral bis(sulfonamides) derived from cyclo-hexanediamine have been successfully employed as promoters of the enantioselective Simmons-Smith cyclopropanation of a series of allylic alcohols. Excellent results in terms of both yield and stereoselectivity were obtained even with disubstituted allylic alcohols, as shown in Scheme 6.20. Moreover, this methodology could be applied to the cyclopropanation of stannyl and silyl-substituted allylic alcohols, providing an entry to the enantioselective route to stannyl- and silyl-substituted cyclopropanes of potential synthetic intermediates. On the other hand, it must be noted that the presence of a methyl substituent at the 2-position of the allylic alcohol was not well tolerated and led to slow reactions and poor enantioselectivities (ee<50% ee). ... 

Carbonyl Allylation and Propargylation. Boron complex (8), derived from the bis(tosylamide) compound (3), transmeta-lates 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). 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 1992 Kobayashi et al. [47] reported the first catalytic and enantioselective cyclo-propanation using the Furukawa modification [48] of the Simmons-Smith reaction of allylic alcohols in the presence of a chiral bis(sulfonamide)-Zn complex, prepared in-situ from the bis(sulfonamide) 63 and diethylzinc. When cinnamyl alcohol 62 was treated with EtgZn (2 equiv.), CHgIg (3 equiv.), and the bis(sulfonamide) 63 (12 mol %) in dichloromethane at -23 °C, the corresponding cyclopropane 64 was obtained in 82 % yield with 76 % ee (Sch. 26). They proposed a transition state XXIII (Fig. 5) in which the chiral zinc complex interacts with the oxygen atom of the allylic alkoxide and the iodine atom of iodomethylzinc moiety. They also reported the use of the bis(sulfonamide)-alkylaluminum complex 65 as the Lewis acidic component catalyzing the Simmons-Smith reaction [49]. 

The A, A -bis(arenesulfonyl)cyclohexane-1,2-diamines used as chiral controllers (see also Houben-Weyl, Vol. E21, pp 1327, 3895) can also be employed as their aluminum complexes to catalyze the cyclopropanation of allylic alcohols with diethylzinc and diiodomethane. ° The bis(sulfonamide)aluminum complex was first prepared in situ in 1,2-dichloroethane and after removal of the solvent in vacuo, cyclopropanation was carried out in dichloromethane at — 20 °C. The enantioselectivities are similar to those obtained with the chiral zinc catalyst described above. However, the most characteristic feature of the chiral aluminum complex catalyzed reaction is that no decrease in the enantioselectivity was observed even at a higher concentration. An electron-withdrawing group on the benzene ring of the sulfonamide or the... 

Optimization of the reaction protocol and the study of the effect of promoter structure on selectivityin the catalytic enantioselective cyclopropanation with bis(halomethyl)zinc reagents have been reported recently. Prior formation of a zinc alkoxide and the use of added zinc iodide are critical for efficient catalytic enantioselective cyclopropanation of allylic alcohols using chiral bis(sulfonamides), the simple A7,iV -dimesylcyclohexane-l,2-diamine being the most effective in terms of rate and enantioselectivity. 

Although the enantioselective stoichiometric addition of chiral aryltitanium reagents have been reported in 1987 [66], the catalytic enantioselective aryl addition to carbonyl compounds with titanium catalyst was realized by Walsh using the catalyst prepared from bis(sulfonamide) ligand and Ti(OTr)4 with diarylzinc as the nucleophiles, to afford the tertiary alcohol in good to excellent enantioselectivities for a range of ketone substrates [67]. Very recently, Gau reported that... 

The reaction of 2-bromoacrolein with a-methyl buta-1,3-diene was demonstrated to be efficiently catalyzed by the chiral titanium complex derived from a sulfonamide of an amino alcohol, affording the DA product with high enantioselectivity [153] (Scheme 14.62). 

Kobayashi and coworkers reported catalytic asymmetric Simmons-Smith type reaction of allylic alcohols (Scheme 6.98). In this reaction, Lewis acid (R,R)-(112) prepared by premixing of (1R,2R)-cyclohexane bis-sulfonamide and i-Bu2AlH was found to realize good enantioselectivity. Since, in the similar reaction catalyzed by chiral Zn complex derived from (1R,2R)-cyclohexane bis-sulfonamide and Et2Zn instead of chiral aluminum complex, the same enantioselectivity was observed, chiral Zn carbenoid species formed from (R,R)-(112) and Et2Zn via Al-Zn transmetallation was proposed as an active species [117]. 

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