Chiral disulfonamide

Ukaji et al.117 reported an enantioselective cyclopropanation reaction in which moderate enantiomeric excess was obtained when a stoichiometric amount of diethyl tartrate was used as a chiral modifier. Takahashi et al.118 achieved better results using the C2-symmetric chiral disulfonamide 205 as the chiral ligand. 

Enantioselective addition of functionalized diorganozincto benzaldehyde catalysed by chiral disulfonamide-Ti(Oi-Pr)2 (Structure 15)16 ... 

There is only one example of a catalytic enantioselective cyclopropanation of allylic alcohols using an electron withdrawing chiral disulfonamide 19 as a chiral ligand (Protocol 6).33 Stoichiometric highly enantioselective cyclo-propanations of allylic alcohols are reported using a chiral diethyl tartrate34 and a chiral tartamide.35... 

Enantioselective cyclopropanation of an allylic alcohol using chiral disulfonamide (Structure 19) as a chiral catalyst336... 

Recently, many efforts have focused on the development of the enantioselective (iodomethyl)zinc-mediated cyclopropanation of allylic alcohols. Kobayashi and co-workers reported that moderate to good enantioselectivities were observed if a C2-symmetric chiral disulfonamide was added. To reduce the rate of uncatalyzed... 

A more convenient method for the preparation of functionalized organozinc species is hydroboration of an alkene followed by transmetalation with Et2Zn [36]. In this scheme, a wider range of functional organozincs is readily synthesized. For example, Knochel et al. reported that a dialkylzinc, prepared from a dienic silyl enol ether, enantiomerically added to various aldehydes in the presence of the chiral disulfonamide-titanium system (Scheme 12) [37]. 

CH2I2, Et2Zn, chiral disulfonamide (enantioselective) CH2I2, Et2Zn, chiral dioxaborolane (enantio-selective)... 

Recently, many efforts have been focused on the development of the enantioselective (iodomethyl)zinc-mediated cyclopropanation of allylic alcohols. Kobayashi and co-workers reported that moderate to good enantioselectivities were observed if a Ci-symmetric chiral disulfonamide was added. " To reduce the rate of uncatalyzed process responsible for decrease of enantioselectivity, Charette and Brochu studied the effect of addition of Lewis acid, and proved that TiCU accelerates the reaction. The addition of the chiral titanium catalyst 548 allowed the conversion of 3-aryl and 3-heteroaryl-substituted allylic alcohols to the corresponding cyclopropane derivatives in enantiomeric ratios up to 97 3 (Scheme 2-154, eq. (a)). The dioxaborolane ligand 549 is an efficient chiral reagent for the enantioselective cyclopropanation not only of allylic alcohols but also of unconjugated and conjugated... 

In 2000, these workers described disulfonamide ligands derived from camphor, which could be easily prepared from chiral camphorsulfonyl chloride, and further successfully used in the enantioselective addition of ZnEt2 to... 

The use of chiral C2-symmetric trifluoromethanesulfonamides derived from (i )-1,1 -binaphthyl-2,2 -diamine in similar reactions to those described above has led to the formation of the expected alcohols with enantioselectivities of 43-54% ees. Better enantioselectivities were observed by Paquette et al, resulting from the use of chiral C2-symmetric VERDI (verbenone dimers) disulfonamides derived from the dimerisation of (+ )-verbenone. Stereoselectivity levels ranging from 72 to 98% ee were observed, depending on the structural characteristics of the aldehyde (Scheme 3.45). ... 

Lewis acid-promoted asymmetric addition of dialkylzincs to aldehydes is also an acceptable procedure for the preparation of chiral secondary alcohol. Various chiral titanium complexes are highly enantioselective catalysts [4]. C2-Symmet-ric disulfonamide, chiral diol (TADDOL) derived from tartaric acid, and chiral thiophosphoramidate are efficient chiral ligands. C2-Symmetric chiral diol 10, readily prepared from 1-indene by Brown s asymmetric hydroboration, is also a good chiral source (Scheme 2) [17], Even a simple a-hydroxycarboxylic acid 11 can achieve a good enantioselectivity [18]. 

The alternative method shown in equation 18, using a chiral alcohol, like (S,S)-97, as the chiral Brpnsted acid, affords a high level of facial selectivity for the enantioselective protonation of lithium enolate 95 to give the required 2-methyltetralone (5)-93 in yields and enantiomeric purity similar to those of equation 17 °. The concept of internal versus external proton delivery has been probed ° . The use of disulfonamide (R,R)-9S as chiral Brpnsted acid leads to the (R)-93 enantiomer (equation 19), whereas using as chiral scaffold (R,R)-99, the (V,(V -dilithio salt of (R,R)-99 and acetic acid (as external proton source) gives (S)-93 (equation however, in poorer yield and enantiomeric... 

Ohno et al. developed an enantioselective alkylation by the use of a C2-sym-metric disulfonamide as a chiral ligand[ 19,20,21 ]. They designed the chiral catalyst based on the concept that coordination of an electron-withdrawing chiral ligand to the Lewis acid, Ti(0-z-Pr)4, enhances the catalytic activity. Actually, the acidity of the disulfonamide has an influence on the enantioselectivity and fluorine-containing disulfonamides, especially trifluoromethylsulfonamide, were found to be the best choice of chiral catalyst (Scheme 7). It should be noted that a decrease in the amount of chiral ligand from 0.02 equiv. to 0.0005 equiv. has no effect on the yield and ee and the turnover reached 2,000. Also in the alkylation of aliphatic aldehydes, very high enantioselectivities can be attained. 

A special case of acylation of amines occurs when using the chiral supported 1,2-disulfonamide 66 (0.58mmolg 1 loading), which can be considered the first polymeric reagent employed in the kinetic resolution of primary amines through enantioselective acetylation of one of the enantiomers in the racemic mixture [79]. The Merrifield-derived chiral scaffold could be quantitatively recovered and recycled. 

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