Chiral dioxaborolane ligands

Unprecedented high ann-selectivities are obtained when E-substituted chiral allylic alcohols are treated with bis(iodomethyl)zinc and the dioxaborolane ligand (eq 8). In contrast, the ryn-isomer is obtained if the substrate is treated with the zinc reagent in the absence of the chiral ligand. The method complements that involving the direct reduction of cyclopropylketones with LiAlH4 or DIBAL-H. z... 

The tartaric acid scaffold also led to the design of one of the most effective and general methods to generate enantiomerically enriched substituted cyclopropyhnethanol derivatives. Indeed, the chiral dioxaborolane ligand 19, prepared from tetramethyltartramide and butylboronic acid, is a superb chiral additive in allylic alcohol-directed cyclopropanation reactions (equation 83) . The best procedure requires the use of the soluble bis(iodomethyl)zinc DME complex . The reaction affords high yields and enantiomeric... 

A case of matched and mismatched pairs was observed in the reagent-controlled cyclopropanation of chiral allylic alcohols. When the chiral, nonracemic allylic alcohol was treated with one enantiomer of the dioxaborolane ligand, the anti diastereomer was... 

A number of good reagent-based approaches have appeared in the last few years,30 but the chiral dioxaborolane ligand 18 has turned out to be superior.31... 

The enantioselective cyclopropanation of acyclic allylic alcohols can be achieved with excellent enantioselectivities when the reaction is carried out in the presence of the chiral dioxaborolane ligand 18 (Equation 13.6, Protocol 11). This reaction also features the preparation of Zn(CH2I)2 DME complex which is soluble in dichloromethane.32 This chiral additive is also very effective for the synthesis of 1,2,3-substituted cyclopropanes, when 1,1-substituted diiodoalkanes are used as precursors.33 Finally, this method has been used extensively in natural product synthesis.34... 

Enantioselective Synthesis of 1,2,3-trisubstituted Cycio propanes. The chiral dioxaborolane ligand can also be used to generate 1,2,3-substituted cyclopropyl units when the appropriate 1,1-diiodoalkane is used in the preparation of the zinc reagent (eq 9). The reaction affords 1,2,3-trisubstituted cyclopropanes with excellent enantio- and diastereocontrol, including those obtained from functionalized zinc reagents (eq 10). 

For example, it has been used to elaborate the chiral cyclopropanes subunits of Curacin A[60], and of the structurally fascinating FR-900848 [61] and U-106305 [62]. The chiral dioxaborolane-derived ligand was also effective to synthesize 1,2,3-substituted cyclopropanes [63]. Excellent to outstanding diastere-oselectivities and enantioselectivities were observed when a variety of allylic alcohols were treated with the reagent formed by mixing 1,1 -diiodoethane and di-ethylzinc. It was also shown that functionalized 1,1-diiodoalkanes could also be used in this reaction. 

The cyclopropanation of cinnamyl alcohol is a good example of the use of dioxaborolane ligand 3 as chiral additive to synthesize chiral cyclopropanes. 

Figure 2 Representative examples of enantioenriched cyclopropylmethanols obtained from chiral allylic alcohols using the dioxaborolane ligand 1 and bis(iodomethyl)zinc.

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... 

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