Dioxaborolane ligand

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... 

The enantioselective cyclopropanation leading to 1,2,3-snbstitnted cyclopropane derivatives proceeds with high diastereocontrol (equation 86) . It is quite interesting to observe that the same reaction, when run in the absence of the dioxaborolane ligand, led to lower diastereoselectivity. Other functionalized 1,1-diiodoaLkanes can be used as the zinc carbenoid precursor, but it should be noted that up to 2 equivalents of the reagent (4 equivalents of RCHI2) are needed in this process. This reaction has been applied in the synthesis of ambruticin. ... 

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... 

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... 

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). 

Dinitrobenzoyl chloride Benzoyl chloride, 3,5-dinitro- (99-33-2), 76, 277 2,4-Dinitrofluorobenzene, 76, 52 Diol metabolites, 76, 82 Dioxaborolane ligand, 76, 89... 

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

The second procedure takes into account the possible complications that could be encountered and it takes advantage of the use of the air-stable diethanolamine derivative 4. Treatment of 4 with tartaramide 2, under biphasic conditions generates the dioxaborolane ligand 1 (Eq 3). Although this second protocol requires one extra step, it is overall more efficient and more convenient than the previous one since both precursors are stable to storage. 

The dioxaborolane ligand 1 has been found to effectively convert allylic alcohols to their corresponding enantioenriched cyclopropylmethanols in high yields and high enantiomeric excesses. The Zn(CH2l)2 reagent or its DME... 

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

The second site to be altered was the alkyl substituent on the boron center. Initially, it was proposed that the nature of this group should not have a major impact on the level of enantioselection of the cyclopropanation reaction. It is believed that this group simply adopts the pseudoequatorial position of the envelope conformation of the five-membered ring. Several different dioxaborolane ligands were prepared by the same method as that reported earlier. Four novel dioxaborolane additives were prepared with R = Me, Ph, 2-naphthyl and 2,4,6-trimethylphenyl. The enantioselectivities observed for the cyclopropanation reaction are shown in Table I. In all the cases, the enantioselectivities were in the same range as that obtained with R = Bu, except for the 2,4,6-trimethylphenyl substituent. This information suggests that a sterically encumbered substituent on boron may partially prevent the postulated association between the zinc alkoxide and the boron center. In that case, the non-boron-assisted pathway can eventually become competitive. 

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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