Chiral 1,3,2-dioxaborolane

This chiral modifier provides one of the only methods for selective cyclopropa-nation of substrates which are not simple, allylic alcohols. In contrast to the catalytic methods which will be discussed in the following section, the dioxaborolane has been shown to be effective in the cyclopropanation of a number of allylic ethers [67]. This method has also been extended to systems where the double... 

Several detailed studies of reactions of achiral aiiylboronates and chiral aldehydes have been reported4,52 - 57. Diastereofacial selectivity in the reactions of 2-(2-propenyl)- or 2-(2-butenyl-4,4,5,5-tetramethyl-l,3,2-dioxaborolanes with x-methyl branched chiral aldehydes are summarized in Table 252, 53, while results of reactions with a-heteroatom-substituted aldehydes are summarized in Table 34,52d 54- 57. 

Excellent double diastereoselection has also been realized in the reactions of (7 )-2,3-[isopro-pylidenebis(oxy)]propanal and chiral 2-butenylboron reagents (Table 8). The best selectivity for the (3R,4R)- and (SS /Q-diastereomers was obtained by using the tartrate ( )- and (Z)-2-butenylboronates. (S.S -D and (R,R)-D, respectively69,81, while (E)- and (Z)-2-butenyl-2,5-dimethylborolane reagents (R,R)-C and (S,S) C provided the greatest selectivity for the (3S, 45)- and (3y ,4S )-diastereomers< 9. Comparative diastereoselectivity data for reactions with the achiral (E)- and (Z)-2-butenyl-4,4,5,5-tetramethyl-l,3,2-dioxaborolanes have also been provided in the table. 

Sturmer via the reaction of the chiral borate ester (45, 5S)-4,5-dicyclohexyl-2-isopropyloxy-1,3,2-dioxaborolane, and racemic Grignard reagent (l-methyl-2-butenyl)magnesium chloride16. A 97 3 mixture of (S)-4 and its tf-diastereomer was obtained in 89% yield. 

With the analogous reagent 125, however, the corresponding allylboronate intermediate 126 is thought to favor a transition structure 127 where the a-substituent is positioned in a pseudo-axial orientation in order to escape nonbonding interactions with the bulky tetraphenyl dioxaborolane (Eq. 99). This way, a Z-configured allylic alcohol unit of opposite configuration is obtained in diol product 128. This type of steric control with chiral a-substituted allylboronates... 

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... 

CH2I2, Et2Zn, chiral disulfon-amide (enandoselecdve) CH2I2, Et2Zn, chiral dioxaborolane (enantio-selective)... 

Et2Zn, Me2NCHMeCHPhOH/ (ICH Zn (enandoselecdve) Zn(CH2I)2. chiral dioxaborolane (enandoselecdve)... 

The boron atom dominates the reactivity of the boracyclic compounds because of its inherent Lewis acidity. Consequently, there have been very few reports on the reactivity of substituents attached to the ring carbon atoms in the five-membered boronated cyclic systems. Singaram and co-workers developed a novel catalyst 31 based on dicarboxylic acid derivative of 1,3,2-dioxaborolane for the asymmetric reduction of prochiral ketones 32. This catalyst reduces a wide variety of ketones enantioselectively in the presence of a co-reductant such as LiBH4. The mechanism involves the coordination of ketone 32 with the chiral boronate 31 and the conjugation of borohydride with carboxylic acid to furnish the chiral borohydride complex 34. Subsequent transfer of hydride from the least hindered face of the ketone yields the corresponding alcohol 35 in high ee (Scheme 3) <20060PD949>. 

Another common synthesis of cyclic boron compounds involves transesterification. For example, the chiral allyl boronates 155 can be synthesized via the reaction of dioxaborolane 329 with dialkyl tartrate 330 in high yield. The transacetalization affords an attractive alternative to the formation of these chiral boronates, which are otherwise difficult to prepare (Equation 13). 

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). 

Use as a Chiral Auxiliary Synthesis of Cyclopropylboronic Acids. The chiral dioxaborolane unit can also be used as an effective chiral auxiliary in the synthesis of enantiomerically enriched cyclopropylboronic acids. For example, 1-alkenylboronic esters bearing the tetramethyltartramide group undergo diastereoselec-tive cyclopropanations to afford the cyclopropylboronic acid (eq 11). These products can be used for in situ Suzuki coupling reactions or can be oxidized to produce 2-substituted cyclopropanols. 

This method is comparable to similar, catalytic Sim-mons-Smith-type methods employing the titanium TADDOL catalyst 20 (95 5 er) or the Ci-symmetric bis-sulfonamide catalyst 32 (93 7 er) for the cyclopropanation of the allylic alcohol 22 (eq 6). However, due to the preliminary nature of these earlier investigations, substrate scope and generality have not been extensively documented. All of the aforementioned methods are limited by their dependence on the allylic alcohol functionality. Only one method for Simmons-Smith-type cyclopropanation of other substrate classes has been developed. Use of a stoichiometric, chiral dioxaborolane [CAS 161344-85-0] additive allows for selective cyclopropanation of allylic ethers, homo-ally lie alcohols and allylic carbamates. ... 

The first asymmetric Simmons-Smith reaction with a chiral Lewis acid catalyst was introduced in 1994 by Charette and Juteau and featured a chiral boron Lewis acid prepared from tartaric acid [32]. Although this process resulted in excellent enantioselec-tivity, it would not turnover, i.e. the yield was less than 10 %. In the same year Imai, Takahashi and Kobayashi introduced a chiral aluminum Lewis acid that would catalyze the cyclopropanation of allylic aleohols with significant turnover numbers but their system did not lead to asymmetric induction as high as that resulting from the dioxaborolane catalyst [33]. The catalyst is prepared from the bis-sulfonamide 132... 

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. 

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