Enolborinates

Furthermore, both (E)- and (Z)-enolborinates add to aldehydes in a stereoconvergcnt manner, giving predominantly, syn-/J-hydroxycarbonyl compounds49. In contrast, only moderate induced diastereoselectivity is obtained in the reaction of achiral aldehydes with C2-symmetric enolborates, whereby the chiral information is located in the ligand at the metal atom50. The ee of the product /1-hydroxy ketones ranges from 4 to 72%. 

However, if the isopinocampheyl residue is used instead of achiral ligands (such as butyl or cyclohexyl) in the enolborinate, the diastereoselectivity is slightly improved (93 7). Thus, the combination of substrate-induced and auxiliary-induced stereoselectivity has only a marginal effect in this case56. 

The syntheses in Schemes 13.36 and 13.37 illustrate the use of chiral auxiliaries in enantioselective synthesis. Step A in Scheme 13.36 establishes the configuration at the carbon which becomes C-4 in the product. This is an enolate alkylation in which the steric effect of the oxazolinone substituents directs the approach of the alkylating group. Step C also uses the oxazolidinone structure. In this case, the enolborinate is formed and condensed with the aldehyde intermediate. This stereoselective aldol condensation establishes the configuration at C-2 and C-3. The configuration at the final stereocenter is established by the hydroboration in step D. The selectivity for the desired stereoisomer is 85 15. Stereoselectivity in the same sense has been observed for a number of other 2-methyl-alkenes in which the remainder of the alkene constitutes a relatively bulky 135... 

Hooz, J. and Bridson, J. N. A method for the regiospecific synthesis of Mannich bases. Reaction of enolborinates with dimethyl (methylene) ammonium iodide, J. Am. ChertL Soc.. 95, 602, 1973. 

Other Uses. Reagent 1 has been used for enantioselec-tive enolborination, albeit with poor (1.1 1) selectivity. Similar bis-sulfonamide-derived boron Lewis acids have been used for aldol additions, "" ester-Mannich reactions, Diels-Alder reactions, Ireland-Claisen reactions, and [2,3]-Wittig rearrangements. Similar bis-sulfonamide-derived aluminum Lewis acids have been used for aldol additions, Ehels-Alder... 

Enolboration of Ketones and Opening of meso-Epoxides. Methyl alkyl ketones have been successfully enolized by IpciBX (X = OTf or Cl) in the presence of a tertiary amine. The corresponding enolborinates have been used in asymmetric aldol condensations (eq 5). The reagent has also been applied to the enantioselective opening of mcj o-epoxides to form the corresponding nonracemic chlorohydrins (eq 6). ... 

Selective trans deprotonation of the ketone-L2BOTf complex leads to formation of (Z)-enolborinate see Evans, D. A. Nelson, J. V. Vogel, E. Taber, T, R. J. Am. Chem. Soc. 1981, 103, 3099. An alternative explanation for L2BCI to ( )-enol borinate and L2BOTf to (Z)-enol borinate has been proposed by Corey and Kim see Corey, E. J. Kim,... 

Enolization and protonation. 4-Substituted cyclohexanones undergo enolsilylation on treatment with chiral lithium amides 3, 4, and the dilithio derivatives of a urea. Enantioselective enolborination is accomplished with a combination of (-)-Ipc BCl and sparteine. ... 

For a selection of theoretical studies involving enolborinates and lithimn enolates, see ... 

The reactions of aldehydes with enolborinates and allylboranes also take place after coordination of the boron atom with the carbonyl group. An early cyclic transition model C (X = O or CH2) often accounts for the observed selectivity (Figure L20.a) ( 6.6.1 and 6.8). 

The geometry of enolborinates of thiolesters depends mainly upon the nature of the sulfur substituent. Masamune and coworkers [691] have shown that the reaction of thiophenyl propionate (MeCI COSPh) with 2.14 (R = OTf) leads to E-6.85, while triethylmethylthiol propionate (MeCH2COSCEt3) leads to Z-6.85 (Figure 6.75). A similar trend is observed in the reaction of MeCI COS-tert-Bu with 6.83 (X = Br) [1248], The reaction of Z-enolborinates Z-6.85 generated from 2.14 (R = OTf), 2.61 (R = OTf) or 6.83 (X = Br) with aldehydes is highly diaste-... 

Double stereodifFerentiation was used to achieve enantioselective enolborination of chiral ketones by reaction with chlorobis(isopinocampheyl)borane (DIPCl) in the presence of a chiral amine [69]. As an example, reaction of excess ( )-94 with IPC2BCI and sparteine at —78°C produced 95 regioselectively with a 90% ee (evaluated after oxidation into diadds). 

There are still only a few examples of the creation of regiosomeric products from a racemic substrate by a chiral reagent. Two examples are mentioned in Scheme 2.7. The enolborination of racemic ketone 94 with (-)-DipCl has been... 

Attempted Enantioselective Enolborination. Some limitations to the scope of bromoborane 1 in asymmetric processes are documented. For example, atten5)ts to desymmetrize (or Q) symmetric bifunctional substrates by selective enolborination have not been successful (eq 12). ... 

B-Alkenyls-9-BBN prepared by the hydroboration of acetylenes with 9-BBN are transferred in a stereospecific manner to a,p-unsaturated carbonyl compounds in a 1,4-fashion (Scheme 7.6) [10]. The hydrolysis of the enolborinate provides the corresponding y,6-enones. 

The literature describes number of methods for the generation of enolborinates [1]. Enolborinates are valuable intermediates [2] and react with high stereospecificity in aldol condensation [3-8]. Brown and coworkers [9] have carried out a detailed study of the stereochemistry of ketone enolization with B-C1-9-BBN [10], B-OTf-9-BBN [3c], Chx BCl [10], and ChXjBOTf [9] to get ( )- or (Z)-enolborinates. It is found that stereochemical outcome of the reaction varies not only with the steric requirements of RjB and steric requirements of the amine [4, 5b, c], but also with the nature of the leaving group. Cl or OTf (Table 20.1) [9]. 

The effects of varying the amine and alkyl groups on boron are more significant in the case of R BCl than in the case of RjBOTf, and quantitative synthesis of (Z)-enolborinate has been achieved using l-PrjEtN and B-C1-9-BBN, whereas enolization with Chx BCl and amine EtjN gives (E)-enolborinate (Scheme 20.1 Table 20.2) [9], almost exclusively. 

The steric requirement of the substituent R in EtCOR also plays a significant role in the control of enolate geometry. The smaller R groups favor the formation of Z-enolates, while bulkier R groups favor the formation of -enolate. Consequently, EtCOBu-f with all the RjBX (except RjBI) favor the formation of -enolborinate, either exclusively or predominantly (Table 20.5) [11]. 

The stereoselective enolboration of propiophenone (Table 20.6) [11] is also controlled by the nature of leaving groups of H-X-9-BBN and of Chx BX. Chx BI behaves unusually, favoring the formation ofZ-enolate. The selective generation of -enolborinate with Chx BCl/EtjN from propiophenone is one of the significant achievements. 

AUais C, Tsai AS, Nuhant P, Roush WR (2013) Highly diaste-reo- and enantioselective aldol reactions of stereochemically defined tetrasubstituted enolborinates generated by 1,4-hyd-roboration of a, p-unsaturated morpholine ceuboxamides... 

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