Ethylene Chloroboronate1

[1192-03-6]  · C2H4BClO2  · Ethylene Chloroboronate  · (MW 106.32)

(mild Lewis acid, in combination with tertiary amines is a selective enolization reagent for ketones and thioesters;2 the corresponding enolates show a high degree of regio- and stereocontrol in the aldol reaction2)

Physical Data: viscous syrup at rt; bp 70-74 °C/1 mmHg; nD20 1.4640.

Solubility: insol n-pentane, diethyl ether; sol dichloromethane.

Analysis of Reagent Purity: (NMR) 11B -31.20 ppm (monomer), -23.50 ppm (associated); 1H 4.38 ppm; 13C 65.79 ppm.

Preparative Methods: obtained by reaction of Ethylene Glycol with Boron Trichloride in CH2Cl2 (85% yield).2a,3a,b

Handling, Storage, and Precautions: should be used as prepared for best results. The viscous syrup should be handled under N2 in the absence of moisture. 1.0 M Dichloromethane solutions of the reagent are stable for months when stored in the absence of moisture at -15 °C.

Regio- and Stereoselective Aldol Condensations.

Methyl, ethyl, and cyclic ketones react with ethylene chloroboronate (1) and Diisopropylethylamine at -78 °C to give the corresponding enolates (enolborates) with a high degree of regio- and stereocontrol.2a-c The selectivity is as follows: Me &egt; Et; Me > CH2CH2R; Me > CH2CHR2; Me >> CHR2; Et >> CHR2. Ethyl ketone derived enolborates are generated selectively with Z(O)-stereostructure (&egt;95%). An example is shown in (eq 1).

Reaction of enolborates with both aliphatic and aromatic aldehydes at -78 to -15 °C forms b-hydroxy ketones in good yield (60-90%) and with high syn diastereoselectivity (&egt;96:4) (eq 2).1,2

While syn selectivity from Z(O)-boron enolates is an expected result,1b much more surprising is the high syn selectivity observed with E(O)-enolborates, for example the enolate derived from cyclopentanone (eq 3).

To explain the syn selectivity for reactions of both Z(O)- and E(O)-enolates derived from (1), a chair transition state for Z(O)-enolates and a boat transition state for E(O)-enolates were suggested.2c,d Computational studies on aldol reactions using Z(O)- and E(O)-enolborates, as well as enolborinates (-O-BR2), provided a set of data which is consistent with the experimental results and further corroborates the proposed mechanism.4 The following main conclusions are drawn. (i) The ground state conformations of the enolates are important in determining the different reactivities of Z(O)-enolborates and E(O)-enolborates, the latter being much more reactive that the former. (ii) Z(O)-Enolborates prefer chair transition states, while E(O)-enolborates favor twist-boat transition states. Both transition states lead to the formation of syn aldol products. (iii) In contrast, when enolborinates are used, bulky ligands at boron disfavor the twist-boat for the E(O)-enolates, resulting in the formation of anti isomers.4

Pinacol chloroboronate-derived enolborates are also stereoconvergent, giving high yields of the syn diastereoisomers irrespective of the enolate geometry (eq 4).5

The enantioselective version of this reaction is also known, using chiral diols, but the ee's are modest (eq 5).6

Reaction of phenyl thiopropionate with (1) and diisopropylethylamine provides the corresponding enolate, whereas esters give unsatisfactory yields. Enolization at -78 °C results in a 70:30 Z(O):E(O) enolate mixture, whereas the reaction at 25 °C furnishes an 18:82 mixture. However, both enolates react with aldehydes with high syn distereoselectivity. The addition to chiral aldehydes has also been studied (eq 6).2d

1. (a) Fieser, M. FF 1986, 12, 224. (b) Kim, B. M.; Williams, S. F.; Masamune, S. COS 1991, 2, 239.
2. (a) Gennari, C.; Colombo, L.; Poli, G. TL 1984, 25, 2279. (b) Gennari, C.; Cardani, S.; Colombo, L.; Scolastico, C. TL 1984, 25, 2283. (c) Gennari, C.; Colombo, L.; Scolastico, C.; Todeschini, R. T 1984, 40, 4051. (d) Gennari, C.; Bernardi, A.; Cardani, S.; Scolastico, C. T 1984, 40, 4059.
3. (a) Blau, J. A.; Gerrard, W.; Lappert, M. F. JCS 1957, 4116. (b) Shore, S. G.; Crist, J. L.; Lockman, B.; Long, J. R.; Coon, A. D. JCS(D) 1972, 1123.
4. (a) Gennari, C.; Todeschini, R.; Beretta, M. G.; Favini, G.; Scolastico, C. JOC 1986, 51, 612. (b) Hoffmann, R. W.; Ditrich, K.; Froech, S.; Cremer, D. T 1985, 41, 5517. (c) Li, Y.; Paddon-Row, M. N.; Houk, K. N. JACS 1988, 110, 3684. (d) Li, Y.; Paddon-Row, M. N.; Houk, K. N. JOC 1990, 55, 481.
5. Hoffmann, R. W.; Ditrich, K. TL 1984, 25, 1781.
6. (a) Chow, H. F.; Seebach, D. HCA 1986, 69, 604. (b) Boldrini, G. P.; Lodi, L; Tagliavini, E.; Trombini, C.; Umani-Ronchi, A. JOM 1987, 336, 23.

Cesare Gennari

Università di Milano, Italy

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