(4R,5R)‐4,5‐Dicyclohexyl‐2‐ethyl‐1,3,2‐dioxaborolane

[152428-72-3] C16H29BO2 (264.21) InChI = 1S/C16H29BO2/c1-2-17-18-15(13-9-5-3-6-10-13)16(19-17)14-11-7-4-8-12-14/h13-16H,2-12H2,1H3/t15-,16-/m1/s1 InChIKey = CPSCOPNVLILSKG-HZPDHXFCSA-N (representative starting material for asymmetric synthesis via α-halo boronic esters1, 2) Alternate Name: ethylboronic acid, (R,R)-1,2-dicyclohexyl-1,2-ethanediol ester; (R,R)-DICHED ethylboronate. Physical Data: bp 85–87°C (100–200 Pa); 1H NMR δ 0.78 (q, BCH2), 0.96 (t, CH3), 0.90–1.28 Hz and 1.50–1.77 (m, cyclohexyl), 3.82 (m, OCH).1 Preparative Methods: transesterification of B(O-i-Pr)3 with (R,R)-1,2-dicyclohexyl-1,2-ethanediol2 yields (4R,5R)-4,5-dicyclohexyl-2-isopropoxy-1,3,2-dioxaborolane, which reacts with ethylmagnesium chloride in THF at −78°C.1 Another simple route to (R,R)-1,2-dicyclohexyl-1,2-ethanediol [(R,R)-DICHED] ethylboronate 3 involves transesterification of dibutyl ethylboronate 1 with (R,R)-DICHED 2 (eq 1).1 (1) The original preparation of 2 by hydrogenation of 1,2-diphenyl-1,2-ethanediol 4 over a rhodium on alumina catalyst2 has been substantially improved by in situ conversion of 4 to its methoxyborate ester 5 (eq 2), which allows the use of an active catalyst prepared in situ from rhodium chloride with ∼2% reductive cleavage of the benzylic hydroxyl groups, a major side reaction if the free diol is hydrogenated.3 (2) The hydrogenation is necessary because 4 is not a satisfactory chiral director.2, 3 The large-scale preparation of 4 or its (S,S)-enantiomer from trans-stilbene is easily accomplished via Sharpless dihydroxylation.4 However, commercial samples of potassium osmate are sometimes less soluble than the batch used by Wang and Sharpless. The oxidation is fully reliable if the osmium compound is dissolved in water and added slowly to the reaction mixture.3 Ethylboronic esters such as 1 are readily accessible via the classical reaction of the ethyl Grignard reagent with a trialkoxyborane5 or the recent hydroboration of ethylene with boron trichloride and triethylsilane.6 However, an efficient and practical alternative is the direct ethylation of (R,R)-DICHED isopropoxyborate 6, prepared in situ from 2 and triisopropyl borate, with ethylmagnesium chloride (eq 3).1 It is important to prepare 6 that is free from hydroxylic contaminants and to ethylate it with a full equivalent of Grignard reagent in order to avoid the formation of by-product difficult to separate by distillation, most likely the B-O-B linked dimeric anhydride of DICHED borate. (3) A close analog of 3, (R,R)-DICHED methylboronate 8, has been made from commercially available trimethylboroxine and 1,2-diphenyl-1,2-ethanediol via the corresponding boronic ester 7 by hydrogenation over rhodium on alumina, prepared in situ from rhodium chloride (eq 4).3 This hydrogenation resulted in no detectable benzylic cleavage. In any attempt to adapt this approach to compounds of higher molecular weight, it should be taken into account that diphenylethanediol esters such as 7 can decompose, probably via pinacol rearrangement, if overheated during distillation. (4) Handling, Storage, and Precautions: (R,R)-DICHED ethylboronate 1 and similar boronic esters are generally stable during transfer and weighing in air, and do not hydrolyze. Their susceptibility to autoxidation appears comparable to that of common aldehydes, and storage in rigorously sealed containers is advised. No special hazards are known.