2,2-Methylenebis(1,3,2-dioxaborinane), Lithium Complex1

(1; n = 2)

[63035-39-2]  · C7H13B2LiO4  · 2,2-Methylenebis(1,3,2-dioxaborinane), Lithium Complex  · (MW 189.76) (2; n = 1)

[57404-82-7]  · C5H9B2LiO4  · 2,2-Methylenebis(1,3,2-dioxaborolane), Lithium Complex  · (MW 161.70)

(converts aldehydes to (E)-alkenylboronic esters,1,2 which can be converted to the homologous aldehyde3 or coupled with alkenyl halides;4 converts primary alkyl halides to 1,1-alkylidenebis(boronic esters)2)

Physical Data: air-sensitive solid; precipitates from THF at 0 °C. The immediate precursor, 2,2-methylenebis(1,3,2-dioxaborinane), crystallizes from 4:1 Et2O/pentane, mp 42-43 °C, 1H NMR d 0.13 (s, BCH2B).

Preparative Methods: methylenebis(boronic acid) tetramethyl ester is prepared by addition of a mixture of (MeO)2BCl and CH2Cl2 to Li dispersion in THF vigorously stirred at -40 to -30 °C,1a,5 then transesterified with 1,3-propanediol.2 The lithium complex is formed by treatment with Lithium 2,2,6,6-Tetramethylpiperidide (LiTMP) and TMEDA in THF.2

Handling, Storage, and Precautions: 2,2-methylenebis(1,3,2-dioxaborinane) can be transferred and weighed in air, but should be stored under an inert atmosphere. The lithium complex is generated as needed and must be protected from moisture and oxygen.

Reagent Preparation.

Dimethoxyboron chloride is prepared by mixing Trimethyl Borate with Boron Trichloride below 0 °C, then mixed with dichloromethane and added to a vigorously stirred suspension of lithium metal dispersion in THF kept at an internal temperature between -40 and -30 °C by manipulating the rate of addition and the position of the -78 °C cooling bath.1a,5 It is essential that the stirring be very vigorous, that there be some excess of (MeO)2BCl and CH2Cl2 over the amount of Li, and that large amounts of unreacted (MeO)2BCl/CH2Cl2 not be allowed to accumulate before the exothermic reaction sets in. The lithium salts are filtered with the aid of celite in a large Büchner funnel under a blanket of argon (CAUTION: some pyrophoric lithium metal may remain). The filtrate is given an initial rapid distillation, and the distillate is redistilled to separate the CH2[B(OMe)2]2 (3), bp 48-52 °C 15 mmHg (35%). Treatment of (3) with 1,3-propanediol and crystallization from 4:1 Et2O/pentane yields 2,2-methylenebis(1,3,2-dioxaborinane) (4), mp 42-43 °C (78%). The lithium complex of 2,2-methylenebis(1,3,2-dioxaborinane) (1) precipitates on treatment of (4) with LiTMP and TMEDA in THF (eq 1).2 For some purposes, (1) can be used as a slurry, but for reaction with aldehydes the yields are much improved if (1) is filtered in a Schlenk apparatus first.2

Substitution of CHCl3 for CH2Cl2 in the above procedure provides HC[B(OMe)2]3,1a,5 which with ethylene glycol yields 2,2,2-methanetris(1,3,2-dioxaborolane) (5), which with BuLi forms the lithium complex of 2,2-methylenebis(1,3,2-dioxaborolane) (2) (eq 2).6 Yields of HC[B(OMe)2]3 varied more than those of (3),2 and the deprotonation of (4) is generally more practical even though the lithiation of (2) is cleaner, and use of (2) does not require the Schlenk filtration.

Alkenylboronic Esters.

A key step in the palytoxin synthesis was reaction of (1) with a structurally complicated aldehyde to form the corresponding (E)-1-alkenylboronic ester (eq 3), (E):(Z) ratio 8:1.4 The usual route to (E)-1-alkenylboronic esters, hydroboration of an alkyne with catecholborane,7 could not be used in this case because of interference by a remote urethane substituent.

The model reactions for the foregoing chemistry were previous work done with (2), which yielded a series of (E)-1-alkenylboronic esters in ~10:1 (E):(Z) ratio.6

Carbonyl Homologation.

Reaction of (2) with aldehydes followed by in situ oxidation with Hydrogen Peroxide buffered with NaHCO3 or, preferably, Sodium Perborate yields the homologous aldehydes (eq 4).3

Ketones R2C=O were similarly converted to R2CH-CHO (65-81%). The use of (1) for this purpose has been shown to give equivalent results in the one example tested, heptanal to octanal, but only if the (1) is collected by filtration in a Schlenk apparatus before reaction with the aldehyde.3

Alkylation and Acylation of (1).

Primary alkyl bromides or iodides alkylate (1), and the resulting 1,1-diboronic esters (6) can be deprotonated and alkylated a second time (eq 5).2 In general, a better route to (6) is provided by dihydroboration of an alkyne with HBCl2,8 provided there is no interfering functionality or chain branching in R1.

Reaction of (1) or the anion from (6) with carboxylic esters yields ketones (eq 6).2 The recent ready availability of RCH2CH(BCl2)2 and hence (6) via hydroboration8 makes this route potentially useful.

Related Reagents.

Other boronic esters that can be deprotonated and undergo reactions analogous to those of (1) include Me3SiCH2BO2C2Me49 and PhSCH2BO2C2Me4.10


1. (a) Matteson, D. S. In Gmelin's Handbuch der Anorganischen Chemie, 8th ed. Suppl.; Springer: Berlin, 1977; Vol. 48, Part 16, pp 37-72. (b) Matteson, D. S. In The Chemistry of the Metal-Carbon Bond; Hartley, F.; Patai, S. Eds.; Wiley: New York, 1987; Vol. 4, pp 307-409. (c) Matteson, D. S. T 1989, 45, 1859.
2. Matteson, D. S.; Moody, R. J. OM 1982, 1, 20.
3. Matteson, D. S.; Moody., R. J. JOC 1980, 45, 1091.
4. Armstrong, R. W.; Beau, J.-M; Cheon, S. H.; Christ, W. J.; Fujioka, H.; Ham, W.-H.; Hawkins, L. D.; Jin, H.; Kang, S. H.; Kishi, Y.; Martinaelli, M. J.; McWhorter, W. W., Jr.; Mizuno, M.; Nakata, M.; Stutz, A. E.; Talamas, F. X.; Taniguchi, M.; Tino, J. A.; Ueda, K.; Uenishi, J.; White, J. B.; Yonaga, M. JACS 1989, 111, 7525.
5. Castle, R. B.; Matteson, D. S. JOM 1969, 20, 19.
6. Matteson, D. S.; Jesthi, P. K. JOM 1976, 110, 25.
7. Brown, H. C.; Gupta, S. K. JACS 1972, 94, 4370.
8. Soundararajan, R.; Matteson, D. S. JOC 1990, 55, 2274.
9. Matteson, D. S.; Majumdar, D. OM 1983, 2, 230.
10. Matteson, D. S.; Arne, K. H. OM 1982, 1, 280.

Donald S. Matteson

Washington State University, Pullman, WA, USA



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