Chloro(thexyl)borane-Dimethyl Sulfide

[75067-06-0]  · C8H20BClS  · Chloro(thexyl)borane-Dimethyl Sulfide  · (MW 194.57)

(highly regioselective, monohydroborating agent for alkenes and alkynes, producing thexylalkylchloroboranes or thexylalkenylchloroboranes, respectively, which are synthetically useful intermediates;1 reduces carboxylic acids to aldehydes;2 reduces aldehydes and ketones to alcohols2b)

Solubility: sol CH2Cl2, ether, and THF, but CH2Cl2 is the solvent of choice;3 reacts rapidly with protic solvents.2b

Form Supplied in: prepared in situ.

Preparative Method: most conveniently prepared from commercially available monochloroborane-dimethyl sulfide complex and 2,3-dimethyl-2-butene in CH2Cl2 (eq 1).1a,3

Analysis of Reagent Purity: analyzed by 11B NMR and IR spectroscopy and by hydrogen evolution upon reaction with methanol.3

Handling, Storage, and Precautions: very reactive with oxygen and moisture and must be handled using standard techniques for handling air-sensitive materials.4 Reported to be stable for at least two months when stored at 0 °C in CH2Cl2 solution under N2.2b

Hydroboration of Alkenes and Alkynes.

Chloro(thexyl)borane-dimethyl sulfide (ThxBHCl.SMe2) in CH2Cl2 is a monohydroborating agent with exceptionally high regioselectivity.1 This reagent has also been prepared in THF/Et2O by the reaction of Thexylborane-Dimethyl Sulfide with one equivalent of HCl.5 However, CH2Cl2 is superior to Et2O or THF as a solvent for hydroborations with this reagent.3 Like Disiamylborane (Sia2BH) and 9-Borabicyclo[3.3.1]nonane (9-BBN), ThxBHCl.SMe2 has large steric requirements and reacts preferentially to add boron at the least hindered carbon atom of the carbon-carbon double or triple bond (eq 2).

However, ThxBHCl.SMe2 is more sensitive to electronic factors that either Sia2BH or 9-BBN due to its higher Lewis acidity. Upon reaction with styrene followed by oxidation, ThxBHCl.SMe2 gives a greater than 99:1 ratio of 2-phenylethanol to 1-phenylethanol, which is higher than any of the other common hydroborating agents.1b Internal alkenes are much less reactive than terminal alkenes toward hydroboration with ThxBHCl.SMe2, and this reagent shows a much higher rate of reaction with cis disubstituted alkenes than with the trans isomers.1c Cyclohexenes and trisubstituted alkenes react more slowly with ThxBHCl.SMe2 than do terminal or cis alkenes, and some redistribution of the reagent to ThxBH2.SMe2 and ThxBCl2.SMe2 can be observed with the long reaction times (>10 h) required for the reaction with relatively unreactive alkenes.1b ThxBHCl.SMe2 reacts more rapidly with 1-hexyne or 3-hexyne than with 1-hexene.6 Hydroborations of terminal alkynes with this reagent result in regioselective syn addition, affording the alkenylchloro(thexyl)borane in high yield.

Alkylchloro(thexyl)boranes (1) are useful intermediates in a variety of organic transformations. Reduction of these intermediates with Potassium Triisopropoxyborohydride (KPBH) in the presence of another alkene produces the mixed dialkylthexylborane (2), which can be converted to the corresponding unsymmetrical ketones (eq 3).1b,7 Dialkylthexylboranes (2) are also produced by reaction of alkylchloro(thexyl)boranes (1) with equimolar amounts of organolithium or Grignard reagents.5 Reduction of alkylchloro(thexyl)boranes at -78 °C with KPBH followed by addition of a 1-halo-1-alkyne and warming to room temperature affords B-(cis-1-halo-1-alkenyl)alkyl(thexyl)boranes (3) (eq 4). Treatment with Sodium Methoxide induces a selective migration of the alkyl group, resulting in the formation of B-(trans-1-alkyl-1-alkenyl)thexylborinate (4), which can be converted to the (E)-alkene (5) by protonolysis with isobutyric acid or to the ketone (6) by alkaline hydrogen peroxide oxidation.8 The low migratory aptitude of the thexyl group results in only 2-7% of product where the thexyl group has migrated.

Hydroboration of 1-bromo-1-alkynes with chloro(thexyl)borane leads to the synthesis of alkynyl ketones in 61-63% yields by the sequence of reactions9 shown in eq 5. Sequential treatment of alkenylchloro(thexyl)boranes, which are formed by the reaction of chloro(thexyl)borane with alkynes, with lithium chloropropargylide and aldehydes affords 1,3-enynols or 1,2,4-trienols depending on the reaction conditions.10

Alkylchloro(thexyl)boranes prepared from terminal alkenes can be hydrolyzed with one equivalent of water and then oxidized with Pyridinium Chlorochromate (PCC) to the corresponding aldehyde in moderate yields (eq 6).11

Reduction of Carboxylic Acids to Aldehydes.

Aliphatic carboxylic acids are reduced rapidly (15 min) and aromatic carboxylic acids are reduced slowly (24 h) by chloro(thexyl)borane-dimethyl sulfide to the corresponding aldehydes.2 Sodium bisulfite adducts were prepared to purify the aldehydes. Aliphatic aldehydes are isolated in 80-93% yields, and aromatic aldehydes are isolated in 46-78% yields.2a Alkoxy, nitro, cyano, halo, and ester functional groups are not reduced under these conditions.

Reductive Cyclization of o-Azidoalkenes.

Hydroboration of o-azidoalkenes with chloro(thexyl)borane followed by hydrolysis affords, via an intramolecular reductive cyclization, the corresponding pyrrolidine (78%) or the piperidine (53%) (eq 7).12

1. (a) Brown, H. C.; Sikorski, J. A.; Kulkarni, S. U.; Lee, H. D. JOC 1980, 45, 4540. (b) Brown, H. C.; Sikorski, J. A.; Kulkarni, S. U.; Lee, H. D. JOC 1982, 47, 863. (c) Sikorski, J. A.; Brown, H. C. JOC 1982, 47, 872. (d) Pelter, A.; Smith, K.; Brown, H. C. Borane Reagents; Academic: London, 1988.
2. (a) Brown, H. C.; Cha, J. S.; Yoon, N. M.; Nazer, B. JOC 1987, 52, 5400. (b) Brown, H. C.; Nazer, B.; Cha, J. S.; Sikorski, J. A. JOC 1986, 51, 5264. (c) Brown, H. C.; Cha, J. S.; Nazer, B.; Yoon, N. M. JACS 1984, 106, 8001.
3. Brown, H. C.; Sikorski, J. A. OM 1982, 1, 28.
4. Brown, H. C.; Kramer, G. W.; Levy, A.; Midland, M. M. Organic Syntheses via Boranes; Wiley: New York, 1975; Chapter 9.
5. Zweifel, G.; Pearson, N. R. JACS 1980, 102, 5919.
6. Brown, H. C.; Chandrasekharan, J. JOC 1983, 48, 5080.
7. Kulkarni, S. U.; Lee, H. D.; Brown, H. C. JOC 1980, 45, 4542.
8. Brown, H. C.; Basavaiah, D.; Kulkarni, S. U.; Lee, H. D.; Negishi, E.; Katz, J.-J. JOC 1986, 51, 5270.
9. Brown, H. C.; Bhat, N. G.; Basavaiah, D. S 1983, 885.
10. Zweifel, G.; Pearson, N. R. JOC 1981, 46, 829.
11. Brown, H. C.; Kulkarni, S. U.; Rao, C. G.; Patil, V. D. T 1986, 42, 5515.
12. Jego, J. M.; Carboni, B.; Vaultier, M. BSF(2) 1993, 129, 554.

William S. Mungall

Hope College, Holland, MI, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.