(R,R)-2,5-Dimethylborolane1

[97011-90-0]  · C6H13B  · (R,R)-2,5-Dimethylborolane  · (MW 96.00)

(reagent for asymmetric hydroboration;2 also used as an auxiliary for asymmetric ketone reduction,3 aldol,4 and crotylboration5 reactions; derived reagents are used in double asymmetric syntheses6)

Physical Data: the most stable precursor is a complex with (S)-(+)-prolinol: mp 225-226 °C; [a]21D +23.2° (c 1.28, CHCl3).

Solubility: sol pentane, Et2O, THF.

Analysis of Reagent Purity: optical purity is assayed by oxidation (NaOMe, H2O2) to give 2,5-hexanediol, which has a maximum published rotation [a]23D -35.6° (c 8.29, CHCl3). Derivitization of the diol as the bis-MTPA ester followed by HPLC analysis gives the relative amounts of (R,R)-, (R,S)-, and (S,S)-diols present.

Preparative Methods: a ca. 1:1 mixture of cis- and trans-B-methoxy-2,5-dimethylborolanes is first obtained by reaction of the Grignard reagent derived from 2,5-dibromohexane with diethylaminodichloroborane, followed by acidic methanolysis (eq 1).2

The cis isomer is then selectively complexed with N,N-dimethylaminoethanol, and the resolvable trans isomer is isolated by vacuum transfer (eq 2).

Reagent (1) is obtained by treatment of the racemic trans isomer with 0.45 equiv of (S)-prolinol, followed by vacuum transfer of the volatile fraction containing mostly (S,S)-2,5-dimethyl-B-methoxyborolane (eq 3). Through similar manipulation, (2) is obtained (eq 4).

Handling, Storage, and Precautions: (R,R)-2,5-dimethylborolane is stored as an air- and moisture-stable complex (1) with (S)-(+)-prolinol. The (S,S)-isomer is stored as a stable complex with either (R)-(-)-prolinol or as a complex (2) with (S)-(+)-valinol, which is more readily available. The reagent and many of its derivatives are extremely air- and moisture-sensitive, and may ignite when exposed to air. Precautions for the handling of such materials should be rigorously followed.7

Asymmetric Hydroboration.2

For reaction with a prochiral alkene, (R,R)-2,5-dimethyl-B-methoxyborolane is liberated from (1) and a standard solution of the corresponding lithium dihydridoborate in ether is prepared (eq 5). Hydroboration is effected by addition of Iodomethane to the solution of dihydridoborate and alkene (eq 6). After oxidation, chiral secondary alcohols of high enantiomeric purity and predictable configuration are obtained from cis, trans, and trisubstituted alkenes. As is the case with other known asymmetric hydroborating agents,8 2-methyl-1-alkenes react with low asymmetric induction.

Asymmetric Reduction of Ketones.3a,b

A reagent system consisting of (R,R)-2,5-dimethylborolane (1.0 equiv) and the corresponding borolanyl mesylate (0.2 equiv) reduces a variety of prochiral ketones with asymmetric induction in the range of 80-100% ee. The reagent system is prepared in situ by addition of 1.4 equiv of Methanesulfonic Acid to a solution of the lithium dihydridoborate, prepared as in eq 5 above (eq 7).

Kinetic and molecular modeling studies support the view that asymmetric ketone reduction proceeds through reaction of the borolane with a complex formed by coordination of the borolanyl mesylate syn to the smaller alkyl group (R1) of the ketone (eq 8).3b After reaction is complete, the chiral borolane moiety is recovered as a crystalline complex with 2-amino-2-methyl-1-propanol (eq 9).

Asymmetric Aldol Reactions.4

For use in asymmetric aldol reactions, the dihydridoborate (eq 5) is converted to the borolanyl triflate (eq 10). The derived boron enolates of 1,1-diethylpropyl propanethioate (R = Me) and ethanethioate (R = H) react with representative aldehydes to give b-hydroxythioates with good to excellent enantioselectivity (eq 11). In the propanethioate series (R = Me), the observed 2,3-anti selectivity (anti:syn &egt; 30:1) is related to the preponderance of E(O)-geometry in the enolate.9 The 1,1-diethylpropyl group of the thioate was selected to maximize the E(O):Z(O) ratio. Due to their intrinsically high enantioselectivity, the above enolates undergo highly diastereoselective aldol reactions with chiral aldehydes.10 These double asymmetric6 reactions have been employed in natural product syntheses.11

The borolanyl triflate (eq 10) has also been employed to form the chiral boron enolates of methyl ketones which have additional chiral centers present in their carbon framework. Reaction of these enolates with chiral aldehydes constitutes a triple asymmetric synthesis, in which the approximate multiplicativity of the three diastereofacial selectivities appears to be valid.12

Asymmetric Crotylboration.5

Reagents for crotylboration are prepared from 2,5-dimethyl-B-methoxyborolane (eq 5) by addition of (Z)- or (E)-crotylpotassium under standard conditions. Reactions with representative achiral aldehydes are 93-96% diastereoselective and 86-97% enantioselective for the major diastereomer (eqs 12 and 13). Results with chiral aldehydes conform to the rule of double asymmetric synthesis.6

Related Reagents.

Diisopinocampheylborane; Dilongifolylborane; Monoisopinocampheylborane.


1. (a) Roush, W. R. COS 1991, 2, Chapter 1.1 (b) Kim, B. M.; Williams, S. F.; Masamune, S. COS 1991, 2, Chapter 1.7. (c) Smith, K.; Pelter, A. COS 1991, 8, Chapter 3.10. (d) Nishizawa, M.; Noyori, R. COS 1991, 8, Chapter 1.7
2. Masamune, S.; Kim, B. M.; Petersen, J. S.; Sato, T.; Veenstra, S. J.; Imai, T. JACS 1985, 107, 4549.
3. (a) Imai, T.; Tamura, T.; Yamamuro, A.; Sato, T.; Wollmann, T. A.; Kennedy, R. M.; Masamune, S. JACS 1986, 108, 7402. (b) Masamune, S.; Kennedy, R. M.; Petersen, J. S. JACS 1986, 108, 7404.
4. Masamune, S.; Sato, T.; Kim, B. M.; Wollmann, T. A. JACS 1986, 108, 8279.
5. Garcia, J.; Kim, B. M.; Masamune, S. JOC 1987, 52, 4831.
6. Masamune, S.; Choy, W.; Petersen, J. S.; Sita, L. R. AG(E) 1985, 24, 1.
7. Brown, H. C.; Kramer, G. W.; Levy, A. B.; Midland, M. M. In Organic Synthesis via Boranes; Wiley: New York, 1975.
8. Brown, H. C.; Jadhav, P. K. In Asymmetric Synthesis; Morrison, J. D.; Ed.; Academic: New York, 1983; Vol. 2, Chapter 1.
9. Masamune, S. H 1984, 21, 107.
10. Short, R. P.; Masamune, S. TL 1987, 28, 2841.
11. (a) Blanchette, M. A.; Malamas, M. S.; Nantz, M. H.; Roberts, J. C.; Somfai, P.; Whritenour, D. C.; Masamune, S. JOC 1989, 54, 2817. (b) Kageyama, M.; Tamura, T.; Nantz, M. H.; Roberts, J. C.; Somfai, P.; Whritenour, D. C.; Masamune, S. JACS 1990, 112, 7407.
12. Duplantier, A. J.; Nantz, M. H.; Roberts, J. C.; Short, R. P.; Somfai, P.; Masamune, S. TL 1989, 30, 7357.

Robert P. Short

Polaroid Corporation, Cambridge, MA, USA



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