[2227-29-4]  · C6H15ClSi  · Chlorodiisopropylsilane  · (MW 150.73)

(reagent for the synthesis of O-diisopropylsilyl derivatives for intramolecular hydrosilylation reactions; used in a 1,3-anti-selective reduction of b-hydroxy ketones,1-3 and in a mild method for reducing b-hydroxy esters4)

Physical Data: bp 150-153 °C,5 bp 54-55 °C/45 mmHg;6 d 0.872 g cm-3.6

Solubility: generally sol organic solvents; reacts with alcohols, ammonia,6 and water.

Form Supplied in: neat liquid, commercially available.

Analysis of Reagent Purity: 1H NMR d(CDCl3) 4.35 (Si-H).5 The most likely impurity is tetraisopropyldisiloxane, (i-Pr2SiH)2O, for which the corresponding signal is slightly upfield at 4.28.7

Preparative Method: obtained by reaction of trichlorosilane with isopropylmagnesium chloride;6 the original yield of 45% may be raised to 70-80% by employing conc hydrochloric acid to quench the reaction.2

Purification: distillation at atmospheric or reduced pressure.

Handling, Storage, and Precautions: shelf-stable provided moisture is excluded. Corrosive; yields HCl on reaction with water. Use in a fume hood.

1,3-Anti-Selective Reduction of b-Hydroxy Ketones.

Treatment of b-hydroxy ketones (1) with chlorodiisopropylsilane in the presence of Pyridine, or (more generally) Triethylamine with catalytic 4-Dimethylaminopyridine, gives b-diisopropylsilyloxy ketones (2) (eq 1).1,2 These derivatives may be purified by chromatography on silica gel, and are obtained in yields of ca. 70-80%. Under the influence of Lewis acidic catalysts, most usefully Tin(IV) Chloride, they undergo intramolecular hydrosilylation to give trans-siladioxanes (3), along with minor amounts of cis stereoisomers (4) (e.g. R1, R2 = i-Pr, diastereomer ratio (dr) = 120:1; R1, R2 = Bu, dr = 40:1).1,2 After desilylation, anti-diols (5) may be isolated. The overall yields of (5) from hydroxy ketones (1) are in the region 60-70%.2

The hydrosilylation step is presumed to occur via six-membered cyclic transition state (6). The stereoselectivity results from (a) the equatorial disposition of R1, and (b) steric and stereoelectronic effects (including possibly a C=O&dotbond;Si interaction) which promote the axial orientation for the carbonyl group. The dimethylsilyl derivative (7) has been used in similar sequences,2 but selectivities were found to be lower and optimization was complicated by the hydrolytic instability of Me2Si-O bonds.

The 1,3-anti selectivity is maintained in the presence of an a-substituent, i.e. in substrates such as (8). Thus diisopropylsilylation/hydrosilylation of both diastereomers of (8) gave the 1,3-trans-siladioxane (9), with dr &egt; 250:1 (eq 2).3 However, with the more challenging substrates (10) the a-position was found to have more influence. Both diastereomers gave principally the 1,2-trans product (11) (eq 3) but, while anti-(10) resulted in dr = 97:1, syn-(10) gave only dr = 5:1.

As part of the above work it was found that the superacid TfOH2+B(OTf)4- may also be used as the hydrosilylation catalyst.3 In one case it gave superior results to those obtained with SnCl4.

The 1,3-anti-selective reduction of b-hydroxy ketones may also be accomplished using Tetramethylammonium Triacetoxyborohydride,8 and the samarium-catalyzed intramolecular Tishchenko reduction.9 The former gives the anti-diols directly, although with slightly lower stereoselectivity than the intramolecular hydrosilylation. The latter results in monoacylated products, and gives excellent yields and selectivities.

Intramolecular Reduction of b-Hydroxy Esters.

Intramolecular hydrosilylation is also possible within b-diisopropylsilyloxy esters (13), constituting an exceptionally mild method for reducing ester groups to the aldehyde oxidation level (eq 4).4 The derivatives (13) may be synthesized from b-hydroxy esters (12) as described above for the analogous ketones. Treatment with fluoride ions (but not Lewis acids) induces hydride transfer to give alkoxysiladioxanes (14) in excellent yields (&egt;95%). Although usually performed in dichloromethane, the hydrosilylation may also be accomplished with ethyl acetate as solvent, providing strong evidence for intramolecularity.

While the reduction in eq 4 is not stereoselective, the stereocontrolled elaboration of (14) may be achieved in principle via conformationally biased carbocations (15). This has been demonstrated for the allylation of (14) with Allyltrimethylsilane (eq 5).4 The major products (16) appear to derive from axial attack on (15). The most effective catalyst was TfOH2+B(OTf)4-, which could be used at levels of 1-2 mol % and gave yields of 78-85% with dr &egt; 20:1. While it is possible that the superacid acts by protonation of the alkoxy oxygen in (14), it is probably more likely that the active species is the supersilylating agent Me3Si B(OTf)4,10 derived from superacid and allylsilane.

Intramolecular Hydrosilylation/Oxidation of Alkenols.

Since the advent of methods for the oxidative degradation of organosilicon compounds, it has been possible to develop controlled hydration methodology based on the hydrosilylation of C=C bonds. A useful variant involves the O-silylation of an alkenol with a dialkylsilylating agent R2SiHX, followed by intramolecular hydrosilylation/oxidation to give a diol product.11,12 Because of the intramolecular delivery of the Si-H moiety, these reactions often take place with excellent stereoselectivity. While most of this work has employed Me2SiH as the internal reagent, the use of i-Pr2SiH has been explored occasionally.13,14 An example where it proved advantageous is the conversion of allylic alcohol (17) to syn-diol (18) (eq 6) in dr 30:1.14 A related method involving dimethylsilyl groups gave dr of only 2.4:1 with this substrate.12

Synthesis of Other Organosilicon Reagents.

Aside from the direct applications referred to above, i-Pr2SiHCl serves as an intermediate for the synthesis of certain other reagents. Examples are (a) i-Pr2Si(OTf)2, used for the protection of diols as diisopropylsilylene derivatives,15 (b) dialkylarysilanes (19) for the introduction of a fluorescent O-protecting group,16 and (c) the disiloxane (20), which may be converted to (21) (for diol protection)7 or (22) (used in intramolecular ionic hydrogenation).17

Related Reagents.

Chlorodimethylsilane; Tetramethylammonium Triacetoxyborohydride.

1. Anwar, S.; Davis, A. P. CC 1986, 831.
2. Anwar, S.; Davis, A. P. T 1988, 44, 3761.
3. Anwar, S.; Bradley, G.; Davis, A. P. JCS(P1) 1991, 1383.
4. Davis, A. P.; Hegarty, S. C. JACS 1992, 114, 2745.
5. Bradley, G. MSc thesis, Univ. of Dublin, 1990.
6. Metras, F.; Valade, J. BSF 1965, 1423.
7. Markiewicz, W. T. JCR(S) 1979, 24; JCR(M), 0181.
8. Evans, D. A.; Chapman, K. T.; Carreira, E. M. JACS 1988, 110, 3560.
9. Evans, D. A.; Hoveyda, A. H. JACS 1990, 112, 6447.
10. Davis, A. P.; Jaspars, M. AG(E) 1992, 31, 470.
11. Tamao, K.; Ishida, N.; Tanaka, T.; Kumada, M. OM 1983, 2, 1694.
12. Tamao, K.; Nakajima, T.; Sumiya, R.; Arai, H.; Higuchi, N.; Ito, Y. JACS 1986, 108, 6090.
13. (a) Curtis, N. R.; Holmes, A. B. TL 1992, 33, 675. (b) Denmark, S. E.; Forbes, D. C. TL 1992, 33, 5037. (c) Bergens, S. H.; Noheda, P.; Whelan, J.; Bosnich, B. JACS 1992, 114, 2121.
14. Anwar, S.; Davis, A. P. Proc. R. Irish Acad. 1989, 89B, 71.
15. Corey, E. J.; Hopkins, P. B. TL 1982, 23, 4871.
16. Horner, L.; Mathias, J. JOM 1985, 282, 175.
17. McCombie, S. W.; Ortiz, C.; Cox, B.; Ganguly, A. K. SL 1993, 541.

Anthony P. Davis

Trinity College, Dublin, Ireland

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