Published on Web 05/10/2005
Asymmetric Allyl- and Crotylboration with the Robust, Versatile, and Recyclable 10-TMS-9-borabicyclo[3.3.2]decanes Carlos H. Burgos,† Eda Canales, Karl Matos,‡ and John A. Soderquist* Contribution from the Department of Chemistry, UniVersity of Puerto Rico, Rio Piedras, Puerto Rico 00931-3346 Received October 20, 2004; E-mail:
[email protected] Abstract: The remarkable versatility and selectivity of the 10-(trimethylsilyl)-9-borabicyclo[3.3.2]decanes (10-TMS-9-BBDs) in the allyl- and crotylboration of representative aldehydes are reported. The new reagents are prepared through air-stable crystalline pseudoephedrine borinic ester complexes of the 10-TMS-9BBDs (4), which are available in 63% overall yield from B-MeO-9-BBN through a simple two-step procedure. These complexes 4 are directly converted to the corresponding B-allyl-10-TMS-9-BBDs (1) with allylmagnesium bromide, which either can be isolated (98%) or used in situ for the allylations. The remarkable enantioselectivity (96 to g99% ee) of these reagents in the rapid (99:1 mixture of the (2R,3R)threo (a) and (2R,3S)-erythro (b) diastereomers of 9, whereas (+)-1S gave these products in a 5:95 dr.21 These selectivities for 1 are comparable to the best tartramide reagents for this substrate.4 Synthesis of the Crotylboranes 10. With the general versatility and remarkable selectivities exhibited for 1 in the asymmetric allylboration process, we chose to extend this general reaction protocol to crotylboration. Unfortunately, all attempts to find a clean and effective procedure for the direct conversion of the complexes 4 to the crotyl reagents 10 were unsuccessful. Only reagents of the general type RMgBr appear to be amendable to this method, and Grignard procedures give crotylborane mixtures.22 On the basis of other dialkyl systems, 3 provides the logical precursor to 10 through the standard protocol using the Schlosser reagents.23 As noted above, 3 is a very “user friendly” borinic ester, being distillable, storable, and unusually resistant toward air oxidation. These characteristics of 3 were expected to significantly reduce the complexity of the operations required in generating 10. We considered several potential routes to the optically pure forms of 3, finding that the simplest and most efficient method was through the generation of the allylboranes 1 from either (+)-4R or (-)-4S and their methanolysis (2 h, reflux) to provide, after distillation, pure (-)-3R and (+)-3S, respectively, both in (20) Jadhav, P. K.; Bhat, K. S.; Perumal, P. T.; Brown, H. C. J. Org. Chem. 1996, 51, 432. (21) The 13C NMR signals for the C-4 position in 9a and 9b were cleanly resolved, appearing at δ 38.5 and 37.6, respectively (δ 35.1 and 35.6 in their Mosher esters). (22) Hoffmann, R. W.; Niels, G.; Schlapback, A. Pure Appl. Chem. 1990, 62, 1993. (23) Fujita, L.; Schlosser, M. HelV. Chim. Acta 1982, 65, 1258.
Scheme 4
87% yield (Scheme 3). Because no significant manipulation of 1 is required in the procedure and its methanolysis is very clean, producing only propene as a byproduct, the operation is exceedingly simple, with 3 being easy to isolate, handle, and store. By analogy to Brown’s preparation of his terpene-derived crotylboranes,8 the 3 f 10 conversion was examined with (()-3 employing Schlosser’s “Superbase” to selectively generate the crotylmetallic species from either cis- or trans-2-butene, followed by their addition to 3 giving the borinate complexes 11, which are demethoxylated with a Lewis acid to give the crotylborane 10.8 Our modifications include (1) the use of THF solutions of KO(Bu-t) rather than the solid reagent, which dramatically reduces the time required for the deprotonation of cis-2-butene from 12 f 1 h and increases the geometric purity of E-10 from 94 to 98%; (2) conducting the entire process at -78 °C, which results in the clean formation of 11 (11B NMR δ 3.6), avoiding isomerization of the “crotylpotassium” reagents and the double addition of the crotylmetallic (11B NMR δ -9.6) to 3; and (3) the use of TMSOTf as the Lewis acid, which avoids the unwanted decrotylation of 11 to regenerate 3 [e.g., BF3Et2O or MgBr2 (40%), TMSCl (20%)] and cleanly produces 10 (95%) in high geometric purity (g98%). With these modifications in place, both Z and E isomers of 10 in either enantiomeric form as well as, importantly, also in racemic form, are readily prepared from 3 (Scheme 4). With efficient procedures for all of the isomers of 10 in hand, we chose to examine their configurational stabilities, since J. AM. CHEM. SOC.
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Burgos et al.
ARTICLES Table 3. Asymmetric Crotylboration of RCHO with 10
Scheme 5
R in RCHO
10
product
methoda
yield (%)b
drc syn/anti
eed
Ph Ph Me Me Me Pr Pr t-Bu t-Bu
Z-S E-S Z-S Z-R E-S Z-R E-R Z-S E-R
12a 14a 12b 13b 14b 13c 15c 12d 15d
A B C C C A A B C
72 82 68 68 73 91 94 92 69
g98:2 e2:98 g98:2 g98:2 e2:98 g98:2 e2:98 g98:2 e2:98
98 97 95 95 97 94 96 94 99
a Method A: isolated 10, oxidative workup. Method B: in situ use of 10. Method C: isolated 10, pseudoephedrine workup. b Isolated yield. c Determined by comparison of peak areas for diastereomeric pairs of the alcohols through both 1H and 13C NMR. This was also checked through 13C NMR of the corresponding Mosher esters. d Determined by comparison of the observed peak areas for several sets of signals derived from the diastereomeric pairs in the corresponding R-Mosher esters through both 1H and 13C NMR. For R ) t-Bu, chiral diazaphospholidine derivatives were prepared and these were analyzed through 31P NMR.
crotylboranes are prone to isomerization through 1-methallylboranes via 1,3-boratropic rearrangements.8a This process is normally faster for BR2 vs B(OR′)2 derivatives. Samples of both Z-10 and E-10 were examined by NMR after 1 week at 25 °C in CDCl3 solution. The E isomer, which was initially 98:2 E/Z, was isomerized to 84:16 during this period. The Z isomer (e2: 98 E/Z) was more affected, giving a 53:47 E/Z mixture. As a consequence, the reagents 10 were not stored but rather generated as needed for the crotylboration process. The high reactivity of these trialkylboranes facilitates their clean addition to even highly hindered aldehydes in 98:2) and enantioselectivity (9499% ee) (Table 3). Through the choice of the appropriate crotylborane 10, any and all of the stereoisomers of the β-methyl homoallylic alcohols can be prepared. Three procedures were developed for the crotylboration process, all of which gave similar product yields and selectivities. Method A was developed to demonstrate that 10 is isolable and that its solutions can be used for the process. A standard oxidative workup (3 M NaOH, 30% H2O2) was employed. Method B uses the same workup but without isolation of the reagents 10. Method C employs a solution of 10 followed by a nonoxidative workup through the addition of the appropriate (24) The crotylborane geometry is faithfully reflected in the product alcohols (Table 3). While this is not new, the crotylboration with 10 is much faster than its isomerization, regardless of the reaction temperature. For example, early in the present studies we observed that E-10 produced the β-methyl homoallylic alcohols in a 94:6 anti:syn ratio, both at at 25 and -78 °C. This led us to isolate E-10 and determine its 94:6 E/Z ratio, ultimately optimizing this to g98:2 with our modified protocol. 8048 J. AM. CHEM. SOC.
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enantiomeric form of pseudoephedrine. This permits the efficient recovery of the chiral boron moiety 4 in 70-80% yield for recycling purposes.25 The syn and anti diastereomers of alcohols 12-15 give distinctly different 13C NMR spectra, which were in complete agreement with those reported.7b In each case we determined the dr to be g98:2 for the major diastereomer produced, a direct reflection of the high geometric purities of 10 prepared through the Schlosser reagents. The enantiomeric excess for each β-methyl homoallylic alcohol 12-15 was normally determined from the 1H and 13C NMR analysis of the corresponding Mosher ester derivatives.26 However, for the R ) t-Bu examples (12d, 15d), the product ee’s were determined using chiral diazaphospholidine derivatives and 31P NMR analysis.27 The selectivities observed for 10 generally equal or exceed those of previously existing reagents. Data from the analogous asymmetric allylboration (vide ultra) and allenylboration28 processes with our BBD system, together with the specific rotations for the R ) Me (b) series, were used to assign the absolute stereochemistry of 12-15. As in the allylboration process with 1, MM calculations18 provide useful models for the prediction of the product stereochemistry through the relative stabilities of their diastereomeric pre-transition-state complexes. These calculations reveal that the B-chiral anti-aldehyde complex which forms cis to the 10-TMS group (i.e., Z-16) is favored (∼3 kcal/mol, R ) Ph)
over any conformation of its syn and/or trans counterparts, leading to the selective allylation of the re face of RCHO with the 10R reagent. Calculations with E-16 produce similar results. (25) (26) (27) (28)
For a similar process with terpene-derived reagents, see ref 8b. Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973, 95, 512. Alexakis, A.; Mutti, S.; Mangeney, P. J. Org. Chem. 1992, 57, 1224. Lai, C.; Soderquist, J. A. Org. Lett. 2005, 7, 799.
10-TMS-9-BBDs: Asymmetric Allyl- and Crotylboration
Conclusions
In summary, through the insertion of CH(TMS) with trimethylsilyldiazomethane into a ring B-C bond in 2, the remarkably stable chiral borinic ester 3 is prepared in pure form (97%). Both enantiomeric forms of the air-stable pseudoephedrine complexes 4 are isolable as pure crystalline compounds from 3 in 66% total overall yield. Reaction of AllMgBr and either enantiomer of 4 produces the allylborane 1, which exhibits highly reagent controlled and enantioselective additions to representative aldehydes (99%). The allylborane 1 also serves as a useful intermediate for the synthesis of the optically pure forms of 3 (87%), which are stereospecically converted to the corresponding crotylboranes 10 (94-95%). These reagents undergo the clean addition to even hindered aldehydes in 98:2) and ee (94-99%). Through the appropriate choice of the enantiomeric and geometric form of 10, any and all of the four possible isomers of the product alcohols can be prepared in a predictable manner. Efficient with respect to both the borane and the “allyl” source, asymmetric allyl- and crotylations with 1 and 10, respectively, provide attractive alternatives to existing reagents and processes. Acknowledgment. Dedicated to the memory of Professor Herbert C. Brown. The support of the NSF (CHE0217550), NIH (S06GM8102), and the Department of Education GAANN Program (P200A030197-04) is gratefully acknowledged. Supporting Information Available: Full experimental procedures, analytical data, and selected spectra for 1-15 and derivatives (PDF). This material is available free of charge via the Internet at http://pubs.acs.org. JA043612I
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