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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Org Lett. Author manuscript; available in PMC 2010 December 3.
Published in final edited form as:
PMCID: PMC2803353

Origin of Thermodynamic versus Kinetic Control of Allene Hydroboration with 9-Borabicyclo[3.3.1]nonane and 10-R-9-Borabicyclo[3.3.2]decane


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Density functional theory was used to locate transition states for hydroboration reactions of allenes with 9-borabicyclo[3.3.1]nonane and 10-R-9-borabicyclo[3.3.2]decane, as well as transition states for [1,3]-boratropic shift and aldehyde addition reactions of the derived allylboranes. The origin of kinetic versus thermodynamic control in the allene hydroboration step is described.

The reaction of 1-substituted allenes with dialkylboranes typically gives (E)-allylic boranes.1 Studies by Wang on the reaction of allenylsilanes with 9-borabicyclo[3.3.1]nonane (9-BBN) and dicyclohexylborane (Chx2BH) suggest that hydroboration intially gives (Z)-allylic boranes, which then undergo rapid thermodynamically controlled Z to E isomerization via two [1,3]-boratropic shifts (Scheme 1).2 Because of this facile equilibration, hydroboration of allenes with common dialkylborane reagents such as 9-BBN, Chx2BH, and (Ipc)2BH only give γ-substituted (E)-allylic boranes.

Scheme 1
Example of proposed isomerization mechanism for (Z)-allylic boranes.2

Soderquist has shown that (Z)-crotyl-10-TMS-9-borabicyclo[3.3.2]decanes are thermally stable against Z to E isomerization.3a Based on this unique thermal stability, Roush and co-workers have recently developed a general methodology for generating γ-substituted (Z)-allylic boranes via the hydroboration of monosubstituted allenes with 10-TMS-9-borabicyclo[3.3.2]decane (1a).4 Scheme 2 shows the scope of this methodology. Hydroboration of the indicated allenes with 1a followed by addition of an aldehyde to the derived allyboranes followed by oxidative work up generally gives greater than 90% enantiomeric excess and close to a 9:1 ratio of syn to anti products.4 In contrast, Soderquist has reported that the use of 10-Ph-9-borabicyclo[3.3.2]decane (1b) for similar reactions gives essentially no kinetic diastereochemical control.3b

Scheme 2
Scope of kinetically controlled allene hydroboration.

The novelty that stable (Z)-allylboranes can only be generated from reaction with 1a and not by using 1b or other known dialkylborane reagents has prompted us to use B3LYP/6-31G(d,p)5 density functional theory (DFT) to study the allene hydroboration, and subsequent [1,3]-boratropic shift and aldehyde addition transition states (TSs).6

To start, we explored the reaction of 9-BBN with allene 2a (Scheme 3). In accord with Wang’s speculation,2 the computed TS energetics reveal that formation of Z-3 is kinetically favored by 3.1 kcal/mol over E-3 (Scheme 3a). The bulky TMS group that is directed toward the borabicyclo unit disfavors TS-E2 compared to TS-Z2 (Figure 1a). The two other regiosiomeric TSs are ~6 kcal/mol higher in energy. The ΔHrxn values for 9-BBN addition to 2a are −30.5 and −32.4 kcal/mol for Z-3 and E-3.

Figure 1
a) Hydroboration and b) [1,3]-boratropic shift TSs for 9-BBN addition to allene 2a.
Scheme 3
a) 9-BBN Hydroboration of allene 2a and b) [1,3]-boratropic shift energetics relative to separated reactants.

Two concerted [1,3]-boratropic shift TSs are required to convert Z-3 into E-3. This general type of TS consists of a boron atom interacting with a π-allyl carbon fragment.7 The first transition state, TS-Z3, gives intermediate INT-3 with a ΔH of 19.3 kcal/mol relative to Z-3 (Scheme 3b, Figure 1b). Rotation of the alkene group sets up a second [1,3]-boratropic shift to give E-3 via TS-E3 with a lower ΔH of 14.3 kcal/mol. TS-Z3 and TS-E3 have similar forming and breaking B-C bond lengths of ~1.9Å and ~1.8Å for the unsubstituted and substituted carbon centers, respectively. To show that there is no unique steric or electronic feature in these TSs caused by the borabicyclo[3.3.1]nonane structure we have also computed the activation enthalpy for dimethylallylborane rearrangement. The ΔH for this [1,3]-boratropic shift is 20.1 kcal/mol, which is very close to the 19.3 kcal/mol for TS-Z3.

The reaction of 1a with methylallene (2b) and phenylallene (2c) also show a kinetic preference for giving (Z)-allylic boranes Z-5 and Z-7 (Scheme 4a). Figure 2a shows the lowest energy boat/chair ring borabicyclo[3.3.2]decane conformation TS for hydroboration of phenylallene with 1a, TS-Z6, to give Z-7. TS-Z6 is 3.3 kcal/mol lower than TS-E6, which gives E-7. In TS-E6, repulsion with the borabicyclo ring causes the phenyl group to twist by 38°.8 Although phenylallene shows a large Z-E hydroboration selectivity, the ΔΔH(E-Z) for methylallene is only 0.4 kcal/mol, but does favor the (Z)-crotyl borane Z-5. This predicted decrease in hydroboration selectivity is in agreement with the 60:40 ratio of syn to anti 1,2-diols formed from the reaction of 1a with n-C8H17-CH=C=CH2 (Scheme 2).

Figure 2
a) Hydroboration and b) [1,3]-boratropic rearrangment TSs for reaction of 1a with allene 2c.
Scheme 4
a) Allene hyroboration by 1a and b) [1,3]-boratropic shift energetics relative to separated reactants.

After Z-7 is formed there is only one boratropic shift TS, TS-Z7, that converts Z-7 into INT-7 (Scheme 4b, Figure 2b). Location of TS-Z7 and no alternative TS reveals that the allene R (phenyl or for TS-Z5 methyl) group is oriented away from the 10-TMS group and that it is not involved in steric interactions and does not slow down the [1,3]-boratropic rearrangement. Rather, it is the interaction between the π-allyl methine C-H bond with the 10-TMS group (2.20 Å) that results in a steric repulsion and raises the barrier for rearrangement. This steric interaction raises the ΔH for TS-Z7 to 25.1 kcal/mol. This is 5.8 kcal/mol larger than the ΔH for TS-Z3 and accounts for the unusually large stability of Z-7 compared to Z-3. In addition, the ΔH for rearrangement of Z-5, via TS-Z5, is 25.8 kcal/mol, indicating that the steric bulk of the allene R group does not influence the (Z)-allylic borane stability.

INT-7 is less exothermic by 7.2 kcal/mol compard to Z-7 and a second rearrangement TS, TS-E7, leads to the (E)-allylic borane E-7. Although the allene phenyl group is directed away from the TMS group, the methylene C-H bond is now in close contact with the 10-R group and raises the barrier for rearrangement.

For a direct comparison of 1a versus 9-BBN for slowing down the [1,3]-boratropic shift, we have also computed the barrier for rearrangement for reaction of 9-BBN with phenylallene. In this rearrangement the ΔH is only 17.1 kcal/mol. This is an 8 kcal/mol lower barrier than TS-Z7.

Although the R-group of 1-substituted allenes does not directly interact with the 10-TMS group of 1a, these TS geometries indicate that in 1,1-disubstituted allenes a second methyl group would be in close proximity to the 10-TMS group. To probe this possible interaction, the rearrangement barrier for 1,1-dimethylallene was computed. The ΔH increases to 33.0 kcal/mol because of the close interaction of the second methyl group with the 10-TMS group.9

Although 1-substituted phenyl and methyl allenes have similar rearrangement barriers, the allene R group can have a substantial impact on the electronic nature of the TS and lower the barrier. For example, the ΔH for rearrangement of the pinacolborane substituted (Z)-allylic borane is only 20.0 kcal/mol.10

To probe the 1-substituted allene steric model we have also computed the activation enthalpies for rearrangement with 1b and 10-t-Bu-9-borabicyclo[3.3.2]decane (1c). When R = Ph, ΔH for the rearrangment of the (Z)-allylic borane derived from phenylallene is only 19.3 kcal/mol via TS-Z8 (Figure 3a). The second rearrangment TS, TS-E8, has a ΔH value of 20.8 kcal/mol. These barriers are 5–6 kcal/mol lower than the rearrangment barriers when R = TMS. Both TS-Z8 and TS-E8 show a large intramolecular distance between the π-allyl methine and methylene C-H bonds and the 10-Ph group. For R = t-Bu, the ΔH for both [1,3]-boratropic rearrangements are 26.1 kcal/mol (TS-Z9 and TS-E9, Figure 3b), which is larger than TS-Z7 and TS-E7. Again, these large barriers for rearrangement are due to the steric congestion between the 10-t-Bu group and the π-allyl C-H bonds (1.96Å and 1.82Å).

Figure 3
Comparison of 10-R [1,3]-boratropoic transition states for a) R = Ph and b) R = t-Bu.

An alternative possibility that we have considered for explaining the high barrier of TS-Z7 is σ-p type hyperconjugative stabilization from the C-Si bond of the TMS group into the empty boron p-orbital of Z-7. The Si-C bond is angled at ~70° relative to the B-C bond. Natural orbital populations of the boron p-orbital were computed for the ground states of the (Z)-allylic boranes with 10-R groups = t-Bu, TMS, SnMe3, and Ph.11 The relative populations are: 0.16, 0.20, 0.24, and 0.20e, respectively. This indicates that σ-p orbital hyperconjugation occurs but the 10-phenyl group induces roughly the same orbital population as the 10-TMS group.12

For the benefits of the kinetic hydroboration of allenes with 1a to be realized, the ΔG for the reaction of the derived (Z)-allylic borane with aldehydes must be lower in energy than the ΔG for [1,3]-rearrangement. To probe this question, the TSs for Z-7 addition to MeCHO were explored. There are four distinct TSs resulting from approach of the aldehyde to the allylic borane on the same or opposite side of the 10-TMS group and whether the acetaldehyde methyl group is oriented in an axial or equatorial position. In addition, there are four boat/chair conformations of the borabicyclo auxiliary. TS-10 (Figure 4) is the lowest energy structure.13 Indeed, the free energy barriers for TS-Z7 and TS-E7, 28.4 and 29.8 kcal/mol, are higher than that for allylboration of MeCHO, ΔG = 21.2 kcal/mol. Consequently, the syn-homoallylic alcohol is the major product of this reaction sequence.

Figure 4
Lowest energy MeCHO addition transition state.

In conclusion, exploration of allene hydroboration, [1,3]-boratropic shift, and aldehyde addition TSs has revealed that reagent 1a gives unusually stable (Z)-allylic boranes because the 10-TMS group interacts with the π-allyl methine and methylene C-H bonds in the boratropic isomerization TS. This raises the barrier for [1,3]-boratropic rearrangement thus allowing kinetic control of the allene hydroboration.

Supplementary Material



This work was supported by the NIH (GM038436 and GM026782) and a postdoctoral fellowship to J.K. from the Ministère des Affaires Etrangères et Europèennes (France).


Supporting Information Available. Cartesian coordinates and abolute energies.


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4. Kister J, DeBaillie AC, Lira R, Roush WA. J. Am. Chem. Soc. 2009;131:14174. [PubMed](b) The S-configuration of 1a was used in all calculations
5. Jaguar . version 7.5. New York, NY: Schrodinger, LLC; 2009. All stationary points were verified as minima or first-order saddle points by calculation of the full Hessian. Enthalpy and free energy corrections were applied at 298 K and all energies are reported in kcal/mol.
6. This level of theory gives energetics in agreement with CCSD(T) theory for [1,3]-boratropic shifts. See:Choi JY, Kim CK, Kim CK, Lee I. J. Phys. Chem. A. 2002;106:5709.
7. The other extreme on a closed-shell More O–Ferrall-Jencks diagram would be a charge-separated boracyclobutane. Between the ground state and TS, the NBO charges change most significantly at the boron center, which loses positive charge.
8. In both TS-Z6 and TS-E6, allene 2c approaches the borane face opposite of the 10-TMS group. Hydroboration from the side nearest the 10-TMS group is disfavored by ~3 kcal/mol. Also see:Ess DH, Kister J, Chen M, Roush WA. J. Org. Chem. 2009 DOI: 10.1021/jo901737d. [PMC free article] [PubMed]
9. This prediction is in accord with the experimental observation that Ipc2BH hydroboration of 1,1-disubstituted allenes shows high kinetic control. See:Chen M, Handa M, Roush WR. J. Am. Chem. Soc. 2009 DOI: 10.1021/ja904599h.
10. Substituent effects on the barrier for the [1,3]-boratropic shift of dimethyl borane is given in the SI.
11. Glendening ED, Badenhoop JK, Reed AE, Carpenter JE, Bohmann JA, Morales CM, Weinhold F. NBO 5.0. Madison, WI: Theoretical Chemistry Institute, University of Wisconsin; 2001.
12. The C-Si bond length decreases by only 0.004Å between Z-7 (1.930Å) and TS-Z7 (1.934Å). The barrier for rearrangement of TS-Z7 decreases by 6.4 kcal/mol when the 10-TMS group is deleted and replaced with hydrogen. When the 10-TMS is is deleted and replaced with SiH3 the barrier is intermediate between TMS and hydrogen because there is both a small hyperconjugative effect and reduced steric interactions.
13. Sarotti AM, Pellegrinet SC. J. Org. Chem. 2009;74:3562. [PubMed]