Tesis
10‒R‒Borabicyclodecanes: Asymmetric Hydroboration of Alkenes and Cyclic Dienes and the Asymmetric Synthesis of Homoallylic Amines and Erythro Homoallylic Cycloalkenols Through Allylboration
Autor
González Sierra, Eduvigis
Soderquist, John A. (Consejero)
Institución
Resumen
Asymmetric conversions such as the allyboration of N-H aldimines, hydroboration
of prochiral alkenes and cyclohexadienes and the cycloalkenylation of prochiral
aldehydes and ketones through Soderquist’s reagents are the main focus of the
present work. B-OMe-10-TMS-9-BBD and B-OMe-10-Ph-9-BBD are readily
prepared and converted to the air stable optically pure PE-complexes by
thermodynamic resolution with pseudoephedrine (TMS) and N-Mepseudoephedrine
(Ph), respectively. The scope of these reagents has been
tested on known processes as well as new ones. Important C-C bond forming
processes have been achieved successfully, namely, allyboration, allenylboration
and propargylboration. The results revealed the chemodivergency between the
two BBD systems. 10-TMS-BBD is suitable for aldehydes while the Ph-BBD
works best with the ketones. The success with the known transformations
encouraged us to explore other conversions in which other organoboranes have
limitations.
The asymmetric allyboration of N-H aldimines, generated from either NTMS
or N-diisobutylalanyl precursors, with B-allyl-9-TMSborabicyclo[
3.3.1]decane provided homoallylic amines in good yields (60-90%)
and good to high selectivity (60-89%). The allyborating agent was prepared in
either enantiopure form by adding allymagnesium bromide to the corresponding
PE-BBD chelate complex. The homoallylic amine from N-TMS was isolated by a
non-oxidative work-up with pseudoephedrine, thus providing the amine and the
recovery of the chiral boron moiety (50-68%). On the other hand, typical oxidative work-up was performed for the N-alanyl examples. The absolute stereochemistry
of the amines was assigned based on literature values and the mechanistic
details of the transformation were studied by molecular mechanics calculations.
The asymmetric hydroboration of prochiral alkenes and cyclohexadienes
with B-H-10-TMS-9-BBD and B-H-10-Ph-9-BBD was explored. The borohydride
reagents were prepared by adding lithium monoethoxyaluminum hydride to either
the 10-TMS or 10-Ph BBD chelate complex to provide the B-H2-10-TMS(Ph)-9-
BBD quantitatively. Addition of TMSCl, followed by the olefin, produces the
corresponding trialkylborane, which upon oxidation, provided the optically active
alcohols. Hydroboration of 1,1-disubstituted, 1,2-disubstituted (cis or trans) and
trisubstituted olefins provided the corresponding alcohols in good yields and
good to excellent enantioselectivity. The hydroboration of 1,1-disubstituted
alkenes gave unprecedented results. Noteably, B-H-10-Ph-BBD reagent
provided the α-chiral secondary alcohols in excellent yields (83-97%) and good to
excellent enantioselectivity (28-92%). More importantly, the enantioenriched
trialkylboranes obtained from the hydroboration of 1,1-disubstituted olefin proved
to be excellent coupling partners in the Suzuki coupling, thus providing the
corresponding hydrocarbons in good yields (50-84%). On the other hand,
hydroboration of 1,2-disubstitued olefins provided interesting results. B-H-10-
TMS-BBD proved to be very selective with cis-2-butene (84% ee) and trans-2-
butene (95% ee). However, B-H-10-Ph-BBD behaved differently with these
olefins. While trans-2-butene was selectively hydroborated (96% ee) as observed
with its TMS-BBD counterpart, cis-2-butene gave 2-butanol in only 32% ee. The absolute configuration at the alcohol center was assigned by comparison to
literature values.
The asymmetric hydroboration of 1,3-cyclohexadiene and 1,4-
cyclohexadiene behaves similarly to the hydroboration of cis-alkenes.
Hydroboration of 1,3-cyclohexadiene with B-H-10-TMS-9-BBD afforded a 93:7
mixture of regioisomers, (S)-2-cyclohexenol(> 99% ee) and 3-cyclohexenol.
Similarly, the hydroboration of 1,4-cyclohexadiene with the same hydroborating
agent provided (S)-3-cyclohexenol in 90% ee and 80% yield. By contrast, the
hydroboration of 1,3-cyclohexadiene with B-H-10-Ph-9-BBD afforded essentially
a racemic mixture of 2-cyclohexenols (10% ee). Similar results were also
observed for 1,4-cyclohexadiene.
We were interested in the asymmetric synthesis of homoallylic
cycloalkenols as potential intermediates for the synthesis of cyclic natural
products. The resulting trialkylborane obtained from the hydroboration of 1,3-
cyclohexadiene with B-H-10-TMS-9-BBD was employed in the cycloalkenylation
of aldehydes. Despite the discouraging results obtained for hydroboration of 1,3-
cyclohexadiene with the B-H-10-Ph-9-BBD, we also decided to explore the
cycloalkenylboration of ketones. Asymmetric synthesis of homoallylic
cycloalkenols was successfully achieved with B-2-cyclohexenyl-10-TMS-BBD
which provided the corresponding homoallylic alcohols in moderate to good
yields (35-75%) and excellent selectivity (90-99% ee). On the other hand,
homoallylic cycloalkenols from B-2-cyclohexenyl-10-Ph-BBD provided the
corresponding cycloalkenols in excellent selectivity (80-99% ee) but in low yields (17-52%). These results were surprising and the careful examination of the
hydroboration step and the subsequent alkylation step were undertaken. These
studies revealed that only one of the isomeric cyclohexenylborane intermediates
was undergoing the addition to ketones. The absolute configuration of the
cycloalkenols from the aldehydes was determined by optical rotation values
comparison from the literature. For the ketones, the absolute configuration was
assigned by means of chemical transformations. Details from these interesting
results regarding the 10-Ph-BBD behavior are discussed in the Results and
Discussion section.