Puerto Rico
| Tesis
10‒R‒Borabicyclodecanes: Asymmetric Hydroboration of Alkenes and Cyclic Dienes and the Asymmetric Synthesis of Homoallylic Amines and Erythro Homoallylic Cycloalkenols Through Allylboration
| dc.creator | González Sierra, Eduvigis | |
| dc.creator | Soderquist, John A. (Consejero) | |
| dc.date | 2014-07-01T19:43:47Z | |
| dc.date | 2014-07-01T19:43:47Z | |
| dc.date | 2014-07-01T19:43:47Z | |
| dc.date.accessioned | 2017-03-17T16:54:36Z | |
| dc.date.available | 2017-03-17T16:54:36Z | |
| dc.identifier | http://hdl.handle.net/10586 /501 | |
| dc.identifier.uri | http://repositorioslatinoamericanos.uchile.cl/handle/2250/647622 | |
| dc.description | 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. | |
| dc.language | en | |
| dc.subject | Hydroboration | |
| dc.subject | Homoallylic Amines | |
| dc.subject | 10-R- BBD | |
| dc.subject | Homoallylic cycloalkenols | |
| dc.subject | Asymmetric Synthesis | |
| dc.subject | Organoboranes | |
| dc.subject | Chemodivergency | |
| dc.subject | 1,3- borotropic shift | |
| dc.subject | Allyboration | |
| dc.subject | Chemical transformations | |
| dc.title | 10‒R‒Borabicyclodecanes: Asymmetric Hydroboration of Alkenes and Cyclic Dienes and the Asymmetric Synthesis of Homoallylic Amines and Erythro Homoallylic Cycloalkenols Through Allylboration | |
| dc.type | Tesis |