We are interested in the invention and development of new asymmetric reagents and catalysts derived from organometallic derivatives of Main Group elements
such as boron and silicon. We are also interested in the design and total synthesis of natural products and pharmaceuticals through the use of these novel reagents and catalysts. Much of our efforts in this
regard have been directed toward the use of bulky silicon groups to influence the chemistry of organoborane processes in synthetically useful ways.
Our research in the chemistry of organoboranes has centered around the use of the particularly stable 9-borabicyclo[3.3.1nonane (9-BBN) ring system. We have discovered numerous
applications of this boron ligation for the important Pd-catalyzed cross coupling process termed the "Suzuki-Miyaura Coupling" including new enantioselective routes to frontalin and exobrevicomin. We have found that by substituting the hydrogen of
an acetylene with a trialkylsilyl group, its monohydroboration with 9-BBN-H could be markedly enhanced thereby providing stereodefined silylated vinylboranes efficiently which function as highly effective partners for the
Suzuki-Miyaura coupling. This led us to develop novel all-boron routes to such important pharmaceuticals as ibuprofen and naproxen. We also discovered that with the simple mono-oxidation of 9-BBN derivatives,
the resulting air-stable borinate esters, that is the 10-bora-9-oxabicyclo[3.3.2]decane (OBBD) system. The B-substituted OBBDs are extremely convenient to use in the coupling process matching the excellent
efficiencies achieved with 9-BBN derivatives while being much easier to handle. Of particular significance is the ease of methylation or silylmethylation which can be achieved with these reagents. We have
also developed novel routes to cis, trans, and Markovnikov vinylboranes which we have used in this coupling. Moreover, we also developed a new way to utilize 9-BBN derivatives in the coupling
process which avoids having to isolate these intermediates when they are generated through organometallic processes. For example, the addition of alkynyllithiums to 9-MeO-9-BBN produces an intermediate methoxyborate
complex which is directly coupled to electrophilic substrates without added base or requiring the isolation of the organoborane, a particularly difficult task in these cases. This breakthrough made possible
the simple synthesis of substituted acetylenes with alkynylboranes for the first time. After a thorough mechanistic study of the coupling process, have also utilized these findings in novel cyclopropylation process.
T>he triisopropylsilyl (TIPS) group has also played a central role in our discovery of new ways to block reactive sites on protic functionality to conduct selected transformations. For example the silanethiol, (TIPS)SH provides a highly effective reagent for the synthesis of mercaptans, unsymmetrical sulfides and thiono esters, while its oxygen counterpart, TIPSOH, is a particularly effective new phase-transfer catalyst for dehydrohalogenation. The novel TIPS hydrazine not only protects aldehydes and ketones from organometallic reagents, but also provides a useful way to prepare unsymmetrical azines. We also utilized the stabilizing properties of the TIPS group to prepare a stable formylsilane viewing its chemistry as a highly unusual unsymmetrical form of formaldehy.
Selected Publications:
Hernandez, E.; Canales,
E.; Gonzalez, E.; Soderquist, J. A. Asymmetric
Synthesis with the Robust and Versatile 10-Substituted
9-Borabicyclo[3.3.2]Decanes: Homoallylic Amines
from Aldimines, Pure Appl. Chem. 2006, 7, 1389.
Soderquist, J.A.;
Kock, I.; Estrella, M.E. Reductive Cleavage of
Acetals and Ketals with 9-Borabicyclo[3.3.1]nonane,
Org. Proc. Res. Dev. 2006, 10, 1076.
Gonzalez,
A. Z.; SoderquistJA. b -Silylated Homopropargylic
Amines via the Asymmetric Allenylboration of
Aldimines , , J. A. Org. Lett. 2007, 9, 1081.
Canales E, Gonzalez AZ, Soderquist JA. Asymmetric synthesis
of isomerically pure allenyl boranes from alkynyl
boranes through a 1,2-insertion-1,3-borotropic
rearrangement. Angew Chem Int Ed Engl. 2007;46(3):397-9.
Hernandez E, Burgos
CH, Alicea E, Soderquist JA. B-allenyl- and B-(gamma-trimethylsilylpropargyl)-10-phenyl-9-borabicyclo[3.3.2]decanes:
asymmetric synthesis of propargyl and alpha-allenyl
3-degree-carbinols from ketones. Org Lett. 2006
Aug 31;8(18):4089-91.
Gonzalez
AZ , Canales E, Soderquist JA. N-propargylamides
via the asymmetric michael addition of B-alkynyl-10-TMS-9-
borabicyclo[3.3.2]decanes to N-acylimines. Org
Lett. 2006 Jul 20;8(15):3331-4.
Canales E, Hernandez E, Soderquist JA. Nonracemic 3 degrees-carbamines
from the asymmetric allylboration of N-trimethylsilyl
ketimines with B-allyl-10-phenyl-9-borabicyclo[3.3.2]
decanes. J Am Chem Soc. 2006 Jul 12;128(27):8712-3.
Book Chapter Addition:
Disiamylborane, First Update, Soderquist, J. A.; Matos, K., e-EROS Encyclopedia of Reagents
for Organic Synthesis, J. Wiley & sons, New York, 2007, posted March 15, 2007.
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