This project will continue work on the development of methods for the asymmetric formation of C-C bonds through organoborane reactions employing the stable and robust 9-borabicyclo[3.3.2]decanes (BBDs). While a wide variety of asymmetric organoborane conversions are known, prior to the development of the BBDs, the air-sensitivity and thermal instability of the available trialkylborane reagents has limited the discovery of new reagents and reactions. The present studies will focus on the invention of new organoborane chemistry based upon the recyclable and selective BBDs. The rates and enantioselectivities of the reactions of new 10-substituted BBDs will be compared to those of the reagents that have been previously examined.
With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor John A. Soderquist of the Department of Chemistry at the University of Puerto Rico. Professor Soderquist's research efforts revolve around the development of new asymmetric organoborane conversions for the selective formation of C-C bonds. Such chemistry will contribute to environmentally benign methods for chemical synthesis as all of the organoborane reagents are recyclable through simple procedures. Successful development of the methodology will have an impact on synthesis in the pharmaceutical and agricultural industries.
All life processes depend upon chirality because Nature builds DNA, RNA, proteins, sugars, enzymes and virtually everything else as single enantiomers, that is a handedness, right or left. The wrong enantiomers can have disastrous effects. When pregnant women took the drug thalidomide to alleviate nausea and morning sickness, both the R and S forms of the drug were present. While the R form treated the nausea, the (S)-(-)-thalidomide was teratogenic causing major birth defects and deaths in the new born infants. This resulted in major changes in the regulations for the pharmaceutical industry and the asymmetric synthesis of drugs and bioactive compounds has been of paramount importance ever since. The stereoselective addition of reagents containing the chiral 10-substituted-9-borabicyclo[3.3.2]decane (BBD) moiety to aldehydes, ketones, aldimines and ketimines has been examined. The R = allyl, allenyl, crotyl, TMS-propargyl, alkynyl, 2-dienyl, and gamma-alkoxyallyl BBD reagents have been prepared for the 10-TMS BBD reagents and these are are effective for aldehydes and aldimines. Their 10-Ph counterparts are effective for ketones and ketimines. The goals of this research have been to provide new highly selective new boron reagents which set the gold standards for these additions. These goals have been realized in large part, although some challenges remain. The rigid and robust nature of these systems permits a wide variety of organoborane conversions to not only be conducted in a highly enantioselective manner, but also, it facilitates the recovery of the chiral borane by-product which can be recycled through simple operations. Moreover, numerous chemical conversions can be performed on these organoboranes providing remarkable new reagents for organic synthesis.1-8 The origin of the observed selectivities can be understood in terms of the BBD systems having an "enzyme-like" C1-symmetry (no symmetry) which derives its selective orchestration of chemical reactions on the basis of steric effects which favor bonding in only one of several possible reaction orientations. The present cycle has resulted in four (4) new PhD chemists entering the scientific community, eight (8) major publications (see below) and fifty-two (52) scientific presentations around the world. The chemical products resulting from these studies have resulted in new methods for the synthesis of alcohols, amines and amino acids. A major advance for this project was to develop new reagents for both the common secondary, as well as the unusual, tertiary compounds. The 10-TMS reagents (Z = trimethylsilyl) are now commercially available which has stimulated their use in synthesis (Aldrichimica Acta 2007, 40, 2). Bibliography 1. González, A. Z.; Román, J. G.; Alicea, E.; Canales, E.; Soderquist, J. A. J. Am. Chem. Soc., 2009, 131, 1269. DOI: 10.1021/ja808360z 2. Soto-Cairoli, B.; Soderquist, J. A. Org. Lett., 2009, 11, 401. DOI: 10.1021/ol802685e 3. Mu?oz-Hernández, L.; Soderquist, J. A. Org. Lett., 2009, 11, 2571. DOI: 10.1021/ol900865y 4. González, J. R.; González, A. Z.; Soderquist, J. A. J. Am. Chem. Soc. 2009, 131, 9924. DOI: 10.1021/ja9047202. 5. Chiral Ligation for Boron and Aluminum in Stoichiometric Asymmetric Synthesis, 3.22, Soderquist, John A. In Comprehensive Chirality, H. Yamamoto, E. Carreira (Eds.); Elsevier: Amsterdam, 2012; pp 691-739, DOI: 10.1016/B978-0-08-095167-6.00322-0 6. (E)-2-Boryl-1,3-dienes from the 10-TMS-9-BBDs: Highly Selective Reagents for the Asymmetric Synthesis of anti-α,β-Disubstituted-β-allenylamines from the Allylboration of Aldimines, González, J. A.; Soderquist, J. A. Org. Lett., 2014, 16 (14), pp 3840–3843, DOI: 10.1021/ol501892a 7. Highly Functionalized tertiary-Carbinols and Carbinamines from the Asymmetric γ-Alkoxyallylboration of Ketones and Ketimines with the Borabicyclodecanes, Muñoz-Hernández, L.; Seda, L. A., Wang, B.; Soderquist, J. A. Org. Lett., 2014, 16, ASAP, DOI: 10.1021/ol5019486. 8. Cyclohexenylboration of Aldehydes and Ketones with the BBDs, González, E.; Soderquist, J. A. Org. Lett., 2014, 16, submitted.
