37526-88-8Relevant academic research and scientific papers
Dienolates of Cycloalkenones and α,β-Unsaturated Esters Form Diels–Alder Adducts by a Michael/Michael-Tandem Reaction Rather Than in One Step
Loesche, Ann-Christine,Brückner, Reinhard
supporting information, p. 562 - 573 (2018/12/11)
α,β-Unsaturated esters and lithium 1,3-dien-2-olates are known to furnish bicyclic lithium enolates by anionic Diels–Alder reactions. However, in principle, the respective products might form not only in a single step but also in two consecutive – or “tandem” – Michael additions, the first of which occurs intermolecularly, the second intramolecularly. Three cyclic lithium dienolates and four esters with a stereogenic Cα=Cβ bond reacted to give Diels–Alder adducts (10 times) or failed to react (2 times). Seven of the reactive combinations furnished adducts wherein the configuration of the former ester moiety had in part inverted. This precludes concerted pathways as their origins. This was a surprise since donors at C-2 of the 1,3-diene accelerate normal electron-demand Diels–Alder reactions in the order alkyl ⊕O? being a far better donor still, it is not obvious why the mechanism is non-concerted rather than concerted (and still more asynchronous).
Highly enantioselective iridium-catalyzed hydrogenation of α,β-unsaturated esters
Li, Jia-Qi,Quan, Xu,Andersson, Pher G.
supporting information, p. 10609 - 10616 (2012/11/07)
α,β-Unsaturated esters have been employed as substrates in iridium-catalyzed asymmetric hydrogenation. Full conversions and good to excellent enantioselectivities (up to 99 % ee) were obtained for a broad range of substrates with both aromatic- and aliphatic substituents on the prochiral carbon. The hydrogenated products are highly useful as building blocks in the synthesis of a variety of natural products and pharmaceuticals. Asymmetric hydrogenation: A variety of α,β-unsaturated esters were hydrogenated with high enantioselectivities (see scheme). The hydrogenated products have been used in synthetic transformations as well as in formal total syntheses. Copyright
Chiral bis(N-arylamino)phosphine-oxazolines: Synthesis and application in asymmetric catalysis
Schoenleber, Marc,Hilgraf, Robert,Pfaltz, Andreas
supporting information; experimental part, p. 2033 - 2038 (2009/08/07)
N-Arylation or N-alkylation of chiral 1,2-diamines followed by ring closure with phosphorus trichloride (PCl3) and subsequent coupling with an oxazoline alcohol resulted in a new class of N,P ligands. The corresponding iridium tetrakis[3,5-bis(trifluormethyl)phenyl]borate (BArF) complexes were found to be efficient catalysts for the enantioselective hydrogenation of unfunctionalized olefins and α,β-unsaturated carboxylic esters.
Asymmetric hydrogenation routes to deoxypolyketide chirons
Zhou, Jianguang,Ogle, James W.,Fan, Yubo,Banphavichit, Yorawit,Zhu, Ye,Burgess, Kevin
, p. 7162 - 7170 (2008/03/12)
Asymmetric hydrogenations of monoenes and dienes were performed to obtain terminal deoxypolyketide fragments A and the corresponding internal Chirons B and C. The chiral N-heterocyclic carbene catalyst 1 was used throughout. Modest selectivities for hydrogenations of simple monoenes relayed into high selectivities for preparations of the terminal deoxypolyketide fragments in which either two hydrogenations or one and an optically pure starting material were used. Curiously, the face selectivities for hydrogenation of α,β-unsaturated esters were consistently opposite to those that had been observed for styrene and stilbene derivatives in previous work, and to closely related allylic alcohol and ether derivatives in this work. Plausible mechanisms for this differing behavior were deduced by using DFT calculations. It appears that the origin of the unusual stereoselectivity for the ester derivatives is transient metal-coordination of the ester carbonyl whereas there is no evidence that the allylic alcohol or ethers coordinate. The routes developed to α,ω-functionalized internal deoxypolyketide fragments are extremely practical. These begin with the Roche ester being converted into alkene and, in one case, diene derivatives. Catalyst control prevails in the hydrogenations of these substrates, but there is a significant "substrate vector" (a term we used to describe the influence of the substrate on a catalyst-controlled reaction). This is determined by minimization of 1,3-allylic strain and, in some cases, syn pentane interactions. This substrate vector can be constructively paired with the (dominant) catalyst vector by use of the appropriate enantiomer of 1. In the hydrogenation of a diene derivative, two chiral centers could be formed simultaneously with overall 11:1.0 selectivity; this is the first time this has been achieved in any asymmetric synthesis of a deoxypolyketide fragment. Throughout, diastereo-selectivities of the crude material in the syntheses of α,ω-functionalized internal deoxypolyketide fragments were in excess of 11:1.0 and chromatographically purified samples could be isolated in high yields with dr (dr = diastereomeric ratio) values consistently in excess of 40:1.0.
CCR5 antagonists: 3-(pyrrolidin-1-yl)propionic acid analogues with potent anti-HIV activity
Lynch, Christopher L.,Hale, Jeffrey J.,Budhu, Richard J.,Gentry, Amy L.,Finke, Paul E.,Caldwell, Charles G.,Mills, Sander G.,MacCoss, Malcolm,Shen, Dong-Ming,Chapman, Kevin T.,Malkowitz, Lorraine,Springer, Martin S.,Gould, Sandra L.,DeMartino, Julie A.,Siciliano, Salvatore J.,Cascierl, Margaret A.,Carella, Anthony,Carver, Gwen,Holmes, Karen,Schleif, William A.,Danzeisen, Renee,Hazuda, Daria,Kessler, Joseph,Lineberger, Janet,Miller, Michael,Emini, Emilio
, p. 2473 - 2475 (2007/10/03)
(Matrix presented) A novel approach to α,α-disubstituted-β -amino acids (β2,2-amino acids) was employed in the synthesis of a series of 3-(pyrrolidin-1-yl)-propionic acids possessing high affinity for the CCR5 receptor and potent anti-HIV activity. The rat pharmacokinetics for these new analogues featured higher bioavailabilities and lower rates of clearance as compared to cyclopentane 1.
Stereospecific synthesis of chiral tertiary alkyl-aryl ethers via Mitsunobu reaction with complete inversion of configuration
Shi, Yao-Jun,Hughes, David L.,McNamara, James M.
, p. 3609 - 3611 (2007/10/03)
Mitsunobu reaction of chiral tertiary alcohol (S)-2 with phenol 3 provides the desired ether (R)-1 in moderate yields at elevated temperatures (80-100°C). The SN2 displacement pathway is evident by complete inversion of the (S)-alcohol to (R)-e
Direct ester condensation from a 1:1 mixture of carboxylic acids and alcohols catalyzed by hafnium(IV) or zirconium(IV) salts
Ishihara, Kazuaki,Nakayama, Masaya,Ohara, Suguru,Yamamoto, Hisashi
, p. 8179 - 8188 (2007/10/03)
To promote atom efficiency in synthesis and to avoid the generation of environmental waste, the use of stoichiometric amounts of condensing reagents or excess substrates should be avoided. In esterification, excess amounts of either carboxylic acids or alcohols are normally needed. We found that the direct condensation of equimolar amounts of carboxylic acids and alcohols could be achieved using hafnium(IV) or zirconium(IV) salts. These metal salts are highly effective as catalysts for the selective esterification of primary alcohols with carboxylic acids in the presence of secondary alcohols or aromatic alcohols. The present methods can be applied to direct polyesterification and may be suitable for large-scale operations.
