150895-72-0Relevant articles and documents
Synthesis of enantioenriched α-chiral bicyclo[1.1.1]pentanes
Wong, Marie L. J.,Mousseau, James J.,Mansfield, Steven J.,Anderson, Edward A.
supporting information, p. 2408 - 2411 (2019/03/26)
Bicyclo[1.1.1]pentanes (BCPs), useful surrogates for para-substituted arenes, alkynes, and tert-butyl groups in medicinal chemistry, are challenging to prepare when featuring stereogenic centers adjacent to the BCP. We report the development of an efficie
The Knight route to cyclopiazonic acid: Enantioselective synthesis of a key intermediate
Beyer, Christian,Scherkenbeck, Jürgen,Sondermann, Frank,Figge, Axel
experimental part, p. 7119 - 7123 (2010/09/14)
The indole alkaloid α-cyclopiazonic acid (CPA) is one of the few known inhibitors of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) besides thapsigargin and artemisinin. Inhibitors of SERCA hold promise as novel anticancer and antimalarial drugs. Since its structure elucidation three racemic syntheses of α-cyclopiazonic acid have been published. We report now the first enantioselective and high yielding synthesis of a key-intermediate of the Knight synthesis, currently the most efficient route to CPA. Our synthesis is based on a diastereoselective 1,4-cuprate addition followed by an enolate azidation of an indolylacrylic acid modified with the Evans auxiliary.
Asymmetric Samarium-Reformatsky Reaction of Chiral α-Bromoacetyl-2-oxazolidinones with Aldehydes
Fukuzawa, Shin-Ichi,Matsuzawa, Hiroshi,Yoshimitsu, Shin-Ichi
, p. 1702 - 1706 (2007/10/03)
The samarium(II) iodide mediated asymmetric Reformatsky-type reaction of chiral 3-bromoacetyl-2-oxazolidinones with various aldehydes was studied. A series of chiral 4-substituted 2-oxazolidinones 1-3 and 5,5-disubstituted "SuperQuat" oxazolidinones 4-5 were employed as chiral auxiliaries of the α-bromoacetic acid. The reaction of 1 with various aldehydes gave the α-unbranched β-hydroxy carboximides in good yields with high diastereomeric excess values (up to >99% de). The majority of the reaction product derived from 5,5-diphenyl SuperQuat 5 were highly crystallinity; a single recrystallization yielding a diastereomerically pure product with the other diastereomer not detectable by spectroscopic methods. The absolute configurations of the β-hydroxy carboximides were determined by signs of optical rotations of the corresponding known ethyl esters referring to the literature values. Hydrolytic cleavage of the appended of β-hydroxy moieties from the auxiliary SuperQuats was readily achieved under mild conditions using lithium hydroxide; the corresponding carboxylic acids and the returned SuperQuats were obtained in good yields without any evidence of racemization. The first step of the reaction is the reduction of the α-bromo group to produce the samarium enolate, which adds to an aldehyde. The absolute configuration of the adduct (7i) derive from benzaldehyde was found to be R, with the samarium enolate favoring the transition state predicted from chelation control of the reagent; this is in analogy to the discussion that has been used for the corresponding titanium enolate. The stereochemistry of the reaction may be explained by incorporating the Nerz-Stormes-Thornton chair transition structure model.
Chelation Control in Metal-Assisted Aldol Addition Reactions of α-Halogenated Imide Enolates Leading to Predominantly Anti Stereoselectivity. An Example of a Stereocontrolled Darzens Reaction
Pridgen, Lendon N.,Abdel-Magid, Ahmed F.,Lantos, I.,Shilcrat, Susan,Eggleston, Drake S.
, p. 5107 - 5117 (2007/10/02)
The aldol reaction of enantiopure N-(haloacetyl)-2-oxazolidinone enolates with aromatic aldehydes was studied for conditions that would induce the reaction to yield predominantly anti adducts.It was found herein that the inherent steric and stereoelectronic properties of the aldehyde (R), as well as its chelative ability with the enolate countercation, are crucial in determining which of its enantiotopic faces reacts.Certain metallic enolates (Sn(IV)), Zn, and Li) are postulated to react through a threepoint coordination transition state to yield mainly anti adducts, while others (Sn(II), B, Ti) are shown to react via noncoordinated transition states to yield either syn or anti adducts.X-ray crystallography was instrumental in fully defining the absolute stereochemistry of each product, providing insight into the mechanisms of stereocontrol.The major anti producing pathway for reaction of aromatic aldehydes is postulated to proceed via boatlike or a high-energy "unfavored chair" transition state (TS).Finally, using our protocol of varying either the enolate countercation or the substitution pattern on the aromatic aldehyde, we demonstrate how one may synthesize three of the four possible stereoisomers available from this aldol-type reaction, the syn Li isomers 7 being the only inaccessible isomer as a major product in this α-halo-2-oxazolidinone system.The anti halohydrins were converted stereospecifically to the trans epoxy esters or epoxy amides in high enantiomeric purity.
