| Lanthanides have provided many exciting opportunities in the metal-catalyzed reactions and reductive chemistry in organic chemistry area, with samarium diiodide (SmI2) being the most popular reagent. This thesis research deals with the acrylates and crotonates possessing anelectron-withdrawing achiral or chiral aryloxy group for the SmI2-mediated reductive couplingwith aliphatic aldehydes. The products, alpha,gamma-trans - and beta,gamma-cis-disubstituted y-butyrolactones,obtained in high stereoselectivity and yields, are the versatile precursors to trisubstitutedtetrahydrofurans and other stereochemically defined building blocks. Applications in divertedtotal synthesis of natural macrolides and designed analogues are demonstrated.;A brief overview is given in Chapter 1 about target-oriented synthesis (TOS),diversity-oriented synthesis (DOS), and diverted total synthesis (DTS), and selective examplesof the SmI2-mediated reductive coupling reactions used in total synthesis. It is followed by thestructural analysis of apratoxin A, palmyrolide A, and laingolides consisting of a unique1,3-anti-Me/t-Bu subunit, and the progress in total synthesis of apratoxin A and palmyrolide A. Chapter 2 summarizes in more details the representative types of reductive carbon-carbonbond-forming reactions mediated by SmI2 and the two proposed single-electron transferpathways for reductive coupling of acrylates/crotonates with carbonyl compounds. Our newresults on SmI2-mediated reductive coupling reactions of alpha-substituted acrylates in achiral andchiral forms are then complied for efficient formation of trans-alpha,gamma-disubstituted gamma-butyrolactones in high stereoselectivity and high chemical yields. Particularly, racemic orchiral form of trans-5-tert-butyl-3-methyldihydrofuran-2-one serves as the synthetic precursorto 1,3-anti-Me/t-Bu subunit.;Usefulness of the SmI2-mediated reductive coupling of the chiral crotonate consisting ofan axially chiral naphthyloxy group with a non-branched aldehyde, (S)-citronellal, is illustratedin the diverted total synthesis of the designed analogues of amphidinolide T congeners. Thecis-5-alkyl-4-methyldihydrofuran-2-one is readily transformed into the C1-C11 trisubstitutedtetrahydrofuran-containing acid fragment and incorporation of this acid fragment into thedesigned macrolactones of 17- to 19-membered rings affords the analogues showing the samecytotoxicity against mouse lymphocytic leukemia cell line L1210.;Chapters 4 and 5 present the main results of this thesis research on diverted total synthesisof palmyrolide A and laingolide A using the pentamodule synthesis strategy in which trans-5-tert-butyl-3-methyldihydrofuran-2-one and its cis isomer, in both racemic and enantio enriched forms, are used as the key building blocks for the 1,3-anti- and1,3-syn-Me/t-Bu subunits, respectively. The Pd(OAc)2-Aphos-Y-catalyzed "9-MeO-9-BBNvariant" of B-alkyl Suzuki-Miyaura cross-coupling reaction and the Negishi cross-coupling reaction with a chiral organozinc reagent are employed for the key fragment assembly. The15-membered macrocyclic ring consisting of the trans-enamide moiety is constructed through sequential RCM/olefin isomerization protocol. These efforts result in diverted total synthesis of(-)-palmyrolide A and its 5,7-epimer, and all four C7 ,C9-diastereoisomers of laingolide A. By comparing the 13C NMR data of four C7,C9-diastereoisomers of laingolide A with those of the natural form, it allows us to assign the relative configuration of laingolide A as (2R*,7R*,9S*).Therefore, for the first time, we have revealed that the 1,3-syn-Me/t-Bu relationship does exist in Nature.;The main experimental procedures, the characterization data of major compounds, and the cited references are found at the end of the thesis. Copies of original 1H and 13C NMR spectra of key compounds are given in Appendix. |
