Preparation, Structure, and Reactivity of Thioxo and Imino Derivatives of the Triolide (and Pentolide) from (R)‐3‐Hydroxybutanoic Acid

Abstract

Reaction of the triolide 1 from (R)-3-hydroxybutanoic acid with Lawesson's reagent 5 leads to the mono-, di-, and trithio derivatives 6-8 which can be isolated in pure form (2040% yields), and which have crystal structures very similar to the parent triolide 1 (Fig.1). Similarly, pentolide 3 is converted to mixtures of various thio derivatives, three of which are separated (1612) by HPLC and fully characterized. The X-ray structures of the mono-and of one of the dithiopentolides (10, 12) differ remarkably from each other (Fig.3). Reduction of the thiotriolides 6-8 (NaBH,, R,SnH, Cl,SiH, Raney -Ni) gives 12-membered rings containing up to three ether groups (chiral crown ethers, 15, 17-19) in poor yields. The thiotriolides react spontaneously and in yields of up to 96% with ammonia, certain primary amines, and hydroxylamine to give imine and oxime derivatives with intact 12-membered-ring backbones (20, 22-24, 30, see crystal structures in Figs. 4-7). The rigid structure of all the derivatives of triolide 1 puts the C=O, C=S, and C=NR 0-, S-, and N-atoms in juxtaposition (a feature reminiscent of the side chains in the iron-binder enterobactin, Fig. 6). Imines containing PPh, groups are prepared (30,33,35) from the thiotriolides and tested as chiral ligands for PdT'-catalyzed 1,3-diphenylallylations (-37, enantiomer ratio up to 77:23). The reactions described demonstrate that multiple reactions of the triolide 1 from (R)-3-hydroxybutanoic acid which proceed through tetrahedral intermediates are possible without ring opening -the skeleton is remarkably stable, and this might be exploited as a template for bringing up to three pendent substituents into close proximity to allow a study of their interactions and cooperative properties. Also, the di-and trithio derivatives 7 and 8 could be used for cross-linking in molecules containing primary NH2 groups.

Preparation and NMR Structure of the Cyclo-β-tripeptide [β3-HGlu]3 in Aqueous Solution: A New Class of Enterobactin-TypeC3-Symmetrical Ligands?, Preliminary Communication

“…Furthermore, the J values measured are nearly identical to those observed for the corresponding H-atoms in the 3 1 -helix of b-peptides [28] [29]. Therefore, the structure may be referred to as a helix without a pitch or, conversely, the 3 1 -helix may be considered to be composed of trilactam units cut open and bent to form a left-handed single helix pitch 8 ).…”

“…7 ) The NH resonance dissapears after several min due to exchange with D 2 O. 8 ) Cf. the X-ray crystal structure of a linear b-tripeptide containing a nascent helix, Fig.…”

Chromium Imidate Complexes from the Metathesis-Like Reaction of Phosphinimines and Chromium(0) Fischer Carbene Complexes

“…2-(Diphenylphosphino)benzylamine was prepared according to literature methods. 14 General Procedure for the Synthesis of Phosphinimines 8a-g. A solution of 2-(diphenylphosphino)ethylamine, 3-(diphenylphosphino)propylamine, or 2-(diphenyphosphino)benzylamine and the corresponding benzaldehyde in stoichiometric amounts and a large excess of MgSO4 in dry CH2Cl2 were stirred at room temperature for 24 h. The mixture was filtered, and the solvent was removed under reduced pressure to yield the corresponding imines.…”

“…All commercially available compounds were used without further purification. 2-(Diphenylphosphino)benzylamine was prepared according to literature methods …”

Applications of Lawesson′s Reagent in Organic and Organometallic Syntheses

“…Thioxo derivates of triolide and pentolide 53 can be synthesized by reaction of triolide and pentolide 54 with LR, respectively (Scheme 18). 86 Thionation with LR yields a mixture of mono-, di-and trithiotriolide, and thiopentolide derivatives. The ester group is transformed into a thionoester functionality.…”