Ramon Berenguer

A synthetic approach towards octalactin A, based on the stereoselective reduction of α,β-unsaturated ketones

Abstract An efficient enantioselective synthesis of the C3C9 fragment of Octalactin A and studies aimed at the conversion of Octalactin B into Octalactin A are described, which are based on the borane-mediated reduction of α,β-unsaturated ketones catalysed by B -methyl-4,5,5-triphenyl-1,3,2-oxaza-borolidines ( 9 ). A comparative study of the reduction of 2-methylnon-1-en-3-one ( 10 ) —a model of the Octalactin-A C3C9 moiety— with different chiral reagents has also been performed.

Enantioselective reduction of ketones catalysed by 1,3,2-oxazaborolidines prepared from phenylglycine

Abstract ( R )- B -methyl-4,5,5-triphenyl-1,3,2-oxazaborolidine ( 1 ) and ( R )- B -allyl-4,5,5-triphenyl-1,3,2-oxazaborolidine ( 2 ), prepared from ( R )-phenylglycine, catalyse the reduction of prochiral ketones with borane, to afford the corresponding secondary alcohols in good chemical yields and with moderate to high (61%–96%) enantiomeric excesses. These compounds gave the best results reported so far regarding the reduction of linear alkyl methyl ketones catalysed by oxazaborolidines.

Enantioselective reduction of acetophenone with 1,3,2-oxazaborolidines derived from ephedrine, pseudoephedrine, and phenylglycine

Abstract The performance of several 1,3,2-oxazaborolidines as chiral catalysts in the reduction of acetophenone has been compared, to gain insight into the more relevant structural factors as far as yield and enantioselectivity are concerned. B-Alkyl-4,5,5-triphenyl-1,3,2-oxazaborolidines have emerged as effective catalysts for this reaction when nitrogen is not substituted. The origin of the enantioselectivity for this kind of catalysts is discussed.

Stereoselective reduction of unsaturated 1,4-diketones. A practical route to chiral 1,4-diols

Abstract A new synthetic route to C 2 -symmetric chiral 1,4-diols based on the borane-mediated oxazaborolidine-catalysed reduction of 2-ene-1,4-diones ( 2 ), of 2-yne-1,4-diones ( 3 ), and/or of Co-complexed diketones 4 is described. Good to excellent enantio- and diastereoselectivities have been obtained in the reduction of diketones 3 and 4 , catalysed by oxazaborolidines 6 and 5 , respectively.

Allylic alcohols of unexpected configuration by oxazaborolidine-catalysed reduction of α,β-unsaturated ketones. An explanation based on MO calculations

Abstract While the reduction of most α,β-unsaturated ketones with BH 3 :SMe 2 in the presence of ( R )- B -methyl-4,5,5-triphenyl-1,3,2-oxazaborolidine [(R)- 2 ] affords allylic alcohols of the S configuration, that of α,β-unsaturated ketones branched at both the α and α′ positions gives alcohols of the R configuration. Theoretical calculations on complexes of representative enones with BH 3 (6–31G ∗ ) or with BH 3 :(R)- 2 (AM1) may account for the apparent changes in the steric requirements on either side of the CO group.

Total synthesis of entecavir

Entecavir (BMS-200475) was synthesized from 4-trimethylsilyl-3-butyn-2-one and acrolein. The key features of its preparation are: (i) a stereoselective boron-aldol reaction to afford the acyclic carbon skeleton of the methylenecylopentane moiety; (ii) its cyclization by a Cp2TiCl-catalyzed intramolecular radical addition of an epoxide to an alkyne; and (iii) the coupling with a purine derivative by a Mitsunobu reaction.

Enantioselective synthesis of α-hydroxy thioesters via oxazaborolidine-mediated reduction of α-phenylthio enones

Abstract α-Phenylthio-α,β-alkenones ( 2 ), readily available by Pd(II)-catalysed coupling of ( E )-1-phenylthio-1-tributylstannylhex-1-ene with the corresponding acid chlorides, have been treated with borane in the presence of phenylglycine- or proline-derived oxazaborolidines to afford 2-phenylthio-2-alken-1-ols ( 3 ) with good to excellent enantioselectivities. Ozonolysis of 3 provides a new and efficient route to chiral α-hydroxy thioesters 4 .