Highly diastereoselective synthesis of anti-gamma-N-benzylamino-beta-hydroxyphosphonates

The reduction of gamma-N-benzylamino-beta-ketophosphonates derived from readily available amino acids can be carried out stereoselectively with Zn(BH(4))(2) at -78 degrees C to produce the anti-gamma-amino-beta-hydroxyphosphonates.     

Highly diastereoselective synthesis of tetrahydrobenzofuranones by palladium-catalyzed reaction of propargylic carbonates with 2-substituted cyclohexane-1,3-diones

The reaction of propargylic carbonates with 2-substituted cyclohexane-1,3-diones in the presence of palladium catalyst is described. Substituted tetrahydrobenzofuranones having a quaternary carbon stereocenter were synthesized in a highly diastereoselective manner.     

Highly diastereoselective formation of 1,2,3-trisubstituted cyclopropane derivatives

A highly diastereoselective formation of cyclopropane derivatives was reported. When the chiral phenylvinyl epoxide reacted with lithiated 2-alkyl-1,3-dithiane or lithiated alkyl carbonanion in the presence of HMPA, cyclopropanes bearing stereochemistry at all three positions on the ring were readily obtained in high yields of 80-97% and high dr values of 68:32-99:1. This reaction was supposed to be a tandem conjugation addition-epoxide opening sequence. [reaction: see text]     

Highly diastereoselective multicomponent synthesis of unsymmetrical imidazolines

We report here a highly diastereoselective multicomponent synthesis of imidazolines. These low molecular weight scaffolds contain a four-point diversity applicable to alkyl, aryl, acyl, and hetereocyclic substitutions. [structure: see text]     

Highly diastereoselective synthesis of two analogues of dihydrosphingosine

Diastereomeric analogues 8 and 9 of dihydrosphingosine 2 with a shortened alkyl chain were obtained with high diastereoselectivity via addition of n-hexyl magnesium bromide or dihexylzinc to a chiral aldehyde 3, respectively. These compounds are precursors of new potentially hydrosoluble analogues of glycosphingolipides.     

Highly diastereoselective Michael addition of alpha-hydroxy acid derivatives and enantioselective synthesis of (+)-crobarbatic acid

[reaction: see text]. Michael addition of enolates of 2a and 2b to alpha,beta-unsaturated esters took place selectively on different faces (Si and Re, respectively) of the double bond to give the corresponding products 4 and 5, respectively, with >98% de. Subsequent hydrolysis of these Micheal adducts gives 3,4-disubstituted gamma-lactones with high enantiomeric excesses.     

Highly diastereoselective heterogeneously catalyzed hydrogenation of enamines for the synthesis of chiral beta-amino acid derivatives

Pure (Z)-enamines readily prepared from beta-ketoesters and amides using (S)-phenylglycine amide were hydrogenated with very high diastereoselectivities (up to 200:1) using heterogeneous catalysis. Hydrogenolytic cleavage of the (S)-phenylglycine amide afforded the corresponding chiral beta-aminoesters and amides. The high geometrical purity of the (Z)-enamine and a simple activation procedure for the PtO2 catalyst are essential in achieving high selectivity.     

Highly efficient and diastereoselective synthesis of (+)-lineatin

[reaction: see text] A linear sequence was used to synthesize (+)-lineatin in 14 steps and 14% overall yield from a homochiral 2(5H)-furanone. Key steps of this synthetic approach feature the diastereoselective construction of a cyclobutene through a photochemical [2 + 2] cycloaddition and a regiocontrolled oxymercuration reaction.     

Highly diastereoselective synthesis of C6-functionalized dihydroimidazotriazines

[reaction: see text] The first examples of C(6)-substituted 7-hydroxy-6,7-dihydro-5H-imidazo[1,2-b][1,2,4]triazines have been prepared by ring closure of different 5(2H)-1,2,4-triazin-3-ones 1a-c with 40% aqueous glyoxal and various nucleophiles (alcohols, thiols, or amines). The structure and exact stereochemistry of 2a was established by a single X-ray diffraction study and (1)H and (13)C NMR spectra analysis. The process was shown to be totally regio- and diastereoselective. A mechanism involving an imine intermediate was proposed.     

Highly diastereoselective synthesis of trans-2,5-disubstituted tetrahydrofurans

trans-2,5-Disubstituted tetrahydrofurans were obtained as major diastereomers (trans/cis ratio 90:10-100:0) when acetylated gamma-lactols derived from (S)-glutamic acid were treated with titanium enolates of N-acetyl (R)-oxazolidin-2-thiones. A simple transesterification allowed us to obtain the corresponding methyl esters and recover the chiral auxiliary.     

Highly diastereoselective synthesis of vicinal quaternary and tertiary stereocenters using the iodo-aldol cyclization

The intramolecular iodo-aldol cyclization of alpha-substituted enoate aldehydes and ketones is described. Using prochiral starting materials, the reaction produces hetero- and carbocycles containing quaternary centers adjacent to secondary or tertiary centers. The reactions occur in good yields and are highly selective for the trans-products, having the hydroxyl and iodomethyl groups on opposite faces of the ring system.     

Highly diastereoselective synthesis of arylglycine derivatives via TFA-promoted Friedel-Crafts reactions of phenols with cyclic glyoxylate imines

Optically active α-arylglycine derivatives were synthesized by Brønsted acid (TFA)-promoted Friedel-Crafts reaction of various phenols with chiral cyclic glyoxylate imines (2a-c), followed by deprotection with Pd(OH)₂/C under H₂. The diastereoselectivities of the initially formed F-C reaction products are up to 99%.     

Highly diastereoselective synthesis of vinylcyclopropane derivatives with (-)-8-phenylmenthol as chiral auxiliary

The silylated telluronium allylide 4, generated in situ from the corresponding telluronium salt in the presence of LiTMP, reacted with (-)-8-phenylmenthyl alpha,beta-unsaturated esters to afford trans-2-silylvinyl-trans-3-substituted cyclopropyl esters with high diastereoselectivity in high yields. The absolute configuration was determined by chemical transformation. A mechanistic rationale is proposed.     

Highly diastereoselective nitroaldol reactions with chiral derivatives of glyoxylic acid

N-Glyoxyloyl-(2R)-bornane-10,2-sultam (1a) and (1R)-8-phenylmenthyl glyoxylate (1b) react stereoselectively with simple nitroalkanes giving diastereomeric nitroalcohols with high asymmetric induction. The glyoximide 1a is proved to be a highly efficient chiral inducer, superior to glyoxylate 1b. In all cases, the absolute configuration (2S) and relative configuration, syn for the major diastereoisomers, were confirmed.     

Highly diastereoselective addition of cinnamylzinc derivatives to alpha-chiral carbonyl compounds

Cinnamylzinc reagents react with cyclic and acyclic alpha-chiral ketones under very mild conditions (-78 degrees C, 1 h), yielding the corresponding homoallylic alcohols bearing three adjacent stereocenters with high diastereoselectivity. An extension of this reaction to enantioenriched alpha-chiral ketones is also described.     

Highly diastereoselective switchable enantioselective Mannich reaction of glycine derivatives with imines

Tuning of diastereoselectivity was realized in the Mannich reaction of glycine derivatives with aromatic and aliphatic N-Ts imines using CuClO4-FcPHOX ligand 4b and 4f having an MeO group at the 4-position and F atom at the 3,5-position of the phenyl ring on the P-atom respectively as catalyst, providing either anti- or syn-alpha,beta-diamino acid derivatives in high yields and in high diastereo- and enantioselectivities.     

Highly diastereoselective synthesis of tetrahydropyridines by a C-H activation-cyclization-reduction cascade

A versatile reaction cascade leading to highly substituted 1,2,3,6-tetrahydropyridines has been developed. It comprises rhodium(I)-catalyzed C-H activation-alkyne coupling followed by electrocyclization and subsequent acid/borohydride-promoted reduction. This one-pot procedure affords the target compounds in up to 95% yield with >95% diastereomeric purity.