Stereoselective reactions. XXXIV. Enantioselective deprotonation of prochiral 4-substituted cyclohexanones using chiral bidentate lithium amides having a bulky group instead of a phenyl group on the chiral carbon

Using chiral bidentate lithium amides having a bulky group instead of a phenyl group on the chiral carbon, enantioselective deprotonation of prochiral 4-substituted cyclohexanones in the presence of excess trimethylsilyl chloride was examined in THF in the absence and in the presence of HMPA. It is shown that enantioselectivity of the reactions decreases as the substituent on the chiral carbon of the chiral lithium amides and the substituent at the 4-position of cyclohexanones become reasonably bulky. An eight-membered cyclic transition state model is proposed for this deprotonation reaction.     

Stereoselective reactions of chiral enolates. Application to the synthesis of (+)-prelog-djerassi lactonic acid.

The application of chiral metal enolates 3 and 4 have been employed in an efficient synthesis of (+)-Prelog-Djerassi lactone (1).     

Stereoselective ring-opening polymerization of rac-lactide by bulky chiral and achiral N-heterocyclic carbenes

Despite the extraordinary success has been achieved in metal catalyst-promoted stereoselective ring-opening polymerization(ROP) of rac-lactide(rac-LA), well-controlled stereoselective rac-LA ROP by organic catalyst still remains a scientific challenge. Here we report our investigations into organocatalytic stereoselective ROP of rac-LA by utilizing novel bulky chiral and achiral N-heterocyclic carbenes(NHC), 1,3-bis-(1′-naphthylethyl)imidazolin-2-ylidene. The effect of polymerization conditions(e.g. solvent, temperature, alcohol initiator) on ROP behavior by these bulky NHCs has been fully studied, leading to the formation of isotactic-rich stereoblock polylactide(P_i = 0.81) under optimized conditions with high activity(Conv. = 98% in 30 min) and narrow molecular weight dispersity(? = 1.05).     

Synthetic studies on maitotoxin. 1. Stereoselective synthesis of the C'D'E'F'-ring system having a side chain

The stereoselective synthesis of the maitotoxin C'D'E'F'-ring system having a side chain has been accomplished through a convergent strategy. The key reactions include Horner-Wadsworth-Emmons coupling of the C'D'E'-ring and the side chain and subsequent construction of the F'-ring by silane reduction of dihydropyran.     

Modular chiral bidentate phosphonites: design, synthesis, and application in catalytic asymmetric hydroformylation reactions

A new class of C(2)-symmetric chiral bidentate phosphonite ligands has been synthesized in moderate to good yields from readily available starting materials. Application of these air-stable chiral phosphonites in the Rh(I)-catalyzed asymmetric hydroformylation of styrene derivatives, vinyl acetate, and allyl cyanide afforded the corresponding chiral aldehydes with high regio- and enantioselectivities under mild reaction conditions. The modular nature of the ligands allows fine-tuning of the selectivities through judicious modifications of the substituents on the ligand backbone. X-ray structural analysis of the catalyst precursor suggested that the steric hindrance caused by the protruding remote substituents of the ligands into the vicinity of the metal center might be an important factor for the enantio-control of the reaction, whereas the sense of asymmetric induction can be rationalized on the basis of a trigonal-bipyramidal transition state diagram.     

Stereoselective Michael-alkylation and Michael-oxidation reactions of chiral 1,3-dioxolanones

A highly diastereoselective Michael-alkylation/oxidation methodology has been developed for the synthesis of optically active α-hydroxy-1,5-diester subunits. Inverse stereochemistry at the C_2′ position could be achieved by using a Michael acceptor equipped with a suitable group followed by a highly stereoselective protonation. This methodology has been applied to the enantioselective synthesis of the upper fragment of (+)-retusine.     

One-pot synthesis of chiral azetidines from chloroaldehyde and chiral amines

A variety of chiral azetidinepiperidines have been synthesized utilizing an expedient one-pot union of piperidine chloroaldehyde with chiral amines. This two step one-pot procedure provides access to an interesting set of compounds that retain the chiral purity of the starting chiral amine.     

Stereoselective synthesis of (+)-polyoxamic acid based on the synthesis of chiral oxazine

A concise, stereocontrolled synthesis of (+)-polyoxamic acid was achieved. Starting from trans-oxazoline as a chiral building block, the key step involves diastereoselective oxazine formation catalyzed by palladium(0).     

Chemoenzymatic synthesis of boron-containing chiral amines and amides

The first application of lipases as catalysts to obtain optically active boron-containing amines and amides is described. We studied several reaction conditions to achieve the kinetic resolution of boron-containing amines via enantioselective acylation mediated by Candida antarctica lipase B (CAL-B). Excellent enantioselectivity (E >200) and high enantiomeric excess (up to >99%) of both the remaining amines and amides were obtained.     

Stereoselective and diversity-oriented synthesis of trisubstituted allylic alcohols and amines

Stereoselective and diversity-oriented synthesis of trisubstituted olefins was achieved by using ortho-diphenylphosphanyl benzoate (o-DPPB) as a directing group for allylic substitution. The starting point of this methodology was a set of α-methylene aldehydes derived from Baylis-Hillman adducts. Subsequent addition of different organometallic reagents led to a variety of allylic alcohol substrates. After introduction of the reagent-directing o-DPPB group, copper-mediated allylic substitution with a wide range of Grignard reagents enabled the stereoselective construction of a large number of E-configured trisubstituted allylic alcohols and amines in excellent yields and stereoselectivities. Remarkable is the synthetic flexibility, which allows a wide range of permutations starting from an aldehyde followed by successive introduction of the substituents R(2) and R(3) from organometallic Grignard based reagents. Thus, starting from only a few precursors, a diversity-oriented synthesis of stereodefined trisubstituted allylic alcohols and amines becomes possible.     

Stereoselective synthesis of chiral tertiary alcohol building blocks via neighbouring group participation from tri-substituted olefins

A regio- and stereoselective preparation of chiral quaternary 1,2/1,3-diols from acyclic tri-substituted alkenes is disclosed. Optically active tertiary alcohols are the constituents of several bioactive natural products, pharmaceuticals and a general method for their preparation is desirable. A sulfinyl moiety has been utilized as an intramolecular nucleophile.     

Diastereoselective Ugi reaction without chiral amines: the synthesis of chiral pyrroloketopiperazines

The three-component Ugi reaction with chiral 2-(2-formyl-1H-pyrrol-1-yl)acetic acids prepared from natural l-aminoacids was investigated. The reaction opens a new route to chiral substituted pyrroloketopiperazines. One of the first examples of an asymmetric Ugi reaction without chiral amines is described. The reaction proceeds with moderate diastereoselectivity to give the target compounds in good yields. The scope and limitation of the approach are discussed.     

Aziridines as a protecting and directing group. Stereoselective synthesis of (+)-bromoxone

[reaction: see text] The directing ability of an aziridine group for the epoxidation of adjacent double bonds is demonstrated. The aziridine group is also used to effectively protect a double bond in a cycloenone system for a short synthesis of the title compound.     

Stereoselective synthesis of a chiral ferrosalen ligand using an aromatization strategy

A new chiral salen ligand based on two ferrocenyl groups is designed. Unlike known salen ligands, of which chirality originates from central and axial chiral centers, the chirality of this ligand comes from the planar chiral ferrocenyl groups. The ligand is synthesized stereoselectively using a novel aromatization strategy starting from a ferrocene derivative, which was readily prepared using a known chiral auxiliary approach.     

Stereoselective synthesis of chiral atropisomerically stable ferrocenyldiols containing a biphenyl unit

Two different ferrocenyldiketones 1 and 2 containing a biphenyl unit were prepared by Ni(0) promoted homocoupling of suitable ferrocenyl-aryl halides. The atropisomeric stability of the corresponding diols and other related derivatives was investigated. Chiral 2,2′-bis-(ferrocenylhydroxymethyl)-1,1′-biphenyl, (−)-5c, and 1(1,1′)-ferrocena-2,5-dihydroxy-3,4(1,2)dibenzenacyclopentaphane, (+)-6a and (−)-6b, were prepared as single diastereoisomers with defined central and axial chiralities by CBS-catalyzed asymmetric reduction of 1 and 2, respectively. During the reaction, that proceeded with high stereoselectivity affording the above mentioned diols in satisfactory enantiomeric excess, we noticed the occurrence of an unusual reductive deoxygenation process. Absolute configurations of the chiral diols were assigned by means of X-ray crystallographic and circular dichroism analyses.     

Synthesis and reactions of benzopentathiepin having hydroxyl group

The synthesis of benzopentathiepin having a hydroxyl group at the neighboring position of polysulfur ring was performed by demethylation of 6-ethyl-9-methoxybenzopentathiepin with hydrogenbromide. Benzotrithiole having hydroxyl group was not isolated at all. The hydroxyl group was also alkylated with alkyl iodide in the presence of weak base.     

Imino sulfinamidines: synthesis and coordination chemistry of a novel class of chiral bidentate ligands

The new imino sulfinamidine ligand PhS(NHt-Bu)=NC(Me)=N(C6H3-2,6-iPr2), LH (11) was synthesized from N-(2,6-diisopropylphenyl)acetamidine (9) and N-tert-butyl phenylsulfinimidoyl chloride (10). Reaction of LH (11) with ZnEt2 or AlMe3 gave the complexes LZnEt (12) and LAlMe2 (13), respectively. The structures of 12 and 13 were determined by X-ray diffraction and were shown to contain L as a kappa2-N1,N5 bidentate ligand in a six-membered chelate. Formation of the magnesium complex (LMgN(TMS)2 x L2Mg) (14) from 11, MgI2, and KN(SiMe3)2 highlighted a secondary coordination mode of L, binding through the sulfinamidine nitrogens in a four-membered chelate.     

One-pot synthesis of polysaccharide 3,5-dimethylphenylcarbamates having a random vinyl group for immobilization on silica gel as chiral stationary phases

Different kinds of vinyl groups were randomly introduced onto the glucose units of cellulose 3,5-dimethylphenylcarbamates by a one-pot method using the bifunctional reagents dec-1-ene-10-isocyanate, 2-isocyanatoethyl methacrylate, and methacryloyl chloride. The chiral recognition properties of the prepared derivatives were then evaluated by coating and immobilizing them on silica gel as HPLC packing material. Immobilization was carried out by radical copolymerization with a vinyl comonomer, 1,5-hexadiene, in toluene at 80 degrees C. The effects of the structures and content of the vinyl groups on the immobilization and on enantioseparations were investigated. This one-pot method was also extended to the synthesis of amylose 3,5-dimethylphenylcarbamates having a random vinyl group. Comparisons of the chiral resolution powers of our laboratory-made packing materials and the newly commercialized Chiralpak IA with immobilized amylose 3,5-dimethylphenylcarbamate and Chiralpak IB with immobilized cellulose 3,5-dimethylphenylcarbamate are discussed.     

Efficient one-step synthesis of chiral bidentate oxazoline-alcohol ligands via a cyclic imidate ester rearrangement

Various chiral bidentate oxazoline-alcohol ligands were obtained in a straightforward one-step synthesis via a cyclic imidate ester rearrangement. These chiral ligands were tested and compared in asymmetric diethylzinc additions to aldehydes resulting in selectivities of up to 87% ee. An interesting chirality switch was observed when a CPh₂-tether instead of a CH₂ was present, offering the opportunity for dual stereocontrol.