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Efficient synthesis of l -α-phosphatidyl- d - myo -inositol 3,5-bisphosphate was achieved from 1,2,5,6-diisopropylidene- d -glucose by utilizing ring-closing metathesis and catalytic OsO 4 dihydroxylation.

Catalytic protonation of achiral lithium enolates (derived from 2-substituted-1-tetralones), mediated by a chiral tetraamine ligand [( R , R )- N , N ′-bis[1-phenyl-2-(1-piperidinyl)ethyl]-1,3-propanediamine (0.10 equiv.)], was achieved with high enantioselectivity (up to 93% ee) by using water (10% aqueous citric acid) as a proton source. A possible mechanism of highly efficient catalytic turnover of the chiral tetraamine ligand is discussed.

The rate of the reaction of the lithium enolate of 1-tetralone with alkyl halides was enhanced greatly in the presence of 3 equivalents of 1,1,4,7,10,10-hexamethyltriethylenetramine. The ratio of the monoalkylated product to the dialkylated product was found to have increased under a shorter reaction time.

Enantioselective asymmetric alkylation of achiral lithium enolates mediated by chiral tetradentate amine ligands is achieved to give chiral quaternary carbon centers. Turnover of a chiral tetradentate amine in the presence of an achiral bidentate amine during the reaction is also realized.

Enantioselective alkylation of lactams and lactones can be realized up to 98% ee by deprotonation with a chiral tetradentate lithium amide (4b) in the presence of lithium bromide, and subsequent alkylation with active alkylating agents in non-chelating solvents.

The diastereo- and enantioselective Michael reaction of ketone lithium enolates using a chiral amine ligand (1) was examined. Michael adducts (4) were obtained in excellent chemical yields (95∼99%) with high stereoselectivities ( syn- 4 anti- 4 : 16 84 ∼ 1 99 ; ee of anti- 4 : 81∼99 %) by the reaction between alkyl phenyl ketones (2) and Michael acceptors (3) having an alkylidene group.

Chiral C 2 -symmetric DMEU derivatives were designed and synthesized as chiral ligands for lithium. The reaction of the lithium enolate ( 2 ) of 1-tetralone ( 1 ) with methyl iodide in toluene in the presence of a DMEU derivative ( 11 ) and hexamethyl-disilazane gave ( S )-2-methyl-1-tetralone ((S)- 3 ) in up to 92% ee.

Enantioselective deprotonation of 4-substituted cyclohexanones (1) in the presence of excess trimethylsilyl chloride was examined using chiral bidentate lithium amides ((R)-3∼(R)-7) in THF. The solution structures of (R)-3a in THF in the presence and in the absence of lithium chloride were studied by NMR. It is concluded that the eight-membered cyclic transition state (10) offers reasonable explanation of the stereochemical course of the present reaction using (R)-3a.

Lithium-hydrogen interchange between a chiral bidentate amine ((R)-4b) and an achiral tridentate lithium amide (8) occurs rapidly in situ, favoring the exclusive formation of a chiral bidentate lithium amide ((R)-5b). Based on this finding, catalytic asymmetric deprotonation of 4-substituted cyclohexanones (1a∼d) was realized by using less than a stoichiometric amount of (R)-4b as a chiral auxiliary.

Enantioselectivity of deprotonation reaction of 4-tert-butylcyclohexanone (2) by a monodentate chiral lithium amide ( (R,R)- 1 ) in THF is strongly influenced by the presence of lithium halides. Aggregation states of this chiral lithium amide in THF-d8 in the absence and in the presence of lithium halides were studied by 6Li and 15N NMR. It is concluded that the mixed dimer (D) is the species to give the high enantioselectivity of the reaction.

The enantioselective Michael reaction of ketone lithium enolates using a chiral amine ligand ( 1 ) was studied. Michael adducts ( 4 ) of up to 94% ee were obtained by the reaction between methyl ketones ( 2 ) and Michael acceptors ( 3 ) having a benzylidene group.

In the presence of the palladium complex with the phosphorus-containing C2-symmetric chiral amine ligand 2, 3, the asymmetric allylic substitution of racemic 1,3-diphenyl-2-propenyl acetate 8 with dimethyl malonate proceeded in high yield with remarkable enantiomeric excess.

A pyridine derivative (3) and TsOH form a 2 + 2 salt with six hydrogen bonds in the solid state, although there are equilibria between some aggregation states induced by hydrogen bonding in solution.

A C2-symmetric chiral diamine ligand 1 was found to be effective for palladium catalyzed asymmetric allylic substitution of racemic 1,3-diphenyl-2-propenyl acetate 5 with dimethyl malonate. The X-ray analysis and NMR study of the palladium complex 7 with chiral diamine 1 have revealed the mechanism of high enantioselection.

Mono-deuterated derivatives of optically active 3-keto steroids ( 4 -2α-d, 4 -2β-d, 5 -4α-d, 5 -4β-d, 6 -2α-d, and 6 -2β-d) were treated with a chiral lithium amide (( S )- or ( R )- 2b ) in the presence of excess trimethylsilyl chloride to give the corresponding diastereomeric Δ 2 - and ΔA 3 -silyl enol ethers. It is concluded that the present deprotonation reaction occurs in chair conformation in 6 , while in boat (skew-boat) conformation about the A-rings in 4 and 5 .

Chiral chelated lithium armides (2e∼h) having a fluorine-containing alkyl group on amide nitrogen were found to induce high enantioselectivity in kinetic deprotonation of 4-substituted cyclohexanones (1a∼2d).

Diastereoselective alkylation of chiral lithium enolates (dl-, (R)- and (S)-9) derived from 4-t-butylcyclohexanone in the presence of a chiral seco

Based on the concept of a metal differentiating coordination, a new chiral amidophosphine ligand 2 was designed, synthesized, and applied in an enantioselective conjugate addition of lithium dimethylcuprate to chalcone providing the corresponding adduct in 84% ee.

Negatively-charged cyclophanes ( 2a,2b ) having eight carboxylate groups on the aromatic rings were designed and synthesized. It is shown that they work as hosts that form inclusion complexes selectively with positively-charged aromatic compounds as guests in alkaline water.

An asymmetric 1,2-addition of organolithiums to imines (1) was catalyzed by a substoichiometric amount (0.05-0.3 equivalent) of a chiral aminoether (2) to provide the corresponding optically active amines (3).

Total synthesis of dolastatin 10 (1) was completed by developing an efficient synthesis of two key amino acid components, Dil (6) and Dap (11), and subsequent stepwise coupling of five amino acid components from C-terminal Doe.

An attempt was made to accelerate intramolecular amide bond formation by introducing additional catalytic groups to the crown ether having two thiol groups as the enzyme model for the peptide synthesis. The host with methyl ester groups performed the reaction more effectively than that without them. It has been suggested that the ester groups can achieve acceleration through their preorganization in the crown host.

The reaction of methyllithium with 4-methoxyphenylimine of 1-naphthalenecarbaldehyde (1) in the presence of the chiral ligand A afforded, contrary to 1,4-addition with the cyclohexylimine, the corresponding 1,2-addition product as an optically active amine (2) in 70% ee.

An α-phenethylamine-derived chiral lithium amide ( (R) - 5c ) possessing a 2,2,2-trifluoroethyl group on the amide nitrogen was found to induce high enantioselectivity in the kinetic deprotonation of 4- tert -butylcyclohexanone ( 1 ) in the presence of excess trimethylsilyl chloride to give the corresponding silyl enol ether ( (S) - 2 ) in up to 92% ee (86% chemical yield). © 1997 Elsevier Science Ltd.

Aerobic oxidative coupling of 2-naphthol derivatives by the use of 1 mol% of CuCl-amine complex afforded binaphthol derivatives in excellent yields.

In the Presence of both stoichiometric and catalytic amounts of a chiral dieter 1, aryllithiums reacted with BHA-esters of naphthalenecarboxylic acids 2, 5 to afford the corresponding adducts 4, 6 in high ee.

A slight structural modification of a chiral diamine 1 caused a dramatic change in a sense of enantioselectivity in dihydroxylation of olefins with chiral amine-osmium tetroxide complex.

Reaction of 2,6-di-tert-butyl-4-methoxyphenyl naphthalenecarboxylates with organolithiums provided the addition products to naphthalene nucleus in quantitative yield.

Control elements in the highly selective construction of contiguous tertiary and quaternary carbon centers by the tandem alkylation of α-alkylidene-γ-butyrolactone derivatives were studied. It is clarified that the stereochemical course of the reaction is rationalized by evaluating highly selective 1,2-, 1,3-, and 1,4-asymmetric inductions.

The title compound((±)-3) was prepared from readily available 5,8-dimethoxy-3,4-dihydro-2-naphthoic acid(4), according to the novel synthetic route visualized in Scheme I .

The bromolactones(3) prepared from α,β-unsaturated acids(1) were converted to optically active α,β-epoxyaldehydes(2(R),3(S)-6)(84–98% ee) by successive epoxide formation and reductive cleavage of the proline moiety. The overall process constitutes a highly efficient asymmetric synthesis of 2(R),3(S)-6 from 1.

Enantiospecific total synthesis of (-)-megaphone ( 1 ) is reported. The key synthetic tactic is the use of (4 S )-2 Z -ethylidene-4-trityloxymethyl-butan-4-olide ( 6 ) to both establish the relative and absolute stereochemistry of the contiguous tertiary and quaternary carbon centers by a highly controlled 1,4- and 1,3-asymmetric induction and construct the 4-methoxy-6,6-dialkyl-cyclohexenone portion of 1 .

(+)-Steganacin was synthesized in a new and highly specific asymmetric pathway based on the novel application of chiral γ-lactone as a chiral synthon. By this synthesis the absolute stereochemistry of natural (−)-steganacin could be determined in unequivocal way.

By the self-immolative asymmetric synthesis, optically pure key intermediate β-piperonyl-γ-lactone (R)-(+)- 6 was found to be prepared in reasonable yield from the easily available chiral γ-lactone synthon ( 1 ) which had been also reported to give an antipode (S)-(-)- 6 . The optically pure (R)-(+)- 6 was shown to be converted successfully into several optically pure natural lignan lactones.

The first synthesis of a water-soluble cyclophane possessing a chiral hydrophobic cavity, and the formation of diastereomeric inclusion complexes with chiral hydrophobic guests in water are described.

Stereochemical consideration of the efficient enantioselective oxidation of trans-stilbene employing a C2-symmetric chiral diamine (5) strongly indicates an organometallocycle (2) as a possible intermediate in the oxidation of olefins with osmium tetroxide.

(S)-γ-Trityloxymethyl-γ-butyrolactam (2) serves as a chiral auxiliary in the conjugate addition reaction of the corresponding imide (3) of α,β-unsaturated carboxylic acids with Grignard reagents in the presence of CuBrSMe2 in THF to give, after hydrolysis, the β,β-disubstituted carboxylic acids (5) with predictable absolute configuration and high enantiomeric excess.

The 1,4-addition of Grignard reagents to chiral α,β-unsaturated cyclic aldimines ( 3 ), prepared from the corresponding cycloalkenecarboxaldehydes ( 1 ) and optically active α-amino acid tert-butyl esters ( 2 , was found to give, after hydrolysis, trans-2-substituted cycloalkanecarboxaldehydes ( 5 ) in reasonably high enantiomeric purities.

Complementary asymmetric alkylation reaction of the lithioenamine derived from 2-methoxycarbonylcyclohexanone and ( S )-valine tert -butyl ester was examined by employing the various electron pair donating additives in a toluene solvent, in order to clarify the factors controlling the diastereoface selectivity.

Hydrochinondimethylether (Ia) liefert mit Bernsteinsaureanhydrid die Ketocarbonsaure (Ib), die zu (Ic) reduziert und zu (Id) verestert wird.

Clear stereochemical relationships were observed between the structure of chiral sources of catalysts and absolute configuration of the Diels-Alder adducts.

The one-pot double alkylation reaction of a chiral α,β-unsaturated imine (6) with isopropenyl Grignard reagent followed by methyl iodide has been shown to proceed highly asymmetrically. Subsequent stereoselective transformation of the derived adduct (10) has culminated in a first asymmetric total synthesis of the optically pure eudesmane sesquiterpene (+)-ivalin (1).

Ratios of the diastereomers 4 and 5 in the alkylation of the endocyclic enolates 3 with chirality at the β-position were highly dependent on the steric bulkiness of R 1 and R 2 . It was clarified that, when the allylic strain considerations are acknowledged in 3 , the diastereofacial selection is successfully rationalized by evaluating two competitive 1,2-asymmetric inductions in the conformation 15 .

By the promotion of chlorotrimethylsilane, asymmetric Michael reaction of the chiral enamines ( 2 ) of α-alkyl β-keto esters ( 1 ) with methyl vinyl ketone and ethyl acrylate proceeded to afford, after hydrolysis, either enantiomer of the corresponding adducts ( 4 ) in a good enantioselectivity.

Novel water-soluble bis-paracyclophanes (5, 6, 7) were synthesized and their properties as hosts having two independent binding sites were studied. Examples are presented in which a guest molecule having two aromatic rings forms a complex by binding at two sites cooperatively, when host and guest are complementary.

The title reactions performed with (S)-α-amino acids or their derivatives as chiral sources were found to regioselectively give enantiomeric pairs of optically active 4-acetyl-3, 4-dimethyl-2-cyclohexenone (R)(+)- and (S)(−)- 4 ), 16–25% e.e., and those of optically active 6-acetyl-3,6-dimethyl-2-cyclohexenone((R)(+)- and (S)(−)- 5 , 54–59% e.e., from the open chain triketone( 3 ).

NMR studies (1H and 13C) demonstrating an inclusion complex formation in a particular geometry between a water-soluble paracyclophane, CP44, and hydrophobic substrates in acidic aqueous solution are described.

Kinetic deprotonation of the monoacetals (4) of bicyclo[3.3.0]octan-3,7-dione by chiral lithium amides (5) in the presence of excess trimethylsilyl chloride afforded the corresponding silyl enol ethers (6), useful synthons for the synthesis of optically active carbacyclins, in up to 94% ee.