Palladium-catalyzed intra-molecular olefin insertion reaction of α-alkenyl-α-acyloxytrialkylsilane. Synthesis of optically active carbocycle

Pd-catalyzed intra-molecular olefin insertion/carbonylation reaction of optically active α-alkenyl-α-acyloxysilanes is described. The reactions proceeded in a stereoselective manner to give five- and six-membered optically active carbocycles having (E)-vinylsilane in their side chains. Under CO condition, optically active carbocycles containing one-carbon homologated side chain were produced by Pd-catalyzed tandem olefin insertion-carbonylation reaction.     

Asymmetric synthesis of (+)-allo-quercitol and (+)-talo-quercitol via free radical cycloisomerization of an enantiomerically pure alkyne-tethered aldehyde derived from a carbohydrate.

We describe for the first time the free radical cyclization of enantiomerically pure alkyne-tethered aldehydes obtained from a carbohydrate (6, 7). The synthesis of compounds 6 and 7 obtained from a derivative of D-ribose is reported. These radical precursors have been submitted to cyclization with tributyltin hydride plus azobisisobutyronitrile to yield, after ring closure, two carbocycles, respectively. These carbocycles have been obtained as mixtures of E and Z vinyltin isomers, but with excellent diastereoselection at the new stereocenter formed during the ring closure. After protodestannylation, only one diastereomer was detected and isolated. The absolute configuration at the new stereocenter formed during the carbocyclization has been established by detailed (1)H NMR analysis. The specific transformation of 7-methoxymethoxy-2,2-dimethyl-4-methylene-5-tert-butyldimethylsilyloxy-(3aR,5S,7S,7aS)-perhydrobenzo[d][1,3]dioxole into optically pure (+)-allo-quercitol and (+)-talo-quercitol is described. From these results, we conclude that under an appropriate choice of radical precursors and conditions, the synthesis of highly functionalized cyclohexane derivatives of biological interest is now available.     

Sulfinyl-directed diastereoselective

Introduction of a homochiral p-tolylsulfinyl group at an appropriate position in the alkene accelerates the thermal [5C + 2C] intramolecular cycloaddition to beta-silyloxy-gamma-pyrones and, most importantly, leads to excellent levels of diastereodifferentiation. The resulting adducts can be easily desulfinylated to give optically active 8-oxabicyclic[3.2.1]octane intermediates which by virtue of their rich functionalization might be susceptible to elaboration into enantiomerically pure natural products containing seven-membered carbocycles and tetrahydrofurans.     

Asymmetric Pauson-Khand Reaction. Cobalt-Mediated Cycloisomerization of 1,6-Enynes in Carbohydrate Templates: Synthesis of Bis-Heteroannulated Pyranosides

The Pauson-Khand reaction on the carbohydrate derived precursors 1-6 is reported. We have described for the first time the cobalt-mediated cyclization of some O-branched chain 1,6-enynes in carbohydrate templates. The resulting bis-heteroannulated pyranosides 17-22 have been obtained in diastereomerically pure form, in moderate to good yield, and in one, simple synthetic operation. These enantiomerically pure, densely functionalized carbocycles are attractive advanced intermediates for the synthesis of complex natural products.     

Fragmentation of Optically Active (1-Phenylethyl)- and (1-Naphthylethyl)ureas in Refluxing Alcohols: Easy Preparation of Optically Active Amines of High Optical Purity

(1-Phenylethyl)- and (1-naphthylethyl)ureas, obtained in the reaction of racemic amines with optically pure isocyanates, are separated and then decomposed in refluxing alcohols, to afford optically pure secondary amines and optically pure alkyl carbamates in quantitative yields. The scope of this fragmentation for the resolution of racemic mixtures of amines is illustrated by several examples of biologically important compounds. Carbamates obtained by this fragmentation can readily be recycled.     

Preparation of carbocycles via base-catalyzed endo-mode cyclization of allenes

A new and reliable procedure for constructing five- to seven-membered carbocycles via an endo-mode ring-closing reaction of 1-phenylsulfonylallenes with a substituent that has a terminal active methine moiety at the C1-position has been developed. Trisubstituted 1-phenylsulfonylallenes underwent a similar endo-mode ring-closing reaction to produce the corresponding five- to seven-membered carbocycles, while the formation of six- and seven-membered carbocycles from the corresponding tetrasubstituted allene was not realized. In addition, the introduction of an aromatic ring to the alkyl side chain of the starting allenes made possible the construction not only of normal-sized carbocycles but also an eight-membered framework.     

Enantioselective total synthesis of a potent antitumor antibiotic, fredericamycin A.

The asymmetric total synthesis of both enantiomers of the potent antitumor antibiotic fredericamycin A (1) is detailed based on the protocol for the construction of its peri-hydroxy polyaromatic skeleton bearing the chirality at the spiro carbon via a strong base-induced cycloaddition of suitably substituted homophthalic anhydrides (AB-ring unit) with an optically active CDEF-ring unit. Particular attention has been given to the novel synthesis of the optically active spiro carbon center by a stereospecific rearrangement of optically active benzofuzed-trans-epoxy acylates leading to spirocyclopentane-1,1'-indane systems. This method is quite useful for the construction of an optically active spiro compound and was applied to the synthesis of the optically pure CDEF-ring unit of 1. Cycloaddition of the optically pure CDEF-ring unit to AB-ring units prepared via benzyne afforded two natural and unnatural-type hexacyclic compounds, which were converted to natural and unnatural enantiomers of synthetic 1, and the absolute configuration of natural 1 was determined as S.     

Novel synthetic approach for optical resolution of cryptophanol-A: a direct access to chiral cryptophanes and their chiroptical properties

The separation by crystallization of the pair of cryptophane diastereomers 1 a and 1 b, obtained in 1:1 ratio by treating racemic anti cryptophanol-A (2) with (-)-camphanic acid chloride, provided a substantial amount of optically pure material (diastereomeric excess>98 %). Subsequent hydrolysis afforded the optically pure cryptophanol-A enantiomers (+)-2 and (-)-2, which were submitted to nucleophilic substitution reactions to provide cryptophane-A (+)-3 and cryptophane monoester (-)-4 in optically pure form. The chiroptical properties of the new cryptophanes 1-4 were investigated by using circular dichroism spectroscopy, and the absolute configuration of the molecules was clearly established. These new cryptophanes represent additional interesting examples for studying the Cotton effect of interacting multichromophoric systems. Moreover, this novel approach presents numerous advantages over the other methods developed so far to obtain optically pure cryptophanes, and compounds (-)-2, (+)-2, and (-)-4 can give access to new enantiopure functionalized cryptophanes with host-guest properties similar to those of cryptophane-A.     

Enantiopure eta4-(1-sulfinyldiene)iron(0) tricarbonyl complexes as templates for carbocycle construction via ring-closing metathesis

[reaction: see text] Enantiomerically pure 1-(1Z,3E)-sulfinyl iron(0) dienols have been elaborated to bis-olefins capable of undergoing ring-closing metathesis chemistry. Using Grubbs' ruthenium carbene catalyst, a six-membered carbocycle (with one chiral center) and seven-, eight-, and nine-membered carbocycles (with two chiral centers) have been prepared. Novel transformations include the LiClO4-promoted allylation of an alkylidene malonate and a reductive sulfur-carbon bond cleavage to convert a vinyl sulfoxide into an alkene with SmI2.     

An Efficient Total Synthesis of Carbocyclic 2′-Deoxyribonucleosides

The present work describes a new and efficient method for the preparation of either racemic or enantiomerically pure carbocyclic 2′-deoxyribonucleosides 1 . Key steps are the efficient assembly of the racemic carbocyclic 2′-deoxyribose core (±)- 12 , its enzymatic resolution, and a new approach to covalently link the purine and pyrimidine bases with the cyclopentane moiety via the cyclic sulfate (+)- 19 . This total synthesis of enantiomerically pure and racemic carbocyclic 2′-deoxyribonucleosides 1 represents one of the most efficient approaches reported to date. Starting from cyclopentadiene, the four carbocycles corresponding to the naturally occurring 2′-deoxyribonucleosides could be prepared in 12 steps and 9–12% overall yield. For the corresponding racemic compounds, 10 steps were used with overall yields between 22 and 30%.     

Syntheses and Peculiar Behavior in Solutions of Optically Active Telluronium Salts

A diastereomeric (epimeric) mixture of ethylmethylphenyltelluronium (1S)-(+)-camphor-10-sulfonate (dia.-1) was optically resolved by fractional recrystallization into the diastereomerically pure isomers (R)(Te)-1 and (S)(Te)-1. The absolute configurations of the isomers were determined by the X-ray crystallographic analysis of (R)(Te)-1. Enantiomerically pure (R)-ethylmethylphenyltelluronium perchlorate, tetrafluoroborate, p-chlorobenzenesulfonate, bornane-10-sulfonate, tetraphenylborate, and picrylsulfonate (R)-2-7 were isolated, respectively, by anion-exchange reactions of diastereomerically pure (R)(Te)-1. The optically active telluronium salts were found to show peculiar optical properties on their specific rotations and circular dichroism spectra in solutions compared with those of the corresponding sulfonium and selenonium salts. On the basis of NMR studies, the behavior on the optical properties of the optically active telluronium salts was found to be caused by a strong solvation in polar solvents.     

Preparation of optically pure α-trifluoromethyl-α-amino acids from N-tosyl-2-trifluoromethyl-2-alkyloxycarbonyl aziridine

The preparation of optically pure α-trifluoromethyl-α-amino acids from N-tosyl-2-trifluoromethyl-2-alkyloxycarbonylaziridine is described. Optically pure aziridine was prepared with a 60% yield via three steps from optically pure 2,3-epoxy-1,1,1-trifluoropropane (TFPO). Ring-opening reactions of the aziridine with a variety of nucleophiles and subsequent deprotection of the N-tosyl moieties gave the optically pure β-substituted-α-trifluoromethyl-α-amino acids in moderate to good yields (up to 85%) without racemization at the quaternary stereogenic center of the amino acid.     

Chemiluminescence in molecular recognition: base-induced decomposition of optically active dioxetanes bearing a bisnaphthol moiety with a complex of optically active crown ether-potassium tert-butoxide

Four optically pure isomers of dioxetane (1) were decomposed by the action of the complex of an optically active crown ether with potassium tert-butoxide to afford light with lambda(max)CL and gave four different spectrum shapes.     

Studies directed towards the asymmetric total synthesis of antileukemic lignan lactones. Synthesis of optically pure key intermediate and its utility

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

Enantioselective synthesis of a mitosane core assisted by diversity-based catalyst discovery

[reaction: see text]. Synthesis of mitosane 1 in optically pure form is reported. A retrosynthetic plan that proceeds through racemic allylic alcohol 3 was carried out. This intermediate served as a test substrate for a rapid screen of a small library (152 members) of peptide-based kinetic resolution catalysts. Peptide 9 was found to effect kinetic resolution with k(rel) = 27. Alcohol (-)-3 was then converted to optically pure (-)-1 in eight steps.     

Mutual optical resolution of 2,2′-dihydroxy-1,1′-binaphthyl and alkyl aryl or dialkyl sulfoxides by complex formation

By complexation with optically active 2, 2′-dihydroxy-1, 1′-binaphthyl, alkyl aryl and dialkyl sulfoxides were resolved very efficiently. Reversely, by complexation with optically active alkyl aryl or dialkyl sulfoxides, 2, 2′- dihydoxy-l,l′-binaphthyl was resolved very efficiently, In all cases, 100% optically pure (+)- and (?)-enantiomers were obtained in good yields.     

The first total synthesis of (+)-spatol with natural configuration

The first total synthesis of (+)-spatol (1) with natural configuration is described. The important step utilizes the carbon-carbon bond formation with simultaneous epoxide formation by the reaction of optically pure sulfonium ylide (4) and optically pure epoxy aldehyde (5).     

Synthesis of optically pure 2-azido-1-arylethanols with isolated enzymes and conversion to triazole-containing beta-blocker analogues employing click chemistry

Both antipodes of 2-azido-1-arylethanols were synthesized with excellent optical purity via enzymatic reduction of the corresponding alpha-azidoacetophenone derivatives catalyzed by a recombinant carbonyl reductase from Candida magnoliae ( CMCR) or an alcohol dehydrogenase from Saccharomyces cerevisiae ( Ymr226c). This provides an effective route to this class of important compounds in optically pure form. ( S)-2-Azido-1-( p-chlorophenyl)ethanols reacted with alkynes employing click chemistry to afford high yields of optically pure triazole-containing beta-adrenergic receptor blocker analogues with potential biological activity.     

Generation and reactions of α-trifluoromethyl stabilized aziridinyl anion, a general synthetic precursor for stereospecific construction of α-amino-α-trifluoromethylated quaternary carbon

Optically pure α-trifluoromethylated aziridinyl anions react with various electrophiles to give the corresponding optically pure 2-trifluoromethyl-2-substituted aziridines, which are general synthetic precursors for optically pure α-amino-α-trifluoromethylated compounds, such as trifluoromethylated α/β-amino acids, in good yields.     

Preparation of Optically Active Secondary Amines by Thermal Decomposition of (Methylbenzyl)urea Analogs: Absolute Configuration of (+)- and (−)-Mecamylamine. Preliminary Communication

Thermolysis of the (α-methylbenzyl)urea diastereoisomers 4 and 5 of (±)-mecamylamine ((±)- 1 ) and 6 and 7 of (±)-1-noreseroline O-methyl ether ((±)- 3 ) in refluxing alcohol afforded optically pure amines in high yield, besides optically pure carbamates of (α-methylbenzyl)amine which can be recycled. The absolute configuration of (?)-mecamylamine hydrochloride ((?)- 1 · HCl) was determined by X-ray diffraction analysis.