Novel regioselective C-6 and C-19 alkylation of vitamin D3 via its sulfur-dioxide adducts

Vitamin D-sulfur dioxide adducts undergo regioselective methylation at C-6 with sodium hydride used as the base and at C-19 with lithium tetramethylpiperidide. The methylated adducts are converted to the corresponding vitamin D derivatives by extrusion of sulfur dioxide.     

A novel method of preparing amine-modifying C-4' oxidized nucleotide

A novel method of preparing C-4' oxidized nucleotide, a monomeric model of an alkali labile lesion (1) has been studied. The C-4' selenated 4a and 4b were found to be effective in preparing 3, a monomeric model of 1, by the reaction with NBS (N-bromosuccinimide). The successive reaction of 3 with amine at room temperature afforded the alpha,beta-unsaturated gamma-methylene-gamma-lactam (2) in good yield.     

LiClO4-Activated stereo- and regioselective alkylation of aldehydes

Aldehydes undergo an unusual and very mild alkylation by LiClO₄-activation in the presence of acids. This new methodology enables the inclusion of a broad range of aldehydes as well as tertiary alcohols. Regio- and stereoselectivity observed during this reaction will be discussed.     

An effective procedure for the acylation of azaindoles at C-3

Conditions for attachment of acetyl chloride, benzoyl chloride, and chloromethyl oxalate to the 3-position of 4-, 5-, 6-, or 7-azaindoles were explored. Best results were achieved with an excess of AlCl(3) in CH(2)Cl(2) followed by the addition of an acyl chloride at room temperature.     

A new method of carbon extension at C-4 of azetidinones

Azetidinone carboxylates $\text{7}$, $\text{9}$ and $\text{11}$ were prepared starting from 4-thia azetidinones and carbenes derived from diazoesters.     

Unexpected enzyme-catalyzed regioselective acylation of flavonoid aglycones and rapid product screening

Unprecedented regioselective acylation of flavonoid aglycones was achieved using Candida antarctica lipase B (CALB). The rapid screening of product formation was performed by the use of the high resolution phenol-type OH (1)H NMR spectral region recorded after the addition of picric acid.     

Efficient and regioselective N-1 alkylation of 4-chloropyrazolo[3,4-d]pyrimidine

Efficient and N-1 selective alkylation of 4-chloropyrazolo[3,4-d]pyrimidine can be achieved when the heterocycle is reacted with alcohols under Mitsunobu conditions. The 1-alkyl-pyrazolo[3,4-d]pyrimidines formed can be functionalized further according to known methods, to give a variety of 1,4-disubstituted pyrazolo[3,4-d]pyrimidines. The first example of a palladium-catalyzed coupling reaction on a 4-halopyrazolo[3,4-d]pyrimidine is described.     

Metal-free chemo- and regioselective acylation of pyridine derivatives with alcohols in water

A straightforward acylaltion of pyridine derivatives has been developed using K₂S₂O₈ as the oxidant and water as a green solvent. The corresponding 2-acylpyridines were synthesized with high chemo- and regioselectivity in good to high yields. This efficient and practical method could serve as a new tool for the convenient synthesis of 2-benzoylpyridines of interest for future pharmaceutical and chemical applications.     

A catalytic one-step process for the chemo- and regioselective acylation of monosaccharides

An organocatalytic method for the chemo- and regioselective acylation of monosaccharides has been developed. Treatment of octyl beta-D-glucopyranoside with isobutyric anhydride in the presence of 10 mol % of a C2-symmetric chiral 4-pyrrolidinopyridine catalyst (1) at -50 degrees C gave the 4-O-isobutyryl derivative as the sole product in 98% yield. Thus, chemoselective acylation, favoring a secondary hydroxyl group in the presence of a free primary hydroxyl group, and regioselective acylation, favoring one of three secondary hydroxyl groups, took place with perfect selectivity. A competitive acylation between octyl beta-D-glucopyranoside and a primary alcohol (2-phenylethanol) with 1.1 equiv of isobutyric anhydride in the presence of 1 gave the 4-O-isobutyrate of octyl beta-D-glucopyranoside with 99% regioselectivity in 98% yield, which indicates that acylation of the secondary hydroxyl group at C(4) of the carbohydrate proceeds in an accelerative manner. A possible mechanism, involving multiple hydrogen-bonding between 1 and the monosaccharide, is proposed for the chemo- and regioselective acylation.     

Enantiospecific and regioselective rhodium-catalyzed allylic alkylation: diastereoselective approach to quaternary carbon stereogenic centers

The enantiospecific and regioselective rhodium-catalyzed allylic alkylation of a series of chiral nonracemic allylic carbonates, followed by ozonolysis and reductive lactonization, provides a convenient route to optically active gamma-lactones. Sequential alkylation and reductive alkylation furnished the alpha-quaternary-beta-ternary substituted gamma-lactone derivative as a >/=10:1 mixture of diastereoisomers.     

A convenient method for regioselective C-5 halogenation of 4(3H)-oxo-7H-pyrrolo[2,3-d]pyrimidines

N-7, O-Disilylation of 4(3H)-oxo-7H-pyrrolo[2,3-d]pyrimidines provides a convenient method for activation of these compounds toward regiospecific halogenation at C-5. The sequence is conveniently carried out without isolation of the silylated derivatives and desilylation is spontaneous upon addition of water to the reaction mixture.     

A convenient method for the preparation of mono- and bis-substituted photochromic bis(benzothienyl)perfluorocyclopentenes via regioselective Friedel-Crafts acylation

The regioselective Friedel-Crafts acylation of 1,2-bis(2-methylbenzo[b]thien-3-yl)hexafluorocyclopentene was developed. Depending on the reaction conditions, mono- or bis(bromoacetyl) derivatives are formed as single products in good yields. Further heterocyclizations involving α-bromoketone moieties gave a series of new photochromic compounds.     

C-2/c-3 annulation and C-2 alkylation of indoles with 2-alkoxycyclopropanoate esters

The annulation reaction between various indoles and 2-alkoxycyclopropanoate esters is reported. Both high efficiency and complete stereochemical control were observed in some cases with this annulation process. A single stereocenter on the cyclopropane controls the diastereoselective formation of up to four new stereocenters. A different reaction course was observed with 3-substituted indole substrates, and an intervening C-3 to C-2-migration process arose that gives synthetically useful C-2 alkylation indole products.     

An Unusual Formation of Cyclic Sulfite at C-4 and C-5 Positions of Taxane

An unusual formation of cyclic sulfite at C-4 and C-5 positions of taxane was accomplished by treatment of compound 1 with excess MeSOEC1/Et3N and a possible mechanism was proposed.     

Functionalization at C-5 and at the C-6 methyl group of 4-methoxy-6-methyl-2-pyrone

A new entry to C-5 substituted 4-hydroxy-6-methyl-2-pyrones has been achieved. The best conditions to prepare the monobromo and the dibromo derivatives at C-3 and the C-6 methyl group of the title pyrone have been defined. The synthetic applicability of the phosphonium salts at CH₃-C-6 of both 4-methoxy-6-methyl-2-pyrone, 5 , and dehydroacetic acid, 2 , has also been evaluated.     

Deoxygenation at C-4 and Stereospecific Branched-Chain Construction at C-3 of a Methyl Hexopyranuloside. Synthetic Approach to the Amipurimycin Sugar Moiety

A five-step synthesis from 3 leading to a partially protected amipurimycin sugar moiety 14 in an overall yield of 47% is described and includes deoxygenation at C-4 and regio- and stereoselective construction of the branched chain. Deoxygenation at C-4 of 3 was possible by three different methods. Radical reduction with tri-n-butyltin hydride of the appropriate phenoxythiocarbonyl derivative afforded the desired deoxysugar 5 in 47% overall yield together with the secondary products 6 and 7 due to depivaloylation at C-2 and elimination of methanol. The most adequate deoxygenation procedure used the system Ph(3)P/I(2)/imidazole which led to the preparation of 5 in one step in 61% yield. When the system Ph(3)PBr(2)/Ph(3)P was tried, only 8 was formed due to elimination of methanol. The synthesis of 5 was then accomplished by reaction of 8 with methanol in the presence of triphenylphosphine hydrobromide in 37% overall yield. Branched-chain construction was accomplished by Wittig reaction of 5 with [(ethoxycarbonyl)methylene]triphenylphosphorane, followed by osmilation and reduction with lithium aluminum hydride. Isopropylidenation of 14 afforded 16 with a free hydroxy group at C-6 for chain elongation and further synthesis of amipurimycin.     

Conversion of glucosamine to galactosamine and allosamine derivatives: control of inversions of stereochemistry at C-3 and C-4.

The reactions of sodium benzoate with a series of trimesylates derived from glucosamine have been examined in an attempt to gain facile access to galactosamine analogues. Trimesylate 17, in which the amino group was protected as a phthalimide, underwent double displacement at positions 4 and 6 to give the dibenzoate 18 with the desired galactosamine configuration. In contrast, trimesylates 21 and 27, in which the amino groups were protected as acetamides, unexpectedly underwent double displacement at positions 3 and 6, giving products 22 and 28, respectively, with allosamine configurations.     

A new method of acylation at β-position of aliphatic amines

A new method to introduce an acyl or a formyl group to β-position of aliphatic amines was studied using encarbamates, prepared from α-methoxycarbamates, as key intermidiates.