Short and efficient synthetic route to methyl α-trioxacarcinoside B and anomerically activated derivatives

A 9-step synthetic route to the complex carbohydrate methyl α-trioxacarcinoside B from 2-acetylfuran is described. Anomerically activated forms, including 1-phenylthio, 1-O-(4'-pentenyl), 1-fluoro, and 1-O-acetyl derivatives are also prepared.     

An efficient synthesis of α-hydroxyphosphonates and α-aminophosphonates in the presence of chlorotrimethylsilane

Abstract

Solvent free, and quantitative yielding synthesis of α-hydroxyphosphonates (2a–h) from 2-chloroquinolin-3-carbaldehyde (1a–h) and α-aminophosphonates (4a–p) from imines (3a–p), obtained from 2-chloroquinoline-3-carbaldehyde by using triethylphosphite in the presence of chlorotrimethylsilane at room temperature in short time.     

Short Synthesis of α-Nitrile Sulfones

A short synthesis of α-(4-tolylsulfonyl)arylacetonitriles from the reaction of phenyl tosylate and α-lithiated nitriles is described.     

Short and efficient route toward α-substituted N-arylazetidines from acetanilides via Mitsunobu reaction

N-Arylazetidines are efficiently obtained in a three-step procedure, providing a wide diversity of derivatives on multigram scale with overall yields of 21–55%. Cheap or easily available acetanilides are used in an adapted aldolization with aldehydes, furnishing β-hydroxyamides with an 81% average yield over 21 examples. Special Mitsunobu conditions have been developed to ensure the cyclization of these hydroxyamides, giving β-lactams with an 73% average yield over 16 examples. A reduction then provided the N-arylazetidines in high yields.     

Total synthesis and stereochemistry of 13-hydroxy-α-eudesmol

The first total synthesis of both C-11 epimers of 13-hydroxy-α-eudesmol 1a and 1b by the use, as a key reaction, of the Sharpless asymmetric dihydroxylation of alkene 7 is presented. The absolute configuration of natural 13-hydroxy-α-eudesmol is established through comparison of the ¹H NMR spectrum of natural diol and synthetic diols. In our synthesis another natural product (+)-α-selinene 2 has also been accomplished.     

Total Synthesis and Stereochemistry of 13-Hydroxy-α-eudesmol

Recently, 13-hydroxy-α-eudesmol 1a was first isolated from C. uncata Cunn. by King and Robinson et aL and its structure was determined by high field NMR techniques, however, the absolute configuration of C-11 remained unsolved. Herein, we report the first total synthesis and determination of the stereochemistry of 13-hydroxy-α-eudesmol. In our synthesis (+)-α-selinene has also been accomplished.     

Short,Efficient Syntheses of Pyrrole α-Amides

We report an inexpensive method for producing a diverse array of pyrrole amides on a large scale and in good yield. The synthetic sequence allows for the preparation of a number of pyrrole amide derivatives in excellent to moderate yields from commercially available compounds. The diketene adduct, in the presence of an amine nucleophile, provides an excellent method for acetoacetylation. For diversity and versatility, a second method utilizing Meldrum's acid was successfully employed for the preparation of additional acetoacetamide derivatives. Using the Knorr pyrrole synthesis, pyrrole amides were readily prepared from the oxime of the acetoacetamides.     

Catalyst-free facile and efficient one-pot synthesis of densely functionalized pyrroles and α-amino ketones

An efficient catalyst-free one-pot three-component synthesis of penta-substituted pyrroles has been successfully developed. A variety of penta-substituted pyrroles were straightforwardly synthesized from good to excellent yields (78%–93%) by using easily accessible starting materials under mild conditions. This protocol also provided α-amino ketones in good yields (87%–98%) without column chromatography.     

Dynamic kinetic resolution of α-chloro β-keto esters and phosphonates: hemisynthesis of Taxotere® through Ru-DIFLUORPHOS asymmetric hydrogenation

The dynamic kinetic resolution (DKR) of racemic α-chloro β-ketoesters and α-chloro β-ketophosphonates through ruthenium-mediated asymmetric hydrogenation is reported. The corresponding α-chloro β-hydroxyesters and α-chloro β-hydroxyphosphonates were obtained in good to high enantio- and diastereomeric excesses using, in particular, the atropisomeric ligand DIFLUORPHOS. This methodology allowed an efficient preparation of the anti phenylisoserine side chain of Taxotere® which has been used for the hemisynthesis of the cancer therapeutic agent itself. In addition, ¹³C NMR in chiral oriented solvents was used to investigate the DKR effect.     

An efficient boric acid-mediated preparation of α-hydroxyamides

An efficient methodology for the preparation of α-hydroxyamides via boric acid-mediated addition of isonitriles onto aldehydes has been developed. The reaction of isonitriles with α-boronobenzaldehyde takes place under intramolecular catalysis conditions to provide functionalized benzoxaboroles.     

A highly efficient method for the α,β-dehydrogenation of α-amino esters and α-amino-β-diesters

N-monochlorination of N-unprotected α-amino esters and α-amino-β-diesters was efficiently and very simply effected by using inexpensive effervescent sodium dichloroisocyanurate tablets for water disinfection in a biphasic organic solvent-water system. Subsequent dehydrochlorination provided α,β-didehydroaminoacid esters, whose hydrogenation would allow the starting compounds to be easily racemized.     

An efficient synthesis,spectral characterization,antimicrobial, and antioxidant activities of novel α-hydroxyphosphonates and α-hydroxyphosphinates

A simple, novel, and an efficient synthesis of α-hydroxy phosphonates (3a–d) and phosphinates (5a–f) has been accomplished from febuxostat aldehyde (1) with various dialkylphosphites (2) and dialkylphosphinates (4) in the presence of 1, 4-dimethylpiperazine as a strong base with good to excellent yields (78%–95%) is reported. The structures of the title compounds were established by elemental analysis and spectral data (IR, ¹H, ¹³C and ³¹P NMR, and LC-MS). All the title compounds (3a–d) and (5a–f) were tested for their antimicrobial and antioxidant activities. Bioassay results reveal that a few of the title compounds exhibited promising antimicrobial and antioxidant activities.     

Microbiologically-assisted hemisynthesis of 1α-hydroxydrimenol

The hemisynthesis of 1α-hydroxydrimenol has been selected to illustrate a synthetic route involving an initial microbial 3β-hydroxylation of a drimenol derivative followed by a functionalization transfer to position 1α, thus generating a new potentially bioactive hydroxylated terpenic compound. Several methods have been investigated for the protection and the regeneration of the 7,8-double bond of drimenyl derivatives.     

Reactivity of a propiolate dimer with nucleophiles and an efficient synthesis of dimethyl α-aminoadipate

An enyne dimer (1) of methyl propiolate was reacted with amines to form dimethyl (E,E)-2-amino-2,4-hexadiene dioates with remarkable chemospecificity, regiospecificity, and stereospecificity. This enyne was also reduced by Ph₃P stereospecifically to form dimethyl (E,E)-muconic ester. Hydrogenation of the conjugated amino-diene led to an efficient production of dimethyl α-aminoadipate. A lactam of dimethyl α-aminoadipate was obtained in high yield by simply varying the hydrogenation conditions.     

A highly efficient and straightforward stereoselective synthesis of novel chiral α-acetylenic ketones

A very efficient and straightforward synthesis of novel chiral α-acetylenic ketones of type 3 has been developed. Starting from commercially available l-(−)-serine 4, and through the Garner's aldehyde 5, ethynyloxazolidine 2 was formed in good overall yield. Condensation of the corresponding lithium acetylide 7 with different aliphatic and aromatic aldehydes 5 and 8a–h at low temperatures yielded the respective propargylic alcohols 9a–i. Subsequent mild oxidation of 9a–i with 10-I-4-iodinane oxide (IBX) 12 afforded chiral α-acetylenic ketones 3a–i almost quantitatively.     

Iron-catalyzed hydroaminocarbonylation of alkynes: Selective and efficient synthesis of primary α,β-unsaturated amides

α,β-Unsaturated primary amides are important intermediates and building blocks in organic synthesis. Herein, we report a ligand-free iron-catalyzed hydroaminocarbonylation of alkynes using NH₄HCO₃ as the ammonia source, enabling the highly efficient and regioselective synthesis of linear α,β-unsaturated primary amides. Various aromatic and aliphatic alkynes are transformed into the desired linear α,β-unsaturated primary amides in good to excellent yields. Further studies show that using NH₄HCO₃ as the ammonia source is key to obtain good yields and selectivity. The utility of this route is demonstrated with the synthesis of linear α,β-unsaturated amides including vanilloid receptor-1 antagonist TRPV-1.     

Expeditious and efficient synthesis of Strecker’s α-aminonitriles catalyzed by sulfated polyborate

A straightforward, mild, efficient, and environmentally benign protocol for a three-component Strecker reaction of aldehydes or ketones, amines, and trimethylsilyl cyanide catalyzed by sulfated polyborate has been described to afford α-aminonitriles under solvent-free reaction conditions. The major advantages of the present method are excellent yields, shorter reaction time, simple experimental procedure, easy workup procedure, recyclability of the catalyst, solvent-free reaction conditions and ability to tolerate a variety of functional groups which gives economical as well as ecological rewards.     

An efficient and general route to the synthesis of diethyl α,α-bromofluorophosphonates

An efficient and general two-step halogenation procedure to prepare diethyl α,α-bromofluorophosphonates was described, which included bromination by PPh₃, 2,3-dichloro-5,6-dicyanobenzquinone (DDQ) and n-Bu₄NBr, and electrophilic fluorination by N-fluorobisbenzenesulfonimide (NFSI). Both aromatic and aliphatic α,α-bromofluorophosphonates could be prepared by this method.     

An efficient synthesis of 2-isoxazolines from α-haloketone oximes and dimethyl sulfonium salts

2-Isoxazolines were synthesized efficiently from a formal [4+1] cycloaddition of nitrosoalkenes and sulfur ylides, which were generated in situ from α-haloketone oximes and dimethyl sulfonium salts. This approach provides a new method to synthesize a range of 2-isoxazolines in high yields and high regioselectivity.     

Highly enantioselective and efficient organocatalytic aldol reaction of acetone and β,γ-unsaturated α-keto ester

An effective organocatalytic asymmetric aldol reaction of acetone to β,γ-unsaturated α-keto ester has been developed. In the presence of 5 mol % of 9-amino (9-deoxy)-epicinchona alkaloid and 10 mol % of 4-nitrobenzoic acid, the aldol adducts containing a chiral tertiary alcohol moiety were obtained in excellent yields and enantioselectivities.