The synthesis of DL- and L-2-amino-3-fluorobutyric acid

DL- and L-Threonine were esterified to their methyl and ethyl esters which on treatment with sulfur tetrafluoride in anhydrous hydrogen fluoride gave DL- and L-methyl and ethyl 2-amino-3-fluorobutyrates, respectively. Both fluorinated esters afforded on hydrolysis DL- and L-2-amino-3-fluorobutyric acid, respectively.     

Asymmetric desymmetrization based on an intramolecular haloetherification: a highly effective and recyclable chiral nonracemic auxiliary, 2-exo-methyl-3-endo-phenyl-5-norbornene-2-carboxaldehyde, for meso-1,3- and meso-1,4-diols

A new chiral auxiliary, a 3-endo-phenyl norbornene aldehyde derivative, which is a crystalline, very stable, and easily handled, was developed for the desymmetrization of meso-1,3- and meso-1,4-diols. The key step of the method, an intramolecular bromoetherification, proceeded in a highly diastereoselective manner. A four-step sequence, 1) acetalization, 2) intramolecular bromoetherification followed by acid hydrolysis, 3) protection of the alcohol, and 4) retrobromoetherification, transformed the meso-diols into optically active derivatives. The 3-endo-phenyl norbornene aldehyde derivative was simultaneously reformed and could be used repeatedly. This is the first chemical example of a single auxiliary that is applicable for highly enantioselective desymmetrization of meso-1,3- and meso-1,4-diols; to the best of our knowledge, this is the best chemical method available for the desymmetrization of meso-1,4-diols.     

Base-catalyzed cascade 1,6-sulfur-Michael/Henry reaction of trifluoromethyl-substituted styrylisoxazoles: Diastereoselective synthesis of tetrahydrothiophenes with a trifluoromethylated quaternary center

An effective diastereoselective [3+2] annulation of 1,4-dithiane-2,5-diol to trifluoromethyl-substituted styrylisoxazoles catalyzed by DABCO is described, giving highly functionalized tetrahydrothiophenes containing trifluoromethylated quaternary center in excellent yields and diastereoselectivities.     

Total synthesis of (-)-dysibetaine via a nitrenium ion cyclization-dienone cleavage strategy

The diastereoselective total synthesis of the marine natural product (-)-dysibetaine is reported. The key steps in this venture are i) a diastereoselective nitrenium ion spirocyclization, which serves to generate the pyrrolidinone ring and quaternary stereocenter of the target, and ii) use of the 2-methoxycyclohexa-2,5-dienone ring formed during cyclization as a masked 2-amino-1,3-dicarbonyl synthon.     

Total synthesis of (+)-allocyathin B2

The first enantioselective synthesis of (+)-allocyathin was achieved. The synthesis features a Pd-catalyzed asymmetric allylic alkylation to install the first quaternary center, a Ru-catalyzed diastereoselective cycloisomerization to construct the six-membered ring, and a diastereoselective hydroxylative Knoevenagel reaction to introduce the final hydroxyl group. The unusual olefin isomerization of the Ru-catalyzed cycloisomerization was discussed and exploited for the synthesis.     

Enantioselective synthesis of (−)-idiospermuline

The enantioselective total synthesis of the nonacyclic polypyrrolidinoindoline (−)-idiospermuline is described. Stereocontrolled formation of the vicinal quaternary carbon centers is achieved in a single step by dialkylation of an unsymmetrical prostereogenic dienolate with a tartrate-derived chiral dielectrophile. A catalyst-controlled diastereoselective Heck cyclization is employed to form the diaryl-substituted quaternary center.     

Total synthesis of (-)- and ent-(+)-vindoline

[reaction: see text] Two exceptionally concise total syntheses of (-)- and ent-(+)-vindoline are detailed enlisting a diastereoselective tandem [4 + 2]/[3 + 2] cycloaddition of a 1,3,4-oxadiazole. The unique reaction cascade assembles the fully functionalized pentacyclic ring system of vindoline in a single step that forms four C-C bonds and three rings while introducing all requisite functionality and setting all six stereocenters within the central ring including three contiguous and four total quaternary centers.     

Highly diastereoselective synthesis of tetrahydrobenzofuranones by palladium-catalyzed reaction of propargylic carbonates with 2-substituted cyclohexane-1,3-diones

The reaction of propargylic carbonates with 2-substituted cyclohexane-1,3-diones in the presence of palladium catalyst is described. Substituted tetrahydrobenzofuranones having a quaternary carbon stereocenter were synthesized in a highly diastereoselective manner.     

Total synthesis of the immunosuppressants myriocin and 2-epi-myriocin

Total syntheses of the natural immunosuppressant myriocin (1) and the equipotent unnatural analogue 2-epi-myriocin (in protected form) have been achieved through a common strategy. The key transformations are the efficient synthesis of a quaternary (E)-vinylglycine by asymmetric deconjugative alkylation of a dehydroamino acid and an unusually highly diastereoselective dihydroxylation of the vinylglycine alkene.     

Highly diastereoselective synthesis of tetrahydrobenzofuran derivatives by palladium-catalyzed reaction of propargylic esters with substituted β-dicarbonyl compounds

Reactions of propargylic esters with 2-substituted cyclohexane-1,3-diones and 2-oxocyclohexanecarboxylic esters in the presence of palladium catalyst are described. Substituted tetrahydrobenzofuran derivatives having a quaternary carbon stereocenter were synthesized in a highly diastereoselective manner.     

Exploiting the Pd- and Ru-catalyzed cycloisomerizations: enantioselective total synthesis of (+)-allocyathin B2

Pd- and Ru-catalyzed cycloisomerizations of 1,6-enynes are compared and contrasted. Such considerations led to the enantioselective synthesis of a cyathin terpenoid, (+)-allocyathin B(2) (1). The synthesis features a Pd-catalyzed asymmetric allylic alkylation (AAA) to install the initial quaternary center, a Ru-catalyzed diastereoselective cycloisomerization to construct the six-membered ring, and a diastereoselective hydroxylative Knoevenagel reaction to introduce the final hydroxyl group. We demonstrate for the first time a mechanism-based stereochemical divergence in Pd- and Ru-catalyzed cycloisomerization reactions as well as in creation of alkene geometry with alkynes bearing a carboalkoxy group. Mechanistic rationalization is proposed for these observations.     

Asymmetric synthesis of quaternary alpha-amino phosphonates using sulfinimines

The addition of lithium diethylphosphonate to enantiopure ketosulfinimines is highly diastereoselective (>95%), affording the first examples of quaternary alpha-alkyl alpha-amino (arylmethyl)phosphonates.     

Total synthesis of (+)-pinnatoxin A

A convergent enantioselective total synthesis of (+)-pinnatoxin A is described. The synthesis capitalizes on the highly diastereoselective Ireland-Claisen rearrangement of an acyclic alpha-branched allylic ester to set the quaternary stereogenic center at the core of the spiroimine ring system along with the adjacent tertiary stereocenter. The all-carbon macrocyclic ring system was formed by ring-closing metathesis.     

Visible light induced intermolecular [2+2]-cycloaddition reactions of 3-ylideneoxindoles through energy transfer pathway

A highly diastereoselective and regioselective [2+2]-cycloaddition reaction of 3-ylideneoxindoles has been accomplished using visible light photocatalysis. This visible light photocatalytic protocol allows an expedient access to diversely functionalized and structurally constrained oxindole derivatives containing two spirocycles and four stereogenic centers, including two all-carbon quaternary centers.     

Diastereoselective synthesis of the indeno-tetrahydropyridine core bearing a diaryl-substituted stereogenic quaternary carbon center of haouamine B

The characteristic indeno-tetrahydropyridine core of cytotoxic haouamine B (2) was efficiently synthesized featuring the diastereoselective construction of a diaryl-substituted stereogenic quaternary center by an intramolecular Pd-catalyzed α-C-arylation and subsequent direct conversion of the vinylogous imide function into the C2-C25 double bond by TsNHNH(2).     

Studies toward the synthesis of pinnatoxins: the spiroimine fragment

An enantioselective approach to the spiroimine fragment of pinnatoxins is described. The strategy is based on a recently developed diastereoselective Ireland-Claisen rearrangement to establish the challenging congested quaternary and tertiary stereocenters within the cyclohexene ring.     

Kinetics, products, and stereochemistry of the reaction of chlorine atoms with cis- and trans-2-butene in 10-700 Torr of N2 or N2/O2 diluent at 297 K

The reactions of Cl atoms with cis- and trans-2-butene have been studied using FTIR and GC analyses. The rate constant of the reaction was measured using the relative rate technique. Rate constants for the cis and trans isomers are indistinguishable over the pressure range 10-900 Torr of N2 or air and agree well with previous measurements at 760 Torr. Product yields for the reaction of cis-2-butene with Cl in N2 at 700 Torr are meso-2,3-dichlorobutane (47%), DL-2,3-dichlorobutane (18%), 3-chloro-1-butene (13%), cis-1-chloro-2-butene (13%), trans-1-chloro-2-butene (2%), and trans-2-butene (8%). The yields of these products depend on the total pressure. For trans-2-butene, the product yields are as follows: meso-2,3-dichlorobutane (48%), dl-2,3-dichlorobutane (17%), 3-chloro-1-butene (12%), cis-1-chloro-2-butene (2%), trans-1-chloro-2-butene (16%), and cis-2-butene (2%). The products are formed via addition, addition-elimination from a chemically activated adduct, and abstraction reactions. These reactions form (1) the stabilized 3-chloro-2-butyl radical, (2) the chemically activated 3-chloro-2-butyl radical, and (3) the methylallyl radical. These radicals subsequently react with Cl2 to form the products via a proposed chemical mechanism, which is discussed herein. This is the first detailed study of stereochemical effects on the products of a gas-phase Cl+olefin reaction. FTIR spectra (0.25 cm(-1) resolution) of meso- and DL-2,3-dichlorobutane are presented. The relative rate technique was used (at 900 Torr and 297 K) to measure: k(Cl + 3-chloro-1-butene) = (2.1 +/- 0.4) x 10(-10), k(Cl + 1-chloro-2-butene) = (2.2 +/- 0.4) x 10(-10), and k(Cl + 2,3-dichlorobutane) = (1.1 +/- 0.2) x 10(-11) cm3 molecule(-1) s(-1).     

Asymmetric synthesis of homoallylic amines bearing adjacent stereogenic centers by addition of substituted allylic zinc reagents to N-tert-butanesulfinylimines

A highly diastereoselective addition of substituted racemic allylic zinc reagents to chiral N- tert-butanesulfinylimines resulting in the formation of homoallylic amines is reported. This method is quite general and also efficient for the preparation of enantiomerically pure homoallylic amines bearing quaternary centers and also adjacent quaternary centers.     

2′-Methyl taxanes: synthesis and NMR configurational assignment

Capitalizing on an oxidation-alkylation approach, a non-diastereoselective entry into 2′-methyl taxanes was developed. The issue of configurational assignment at the newly formed side-chain quaternary stereocenter was solved and put into a more general context by integrating information from an alternative diastereoselective synthesis of model compounds and from spectroscopic measurements, critically comparing the J-Based and the Universal NMR Database approaches.     

Diastereoselective construction of chiral building blocks for the synthesis of indole alkaloids using an intramolecular Heck reaction

Highly diastereoselective construction of the chiral building blocks, with an allylic quaternary carbon stereogenic center, for the synthesis of indole alkaloids has been accomplished by employing a 1,4-chirality transfer via the intramolecular Heck reaction.