Stereoselective synthesis of 2,3,6-trisubstituted tetrahydropyridines via Tf(2)O-mediated Grob fragmentation: access to indolizidines (-)-209I and (-)-223J

Herein we describe the γ-amino hydroxide Grob fragmentation of the aza-bicyclo[2.2.2]octene 1 using triflic anhydride as the activating agent. The resulting dihydropyridinium ion can react with a wide variety of Grignard reagents, giving access to 2,3,6-trisubstituted tetrahydropyridines (2) with high regio- and stereoselectivities. This methodology has been applied to the short synthesis of natural indolizidines (-)-209I (3) and (-)-223J (4).     

(Z)-tamoxifen and tetrasubstituted alkenes and dienes via a regio- and stereospecific three-component magnesium carbometalation palladium(0) cross-coupling strategy

[reaction: see text] The synthesis of various tetrasubstituted alkenes and dienes in a regio- and stereocontrolled manner is described. This three-component coupling strategy involves the addition of Grignard reagents to propargyl alcohols followed by palladium(0)-mediated cross-coupling with aryl or vinyl halides. This protocol has been applied to the synthesis of (Z)-Tamoxifen and related mimics.     

Hybrid Birch-Claisen Methodology for arylation at allylic termini: synthesis of (±)-herbertene

A hybrid Birch-Claisen methodology has been developed for the regio- and stereo-controlled arylation of allyl groups, and applied to a synthesis of (±)-herbertene.     

CuCl-K(2)CO(3)-catalyzed highly selective borylcupration of internal alkynes - ligand effect

An efficient and practical copper-catalyzed highly regio- and stereoselective borylcupration of internal alkynes with bis(pinacolato)diboron using a catalytic amount of K(2)CO(3) as base producing Z-alkenylboron compounds has been demonstrated by applying the ligand effect: commercially available electron-rich tris(p-methoxyphenyl) phosphine ensures a smooth and efficient reaction. Functionalized alkynes, such as propargylic alcohols and derivatives as well as N-propargyl tosylamide, may also be used with excellent selectivity.     

Regio- and stereoselective selenium dioxide allylic oxidation of (E)-dialkyl alkylidenesuccinates to (Z)-allylic alcohols: synthesis of natural and unnatural butenolides

The first SeO(2) induced (Z)-selective allylic alcohol formation of dialkyl alkylidenesuccinates has been demonstrated to accomplish one-step syntheses of several essential butenolides and fused butenolides via an unusual E- to Z- carbon-carbon double bond isomerisation followed by the lactonization pathway. The observed regio- and stereoselective SeO(2) allylic oxidation protocol has also been extended to the diastereoselective total synthesis of bioactive natural product isomintlactone, its direct conversion to mintlactone and an example of the base-catalyzed intramolecular rearrangement of γ-lactone to δ-lactone.     

Toward a modular, bidirectional synthesis of (−)-mucocin

A convergent stereoselective synthesis of the C13-C34 fragment of (−)-mucocin is described. The salient features include (a) the bidirectional synthesis of the C-2 symmetric C13-C21 subunit, (b) regio- and stereoselective preparation of a 1,3-diol derivative from a diene activated by NBS via intramolecular nucleophilic sulfinyl group participation, (c) utilizing the self-metathesis reaction to prepare a functionalized C10 alkene, and (d) regio- and stereoselective intermolecular epoxide opening to construct the ether bond between C20 and C24. An organocatalytic α-hydoxylation has been employed to create the C4 stereogenic center of C1-C12 subunit. Attempted union of the two subunits utilizing the B-alkyl Suzuki coupling did not succeed.     

Stereoselective synthesis of the C(1)-C(12) segment of iriomoteolide 1a: a very potent macrolide antitumor agent

A stereoselective synthesis of the C(1)-C(12) segment of the potent cytotoxic macrolide, iriomoteolide 1a, has been accomplished. The key steps involve an enzymatic kinetic resolution of a β-hydroxy amide, a Pd-catalyzed cross-coupling to a substituted allylsilane, a highly regio- and stereoselective conjugate addition of lithium dimethylcopper to an α, β-acetylenic esters and an elaboration of the C(6)-C(7) trans-olefin geometry by a Julia-Kocienski olefination.     

Synthesis of (±)-angustione by the regioselective alkylation of enaminodiketones under the action of strong bases

The synthesis of (±)-angustione has been carried out on the basis of a method that we have developed for the regio- and stereoselective alkylation of enaminodiketones of the cyclohexane series.     

One-pot rhodium(i)-catalyzed hydroboration of alkenes: radical conjugate addition

B-Alkylcatecholboranes, prepared by rhodium(I)-catalyzed hydroboration of alkenes, are suitable radical precursors for conjugate addition to activated olefins. This procedure proved to be particularly useful for the control of the regio- and chemoselectivity of such tandem processes. Enantioselective hydroboration has also been successfully coupled with radical chain reaction in a one-pot process.     

Radical (phenylsulfonyl)difluoromethylation with iododifluoromethyl phenyl sulfone

An unprecedented radical (phenylsulfonyl)difluoromethylation of terminal alkenes with PhSO2CF2I has been achieved by using Et3B/air as an initiator. This synthetic methodology was also used in the one-pot regioselective preparation of PhSO2CF2-substituted alkanes, and in the regio- and stereoselective preparation of PhSO2CF2-substituted alkenes with high E/Z ratio (up to > or =100:1).     

Ru(II)-catalyzed cascade reactions in stereocontrolled construction of rigid as-indacene-bridged bis(alpha-amino acid) derivatives

The key construction in the preparation of as-indacene-bridged bis(alpha-amino acid) derivatives was effected by a Ru(II)-catalyzed RCM cascade reaction of appropriately substituted triynes. The latter were available after stepwise and stereocontrolled alkynylations of (2R)-2,5-dihydro-2-isopropyl-3,6-dimethoxypyrazine as chiral auxiliary. The regio- and stereochemical transformations have been verified by a single-crystal X-ray analysis.     

A new method for the preparation of silyl enol ethers from carbonyl compounds and (trimethylsilyl)diazomethane in a regiospecific and highly stereoselective manner

The reaction of lithium (trimethylsilyl)diazomethane with aldehydes and ketones has been investigated, and it has been found that quenching at low temperature with MeOH followed by addition of Rh2(OAc)4 gave silyl enol ethers in high yields. Quenching with other electrophiles (e.g., deuterium, MeI) gave terminal and substituted silyl enol ethers with complete control over regio- and stereochemistry. The mechanism of this novel process has been mapped out through a combination of deuterium labeling, ReactIR, and isolation of reaction intermediates.     

Total synthesis of pseudoguaianolides III. (±)-Aromatin

(±)-Aromatin ($\text{5}$), has been assembled from 2-methyl-1,3-cyclopentanedione in a linear synthesis characterized by high regio- and stereoselectivity at all stages. Several contributions to organosynthetic methodology are feature.     

Regio- and stereoselectivity of the 1,3-dipolar cycloaddition of azomethine ylides to (E)-3-(2-oxo-2-(pyren-1-yl)ethylidene)indolin-2-ones: A combined experimental and theoretical study

Functionalized oxindoles and pyrrolizidines form the central structural framework for numerous natural products with extensive biological and pharmacological applications. The requirement for high regio- and stereoselectivity is the main obstacle in the synthesis of such five-membered heterocycles. Multicomponent cycloaddition reactions often provide an efficient and straightforward approach for the preparation of specific regio- and stereoisomers. In this article, the regio- and stereochemistry of the polar [3 + 2]-cycloaddition (32CA) reaction of azomethine ylides prepared by the reaction of isatin derivatives and L-proline with a series of (E)-3-(2-oxo-2-(pyren-1-yl)ethylidene)indolin-2-ones was investigated by experimental and theoretical methods. Among the isatin and (E)-3-(2-oxo-2-(pyren-1-yl)ethylidene)indolin-2-one derivatives, a remarkable inversion of regioselectivity was observed in the 32CA reaction of azomethine ylide generated by the reaction of L-proline and 5-chloroisatin or N-methyl-5-chloroisatin with (E)-5-chloro-3-(2-oxo-2-(pyren-1-yl)ethylidene)indolin-2-one. The regio- and stereochemical assignment of the structures of the cycloaddition products was determined by one- and two-dimensional (1D&2D) homonuclear and heteronuclear correlation nuclear magnetic resonance spectroscopy. The molecular mechanism as well as the regio- and stereoselectivity of the cycloaddition were investigated by means of global and local reactivity indices and a density functional theory (DFT) and explained in detail on the basis of the transition state stabilities of the reactants.     

A one-pot strategy for synthesis of 5-O-(alpha-D-arabinofuranosyl)-6-O-(beta-D-galactofuranosyl)-D-galactofuranose present in motif E of the Mycobacterium tuberculosis cell wall

5-O-(Alpha-D-arabinofuranosyl)-6-O-(beta-D-galactofuranosyl)-D-galactofuranose 6 present in motif E of the Macobacterium tuberculosis cell wall has been regio- and stereospecifically synthesized using 3-O-benzoyl-1,2-O-isopropylidine-alpha-D-galactofuranose (10) as the glycosyl acceptor by the trichloroacetamidate method in a one-pot manner. The diol glycosyl acceptor 10 was smoothly derived from 1,2:5,6-di-O-isopropylidene-alpha-D-galactofuranose (8) by 3-O-benzoylation and then selective 5,6-O-deacetonation. The preparation of 8 was greatly improved by increasing the ratio of DMF to acetone and using a solid-supported catalyst.     

Stereoselective synthesis of (E)-beta-tributylstannyl-alpha,beta-unsaturated ketones: construction of a key intermediate for the total synthesis of zoanthamine

(E)-beta-Trialkylstannyl-alpha,beta-unsaturated ketones are readily available from secondary propargylic alcohols via a two-step sequence involving highly regio- and stereoselective Pd(0)-catalyzed hydrostannation followed by mild oxidation (TPAP). The methodology has been applied to the synthesis of enantiomerically pure enone 12 which is a key intermediate for the total synthesis of zoanthamine, a structurally complex marine natural product.     

Novel bis[(E)-1-(halomethyl)-2-chlorovinyl] chalcogenides as starting materials for the efficient synthesis of bis(chloromethylidene)-1,4-dichalcogenanes

An efficient synthesis of novel bis[(E)-1-(halomethyl)-2-chlorovinyl] sulfides and selenides via regio- and stereoselective electrophilic addition of SCl₂ and SeCl₂ to propargyl halides has been developed. The bis(2-chlorovinyl) chalcogenides prepared represent reagents for the synthesis of chalcogen-containing heterocycles and have been used for the synthesis of novel bis(E-chloromethylidene) derivatives of 1,4-dichalcogenanes with various combinations of sulfur and selenium atoms in the ring.     

Activation of sp3 C-H bonds with cobalt(I): catalytic synthesis of enamines

C-H bond activation has been extensively studied with (Cp*)M(L)n (M = Ir, Rh), but cobalt, the third member of this triad, has not previously been shown to activate sp3 C-H bonds. Further, practical functionalization of the metal alkyl products of oxidative addition has not been fully explored. Toward these ends, we have developed catalytic dehydrogenation of alkyl amines with a Co(I) catalyst. Amine substrates are protected with vinyl silanes, followed by catalytic transfer hydrogenation, to yield a broad range of stable protected enamines and 1,2-diheteroatom-substituted alkenes, including several unprecedented heterocycles. (Cp*)Co(VTMS)2 catalyzes transfer hydrogenation under surprisingly mild conditions with high chemo-, regio-, and diastereoselectivity, while tolerating additional functionality.     

A novel approach to functionalized (E)-1,4-diaryl-1-butenes by Heck reaction and their applications for the construction of dibenzylbutyrolactone lignan skeletons by radical cyclization

A highly regio- and stereoselective [Pd(allyl)Cl]₂ catalyzed Heck reaction of aryl iodides and electronically neutral terminal olefins generated in situ by fluoride induced protiodesilylation of alkenylsilanol derivatives under mild conditions has been developed. The products, viz. terminally substituted styrenes and (E)-1,4-diaryl-1-butenes were obtained in very good yields. The dibenzylbutyrolactone lignan skeletons have been prepared employing two regio- and stereoselective Bu₃SnH-mediated radical cyclization routes.