3,5-bis(trifluoromethyl)phenyl sulfones in the direct Julia-Kocienski olefination

3,5-bis(trifluoromethyl)phenyl (BTFP) sulfones 7 have been employed in the Julia-Kocienski olefination reaction with carbonyl compounds. Sulfones 7 are readily prepared in high yields (64-97%) from commercially available 3,5-bis(trifluoromethyl)thiophenol through an alkylation/oxidation two-step sequence. The stability of metalated BTFP sulfones has been studied and compared with heteroaryl benzothiazol-2-yl (BT), 1-phenyl-1H-tetrazol-5-yl (PT), and 1-tert-butyl-1H-tetrazol-5-yl (TBT) sulfones 9-11 under different reaction conditions. The Julia-Kocienski olefination between alkyl BTFP sulfones 7 and a wide variety of aldehydes affords the corresponding 1,2-disubstituted alkenes and dienes in good yields and stereoselectivities. This one-pot protocol can be performed using KOH at room temperature or the phosphazene bases P2-Et and P4-t-Bu at -78 degrees C or rt and has been successfully used in a high-yielding and stereoselective synthesis of various methoxylated stilbenes such as trimethylated resveratrol. These new reaction conditions for the Julia-Kocienski olefination reaction have been also studied with BT, PT, and TBT sulfones, giving poorer results. Methylenation of aliphatic and aromatic aldehydes, ketones, and 1,2-dicarbonyl compounds is carried out through the modified Julia olefination using BTFP methyl sulfone 7d to give terminal alkenes and dienes. Mechanistic studies of the olefination reaction between benzyl BTFP sulfone 7a and aromatic aldehydes performed by KOH-induced Smiles rearrangement of stereodefined syn- and anti-beta-hydroxyalkyl BTFP sulfones indicate that the stereocontrol of the reaction is determined in the elimination step.     

Julia-Kocienski Olefination: A Tutorial Review

Over the past two decades, Julia-Kocienski olefination has become one of the most powerful and reliable C=C double-bond construction methods typically furnishing E-configured alkenes. This review summarizes the scientific literature of the past decade focusing on the key aspects for successful execution of the olefination step. The main stereoselectivity and yield-determining aspects have been outlined in separate chapters providing all the necessary information for the synthesis of Julia-Kocienski reagents as well as the most commonly used reaction optimization techniques.     

A synthesis of trisubstituted alkenes by a Ru-catalyzed addition

Catalyzed by ruthenium trisacetonitrile hexafluorophosphate 4, the Alder-ene type reaction of alkenes and internal alkynes provides an effective way to synthesize trisubstituted alkenes. Unlike most typical olefination protocols, this reaction is atom economical, and affords trisubstituted alkenes with defined olefin geometry. The regioselectivity can be explained invoking a steric argument based on the proposed mechanism. The first C-C bond formation generally involves sterically less hindered carbons of the alkenes and alkynes. Modest to very high regioselectivity can be achieved depending on the steric difference of the two substituents of alkynes.     

Synthesis of Fluoroolefins via Julia-Kocienski Olefination

The Julia-Kocienski olefination provides a versatile platform for the synthesis of fluorovinyl compounds. This review describes our efforts as well as those of others in the synthesis of various fluorinated aryl and heteroaryl sulfones and their utility as olefination reagents for the modular assembly of fluoroalkenes. Where data is available, the influence of the fluorine atom on the reactivity of the olefination reagents and the stereochemical outcome of the olefination are described.     

A general and stereoselective method for synthesis of tri- and tetrasubstituted alkenes

A convenient, general and stereoselective synthesis of trisubstituted alkenes and tetrasubstituted alkenes containing a cyanide function as well as trisubstituted episulphides have been elaborated. Methodology described for the preparation of these compounds is based on the corresponding readily available selenophosphates 1 and thiophosphates 2.     

Enantioselective organocatalytic formal allylation of α-branched aldehydes

Heteroarylvinyl sulfone 1 has been successfully used as a new sulfonyl Michael acceptor in aminocatalytic reactions with branched aldehydes. Subsequent one-pot Julia-Kocienski olefination allows the challenging preparation of enantiomerically pure α-allylated aldehydes bearing C-α quaternary carbons.     

Enantioselective Total Synthesis of the Putative Biosynthetic Intermediate Ambruticin J

The family of anti-fungal natural products known as the ambruticins are structurally distinguished by a pair of pyran rings adorning a divinylcyclopropane core. Previous characterization of their biosynthesis, including the expression of a genetically modified producing organism, revealed that the polyketide synthase pathway proceeds via a diol intermediate, known as ambruticin J. Herein, we report the first enantioselective total synthesis of the putative PKS product, ambruticin J, according to a triply convergent synthetic route featuring a Suzuki-Miyaura cross-coupling and a Julia-Kocienski olefination for fragment assembly. This synthesis takes advantage of synthetic methodology previously developed by our laboratory for the stereoselective generation of the trisubstituted cyclopropyl linchpin.     

3,5-Bis(trifluoromethyl)phenyl sulfones in the modified Julia olefination: application to the synthesis of resveratrol

The reaction between carbanions derived from alkyl 3,5-bis(trifluoromethyl)phenyl sulfones and aldehydes, affords with good yields and stereoselectivities the corresponding 1,2-disubstituted alkenes through the Julia-Kocienski olefination reaction. This one-pot protocol can be performed using KOH at room temperature or the phosphazene base P4-t-Bu at −78 °C, and has been successfully used in a high yielding and stereoselective synthesis of various stilbenes such as resveratrol.     

Synthesis of chalcones and flavanones using Julia-Kocienski olefination

A new application of Julia-Kocienski olefination for the synthesis of chalcones and flavanones has been described. 2-(Benzo[d]thiazol-2-ylsulfonyl)-1-phenylethanones have been developed as new reagents for direct Julia-Kocienski olefination with aldehydes in the presence of a base, afforded chalcones in good to excellent yields. Whereas, 2-(benzo[d]thiazol-2-ylsulfonyl)-1-(2-hydroxyphenyl)ethanone reacted with the aromatic aldehydes to furnish flavanones in good yields via one-pot intra-molecular cyclization.     

A flexible and unified strategy for syntheses of cladospolides A, B, C, and iso-cladospolide B

A simple, efficient and flexible strategy for the syntheses of cladospolides A-C and iso-cladospolide B is reported here. This strategy involves Julia-Kocienski olefination and Yamaguchi macrolactonization as key steps, starting from either d-ribose or suitable tartaric acid esters. Although our initial efforts towards cladospolide A involving a ring closing metathetic approach were not successful, changing the mode of ring closure and the use of Julia-Kocienski olefination for the construction of the key intermediate solved this issue and paved the way for the completion of total syntheses of this class of natural products.     

Synthesis of an advanced intermediate enroute to thiomarinol antibiotics

A stereoselective synthesis of the C1-C14 fragment of thiomarinols is disclosed. The key steps include the stereoselective preparation of an allylic sulfide via a chloro sulfide by 1,2-asymmetric induction, ring-closing metathesis reaction, Kirmse-Doyle reaction for the preparation of a γ,δ-unsaturated ester, Nozaki-Hiyama-Kishi coupling and Julia-Kocienski olefination reaction. Substrate controlled asymmetric induction has been advantageously employed for the creation of stereogenic centers. Noyori transfer hydrogenation and asymmetric hydrogenation reactions have been utilized for the creation of carbinol stereocenters.     

Improved Julia-Kocienski conditions for the methylenation of aldehydes and ketones

[reaction: see text] The scope of the methylenation of aldehydes and ketones under optimized Julia-Kocienski conditions is broadened by using 1-tert-butyl-1H-tetrazol-5-ylmethyl sulfone. Two different Barbier-type procedures are applied with NaHMDS at -78 degrees C or Cs2CO3 at 70 degrees C. The latter conditions are also adapted for the preparation of 1,2-disubstituted olefins and intramolecular olefination reactions.     

A stereoselective total synthesis of 7,8-O-isopropylidene iriomoteolide-3a

A stereoselective total synthesis of 7,8-O-isopropylidene iriomoteolide-3a has been achieved by using Yamaguchi esterification, Julia-Kocienski olefination, organocatalytic α-oxidation, and ring-closing metathesis reaction as key bond-forming steps.     

Rhodium-catalyzed addition of arylboronic acids to alkynyl aza-heteroaromatic compounds in water

Alkynyl heteroaromatic compounds reacted with arylboronic acids to give addition products in the presence of a rhodium catalyst. The best results were obtained when a novel pyridine-substituted water-soluble phosphine ligand was used. The reactions proceed to give trisubstituted alkenes from various arylboronic acids and alkynyl heteroaromatic compounds with high regioselectivity. Only alkynes with a nitrogen atom in proximity to the triple bond were converted to the corresponding alkenes, as expected for a chelation-controlled addition.     

Solvent-free NbCl5 catalyzed condensation of 1,3-dicarbonyl compounds and aldehydes: a facile synthesis of trisubstituted alkenes

A simple preparation of trisubstituted alkenes by condensation of β-diketones or β-ketoesters with aldehydes in presence of NbCl₅ as a Lewis acid catalyst in solvent-free conditions is described.     

Enantioselective synthesis of the C8-C20 segment of curvicollide C

The enantioselective synthesis of the C8-C20 fragment of curvicollide C has been accomplished. A catalytic asymmetric Claisen rearrangement (CAC), a diastereoselective methyl cupration of an alkynoate, and a Julia-Kocienski olefination served as key C/C-connecting transformations.     

Tf2NH-catalyzed,highly regio-and stereo-selective synthesis of trisubstituted alkenes and indane derivatives from benzylic alcohols and alkenes

A reaction of benzylic alcohols with alkenes has been developed in the presence of bis(trifluoromethane)sulfonimide for the synthesis of trisubstituted alkenes and indane derivatives with high stereoselectivity.In general,benzylic alcohols react with 1,1-diaryl alkenes to afford trisubstituted alkenes,and the reaction with 1,2-disubstituted and trisubstituted alkenes affords indane derivatives through a [3 + 2] annulation reaction.     

Phosphorus Chemistry. III Preparation of Vinyl Deuterated Trisubstituted Alkenes

A facile procedure for the preparation of vinyl deuterated trisubstituted alkenes via reduction of the corresponding (2-oxoalkyl)triphenyl-phosphonium halides with sodium borodeuteride is described.     

Enantioselective total synthesis and absolute configuration of apiosporic acid

The first total synthesis of the polyketide apiosporic acid is presented. Key steps are a Julia-Kocienski olefination, a Suzuki-Miyaura cross-coupling, and an intramolecular Diels-Alder reaction. The absolute configuration of the natural product was determined.     

Modified Julia olefination and α aminoxylation reactions mediated convergent synthesis of 1α, 24 (R)-dihydroxyvitamin D3 (tacalcitol)

A convergent synthesis of tacalcitol has been achieved starting from inexpensive and commercially available isovaleraldehyde and easily available Inhoffen-Lythgoe diol. Key steps include a proline catalyzed α aminoxylation and a Julia-Kocienski olefination.