Regioselective Markovnikov hydrothiolation of 1-aryl-1,3-butadienes with dithiocarbamic acid to allyl dithiocarbamates.

A metal, ligand and solvent-free three component reaction of 1-aryl-1,3-butadienes, CS and amine has been developed. In this process, readily available CS and secondary amines were used for C-N and C-S bonds giving allyl dithiocarbamates with notable Markovnikov selectivity, mild reaction conditions, simple operation and compatibility with various functional groups (37 examples). This is first case of dithiocarbamic acid addition to an unsymmetrical 1,3-diene system.

Oxone-Mediated Regioselective Oxy-iodination of 1-Aryl/Alkyl Butadienes Using TBAI.

A simple, mild, and environmentally benign regioselective oxy-iodination of 1-aryl/alkyl butadienes has been developed. While styrenes have been explored previously, this work on dienes has been highly regioselective and metal-free in oxy-iodination following Markovnikov's rule. The oxy-iodination products were obtained in good to excellent yields using various co-solvents (HO, MeOH, EtOH, AcOH, etc.

KSO-Mediated or Azobisisobutyronitrile-Catalyzed Regioselective Aerobic Oxidative Cleavage of 1-Arylbutadienes to Cinnamaldehydes.

This work reveals the regioselective oxidative cleavage of 1-arylbutadienes to cinnamaldehydes mediated by KSO or catalyzed by azobisisobutyronitrile, a very common free radical initiator, in an easy to handle, simple procedure and free of transition metals. This approach demonstrates excellent regioselectivity, mild reaction conditions, and compatibility with a broad range of functional groups (45 examples).

Stereoselective convergent total synthesis of oxylipins.

We synthesized stereoselectively four stereoisomers of oxylipins (1a-d) by a convergent approach based on chiral catalysis. The synthetic approach involved sequential assembly of two key fragments - ene-diol and allyl alcohol - for an intended convergent cross-metathesis reaction to join these fragments. The key steps include Sharpless kinetic resolution, asymmetric dihydroxylation and Grubbs cross-metathesis.

Asymmetric total syntheses of aspilactonol F and aspiketolactonol and synthetic studies toward diplofuranoxin.

The first asymmetric total synthesis of C polyketides, aspilactonol F and aspiketolactonol has been achieved. Ring-closing-metathesis has been employed as the key step in the synthesis. The total synthesis of aspilactonol F and aspiketolactonol was accomplished in 8 and 10 steps, in good overall yields of 28% and 24%, respectively, with only four column purifications for the former.

Asymmetric Total Synthesis of Cryptorigidifoliol I.

An efficient asymmetric total synthesis of cryptorigidifoliol I based on an unusual Luche reduction leading to bicyclic etherification and acid hydrolysis to a thermodynamically less stable 4-hydroxy-2,6--disubstituted-THP moiety has been achieved. The easy setup of -2,6-substitution on the core pyran ring through bicyclic etherification would enable the synthesis of various THP and bicyclic-THP-lactone natural products.

Unanticipated Bicyclic Etherification in Luche Reduction: Asymmetric Total Syntheses of Diospongins A and B and Tetraketide.

In the synthesis of diospongin B based on rearrangement of δ-hydroxyalkynone to 2,3-dihydro-4-pyran-4-one, we discovered an unanticipated beguiling reaction giving a thermodynamically less stable 4-hydroxy-2,6--disubstituted-THP moiety via bicyclic etherification under Luche reduction conditions and simple acid hydrolysis. The practical applicability of this method is exemplified by the asymmetric total syntheses of diospongins A and B, several analogues, and tetraketide.

Diastereoselective allylation-based asymmetric total synthesis of 1,10--guaianolides.

A Cr(II)-mediated Nozaki-Hiyama allylation of aldehydes with functionalized chiral allylbromolactone paved the way to easily access β-hydroxy-aryl/alkyl-α-methylene-γ-butyrolactones in good yields with high diastereoselectivities. A subsequent undemanding translactonization was orchestrated in the efficient first asymmetric total synthesis of two 1,10--guaianolides as a valuable extension of the strategy developed.

Chiral Pool Meets Chiral Catalysis: Eight-Step Convergent Total Synthesis of Anticancer Natural Lipid Mycalol.

An exemplary blend of chiral pool with chiral catalysis is exhibited in an eight-step (longest) convergent asymmetric total synthesis of mycalol, which is a promising anticancer natural lipid from a marine source. The polyhydroxy lipid is constructed by using four blocks, and two of which are derived from the chiral pool (d-mannitol and d-gluconolactone) and the other two by chiral catalysis (Sharpless epoxidation and Keck allylation). Alkylation and metathesis were used to knit the blocks in an excellent display of a modular convergent eight-step synthesis.

Deciphering the quest in the divergent total synthesis of natural products.

The divergent synthesis of natural products is rapidly developing towards achieving the goal of efficiency and economy in total synthesis. However, presently, the sustainable development of the synthesis of natural products does not permit the linear synthesis of a single target. In this case, divergent total synthesis is based on the identification of an advanced intermediate with structural features that can be mapped in more than two molecules.

Recent advances in the syntheses of guaianolides.

Sesquiterpene lactones, especially guaianolides representing a bigger class of natural products, have served as appealing candidates for total synthesis due to their varied bio- and pharmaceutical activities. This tutorial review delineates the creative efforts of many researchers in the total syntheses of different complex guaianolides recently published in the literature. Many of the syntheses display meticulous interplay between new methods and the ingenuity of strategies achieved through well-planned routes.

Asymmetric total synthesis of diosniponols A and B.

A concise asymmetric total synthesis of diosniponols A and B has been achieved based on an enantioselective Jacobsen kinetic resolution of racemic epoxide and the important 2,3-dihydro-4-pyran-4-one moiety being installed by the metal-free δ-hydroxyalkynone rearrangement catalyzed by -TsOH. A diastereoselective catalytic hydrogenation set the required all- stereochemistry leading to diosniponol A, which then, under the Mitsunobu inversion conditions, provided diosniponol B. The structure and absolute stereochemistry of the natural products were further confirmed.

TBAI-Catalyzed Regioselective Hydroxyperoxidation of 1-Aryl/Alkyl-1,3-dienes.

An efficient, mild, and economical approach for regioselective synthesis of 4-aryl/alkyl-1-peroxy-but-3-en-2-ols from 1-substituted-1,3-butadienes using hydroperoxides and catalyzed by TBAI has been developed. This method can be executed in a simple operation with no dry conditions required and having tolerance to a wide range of substrates to access corresponding hydroxyperoxidates in good yields. Thus, an excellent regioselective orthogonal dioxygenation in a diene system has been achieved.

Protecting-group-directed stereodivergent Tsuji-Trost cyclization: total synthesis of oxylipids and (+)-petromyroxol.

A stereodivergent protecting-group-directed Tsuji-Trost cyclization for efficient synthesis of both 2,5-- and 2,5--disubstituted-THF scaffolds has been realized. The presence of a β--silyl group in allyl acetate results in -2,5-disubstituted-3-oxygenated THF in a good up to 9 : 1 dr. Alternatively, when the free OH at the β-position is available for acetate co-ordination, it gives a -2,5-disubstituted-3-hydroxy THF scaffold almost as a single diastereomer (up to 1 : 0 dr).

Diastereoselective Allylation in the Divergent Total Syntheses of Guaianolides (+)-Ligustrin and (+)-Grosheimin and the Formal Synthesis of (-)-Eupalinilide E.

An efficient diastereoselective allylation of aldehydes with functionalized allyl bromolactone paved an excellent path toward the protecting-group-free divergent total synthesis of various guaianolides (+)-ligustrin, (+)-8--ligustrin, and (+)-grosheimin and the formal synthesis of (-)-eupalinilide E. The key steps include diastereoselective allylation, efficient translactonization, and aldehyde-ene reaction. From the common intermediate molecule (+)-ligustrin, the first asymmetric total synthesis of (+)-grosheimin has been achieved.

Ni-Catalyzed Regioselective C-5 Halogenation of 8-Aminoquinoline and Co-Catalyzed Chelation Assisted C-H Iodination of Aromatic Sulfonamides with Molecular Iodine.

A Ni(II)- and Co(II)-catalyzed sequential iodination of sulfonamides using inexpensive and milder molecular iodine (I ) as an iodinating reagent is reported for the first time. The 8-amino-5-iodoquinoline moiety prepared via nickel catalysis act as a directing group for second iodination by chelation assisted cobalt catalysis resulting in ortho-iodinated arylsulfonamide products. This methodology has been elaborated to various value added products by coupling reactions.

Palladium-Catalyzed Oxidant Dependent Switchable Aza-Wacker Cyclization and Oxidative Dimerization of Benzimidates.

An oxidant dependent switchable palladium-catalyzed synthesis of 1,3-oxazines and benzohydrazonates (azines) from -homoallyl benzimidates has been developed. The reaction involved aza-Wacker-type intramolecular cyclization of -homoallyl benzimidates with Cu(OAc) as oxidant under Pd-catalysis to deliver 4-methylene-1,3-oxazines, whereas dimerization of -homoallyl benzimidates with KSO as oxidant resulted remarkably in benzohydrazonates (azines). The reaction is atom economic with an easily operational procedure for divergent synthesis of important scaffolds.

Asymmetric total synthesis of (+)-dihydroitomanallene B and formal synthesis of (-)-kumausallene.

The first asymmetric total synthesis of (+)-dihydroitomanallene B and its two diastereomers, and the formal synthesis of (-)-kumausallene are reported. The synthesis of the former was completed in 18 steps from 1,4-butanediol (3.4% overall yield), with diastereoselective Tsuji-Trost cyclization to access -2,5-disubstituted-3-oxygenated THF scaffold and a Corey-White-Posner reaction to install the bromoallene moiety as the key steps.

Palladium-Catalyzed Regioselective Intermolecular Hydroalkoxylation of 1-Arylbutadienes.

An efficient method for the synthesis of ()-(3-alkoxybut-1-enyl)benzenes by Pd-catalyzed regioselective intermolecular hydroalkoxylation of 1-arylbutadienes has been developed. This method can be executed in a simple operation with no dry reaction conditions required and having tolerance to a wide range of substrates. Chloromethyl methyl ether (MOMCl) as an additive was found to be essential for the success of the reaction.

Regioselective Disulfide-Catalyzed Photocatalytic Oxidative Cleavage of 1-Arylbutadienes to Cinnamaldehydes.

This work discloses a simple, efficient, and environmentally benevolent disulfide-catalyzed photocatalytic regioselective oxidative cleavage of 1-arylbutadienes to cinnamaldehydes. This methodology illustrates mild reaction conditions, ambient temperature, excellent regioselectivity, and compatibility with wide range of functional groups (38 examples). The method gains significance, as few reports with limited substrate scope are available for such excellent photocatalytic oxidative cleavage of conjugated dienes.

Palladium-catalyzed anti-Markovnikov oxidative acetalization of activated olefins with iron(III) sulphate as the reoxidant.

This paper discloses the efficient palladium-catalyzed anti-Markovnikov oxidative acetalization of activated terminal olefins with iron(III) sulfate as the reoxidant. This methodology requires mild reaction conditions and shows high regioselectivity toward anti-Markovnikov products and compatibility with a wide range of functional groups. Iron(III) sulphate was the sole reoxidant used in this method.

Synthesis of 5-Vinyl-2-isoxazolines by Palladium-Catalyzed Intramolecular -Allylation of Ketoximes.

An efficient method for the synthesis of 5-vinyl-2-isoxazolines by Pd-catalyzed intramolecular -allylation of ketoximes has been developed. The reaction involves Pd(0)-catalyzed π-allyl formation via leaving group ionization or Pd(II)-catalyzed allylic C-H activation followed by intramolecular nucleophilic oxime oxygen attack. This methodology has been elaborated to various value-added products by epoxidation, Wacker oxidation, cross-metathesis, hydroboration-oxidation, dihydroxylation, and catalytic hydrogenation.

Concise Stereoselective Synthesis of β-Hydroxy-γ-lactones: (4,5)-4-Hydroxy-γ-decalactone from the Japanese Orange Fly and Enantiomers of Arachnid Harvestmen Isolates.

The naturally occurring (4,5)-4-hydroxy-γ-decalactone from the Japanese orange fly and the antipode of (4,5)-4-hydroxy-γ-dodecalactone from the harvestmen arachnid and their stereoisomers are synthesized from the chiral pool material d-glucono-δ-lactone in a few steps. The one-pot conversion of the latter to γ-vinyl-β-hydroxy-γ-lactone, cross-metathesis with requisite olefin, and hydrogenation enabled the synthesis of -lactones in just a two-pot operation. An additional efficient Pd-catalyzed allylic isomerization of γ-vinyl-β-hydroxy-γ-lactone led to the -lactones in high yields.

Advances in Cu and Ni-catalyzed Chan-Lam-type coupling: synthesis of diarylchalcogenides, Ar-X (X = S, Se, Te).

Organochalcogenides are an important class of compounds encountered in organic synthesis, chemical biology and materials chemistry. The development of the Ar-S/Se/Te bond formation, mostly in the synthesis of diarylchalcogenides, has garnered considerable attention in recent years. Transition metal catalysis is one of the most used methods for the synthesis of diarylchalcogenides via the traditional cross-coupling strategy.

Muricatacin, a Gateway Molecule to Higher Acetogenin Synthesis.

In this review, we have abstracted the various syntheses of acetogenins where the start point has been muricatacin. The latter can best be synthesized in either enantiomer form by the Sharpless method in three steps and can be admired as a gateway molecule for a quick assembly of many higher acetogenins. Muricatacin with orthogonally differentiated hydroxy groups and the available lactone carbonyl for chain elongation/modification can enable the concise synthesis of higher acetogenins.