K2S2O8-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 K2S2O8 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. The characterization of the synthesized oxylipins revealed spectroscopic data that were consistent with previously reported values.

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

The first asymmetric total synthesis of C9 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. A common strategy for the concise synthesis of the key intermediate of diplofuranoxin is also presented.

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-trans-disubstituted-THP moiety has been achieved. The easy setup of trans-2,6-substitution on the core pyran ring through bicyclic etherification would enable the synthesis of various THP and bicyclic-THP-lactone natural products.

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

A Cr(II)-mediated Nozaki-Hiyama allylation of aldehydes with functionalized chiral allylbromolactone paved the way to easily access ß-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-seco-guaianolides as a valuable extension of the strategy developed.

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-4H-pyran-4-one, we discovered an unanticipated beguiling reaction giving a thermodynamically less stable 4-hydroxy-2,6-trans-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.

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. The modular excess will enable rapid analogue generation as revealed by the convenient synthesis of 4-epi-mycalol similarly in an eight-step sequence.

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. However, the identification of this intermediate and its scalable synthesis in enantiopure form are challenging. Herein, we present the details of the ingenious efforts by researchers in the last six years toward the divergent synthesis of two to as many as eight natural products initially via a single route, and then diverging from a common intermediate and further branching out toward several natural products. The planning and strategies adopted can serve as guidelines for the future development of efficient divergent routes aimed at achieving higher efficiency toward multiple targets, causing divergent synthesis to become an accepted common practice.

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. In some cases, the Chiron approach has come in quite handy, wherein the structural features and stereochemistry of select molecules could map well with naturally available starting materials. A few catalytic methods like diastereoselective aldol reaction, enediyne or dienyne metathesis, or photochemical methods have been efficiently used. This compilation also aims to enhance the diversity space based on these natural products and further interest in the sustainable total synthesis of this class of compounds and related molecules.

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-4H-pyran-4-one moiety being installed by the metal-free δ-hydroxyalkynone rearrangement catalyzed by p-TsOH. A diastereoselective catalytic hydrogenation set the required all-syn 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-cis- and 2,5-trans-disubstituted-THF scaffolds has been realized. The presence of a ß-O-silyl group in allyl acetate results in cis-2,5-disubstituted-3-oxygenated THF in a good up to 9 : 1 dr. Alternatively, when the free OH at the ß-position is available for acetate co-ordination, it gives a trans-2,5-disubstituted-3-hydroxy THF scaffold almost as a single diastereomer (up to 1 : 0 dr). The THF scaffolds synthesized were carried forward in the total synthesis of oxylipids and (+)-petromyroxol.

Palladium-Catalyzed Regioselective Intermolecular Hydroalkoxylation of 1-Arylbutadienes.

An efficient method for the synthesis of (E)-(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.

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-epi-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.

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 cis-2,5-disubstituted-3-oxygenated THF scaffold and a Corey-White-Posner reaction to install the bromoallene moiety as the key steps. In addition, the enantioselective formal total synthesis of (-)-kumausallene involving the key Tsuji-Trost cyclization is also realized.

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 O-homoallyl benzimidates has been developed. The reaction involved aza-Wacker-type intramolecular cyclization of O-homoallyl benzimidates with Cu(OAc)2 as oxidant under Pd-catalysis to deliver 4-methylene-1,3-oxazines, whereas dimerization of O-homoallyl benzimidates with K2S2O8 as oxidant resulted remarkably in benzohydrazonates (azines). The reaction is atom economic with an easily operational procedure for divergent synthesis of important scaffolds.

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 (I2 ) 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.

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. Various olefins like vinylarenes, aryl-allylethers, aryl or benzyl acrylates and homoallylic alcohols all reacted well providing anti-Markovnikov acetals, some of which represent orthogonally functionalized 1,3- and 1,4-dioxygenated compounds.

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

An efficient method for the synthesis of 5-vinyl-2-isoxazolines by Pd-catalyzed intramolecular O-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.