Formal synthesis of schulzeines B and C

A formal synthesis of schulzeines B and C, marine natural products with inhibitory effect against α-glucosidase, has been achieved. The key reactions of the synthesis are N-acyliminium ion cyclization, Sharpless asymmetric dihydroxylation, olefin cross metathesis, and asymmetric allylboration.     

A concise diastereoselective approach to (+)-dexoxadrol, (−)-epi-dexoxadrol, (−)-conhydrine and (+)-lentiginosine from (−)-pipecolinic acid

A new diastereoselective pathway for the total synthesis of (+)-dexoxadrol, first asymmetric synthesis of (−)-epi-dexoxadrol and formal synthesis of conhydrine and (+)-lentiginosine is presented using commercially available (−)-pipecolinic acid. The key reactions utilized are Sharpless asymmetric dihydroxylation and Wittig reaction. The paper further describes the study of effect of protecting groups on dihydroxylation of a terminal olefin in piperidine ring system.     

Synthesis of chiral sultams and their application as chiral auxiliaries in an asymmetric Diels–Alder reaction

A number of bicyclic chiral sultams were synthesized based on 1,3-dipolar cycloaddition reactions of nitrile oxides and nitrones with prop-1-ene-1,3-sultone. The corresponding N-enoyl sultams were prepared by acylation. Their relative effectiveness as new chiral auxiliaries in asymmetric synthesis was evaluated for the asymmetric Diels–Alder reactions with cyclopentadiene. Good chemical yield and excellent endo selectivity were observed. The relationship between the structure and their effectiveness in promoting asymmetric induction of the synthetic chiral sultams was investigated.     

Asymmetric synthesis of macrolactin analogue

Total asymmetric synthesis of macrolactin A analogue was accomplished by the convergent strategy. Rapid access to advanced intermediate 16 through isomerization of ynone to (E,E)-conjugated dienone is a key step of this synthesis. Overall, control of all of the four stereocenters was achieved by means of asymmetric and diastereoselective reactions without using any chiral natural sources.     

Highly enantioselective synthesis of 2H-1-benzothiopyrans by a catalytic domino reaction

A highly enantioselective catalytic asymmetric synthesis of 2H-1-benzothiopyrans is presented. The organocatalytic asymmetric domino reactions between 2-mercaptobenzaldehyde and α,β-unsaturated aldehydes proceed with excellent chemo- and enantioselectivities to give the corresponding pharmaceutically valuable benzothiopyrans in high yields with 91-98% ee.     

A stereoselective approach for the total synthesis of (5R,7R,9R)-7,9-dihydroxy-5-decanolide#

A stereoselective approach for the total synthesis of lactone (5R,7R,9R)-7,9-dihydroxy-5-decanolide is described. The sequence of synthetic reactions involves a Keck asymmetric allylation, diastereoselective iodo-carbonate cyclization, regioselective ring-opening reaction, oxidative lactonization.     

Catalytic asymmetric hydrometallation of cyclobutenes with salicylaldehydes

Chiral, substituted cyclobutanes are common motifs in bioactive compounds and intermediates in organic synthesis but few asymmetric routes for their synthesis are known. Herein we report the Rh-catalyzed asymmetric hydrometallation of a range of meso-cyclobutenes with salicylaldehydes. The ortho-phenolic group promotes hydroacylation and can be used as a handle for subsequent transformations. The reaction proceeds via asymmetric hydrometallation of the weakly activated cyclobutene, followed by a C–C bond forming reductive elimination. A prochiral, spirocyclic cyclobutene undergoes a highly regioselective hydroacylation. This report will likely inspire the development of other asymmetric addition reactions to cyclobutenes via hydrometallation pathways.

Chiral, substituted cyclobutanes are common motifs in bioactive compounds and intermediates in organic synthesis but few asymmetric routes for their synthesis are known.     

Synthetic studies of microtubule stabilizing agent peloruside A: an asymmetric synthesis of C10C24 segment

An asymmetric synthesis of the C₁₀C₂₄ fragment of the potent antitumor macrolide, peloruside A is described. All three stereogenic centers have been enantioselectively constructed utilizing Evans alkylation, Brown asymmetric allylboration, and a substrate controlled epoxide formation. Other key reactions involved Grubbs's ring-closing olefin metathesis and Ando's Z-selective olefination reaction.     

Stereoselective total synthesis of oplopandiol,oploxyne A,and oploxyne B

A stereoselective total synthesis of oplopandiol, oploxyne A, and (−)-oploxyne B is described. The key reactions include Sharpless asymmetric epoxidation, d-proline catalyzed aminoxylation, Cadiot–Chodkiewicz cross-coupling reaction, m-CPBA induced substrate-controlled stereoselective epoxidation, and Lewis acid catalyzed stereo- and regioselective ring-opening of epoxide.     

A facile synthesis of 3-hydroxy-3-(trifluoromethyl)-1H-pyrrol-2(3H)-ones with Brønsted acid-catalyzed condensation–cyclization reactions of β-enamino esters and ethyl trifluoropyruvate

A facile synthesis of 3-hydroxy-3-(trifluoromethyl)-1H-pyrrol-2(3H)-ones based on trifluoroacetic acid-catalyzed condensation–cyclization reactions of β-enamino esters and ethyl trifluoropyruvate is described. These reactions afford a series of α-trifluoromethylated γ-lactam compounds in good to excellent yields under mild conditions. A preliminary trial of an asymmetric catalytic version with chiral BINOL-derived phosphoric acid as enantioselective catalyst was conducted and showed promising enantioselectivity of the desired product.     

Stereoselective synthesis of the C3-C15 fragment of callyspongiolide

The synthesis of C3-C15 fragment of callyspongiolide, a 14-membered macrolides isolated from the marine sponge Callyspongia sp., which was collected from the Indonesia, is reported. Highlights of the synthesis include construction of E-olefin through Julia-Kocienski olefination, Brown asymmetric allylation and base-induced elimination reactions for propargyl alcohol synthesis.     

Stereoselective total synthesis of polyketide lactone, (3R,4S,5S,9S)-3,5,9-trihydroxy-4-methylundecanoic acid δ-lactone

The total synthesis of lactone 1 has been described. The convergent asymmetric synthesis relies on the use of an Evans’ syn-aldol, chain extension with lithio tert-butyl acetate, and the stereoselective reduction of a ketone as the key reactions.     

First stereoselective synthesis of synargentolide A and revision of absolute stereochemistry

The first stereoselective total synthesis of synargentolide A isolated from Syncolostemon argenteus has been achieved from commercially available (R)-benzyl glycidyl ether using Sharpless asymmetric epoxidation and cross-metathesis reactions as the key steps. Comparing the spectral data of the synthesized and naturally occurring synargentolide A, the C4′ and C6′- stereogenic centers of the natural synargentolide A were assigned a corrected anti relationship.     

Synthesis of brasilibactin A and confirmation of absolute configuration of β-hydroxy acid fragment

A synthesis of brasilibactin A, a cytotoxic siderophore from the actinomycete of Nocardia brasiliensis, and three unnatural diastereomers of the natural product is described. Four possible diastereomers of the β-hydroxy acid fragment were prepared via asymmetric aldol reactions and used to synthesize brasilibactin A and its diastereomers. Careful analysis of ¹H NMR data confirmed that brasilibactin A possesses the 17S,18R absolute stereochemistry.     

Synthesis of (−)-(5R,6S)-6-acetoxyhexadecanolide based on l-proline-catalyzed asymmetric aldol reactions

A convenient method for proline-catalyzed asymmetric aldol reactions using synthons of straight-chain aliphatic aldehydes, and aldehydes bearing a 1,3-dithiane moiety at the β-position, has been developed. This method was successfully applied to the synthesis of (−)-(5R,6S)-6-acetoxyhexadecanolide, an oviposition attractant pheromone of the female Culex mosquito.     

A cyclopropanol-based approach to synthesis of Unit A of the cryptophycins

A new asymmetric synthesis of Unit A of the cryptophycins has been carried out yielding 13% of the target product over 14 steps. The key steps of the synthesis were diastereoselective hydroboration–oxidation reactions performed on the alkenyl moiety of a 1,3-dioxane derivative 8, which can be easily prepared via the Kulinkovich cyclopropanation of protected diethyl (S)-(−)-malate followed by transformation of the resulting small rings of the product 6 into the functional groups necessary for the synthesis of the target compound.     

Catalytic enantioselective synthesis of axially chiral allenes

The conventional procedures for preparing optically active axially chiral allenes generally require stoichiometric chiral sources as either substrates or reagents. On the other hand, examples of catalytic asymmetric synthesis of axially chiral allenes are rare and it is a relatively underdeveloped area in synthetic organic chemistry. In this review article, various methods for preparing enantiomerically enriched axially chiral allenes using substoichiometric chiral sources are surveyed. Some reactions with stoichiometric but recoverable chiral sources are also mentioned. Most of the asymmetric reactions in these categories are transition-metal-catalyzed reactions, and there are a few examples of organocatalytic reactions. In addition, some enzymatic/microbial systems are also known.     

Kinetic aspects of non-linear effects in asymmetric synthesis,catalysis, and autocatalysis

The Kagan ML_n models developed for rationalizing non-linear effects of catalyst enantiopurity have become a valuable mechanistic tool for probing complex asymmetric catalytic reactions. This work demonstrates how these models also provide clues about reactivity that may be used for further evidence to test a mechanistic hypothesis. Special considerations for probing non-linear effects in asymmetric synthesis using stoichiometric chiral auxiliaries and in asymmetric autocatalysis are highlighted in comparison with asymmetric catalysis.     

The stereoselective total syntheses of pectinolides A,B, and C

The stereoselective total synthesis of pectinolide B has been accomplished for the first time along with total syntheses of pectinolides A and C. MacMillan α-hydroxylation and Sharpless asymmetric dihydroxylation reactions are involved in generating the three stereogenic centers. Other important transformations in the synthesis are Z-selective Still–Gennari olefination, selective benzylation of the homoallylic alcohol, and a one-pot MOM deprotection followed by lactonization leading to all three pectinolides A–C being synthesized from a common intermediate. Pectinolides A, B, and C were synthesized from n-hexanal in 19, 20, and 18 steps with overall yields of 8.8%, 6.72%, and 9.2%, respectively.     

Enantioselective synthesis of cyclopropyl δ-lactonealdehydes and dodecyl-5-ene-1-yne-3-ol: advanced intermediates of solandelactone A and B

A stereocontrolled synthesis of cyclopropyl δ-lactonealdehydes and dodecyl-5-ene-1-yne-3-ol is accomplished with predictable absolute stereochemistry via organocatalytic and catalytic asymmetric transfer hydrogenation reactions. The salient feature of this protocol is the genesis of chirality through an organocatalytic reaction and utilized for installing a critical bifunctional trans-cyclopropane motif, which is a key segment of every representative member of the oxylipin class of natural products such as solandelactone A and B.