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A chiral aryl iodide promotes the enantioselective oxidative cyclization of 1-naphtholic sulfonamides, albeit in moderate ee and low yield. The products tend to crystallize as conglomerates. Recrystallization thus increases their ee to > 99% ee. This highly enantioenriched material provides seed crystals for the resolution of the racemate (prepared in high yield by oxidative cyclization with (diacetoxyiodo)benzene in trifluoroacetic acid) by coupled preferential crystallization. This enables the production of significant quantities of highly enantioenriched products, despite the low efficiency of the enantioselective reaction.

A chiral aryl iodide enables the catalytic, oxidative kinetic resolution of various 2-[(3-hydroxy-2-alkyl)propyl]naphthalen-1-ols.

Aryl iodides that are unreactive toward various diaryliodonium triflates undergo metathesis reaction with λ 3 -iodanes based on a highly nucleofugal aryl iodide such as 2-iodothiophene. Examples of such reactive iodanes include phenyl(2-thienyl)iodonium triflate and bis-(2-thienyl)iodonium triflate. This observation provides support for a mechanistic hypothesis advanced earlier.

Iodobenzene diacetate in MeOH containing a catalytic amount of TFA efficiently oxidizes aldoximes to nitrile oxides. The latter may be trapped in situ with olefins in a bimolecular or an intramolecular mode. The new method enables the execution of tandem oxidative dearomatization of phenols/intramolecular nitrile oxide cycloaddition sequences leading to useful synthetic intermediates.

An approach to tetrodotoxin that relies on the oxidative amidation of methyl 4-hydroxyphenylacetate as a key step is described. The stereoselective introduction of a beta-hydroxynitrile functionality on one of the double bonds of the emerging dienone is achieved through an intramolecular nitrile oxide cycloaddition-fragmentation sequence.

This contribution reviews a family of reactions devised in our laboratory that effect the oxidative conversion of phenols into 4-amido-dienones. A salient feature of this chemistry is the use of hypervalent iodine reagents, especially diacetoxyiodobenzene (DIB), as uniquely capable oxidants in the context of the new transformation. The advent of this methodology has created new opportunities in alkaloid synthesis. Our efforts toward FR-901483, TAN-1251C, cylindricine C, and other nitrogenous natural products illustrate some applications in that domain. 1 Introduction 2 Background 3 First-Generation Oxidative Amidation of Phenols: The Oxazoline Route 4 Initial Applications: Total Synthesis of FR-901483 and of TAN-1251C 5 Second-Generation Oxidative Amidation of Phenols: Sulfonamide Technology 6 Applications: Total Synthesis of (-)-Cylindricine C 7 Third-Generation Solution: The Bimolecular Reaction 8 Conclusion

[reaction: see text] Ugi reaction between an (S)-alpha-amino acid, an aromatic aldehyde, and an isonitrile proceeds best under catalysis by TiCl(4) in MeOH. The sense of diastereoinduction is (S,S).

A metathesis reaction occurs when a diaryliodonium triflate is heated with an aryl iodide, resulting in the formation of a new diaryliodonium triflate.

A solution to the long-standing problem presented by the oxidative cyclization of a phenolic 3-arylpropionamide to a spirolactam has been developed in this laboratory via oxazoline chemistry. This research was motivated by our interest in some novel tricyclic azaspirane natural products formally derived from tyrosine, such as FR901483 and TAN1251C. In this paper, we disclose full details of the total synthesis of these substances.

The reaction of an α-chloroglycinate ester with the dimethylaluminum acetylide derivative of phenyl propargyl ether provides the corresponding 5-vinyloxazole in 40–50% yield.

We describe a total synthesis of (±)-chlorovulone II that is 10 steps shorter than the best alternative currently available (nine vs 19 steps). The key event of the synthesis is an aldol addition of the enolate of ethyl acetate into 4-cyclopentene-1,3-dione, a substance that has received little attention as an educt for prostanoid synthesis and for which little is known about carbonyl 1,2-addition with enolates. In addition, we provide chemical and stereochemical details of a route to a key intermediate toward the title compound that involves a carbonyl−ene reaction and a radical addition to an aldehyde carbonyl.

N-Acyl derivatives of piperazic acids display an unusual degree of conformational rigidity. As a consequence, α-N-coupling of a piperazic acid of given configuration (d or l) with an α-aminoacyl unit of opposite configuration (l or d) produces a “heterochiral” dipeptide that exists in a conformation conducive to the formation of a peptide turn. Piperazic acids and related compounds may thus be regarded as conformationally rigid analogues of proline, and because they are readily available in either antipodal form by synthesis, they should become of great interest in the study of peptide turns.

(±)-Phyllanthocin has been synthesized through a key step involving the enelike reaction of an aldehyde with 2-methoxypropene recently developed in these laboratories. This work demonstrates that our chemistry is suitable for multistep synthetic applications, and it shows that stereocontrol in the creation of the phyllanthocin structure may be achieved by thermodynamic equilibration of both peripheral stereogenic carbons.

The Ti(IV)-catalyzed Ugi condensation of α-amino acids with electron-rich aromatic aldehydes performs adequately even with sterically demanding α-amino carboxylate salts. The reaction occurs diastereoselectively, in some cases with virtually complete diastereoselectivity. A stereochemical rationale for the reaction is proposed.

Catalytic amounts of Yb(fod) 3 catalyze a bimolecular ene-like reaction between ordinary aldehydes and vinyl ethers, in which the oxygen functionality is located at the central carbon of an allylic system. These reactions proceed at room temperature in high yield.

The use of an acetylenic alane, generated in situ from (IIa), permits the conversion of chloroglycinates into the title compounds with moderate yields.

Catalyst screening reveals that N-phenylurea in combination with Pd(O-Ac)2 is superior, even when compared to “Phos”-type ligands.

We describe a practical five-step synthesis of the unusual hydrazonoacid found in luzopeptins, together with observations concerning its chemical behaviour.

N-acetyl oxazolone derivatives of serine and threonine are readily converted into reactive acid chlorides that condense efficiently with various C-protected aminoacids, even poorly nucleophilic ones.

The abnormal reluctance of piperazic acids to undergo N-2 acylation seems to be due to an electronic effect, not a steric / conformational problem. A system suitable for probing these issues was assembled by methods that have produced a versatile building block for β-hydroxy-α-aminoacids of either relative stereochemistry and of either (L) or (D) configuration.

N-Acyl derivatives of piperazic acids display an unusual degree of conformational rigidity. As a consequence, α-N-coupling of a piperazic acid of given configuration (d or l) with an α-aminoacyl unit of opposite configuration (l or d) produces a “heterochiral” dipeptide that exists in a conformation conducive to the formation of a peptide turn. Piperazic acids and related compounds may thus be regarded as conformationally rigid analogues of proline, and because they are readily available in either antipodal form by synthesis, they should become of great interest in the study of peptide turns.

We describe a total synthesis of (±)-chlorovulone II that is 10 steps shorter than the best alternative currently available (nine vs 19 steps). The key event of the synthesis is an aldol addition of the enolate of ethyl acetate into 4-cyclopentene-1,3-dione, a substance that has received little attention as an educt for prostanoid synthesis and for which little is known about carbonyl 1,2-addition with enolates. In addition, we provide chemical and stereochemical details of a route to a key intermediate toward the title compound that involves a carbonyl−ene reaction and a radical addition to an aldehyde carbonyl.

This contribution reviews a family of reactions devised in our laboratory that effect the oxidative conversion of phenols into 4-amido-dienones. A salient feature of this chemistry is the use of hypervalent iodine reagents, especially diacetoxyiodobenzene (DIB), as uniquely capable oxidants in the context of the new transformation. The advent of this methodology has created new opportunities in alkaloid synthesis. Our efforts toward FR-901483, TAN-1251C, cylindricine C, and other nitrogenous natural products illustrate some applications in that domain. 1 Introduction 2 Background 3 First-Generation Oxidative Amidation of Phenols: The Oxazoline Route 4 Initial Applications: Total Synthesis of FR-901483 and of TAN-1251C 5 Second-Generation Oxidative Amidation of Phenols: Sulfonamide Technology 6 Applications: Total Synthesis of (-)-Cylindricine C 7 Third-Generation Solution: The Bimolecular Reaction 8 Conclusion

We describe a synthesis of ketones 3 (X = O−R or CN; Y = H or alkyl), which are useful building blocks for the preparation of analogs of the potent antifungal agent sordarin, 1. Congeners of 1 constructed from 3 should permit detailed SAR investigations of the terpenoid core of the natural product.

Publisher Summary Since their isolation, luzopeptins have attracted interest in the biomedical arena, but their rarity and chemical sensitivity have precluded any sort of chemical modification that may be required for a thorough medicinal chemistry study. A viable synthesis was needed to address these issues. Thus, the quest for total synthesis of luzopeptins began, which has been documented in this chapter. Inouye confirmed the activity of luzopeptin C against HIV-RT (RT-reverse transcriptase) and disclosed that luzopeptin C suppresses HIV replication in infected MT-4 cells at non-cytopathic concentrations. Luzopeptin C must, thus, be selective for RT vis -a- vis human DNA polymerases. The chapter discusses the mechanism of action of luzopeptins and the minimal structural requisites for anti-HIV activity and reviews answers to whether luzopeptins A and luzopeptins C serve as anti-HIV drugs and, if so, the way could they be modified to further enhance potency and selectivity. Together with quinoxapeptins, sandramycin, and related natural products, luzopeptins form what may be referred to as the “peptin family of natural products.” Peptins display a dimeric peptide scaffold of C 2 -like symmetry that supports a pair of heteroaroyl segments. These appear to be intimately involved in the expression of bioactivity. The synthesis of luzopeptins is fraught with extreme difficulties. At some point, a linear dimer of pentadepsipeptide must undergo cyclization. However, the efficiency of the cyclization of linear peptides is known to be sequence-dependent and sensitive even to minor structural changes in the substrate, including the nature of protecting groups.

We review methods for the preparation of piperazic acids (“piz”) and significant aspects of their chemistry. Special attention is devoted to issues relating to acylation of these non-proteinogenic amino acids, given the importance of these operations for the synthesis of piz-containing oligopeptides. We also provide an account of the unique conformational properties of piperazic acids and discuss their behavior as rigid proline equivalents that should be quite useful for the creation and study of peptide turn mimics.

A palladium-promoted intramolecular arylation of a β-diketone generates a spirocyclic system as a model for Fredericamycin A.

La reaction d'aldehydes avec des diethoxyphosphorylamino-4 benzoates de methyle fournit des aldimines activees qui reagissent, en presence de BF 3 /ether d'ethyle, avec des stannanes allyliques

Dihydropyrans obtained by cyclocondensation of aromatic enones with vinyl ethers are transformed into pyridines by treatment with hydroxylamine hydrochloride.