Esters of 2-iodoxybenzoic acid (IBX-esters) were prepared by the hypochlorite oxidation of the corresponding 2-iodobenzoate esters and isolated as chemically stable, microcrystalline products. These hypervalent iodine compounds are potentially valuable oxidizing reagents belonging to a new class of pentavalent iodine compounds with a pseudobenziodoxole structure. Methyl 2-iodoxybenzoate can be further converted to the diacetate or a bis(trifluoroacetate) derivative by treatment with acetic anhydride or trifluoroacetic anhydride, respectively. Single-crystal X-ray diffraction analysis of methyl 2-[(diacetoxy)iodosyl]benzoate 8a reveals a pseudobenziodoxole structure with three relatively weak intramolecular I...O interactions. The dimethyl and diisopropyl esters of 2-iodoxyisophthalic acid were prepared by oxidation of the respective iodoarenes with dimethyldioxirane. Single-crystal X-ray diffraction analysis of diisopropyl 2-iodoxyisophthalate 6b showed intramolecular I...O interaction with the carbonyl oxygen of only one of the two carboxylic groups, while NMR spectra in solution indicated equivalency of both ester groups. IBX-esters, methyl 2-[(diacetoxy)iodosyl]benzoate, and 2-iodoxyisophthalate esters can oxidize alcohols to the respective aldehydes or ketones in the presence of trifluoroacetic acid or boron trifluoride etherate. The bis(trifluoroacetate) derivative can oxidize alcohols to carbonyl compounds without acid catalyst.

2‐Iodoxybenzenesulfonic acid (in a cyclic tautomeric form of 1‐hydroxy‐1H‐1,2,3‐benziodoxathiole 1,3,3‐trioxide), a thia‐analog of 2‐iodoxybenzoic acid (IBX) and a potentially important oxidizing reagent, was prepared by two different pathways: direct oxidation of 2‐iodobenzenesulfonic acid and hydrolysis of the methyl ester of 2‐iodylbenzenesulfonic acid. The resulting l‐hydroxy‐1H‐1,2,3‐benziodoxathiole 1,3,3‐trioxide was found to be thermally unstable and highly reactive towards organic solvents. The structure of its reductive decomposition product, l‐hydroxy‐1H‐1,2,3‐benziodoxathiole 3,3‐dioxide (the cyclic tautomeric form of 2‐iodosylbenzenesulfonic acid), was established by single‐crystal X‐ray diffraction.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

An account of the total synthesis of celogentin C is presented. A right-to-left synthetic approach to this bicyclic octapeptide was unsuccessful due to an inability to elaborate derivatives of the righthand ring. In the course of these efforts, it was discovered that the mild Braslau modification of the McFadyen-Stevens reaction offers a useful method of reducing recalcitrant esters to aldehydes. A left-to-right synthetic strategy was then examined. The unusual Leu-Trp side-chain cross-link present in the left-hand macrocycle was fashioned via a three-step sequence comprised of an intermolecular Knoevenagel condensation, a radical conjugate addition, and a SmI 2 -mediated nitro reduction. A subsequent macrolactamization provided the desired ring system. The high yield and concise nature of the left-hand ring synthesis offset the modest diastereoselectivity of the radical conjugate addition. Formation of the Trp-His side chain linkage characteristic of the right-hand ring was then accomplished by means of an indole-imidazole oxidative coupling. Notably, Pro-OBn was required as an additive in this reaction. Detailed mechanistic investigations indicated that Pro-OBn moderates the concentration of NCS in the reaction mixture, thereby minimizing the production of an undesired dichlorinated byproduct. The natural product was obtained after macrolactamization and deprotection. The chemical shifts of the imidazole hydrogen atoms exhibited significant dependence on temperature, concentration, and pH. Antitumor screening indicated that celogentin C inhibits the growth of some cancer cell lines.

Two complementary sets of conditions for radical additions of thiols to terminal ynamides are described. The use of 1 equiv of thiol affords the cis-β-thioenamide adducts in rapid fashion (10 min) and good dr, whereas employing excess thiol and longer reaction times favors the trans products.Ynamides are a class of compounds that have gained prominence in recent years. 1 They are electron-rich alkynes, 2 although their nucleophilicity can be tuned by varying the nature of the N-acyl group. Malacria has demonstrated the utility of ynamides as radical acceptors. 3,4 We reasoned that they should react readily with thiyl radicals, which are electrophilic in nature. 5 A recent report by Yorimitsu and Oshima detailing radical additions of arenethiols to internal tosylynamides 6 lent support to this hypothesis.The addition of a thiyl radical to an ynamide produces a β-thioenamide. This moiety is present in unusual cyclic peptides such as thioviridamide 7 (Figure 1) and the lantibiotics. 8 Inspired by the striking architecture of these natural products, we investigated additions of thiyl radicals to terminal ynamides. Herein, we report the initial results of our study, which demonstrate that both cis and trans β-thioenamides can be obtained selectively by simply varying the reaction conditions.The proposed reaction is shown in Figure 2. Regioselective addition of a thiyl radical to the terminal carbon of ynamide A would provide vinyl radicals B and/or C. These intermediates would rapidly equilibrate, and hydrogen atom abstraction from the thiol by the less hindered radical C, according to the precedent of Montevecchi and co-workers, 9 should afford cis-β-thioenamide D as the kinetic product. In contrast, known methods of β-thioenamide construction based on imine acylation 10 or Pummerer rearrangement 11 chemistry deliver predominantly the trans isomers. We also recognized that the presence of excess thiol in the reaction mixture would permit isomerization of D to the thermodynamically more stable trans isomer via a radical addition-β-thiyl radical elimination pathway. 12 Accordingly, we pursued a stereoselective synthesis of both cis-and trans-β-thioenamides by seeking two complementary sets of reaction conditions. We began by studying the additions of commercially available thiols to simple ynamides. Our results are collected in Table 1. Addition of excess n-butyl thiol (4 equiv) to acyclic amide- derived ynamide 1 13 in refluxing t-BuOH with AIBN as initiator 14 afforded β-thioenamide E-3a as the major product of a separable mixture (72%, 15:1 E:Z) after 3 h. In contrast, employing 1 equiv of thiol and 0.5 equiv of AIBN led to Z-3a in good yield (76%, 1:11 E:Z) after only 10 min. Similar trends were observed with thiophenol, although greater quantities of the E isomer were obtained under both sets of conditions. When the radical addition of tert-butyl thiol to 1 was performed under the Z-selective conditions, no reaction was observed. Subjection of this bulky thiol to the typically E-selective conditions a...