NIS/PhI(OAc)2‐Mediated Diamination/Oxidation of N‐Alkenyl Formamidines: Facile Synthesis of Fused Tricyclic Ureas

Facile synthesis of bicyclic ureas by NIS/PhI(OAc)₂‐mediated diamination/oxidation of N‐alkenyl formamidines is reported. Bulky aromatic groups such as 2,6‐diisopropylphenyl and mesityl and alkyl groups were tolerated towards the process. Several control experiments have been performed, and the reaction outcomes indicate that the oxidation process is probably concerted with the diamination cyclization, and succinimide generated from NIS‐mediated aminoamidiniumation step promoted the PhI(OAc)₂‐mediated oxidation step. The new methodology provides an efficient method for the synthesis of fused tricyclic ureas.     

An efficient and mild oxidant for the synthesis of s-tetrazines

PhI(OAc)₂ serves as a mild and effective oxidant for the synthesis of s-tetrazine derivatives—molecules of emerging significance to the field of bioorthogonal chemistry. This reagent serves as a complementary oxidant to harsher nitrous reagents. The use of PhI(OAc)₂ improves the synthesis of 5-amino-di(pyridin-2-yl)-s-tetrazine, a molecule that has been broadly used for cellular imaging and nuclear medicine. The generality of PhI(OAc)₂ as the oxidant for tetrazine synthesis is demonstrated for nine tetrazines in 75–98% yield.     

The total synthesis of psymberin

The total synthesis of a new member of the pederin family of natural products, psymberin 1, was accomplished. Using a recently reported novel and efficient PhI(OAc)2 mediated oxidative entry to 2-(N-acylaminal)-substituted tetrahydropyrans as the key step, this total synthesis was executed in a convergent and efficient manner. The longest linear sequence of this synthesis was 22 steps starting from known 6.     

醋酸碘苯介导的α-重氮羰基化合物的去重氮双氧合反应

报道了一类新颖的醋酸碘苯介导的α-重氮羰基化合物的去重氮双氧合反应.该反应利用醋酸碘苯与N-羟基邻苯二甲酰亚胺(或N-羟基丁二甲酰亚胺)反应能产生氧中心自由基的特性实现了氧中心自由基诱导的α-重氮羰基化合物的双氧合反应,合成了一系列α,α-双氧代芳酮和α,α-双氧代羧酸酯衍生物,产率中等到良好.基于实验结果及文献报道,提出了可能的反应机理,其涉及氧中心自由基加成、C-N键的均裂和自由基交叉偶联等.此外,该反应具有无需金属催化剂、条件温和、操作简便等优点.     

PhI(OTf)2 Does Not Exist (Yet)**

PhI(OTf)₂ has been used for the past 30 years as a strong I(III) oxidant for organic and inorganic transformations. It has been reported to be generated in situ from the reactions of either PhI(OAc)₂ or PhI=O with two equivalents of trimethylsilyl trifluoromethanesulfonate (TMS-OTf). In this report it is shown that neither of these reactions generate a solution with spectroscopic data consistent with PhI(OTf)₂, with supporting theoretical calculations, and thus this compound should not be invoked as the species acting as the oxidant for transformations that have been associated with its use.     

Enantioselective total synthesis of 1-epi-pathylactone A

[structure: see text]. The first enantioselective total synthesis of 1-epi-pathylactone A, 3, has been accomplished using a PhI(OAc)2-mediated domino reaction as a key step. No diastereomeric separation was required throughout the whole synthetic scheme presented in this paper. Comparison of 1H and 13C NMR spectral data of the synthetic product with the reported spectral data of natural pathylactone A, coupled with an X-ray crystallographic analysis, led to the conclusion that the C1 configuration in the original paper was erroneously ascribed to (R).     

Oxidative nitration of the amino group: synthesis of dinitramide and cyanonitramide salts

A convenient preparative method for the synthesis of potassium dinitramide and cyanonitramide salts was developed. The method involves reactions of nitramide or cyanamide with KNO₂ and PhI(OAc)₂ or PhIO in methanol.     

Synthesis of (2-oxoindolin-3-ylidene)methyl acetates involving a C-H functionalization process

A novel palladium-catalyzed oxidative C-H functionalization protocol for the synthesis of (2-oxoindolin-3-ylidene)methyl acetates has been developed. In the presence of Pd(OAc)2 and PhI(OAc)2, a variety of N-arylpropiolamides underwent the C-H functionalization reaction with acids to afford the corresponding (E)-(2-oxoindolin-3-ylidene)methyl acetates selectively in moderate to excellent yields.     

Total synthesis of (+)-rishirilide B: development and application of general processes for enantioselective oxidative dearomatization of resorcinol derivatives

A concise synthesis of (+)-rishirilide B (2) is described. This is the first synthesis to be reported for the (+)-enantiomer of rishirilide B (2) as found in nature. The strategy accentuates the valuable combination of a method for o-quinone methide coupling with a method for enantioselective resorcinol dearomatization, which provides a densely functionalized chiral building block. The convergent synthesis illustrates several improvements and refinements to these methods and their supporting chemistries. Among these is the in situ generation of PhI[OTMS]OTf. Combination of this oxidant with phenol 31 constitutes the first example of a diastereoselective oxidative dearomatization of a resorcinol displaying a 2-alkyl substituent. In addition, the preparation of the cyclic sulfone 34 is reported. As a new dimethide precursor expressing a readily cleavable O-benzyl residue, sulfone 34 should prove useful in future endeavors. A protocol using the aluminum amide of dimethylhydrazine for opening and cleavage of a [1,4]-dioxan-2-one is also described. This procedure unmasks the hydroxy dione 36 by jettisoning the chiral directing group. Regioselective O-carbamylation of the 1,3-dione 36 enables the transformation of the remaining carbonyl into the alpha-hydroxy carboxylic acid found in 2. The total synthesis of (+)-rishirilide B (2) requires 15 pots from benzaldehyde 17 and 13 pots from benzaldehyde 32. The final product emerges in yields of 12.5% and 20.3% from compounds 17 and 32, respectively. The longest linear sequence requires eight chromatographies. Important observations leading to the development of the principle asymmetric method are described within the context of the total synthesis.     

Metal-free synthesis of aryl esters by coupling aryl carboxylic acids and aryl boronic acids

A facile synthesis of aryl esters is developed by coupling aryl carboxylic acids and aryl boronic acids in the presence of PhI(OAc)₂ and carbonyl diimidazole. A wide range of functional groups were tolerant to the metal-free reaction condition that led to the desired products in good yields.     

An efficient one-step synthesis of fulleroisoxazolines and fulleropyrazolines mediated by (diacetoxyiodo)benzene

An efficient one-step strategy for the synthesis of fulleroisoxazolines/fulleropyrazolines from fullerene and aldoximes/hydrazones mediated by PhI(OAc)₂ has been described.     

Copper(I)-catalyzed asymmetric alkene aziridination mediated by PhI(OAc)2: a facile one-pot procedure

A facile one-pot procedure for copper-catalyzed PhI(OAc)₂-mediated asymmetric alkene aziridination had been developed. Commercially available PhI(OAc)₂ and sulfonamides were used to generate the nitrene precursors (PhINR) in situ for olefin aziridination. This one-pot procedure had been optimized using 4-nitrobenzenesulfonamide as the nitrene source. With 5 mol % of the chiral copper catalyst, these conditions afforded 94% yield of the isolated product with 75% ee. We had also developed a simple and rapid method to monitor the rate of this one-pot aziridination.     

A practical synthesis of (−)-oseltamivir

Oseltamivir phosphate (Tamiflu^®) is a potent inhibitor of neuraminidase, and is used worldwide as a drug for type A or B influenza. The industrial synthesis of oseltamivir uses shikimic acid as a starting material, but the price fluctuates, depending on the supply of star anise. We have developed a practical synthesis of oseltamivir from pyridine, which features an asymmetric Diels-Alder reaction of dihydropyridine using MacMillan's catalyst, a bromolactonization, Hofmann rearrangement with PhI(OAc)₂, and a domino transformation of the bicyclo[2.2.2] system into an aziridine compound.     

New polydentate ligand and catalytic properties of the corresponding ruthenium complex during sulfoxidation and alkene epoxidation

Bis(diimine)-ruthenium complexes constitute a class of catalysts with good activity for oxidation reactions, such as sulfoxidation and epoxidation. The synthesis and the full characterization of a new ruthenium complex bearing an original pentadentate ligand (L5pyr for 2,6-bis-(6-ethyl-2,2'-bipyridyl)-pyridine) is reported. Comparison of its activity with regard to[Ru(bpy)2(CH3CN)2](2+) and [Ru(bpy)2(py)(CH3CN)](2+) during alkene and sulfide oxidation allowed us to conclude that the addition of a fifth pyridine ligand in the coordination sphere improves the efficiency of the catalyst. Moreover, under these oxidation conditions a hydroxylation of the ligand L5pyr led to a better activity than its analogue [Ru(bpy)2(py)(CH3CN)](2+), especially during epoxidation of alkenes by PhI(OAc)2.     

Novel Total Synthesis of Mansouramycin B

A novel total synthesis of Mansouramycin B ( 1 ) was performed via 10 steps in 28% overall yield starting from the readily available and cheap salicylaldehyde. Two key steps of this total synthesis are noteworthy. The first one is base‐promoted one‐pot aerobic aromatization of N‐tosyltetrahydroisoquinoline 6 , the second one is oxidation of 5‐hydroxy‐3‐methyl‐isoquinoline 8 with iodobenzene diacetate [PhI(OAc)₂].     

Aziridination of styrene: comparison of [N-(p-tolylsulfonyl)imino]phenyliodinane and chloramine-T as nitrene donors

Chloramine-T and [N-(p-tolylsulfonyl)imino]phenyliodinane (PhI=NTs) are contrasted as nitrene donors for the aziridination of styrene using copper(II) triflate, and copper-exchanged zeolite Y (CuHY) as catalysts. For both catalysts, PhI=NTs is found to give significantly higher yields of the aziridine both in the presence and absence of a chiral bis(oxazoline) modifier. In addition, chloramine-T is found to induce leaching of most of the Cu from CuHY, and with this nitrene donor CuHY does not function as a heterogeneous catalyst. In contrast, PhI=NTs causes negligible leaching of Cu from CuHY and, consequently, for the heterogeneous CuHY catalyst, PhI=NTs is the preferred nitrene donor. With chloramine-T, the beneficial effects observed on addition of copper powder are shown to be due to the copper powder acting as a reservoir for Cu²⁺ in solution, since Cu²⁺ in solution is rapidly deactivated by toluenesulfonamide, a degradation product of the nitrene donor.     

A unique and highly efficient method for catalytic olefin aziridination

A facile, high yielding, and stereospecific method for olefin aziridination is described. This process capitalizes on the unique reactivity of sulfamate esters in combination with 1-2 mol % Rh2(tfacam)4 and PhI(OAc)2 as the terminal oxidant to promote N-atom transfer reactions. A range of structurally and electronically disparate alkenes are found to react under conditions that employ substrate as the limiting reagent and only a slight excess of H2NSO3CH2CCl3 as the nitrogen source. The product alkoxysulfonyl aziridines are useful intermediates that react smoothly with nucleophiles to generate 1,2-amine derivatives. Following aziridine ring-opening, the N-trichloroethoxysulfonyl group can be removed under mild reductive conditions (Zn(Cu)/AcOH-MeOH) to give the corresponding 1 degrees amine. The efficient and convenient performance of this chemistry should establish it as a useful tool for synthesis.     

Direct synthesis of α-hydroxyketone phosphates from terminal alkynes and H-phosphine oxides in the presence of PhI(OAc)_2 and H_2O

A simple and highly efficient one-pot method for the construction of α-hydroxyketone phosphates from terminal alkynes and H-phosphine oxides has been developed in the presence of PhI(OAc)_2 and H_2O.The present protocol provides an attractive approach to α-hydroxyketone phosphates in good to high yields,with the advantages of operation simplicity,the use of commercially available materials,broad substrate scope,high atom efficiency and good tolerance to scale-up synthesis.     

Efficient alkyl ether synthesis via palladium-catalyzed, picolinamide-directed alkoxylation of unactivated C(sp3)-H and C(sp2)-H bonds at remote positions

We report the efficient synthesis of alkyl ethers by the functionalization of unactivated sp(3)- and sp(2)-hybridized C-H bonds. In the Pd(OAc)(2)-catalyzed, PhI(OAc)(2)-mediated reaction system, picolinamide-protected amine substrates undergo facile alkoxylation at the γ or δ positions with a range of alcohols, including t-BuOH, to give alkoxylated products. This method features a relatively broad substrate scope for amines and alcohols, inexpensive reagents, and convenient operating conditions. This method highlights the emerging value of unactivated C-H bonds, particularly the C(sp(3))-H bond of methyl groups, as functional groups in organic synthesis.     

Rhodium(II,II) dimer as an efficient catalyst for aziridination of sulfonamides and amidation of steroids

[reaction: see text] Unsaturated sulfonamides underwent direct intramolecular aziridination catalyzed by Rh(2)(OAc)(4) with PhI(OAc)(2) and Al(2)O(3) to give the corresponding aziridine products in excellent yields (up to 98%) and with good to excellent conversions. High turnovers (up to 1375) were achieved. The intermolecular rhodium-catalyzed amidation of cholesteryl acetate with PhI=NTs or PhI(OAc)(2)/NH(2)R as the nitrogen source exhibited both excellent regio- and alpha-selectivity (alpha/beta ratio up to 9:1).