Amino-λ3 -iodane-Enabled Electrophilic Amination of Arylboronic Acid Derivatives.

In this report, we describe the use of amino-λ3 -iodanes in the electrophilic amination of arylboronic acids and boronates. Iodine(III) reagents with transferable amino groups, including one with an NH2 group, were synthesized and used in the amination, allowing the synthesis of a wide range of primary and secondary (hetero)arylamines. Mechanistic studies by DFT calculations indicate that the reaction proceeds through an electrophilic amination process from a tetravalent borate complex with a B-N dative bond.

α-Amination of Carbonyl Compounds by Using Hypervalent Iodine-Based Aminating Reagents Containing a Transferable (Diarylmethylene)amino Group.

Hypervalent iodine-based aminating reagents containing a transferable (diarylmethylene)amino group can be used for the α-amination of simple carbonyl compounds such as esters, amides, and ketones in the presence of a lithium base. The (diarylmethylene)amino groups of the products can be readily modified, thus providing access to primary amines and diarylmethylamines. The developed method features transition-metal-free conditions and a simple one-pot procedure without the need to prepare enolate equivalents separately, thus offering a general and practical approach to the synthesis of a wide variety of α-amino carbonyl compounds. Experimental mechanistic investigations indicate that this amination proceeds through a unique radical coupling of an α-carbonyl radical with an iminyl radical; they are generated through a single-electron transfer between a lithium enolate and the hypervalent iodine reagent.

Gross anatomical study of the subcutaneous structures that create the three-dimensional shape of the buttocks.

The purpose of this study was to clarify the subcutaneous structures involved in the morphology of the gluteal region for clinical application. Thirty-seven formalin-fixed cadavers and one soft-fixed cadaver were used in this study. Gluteal tissue was removed from five formalin-fixed cadavers. A horizontal section and sections parallel to the long axis of the body were made from the excised tissue, and the subcutaneous fat was removed to observe the fibrous structure within the subcutaneous fat. Two formalin-fixed cadavers and one soft-fixed cadaver were used to perform conventional gross anatomical dissection and histological examination. On 30 formalin-fixed cadavers, the thickness of the subcutaneous fat was measured in various areas of the buttocks. The thickness of subcutaneous fat was thicker in the center of the buttocks and thinner on the lateral buttocks. Superficial fascia (SF) was found only in the upper buttock, being indistinct in the lower buttock. In the sacral and coccygeal areas, the dermis was tightly adhered to the bone as a single mass. Fibers arose from around the iliac crest to the SF. On the medial side of the gluteal fold, a strong fiber arose from the sciatic tubercle and inserted into the gluteus maximus and dermis. By identifying the characteristic subcutaneous structures of the gluteal region, we were able to identify the anatomical structures that shape the three-dimensional morphology of the buttocks. These findings may be useful in surgical treatments such as improving the buttock shape.

Stereospecific Oxycyanation of Alkenes with Sulfonyl Cyanide.

Oxycyanation of alkenes would allow the direct construction of useful ß-hydroxy nitrile scaffolds. However, only limited examples of such reactions have been reported, and some problems including limited substrate scope and the lack of diastereocontrol in the case of the oxycyanation of internal alkenes have arisen. We herein report on the intermolecular oxycyanation of alkenes using p-toluenesulfonyl cyanide (TsCN) in the presence of tris(pentafluorophenyl)borane (B(C6 F5 )3 ) as a catalyst, affording products that contain a sulfinyloxy group and a cyano group at the vicinal position. The reaction features a stereospecific syn-addition. The reaction also shows a broad substrate scope with good functional group tolerance. Mechanistic investigations by experimental studies and density functional theory (DFT) calculations revealed that the reaction proceeds via an unprecedented stereospecific mechanism through the electrophilic cyanation of alkenes, in which B(C6 F5 )3 efficiently activates TsCN through the coordination of the cyano group to the boron center.

Application of Neck Lift Technique for Corrections of Concave Deformity and Scar Contracture After Tracheal Fenestration.

ABSTRACT: Following a tracheostomy or tracheal fenestration procedure, neck concave deformity, and contracture after spontaneous closure are common problems. Since the neck is an exposed part of the body, its concave deformity can cause cosmetic problems and functional problems such as difficulty in neck extension and swallowing due to contracture. We report the case of a 63-year-old man who underwent tracheal fenestration for worsening respiratory status due to sepsis after aspiration pneumonia. After spontaneous closure of the tracheal fenestration, the patient developed a deformity of the neck, impaired neck extension, and dysphagia due to contracture. In this case, the submental sagging skin was used as a subcutaneous pedicle flap to correct the problem, and the result was both functionally and cosmetically satisfactory. We found that the submandibular skin could be used as a random pattern flap for reconstruction of the lower half of the neck. Therefore, this procedure can be an effective method for reconstruction around the tracheal stoma in the future.

Intramolecular C-H Amination of N-Alkylsulfamides by tert-Butyl Hypoiodite or N-Iodosuccinimide.

1,3-Diamines are an important class of compounds that are broadly found in natural products and are also widely used as building blocks in organic synthesis. Although the intramolecular C-H amination of N-alkylsulfamide derivatives is a reliable method for the construction of 1,3-diamine structures, the majority of these methods involve the use of a transition-metal catalyst. We herein report on a new transition-metal-free method using tert-butyl hypoiodite (t-BuOI) or N-iodosuccinimide (NIS), enabling secondary non-benzylic and tertiary C-H amination reactions to proceed. The cyclic sulfamide products can be easily transformed into 1,3-diamines. Mechanistic investigations revealed that amination reactions using t-BuOI or NIS each proceed via different pathways.

Tris(pentafluorophenyl)borane-Catalyzed Formal Cyanoalkylation of Indoles with Cyanohydrins.

Despite the significant achievements related to the C3 functionalization of indoles, cyanoalkylation reactions continue to remain rather limited. We herein report on the formal C3 cyanoalkylation of indoles with cyanohydrins in the presence of a tris(pentafluorophenyl)borane (B(C6F5)3) catalyst. It is noteworthy that cyanohydrins are used as a cyanoalkylating reagent in the present reaction, even though they are usually used as only a HCN source. Mechanistic investigations revealed the unique reactivity of the B(C6F5)3 catalyst in promoting the decomposition of a cyanohydrin by a Lewis acidic activation through the coordination of the cyano group to the boron center. In addition, a catalytic three-component reaction using indoles, aldehydes as a carbon unit, and acetone cyanohydrin that avoids the discrete preparation of each aldehyde-derived cyanohydrin is also reported. The developed methods provide straightforward, highly efficient, and atom-economic access to various types of synthetically useful indole-3-acetonitrile derivatives containing α-tertiary or quaternary carbon centers.

Analysis of Scars and Keloids by Focused Ion Beam/Scanning Electron Microscopy: Distinguishing Between Hypertrophic Scars and Keloids.

BACKGROUND: Histological differentiation between hypertrophic scars (HSs) and keloids has been considered difficult. In this study, we analyzed differences in the 3-dimensional tissue architecture between HSs and keloids using focused ion beam/scanning electron microscopy (FIB/SEM). METHODS: Five specimens each of normal skin, normotrophic scars (NSs), HSs, and keloids were investigated. Three sites in each specimen were observed by FIB/SEM tomography, resulting in an observation of 15 sites per tissue type. We identified fibroblasts and macrophages and assessed the contact ratio and the mode of intercellular contact (planar contact or point contact). The significance of differences among the 4 tissue types was determined by Fisher exact test. RESULTS: In normal skin, contact between fibroblasts and macrophages was observed at all 15 sites, and the mode of contact was always planar. There was contact at 87% of the NS sites (planar: point = 80%: 7%). In HSs, contact was seen at 80% of the sites (planar: point = 20%: 60%). In keloids, contact was found at only 15% of the sites (planar: point = 7.5%: 7.5%). The intercellular contact ratio showed no significant differences among normal skin, NSs, and HSs; however, a significant difference was noted between these tissues and keloids. The intercellular contact mode also showed no significant difference between normal skin and NSs, but a significant difference between these tissues and HSs. CONCLUSIONS: These histopathologic findings suggest that FIB/SEM tomography is useful for distinguishing between HSs and keloids and can provide important knowledge for understanding the pathogenesis of keloids.

Late-Onset Infection of Resorbable Plates After Multiple Facial Fractures.

In recent years, a variety of resorbable plates have been used for craniofacial fractures. The authors report a case of plate infection that occurred more than 1 year after surgery and was difficult to distinguish from a foreign body reaction. A 19-year-old male suffered fractures of the right zygomatic bone, orbital floor, and left maxilla in a motorcycle accident. Reduction was performed using resorbable plates at 7 days after injury. The postoperative course was good. However, the patient presented 396 days after surgery with redness/swelling of the right upper eyelid and right cheek pain. There were no systemic signs of infection such as fever. A foreign body reaction to the plate was suspected. After 1 week, swelling of the patient's upper eyelid was worse, and the remaining resorbable plate was removed via a skin incision. Swelling subsequently extended to the right cheek and upper gingiva, and all plates were removed under general anesthesia on the 418th day after the first operation. The swelling subsided after removal of the plates. Pathological examination revealed neutrophil infiltration and Staphylococcus hominis was detected by bacterial culture, leading to a diagnosis of late-onset plate infection. This coagulase-negative staphylococcus usually causes infection in neonates and immunocompromised individuals. Postoperative complications of resorbable plates include foreign body reaction and infection, which are difficult to differentiate clinically. Removing the foreign body is the principal technique for obvious wound infection. A foreign body reaction with subcutaneous fluid retention is slow to heal. Therefore, early plate removal is also recommended.

Successful Treatment of Full Thickness Frontal Skull Bone Defect With Dermal Fat Grafting and Artificial Bone Grafts.

Rigid reconstruction for frontal bone defects not only improves function, but also approximates more normal appearance. However, in cases involving dural scar contractures, a concave deformation remains when rigid reconstruction is performed without compensating for dead space created by swelling of the brain. This study involved 4 cases in which a 2-stage reconstruction procedure was used to first eliminate dead space by grafting dermal fat, and subsequently carry out rigid reconstruction to achieve a natural forehead configuration. This method is advantageous and considered to be effective in allowing dead space to be easily filled with minimal invasiveness for concave deformations of the dura mater with bone defects. Furthermore, the risk of artificial bone exposure is reduced by adding the dermal component of dermal fat, which is grafted to thinned frontal skin.

Treatment of Abdominal Surgical Wound Dehiscence With Bowel Exposure and Infection: Using Intrawound Continuous Negative Pressure, Irrigation, and Application of Artificial Dermis.

Abdominal surgical wound dehiscence with bowel exposure and infection carries a risk of intestinal fistula, making it extremely difficult to treat. The objective at this time is to heal such wounds safely and absolutely with using intrawound continuous negative pressure and irrigation treatment and artificial dermis. The subjects were 18 patients with abdominal wall dehiscence wounds with bowel exposure. Complications had already developed in 4 of the 18 cases of intestinal fistula. Subsequently, these 4 cases were treated with conservative treatment alone, whereas the other 14 were treated by split-thickness skin grafts. Intrawound continuous negative-pressure therapy has enabled the concomitant use of an artificial dermis inside the infected wound by maintaining irrigation of the wound. This method not only eliminated the danger of perforation from direct contact of the sponge with the bowel but also promoted the early proliferation of dermis-like tissue on the bowel surface, enabling safe and absolute healing.

Synthesis of Hypervalent Iodine(III) Reagents Containing a Transferable (Diarylmethylene)amino Group and Their Use in the Oxidative Amination of Silyl Ketene Acetals.

The preparation of some hypervalent iodine reagents containing a transferable amino group derived from benzophenone imine derivatives is reported. The reagents can be readily prepared and stored as a bench-stable solid, and were successfully used in the transition-metal-free oxidative amination of silyl ketene acetals to afford the corresponding α-amino esters, the benzophenone imine moieties of which could be easily hydrolyzed, thereby leading to the formation of primary amines.

Enantioselective Electrophilic Cyanation of Boron Enolates: Scope and Mechanistic Studies.

Chiral ß-ketonitriles bearing a stereogenic carbon center at the α-position are an important class of compounds, many of which serve as useful synthetic intermediates for the preparation of chiral 1,3-aminoalcohols, ß-hydroxy nitriles, and related derivatives. Although the enantioselective electrophilic cyanation of enolate equivalents is one of the most promising approaches for the synthesis of chiral ß-ketonitriles, the available methods are largely limited to reactions of 1,3-dicarbonyl compounds. Herein, we report on enantioselective electrophilic cyanation of boron enolates, which are readily prepared from α,ß-unsaturated ketones and diisopinocampheylborane (Ipc2 BH) to afford chiral ß-ketonitriles with a high level of enantioselectivity. The present method is scalable and provides facile access to both enantiomers of chiral ß-ketonitriles. Analysis of the in situ generated boron enolates by NMR revealed that hydroboration proceeds in a stereospecific manner, providing α,α-disubstituted boron enolates in the form of single isomers. Furthermore, the results of DFT calculations suggest that the cyanation of the boron enolates with p-toluenesulfonyl cyanide (TsCN) proceeds in a highly enantioselective manner through a unique six-membered ring transition state.

Hypervalent iodine(III)-mediated decarboxylative acetoxylation at tertiary and benzylic carbon centers.

The decarboxylative acetoxylation of carboxylic acids using a combination of PhI(OAc)2 and I2 in a CH2Cl2/AcOH mixed solvent is reported. The reaction was successfully applied to two types of carboxylic acids containing an α-quaternary and a benzylic carbon center under mild reaction conditions. The resulting acetates were readily converted into the corresponding alcohols by hydrolysis.

Hypervalent Iodine(III)-Mediated Decarboxylative Ritter-Type Amination Leading to the Production of α-Tertiary Amine Derivatives.

α-Tertiary amines (ATAs) are attractive structural motifs that are frequently found in biologically active molecules. Therefore, the development of an efficient method for the synthesis of ATAs represents an important research topic in the field of medicinal chemistry as well as organic chemistry. Although the Ritter reaction is a reliable approach for preparing α-tertiary amine derivatives via intermolecular amination reactions, the typical methods suffer from disadvantages such as harsh reaction conditions and the use of strong acids. Because of this, it has been of limited use in the synthesis of ATAs. We report here on the decarboxylative Ritter-type amination of carboxylic acids bearing an α-quaternary carbon center using a combination of PhI(OAc)2 and molecular iodine (I2) to produce the corresponding α-tertiary amine derivatives. This reaction proceeded at ambient temperature on the benchtop with a fluorescent light. Mechanistic investigations suggest that the reaction proceeds via the formation of an alkyl iodide and a higher oxidation state iodine(III) species as key intermediates. Similarly, a stepwise protocol for the Ritter-type amination of alcohols via the formation of oxalic acid monoalkyl esters was also achieved. The present methods represent a useful tool for the synthesis of ATAs that are difficult to prepare by conventional methods.

The Efficacy of Continuous Negative Pressure and Irrigation Treatment Inside the Wound by a Closed System in Reconstruction of All Layers of the Cranium Accompanying Infection and Cerebrospinal Fluid Leakage.

There have been many reports to date with respect to treatments on reconstruction of the cranium without accompanying infections following trauma and tumor resection. The morality is, however, high in patients observed with generation of cranial bone defect of all layers accompanying infection and cerebrospinal fluid leakage, and moreover, there are barely any reports on such cases because of the reconstruction thereof being very difficult. In this study, the authors were able to cure such 2 cases by carrying out continuous negative pressure and irrigation treatment inside the wound by a closed system following transplant of free latissimus dorsi muscle flap. This method is believed to be very effective for cranial bone defect of all layers accompanying infection and cerebrospinal fluid leakage, in which treatment was determined to be very difficult.

Electrophilic Cyanation of Boron Enolates: Efficient Access to Various ß-Ketonitrile Derivatives.

The highly efficient electrophilic cyanation of boron enolates using readily available cyanating reagents, N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) and p-toluenesulfonyl cyanide (TsCN), is reported. Various ß-ketonitriles were prepared by this new protocol, which has a remarkably broad substrate scope compared to existing methods. The present method also allowed efficient synthesis of ß-ketonitriles containing a quaternary α-carbon center. In addition, a preliminary result with the use of a chiral boron enolate for the enantioselective cyanation reaction is described.

Straightforward synthesis of 1,2-dicyanoalkanes from nitroalkenes and silyl cyanide mediated by tetrabutylammonium fluoride.

A straightforward synthesis of 1,2-dicyanoalkanes by reacting nitroalkenes with trimethylsilyl cyanide in the presence of tetrabutylammonium fluoride is described. The reaction proceeds through a tandem double Michael addition under mild conditions. Employing the hypervalent silicate generated from trimethylsilyl cyanide and tetrabutylammonium fluoride is essential for achieving this transformation. Mechanistic studies suggest that a small amount of water included in the reaction media plays a key role. This protocol is applicable to various types of substrates including electron-rich and electron-deficient aromatic nitroalkenes, and aliphatic nitroalkenes. Moreover, vinyl sulfones were found to be good alternatives, particularly for electron-deficient nitroalkenes. The broad substrate scope and functional group tolerance of the reaction makes this approach a practical method for the synthesis of valuable 1,2-dicyanoalkanes.

Iodine-Catalyzed Decarboxylative Amidation of ß,γ-Unsaturated Carboxylic Acids with Chloramine Salts Leading to Allylic Amides.

The iodine-catalyzed decarboxylative amidation of ß,γ-unsaturated carboxylic acids with chloramine salts is described. This method enables the regioselective synthesis of allylic amides from various types of ß,γ-unsaturated carboxylic acids containing substituents at the α- and ß-positions. In the reaction, N-iodo-N-chloroamides, generated by the reaction of a chloramine salt with I2 , function as a key active species. The reaction provides an attractive alternative to existing methods for the synthesis of useful secondary allylic amine derivatives.

Synthesis and Structure of Hypervalent Iodine(III) Reagents Containing Phthalimidate and Application to Oxidative Amination Reactions.

A new class of hypervalent iodine reagents containing phthalimidate was synthesized, and structurally characterized by X-ray analysis. The benziodoxole-based reagent displays satisfactory solubility in common organic solvents and is reasonably stable in solution as well as in the solid state. The reagent was used for the oxidative amination of the C(sp(3))-H bond of N,N-dimethylanilines. In addition, the reagent was also applicable to oxidative amination with rearrangement of trialkylamines as well as enamines that were prepared in situ from secondary amines and aldehydes.