Ketone Products Research Articles

Chemo- and Regioselective Synthesis of Acyl-Cyclohexenes by a Tandem Acceptorless Dehydrogenation-[1,5]-Hydride Shift Cascade

An atom-economical methodology to access substituted acyl-cyclohexenes from pentamethylacetophenone and 1,5-diols is described. This process is catalyzed by an iridium(I) catalyst in conjunction with a bulky electron rich phosphine ligand (CataCXium A) which favors acceptorless dehydrogenation over conjugate reduction to the corresponding cyclohexane. The reaction produces water and hydrogen gas as the sole byproducts and a wide range of functionalized acyl-cyclohexene products can be synthesized using this method in very high yields. A series of control experiments were carried out, which revealed that the process is initiated by acceptorless dehydrogenation of the diol followed by a redox-neutral cascade process, which is independent of the iridium catalyst. Deuterium labeling studies established that the key step of this cascade involves a novel base-mediated [1,5]-hydride shift. The cyclohexenyl ketone products could readily be cleaved under mildly acidic conditions to access a range of valuable substituted cyclohexene derivatives.

Hydrogen-Free Catalytic Reduction of Biomass-Derived 5-Hydroxymethylfurfural into 2,5-Bis(hydroxymethyl)furan Using Copper–Iron Oxides Bimetallic Nanocatalyst

2,5-Bis(hydroxymethyl)furan (BHMF) produced from 5-hydroxymethylfurfural (HMF) plays a significant role in the production of resins, fibers, foams, drugs, polymers, ketones and ethers. In this study, a novel cost-effective copper iron magnetic bimetallic nanocatalyst supported on activated carbon (CuO–Fe3O4/AC) was developed for the selective hydrogenation of HMF into BHMF via Meerwein–Ponndorf–Verley (MPV) reaction using ethanol as a hydrogen donor. Various analytical techniques such as HRTEM-EDX, TGA, ICP-OES, XRD, H2-TPR, XPS, and nitrogen adsorption–desorption isotherms (BET and BJH methods) were used to characterize the prepared catalyst. Reaction parameters affecting the selectivity of BHMF such as catalyst concentration, temperature, and time were studied. Kinetic study indicated a pseudo-first order reaction with a significant high rate constant of BHMF formation compared with the formation rate constants of MF, MFA, and DMF byproducts. At the optimum reaction conditions, 94.8% of BHMF selectivity...

H2 -free Synthesis of Aromatic, Cyclic and Linear Oxygenates from CO2.

The synthesis of oxygenate products, including cyclic ketones and phenol, from carbon dioxide and water in the absence of gas‐phase hydrogen has been demonstrated. The reaction takes place in subcritical conditions at 300 °C and pressure at room temperature of 25 barg. This is the first observation of the production of cyclic ketones by this route and represents a step towards the synthesis of valuable intermediates and products, including methanol, without relying on fossil sources or hydrogen, which carries a high carbon footprint in its production by conventional methods. Inspiration for these studies was taken directly from natural processes occurring in hydrothermal environments around ocean vents. Bulk iron and iron oxides were investigated to provide a benchmark for further studies, whereas reactions over alumina and zeolite‐based catalysts were employed to demonstrate, for the first time, the ability to use catalyst properties such as acidity and pore size to direct the reaction towards specific products. Bulk iron and iron oxides produced methanol as the major product in concentrations of approximately 2–3 mmol L−1. By limiting the hydrogen availability through increasing the initial CO2/H2O ratio the reaction could be directed to yield phenol. Alumina and zeolites were both observed to enhance the production of longer‐chained species (up to C8), likely owing to the role of acid sites in catalysing rapid oligomerisation reactions. Notably, zeolite‐based catalysts promoted the formation of cyclic ketones. These proof‐of‐concept studies show the potential of this process to contribute to sustainable development through either targeting methanol production as part of a “methanol economy” or longer‐chained species including phenol and cyclic ketones.

Ketone production by ketogenic diet and by intermittent fasting has different effects on the gut microbiota and disease progression in an Alzheimer's disease rat model.

The benefits of ketone production regimens remain controversial. Here, we hypothesized that the ketone-producing regimens modulated cognitive impairment, glucose metabolism, and inflammation while altering the gut microbiome. The hypothesis and the mechanism were explored in amyloid-β infused rats. Rats that received an amyloid-β(25–35) infusion into the hippocampus had either ketogenic diet (AD-KD), intermittent fasting (AD-IMF), 30 energy percent fat diet (AD-CON), or high carbohydrate (starch) diet (AD-CHO) for 8 weeks. AD-IMF and AD-CHO, but not AD-KD, lowered the hippocampal amyloid-β deposition compared to the AD-CON despite serum ketone concentrations being elevated in both AD-KD and AD-IMF. AD-IMF and AD-CHO, but not AD-KD, improved memory function in passive avoidance, Y maze, and water maze tests compared to the AD-CON. Hippocampal insulin signaling (pAkt→pGSK-3β) was potentiated and pTau was attenuated in AD-IMF and AD-CHO much more than AD-CON. AD-IMF and AD-CON had similar glucose tolerance results during OGTT, but AD-KD and AD-IMF exhibited glucose intolerance. AD-KD exacerbated gut dysbiosis by increasing Proteobacteria, and AD-CHO improved it by elevating Bacteriodetes. In conclusion, ketone production itself might not improve memory function, insulin resistance, neuroinflammation or the gut microbiome when induced by ketone-producing remedies. Intermittent fasting and a high carbohydrate diet containing high starch may be beneficial for people with dementia.

ОКИСНА МОДИФІКАЦІЯ БІЛКІВ У СИРОВАТЦІ КРОВІ ЩУРІВ ЗА УМОВ ЕКСПЕРИМЕНТАЛЬНОГО ОСТЕОАРТРИТУ ТА СУМІСНОГО ВВЕДЕННЯ ХОНДРОПРОТЕКТОРА ТА МУЛЬТИПРОБІОТИКА

One of the actual problems of modern medicine is joint disease. Among them, osteoarthritis occupies an important place. The formation of osteoarthritis is accompanied by the development of inflammation, which leads to damage to all structures of the joint. An important role in inflammatory processes is played by the intensification of free radical processes. As the disease develops, the joints lose their mobility, which leads to a decrease in the quality of life of patients and the development of disability. In this regard, it is important to search for drugs that have regenerative, anti-inflammatory and antiradical properties. The aim of our study was to investigate the combined effect of chondroitin sulfate and multiprobiotic on the content of oxidative protein modification products and the level of sulfhydryl groups in rat blood serum under conditions of monoiodoacetate-induced osteoarthritis. The study included participation of white male non-linear rats (weighing 180–240 g) adherence to the general ethical principles of animal experiments. An experimental osteoarthritis model was created by introducing 1 mg of sodium monoiodoacetate into the knee ligament. Chondroitin sulfate and multiprobiotic were used as therapeutic agents. The content of products of oxidative modification of proteins was determined by the level of carbonyl derivatives, which are manifested in the reaction with 2,4-dinitrophenylhydrazine. The level of total, protein-bound and non-protein sulfhydryl groups was measured by the Elman method. It was found that under conditions of monoiodoacetate-induced osteoarthritis in the blood serum of rats, the content of products of oxidative modification of proteins increases. The level of neutral aldehyde products (E max = 356 nm) is increased by 2.5 times and neutral ketone products (E max = 370 nm), respectively, by 2,1 times compared to the control. Under the same experimental conditions in the blood serum, the amount of basic aldehyde products (E max = 430 nm) increases by 1.9 times, while the content of the main ketone products (E max = 530 nm) increases by 1,7 times compared to the control groups. In experimental osteoarthritis in the blood serum, the content of sulfhydryl groups decreases: non-protein SH-groups – 1,5 times, protein and general SH-groups – 1,7 times relative to the control. This indicates disturbance of the oxidative-antioxidant balance and the development of oxidative stress in the organism during experimental osteoarthritis. It was shown that the combined administration of chondroitin sulfate and multiprobiotics in animals with experimental osteoarthritis partially restored the above parameters.

Enantioconvergent alkylation of ketones with racemic secondary alcohols via hydrogen borrowing catalysis.

An enantioconvergent method for the alkylation of o-disubstituted aryl ketones with racemic secondary alcohols is described. This process is mediated by a commercially available iridium catalyst and proceeds via hydrogen borrowing catalysis. The highly enantioenriched β-substituted ketone products were readily cleaved to a wide range of functional groups via retro-Friedel-Crafts acylation.

FerrateVI oxidation of polycyclic aromatic compounds (PAHs and polar PACs) on DNAPL-spiked sand: degradation efficiency and oxygenated by-product formation compared to conventional oxidants.

In situ chemical oxidations are known to remediate PAH contaminations in groundwater and soils. In this study, batch-scale oxidations aim to compare the PAC (polycyclic aromatic compound) degradation of three oxidation processes traditionally applied for soil treatment: permanganate, heat-activated persulfate (60 °C) and Fenton-like activated by magnetite, to results obtained with ferrates (FeVI). Widely studied for water treatments, ferrates are efficient on a wide range of pollutants with the advantage of producing nontoxic ferric sludge after reaction. However, fewer works focus on their action on soil, especially on semi-industrial grade ferrates (compatible with field application). Oxidations were carried out on sand spiked with dense non-aqueous phase liquid (DNAPL) sampled in the groundwater of a former coking plant. Conventional 16 US-EPA PAHs and polar PACs were monitored, especially potential oxygenated by-products that can be more harmful than parent-PAHs. After seven reaction days, only the Fenton-like showed limited degradation. Highest efficiencies were obtained for heat-activated persulfate with no O-PAC ketones formed. Permanganate gave important degradation, but ketones were generated in large amount. The tested ferrates not only gave slightly lower yields due to their auto-decomposition but also induced O-PAC ketone production, suggesting a reactional pathway dominated by oxidoreductive electron transfer, rather than a radical one.

Synthesis and Characterization of N-Benzylidene Aniline Ligand for Spectrophotometric Determination of Nickel

Schiff bases are compounds containing azomethine group (-HC=N-). They are condensation products of ketones or aldehydes (aldehydes and ketones) with primary amines. Formation of Schiff base generally takes place under acid or base catalysis or with heat. The spectrophotometric determination of metals using Schiff base metal complex is very important in analytical chemistry. This study has helped to establish a novel, simple and cheap analytical method for the determination of nickel in an environmental sample especially in developing countries where the cost and maintenance of sophisticated instruments are extremely high. In this study, Schiff base ligand was synthesized using benzaldehyde and aniline to form a metal complex with the target analyte (Ni 2+ ). The melting point and electrical conductivity of the synthesized nickel complex were 175.6 o C and 84x10 -6 Ώ -1 cm -1 respectively and the maximum absorbance at 360nm was 0.60. The complex was characterized using different spectroscopic techniques. The peak in FT-IR spectra at 1625.2 cm -1 confirmed the (C=N) stretching vibration. The 13 C and 1 H NMR spectra showed 193.8 and 10.0 ppm respectively of (CH=N) which was assigned to the azomethine carbon atom and the GC-MS analysis revealed a plausible structure of the complex. The stoichiometry of the Schiff base nickel (SB-Ni) complex was established as NiSB 2 by Job’s method of continuous variation, mole- ratio and slope-ratio methods. The three procedures are in agreement over the stoichiometry of the SB-Ni complex. Keywords : Complex, Stoichiometry, N-benzylideneaniline, Spectrophotometric, Ligand DOI : 10.7176/CMR/11-10-04 Publication date: December 31 st 2019

HMGCS2 Mediates Ketone Production and Regulates the Proliferation and Metastasis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor worldwide; however, the traditional therapeutic approaches and survival rates are still limited. To improve current therapies, it is necessary to investigate the molecular mechanisms underlying liver cancer and to identify potential therapeutic targets. The aims of this study were to verify the mechanisms and therapeutic potential of the ketogenesis rate-limiting enzyme 3-Hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) in HCC. Immunohistochemical staining of human liver disease tissue arrays showed that HMGCS2 is abundantly expressed in normal liver tissues but is downregulated in cirrhosis and HCC tissues. In HCC patients, lower HMGCS2 expression was correlated with higher pathological grades and clinical stages. In our investigation of the molecular mechanisms of HMGCS2 in HCC, we showed that knockdown of HMGCS2 decreased ketone production, which promoted cell proliferation, cell migration, and xenograft tumorigenesis by enhancing c-Myc/cyclinD1 and EMT signaling and by suppressing the caspase-dependent apoptosis pathway. Ketone body treatment reduced the proliferation- and migration-promoting effects of HMGCS2 knockdown in cells. In contrast, HMGCS2 overexpression increased the intracellular ketone level and inhibited cell proliferation, cell migration, and xenograft tumorigenesis. Finally, ketogenic diet administration significantly inhibited liver cancer cell growth in mice. Our studies highlight the potential therapeutic strategy of targeting HMGCS2-mediated ketogenesis in liver cancer.

Oxidation of alkylarenes by modified graphite

Herein, an electrochemical method has been introduced and developed for the selective benzylic oxidation of alkylarenes. This work utilizes a simple redox mediator system, N-Hydroxyphthalimide (NHPI), with an inexpensive and innovatory modified graphite and nickel-based electrode using undivided cell setups to the selective oxidation of alkylarenes toward the aldehyde and ketone production. Since, the selective oxidation of alkylarenes toward aldehyde formation (in the aerobic conditions) is a prominent challenge, our method for alkylarenes oxidation with high yield and selectivity in the presence of oxygen under mild and metal free conditions is promising.

Self‐assembled nanoporphyrins in the presence of gold bio‐nanoparticles as heterogeneous nano‐biocatalyst for green production of aldehydes and ketones

We report a simple and facile self‐assembly method for the successful fabrication of a biological macromolecule, MnTPPCl (manganese(III) chloride 5,10,15,20‐tetraphenylporphyrin), intercalated into gold nanoparticles using the cooperative effects of Sesbania sesban plant. This biohybrid was characterized using various techniques for further investigation. The catalytic activity of this biological hybrid was considered in the production of aldehydes and ketones from primary and secondary alcohols, respectively. Excellent conversions and selectivties were obtained applying Au@MnTPPCl colloidal nanocomposite and NaIO4 as an oxygen donor in ethanol.

Copper-Containing Polyoxometalate-Based Metal-Organic Frameworks as Highly Efficient Heterogeneous Catalysts toward Selective Oxidation of Alkylbenzenes.

With a one-pot assembly method, two copper-containing Keggin-type polyoxometalate-based metal-organic frameworks (POMOFs), i.e., [CuI6(trz)6{PW12O40}2] (HENU-2, HENU = Henan University; trz = 1,2,4- triazole) and [CuI3(trz)3{PMo12O40}] (HENU-3), were successfully prepared and structurally characterized. These two compounds, which are generated by the extension of a crown-like {Cu6(trz)6} macrocycle-based sandwich-type structural unit, possess identical noninterpenetration 3D frameworks except for the polyanions difference. Additionally, both of themare assessed as highly effective heterogeneous catalysts in facilitating the oxidation of alkylbenzenes to ketone products in the presence of tert-butyl hydroperoxide. Under optimized conditions, HENU-2 can achieve a 95.2% conversion of diphenylmethane in 20 h with a 100% selectivity toward benzophenone, and it was reused for three runs with constant high activity, which outperforms most POM-based catalysts for this catalytic reaction.

The keto diet and the gut: cause for concern?

The ketogenic (or keto) diet is a rapidly growing dietary trend for weight loss and was initially designed in the USA in the 1920s for treatment of refractory epilepsy. It was a diet that resulted in similar physiological effects to that of fasting, which appeared to reduce the incidence of epileptic seizures, but it could be maintained for a longer time. Since the 1990s, the keto diet has been under scrutiny for its use in the treatment of people with obesity or who are overweight, metabolic syndrome, cancers, and specific psychiatric and neurological disorders. The high-fat diet restricts carbohydrate intake to 20–50 g non-fibre carbohydrate daily (around 5–10% total energy intake): a drastic change from a typical intake of approximately 150–250 g carbohydrate per day in developed countries (up to around 50% total energy intake). In practice, this means consuming eggs, bacon, and avocado for breakfast instead of porridge with milk and fruit, for example. The drastic reduction in carbohydrate intake results in the production of ketones in the liver, which switches the body's fuel source from glucose to fatty acids. This shift affects many fundamental biological systems and molecular intermediate and end-products, which is thought to underlie the keto diet's therapeutic benefit. Interestingly, the neuroprotective effect of a keto diet in animals might be modulated by the gut microbiota, raising the question of the relevance of the keto diet in gastrointestinal disease.

Adding Value to Waste Minerals in a Circular Economy Framework: Ochre-Derived Layered Double Hydroxide Catalysts in Fatty Acid Ketonisation

Transforming waste materials into added-value products is critical for a sustainable and circular economy. Here, Mg/Fe layered double hydroxide (LDH) materials, with a Mg2+:Fe3+ ratio of 2, were successfully synthesized via the co-precipitation method from a dissolved acid mine drainage precipitate waste “ochre”, which is normally put to landfill. The prepared LDH materials were tested as a heterogeneous base catalyst to promote the production of the ketone, 12-tricosanone, from lauric acid, a component of plant oils, through a ketonic decarboxylation reaction, giving a circular economy route to catalysts for sustainable ketone production. The highest yield of the ketone observed was 80%.

In Vitro Metabolic Profile Elucidation of Synthetic Cannabinoid APP-CHMINACA (PX-3).

Indazole carboxamide synthetic cannabinoids remain the most prevalent subclass of new psychoactive substances (NPS) reported internationally. However, the metabolic and pharmacological properties of many of these compounds remain unknown. Elucidating these characteristics allows members of the clinical and forensic communities to identify causative agents in patient samples, as well as render conclusions regarding their toxic effects. This work presents a detailed report on the in vitro phase I metabolism of indazole carboxamide synthetic cannabinoid APP-CHMINACA (PX-3). Incubation of APP-CHMINACA with human liver microsomes, followed by analysis of extracts via high-resolution mass spectrometry, yielded 12 metabolites, encompassing 7 different metabolite classes. Characterization of the metabolites was achieved by evaluating the product ion spectra, accurate mass and chemical formula generated for each metabolite. The predominant biotransformations observed were hydrolysis of the distal amide group and hydroxylation of the cyclohexylmethyl (CHM) substituent. Nine metabolites were amide hydrolysis products, of which five were monohydroxylated, one dihydroxylated and two were ketone products. The metabolites in greatest abundance in the study were products of amide hydrolysis with no further biotransformation (M1), followed by amide hydrolysis with monohydroxylation (M2.1). Three APP-CHMINACA-specific metabolites were generated, all of which were hydroxylated on the CHM group; one mono-, di- and tri-hydroxylated metabolite each was produced, with dihydroxylation (M6) present in the greatest abundance. The authors propose that metabolites M1, M2.1 and M6 are the most appropriate markers to determine consumption of APP-CHMINACA. The methods used in the current study have broad applicability and have been used to determine the in vitro metabolic profiles of multiple synthetic cannabinoids and other classes of NPS. This research can be used to guide analytical scientists in method development, synthesis of reference material, pharmacological testing of proposed metabolites and prediction of metabolic processes of compounds yet to be studied.

Ketone body metabolism in diabetic and non-diabetic heart failure.

Heart failure (HF) is one of the most common cardiovascular diseases, causing large disease and economic burden worldwide. Impaired metabolic balance has been confirmed as a significant aspect of HF, and alteration of substrate utilization plays a vital role in the development of HF. Diabetes mellitus is strictly related with HF, and patients with diabetes show a higher mortality and morbidity of HF. Furthermore, HF patients and animals with diabetes behave different characteristics of metabolic pattern and substrate utilization comparing to those without diabetes. Recently, ketone body has been demonstrated as an alternative energy source in HF, which may improve myocardial energy supply and thus be adaptive for HF. Studies measured ketone body oxidation and production of ketone body metabolism in different groups of patients and animal models. This review focuses on the alteration of ketone body metabolism during HF and compares different results between diabetic and non-diabetic HF and the potential mechanism.

1422 Pancreatogenic Diabetes (Type 3C) Presenting With Diabetic Ketoacidosis

INTRODUCTION: Diabetes type 3c (DM3c) accounts for 5% of diabetics in the US. It is due to chronic pancreatitis leading to the destruction of islet cells. Glucagon and insulin levels are both decreased due to destruction of alpha and beta cells, respectively. This makes the development of diabetic ketoacidosis (DKA) a rare occurance in these patients, as glucagon is one of the key hormones in the production of ketone bodies. We report a case of Type 3C diabetes presenting with DKA. CASE DESCRIPTION/METHODS: A 50-year-old male with chronic alcoholic pancreatitis s/p pseudocyst drainage presented to the ED complaining of epigastric pain for two months. The patient was on oxycodone for pain control and pancreatic enzymes. V/S: BP 100/92, HR 94, RR 16, and O2 sat 97%. Physical exam was notable for epigastric tenderness. Prior imaging studies revealed diffuse pancreatic calcifications. Cardiac enzymes were normal and lipase level was 156. Blood glucose level was notably elevated at 703. Other lab abnormalities included serum bicarbonate of 16, ketones in the urine and acetone in the blood, anion gap of 27 and HbA1C of 16% (prior values were normal). The patient was admitted to the medical ICU for management of DKA. He was started on IV fluids and IV insulin. An autoimmune workup for diabetes was negative. Once anion gap closed, patient was transitioned to SC insulin and subsequently discharged. DISCUSSION: DM3c involves inflammation of the pancreatic islet cells with irreversible fibrotic changes, due to the underlying chronic pancreatitis. Early on, the beta cells and the pancreatic polypeptide cells are affected, but as the disease progresses, glucagon secreting alpha cells are destroyed, making it rare for these patients to present in DKA. However, an upregulation of cortisol, growth hormone and catecholamines make ketone production possible. Due to exocrine pancreatic deficiency, incretin secretory function is lost; thus pancreatic enzyme supplementation can be beneficial for glycemic control. Diagnosing DM3c requires imaging evidence of chronic pancreatitis, pancreatic exocrine insufficiency, glucose intolerance and absence of type 1 DM autoimmune markers. Recognition of DM3c is essential for optimal management of these patients.

Effect of Empagliflozin on Free Fatty Acids and Ketone Bodies in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial.

We report a randomized, double-blind, placebo-controlled, 4-week study to investigate the effect of empagliflozin on free fatty acids and blood ketone bodies in Japanese patients with type 2 diabetes mellitus. Patients (baseline mean [standard deviation] glycated hemoglobin 7.91% [0.80%]; body mass index 24.3 [3.2] kg/m2) were randomized to empagliflozin 10mg (n = 20), empagliflozin 25mg (n = 19), or placebo (n = 21) daily as monotherapy for 28days. Meal tolerance tests (MTTs; breakfast, lunch, dinner) were performed on day - 1, day 1 (first day of treatment), and day 28. On day 1 and day 28, study drug was administered 1h before breakfast. Free fatty acids and blood ketone bodies were measured before and 1, 2, and 3h after each MTT, and the next morning (overnight fast). Empagliflozin significantly reduced plasma glucose and insulin and reduced body weight vs. placebo. Empagliflozin increased free fatty acids and total ketones bodies at day 1 and day 28. At day 28, the adjusted mean (95% confidence interval) difference vs. placebo in the time-corrected area under curve over 24h for total ketone bodies was 67.1 (12.3, 121.8) µmol·h/L·h (P = 0.017) with empagliflozin 10mg and 178.1 (123.9, 232.2) µmol·h/L·h (P < 0.001) with empagliflozin 25mg. Increases in ketones with empagliflozin vs. placebo peaked just before and declined after meals, with the highest peak before breakfast. Changes in total ketone bodies appeared to be associated with changes in plasma glucose, insulin, and free fatty acids. Empagliflozin modestly increased free fatty acids and blood ketone bodies after a single dose and 28days' treatment. Increases in ketones appeared to be related to the duration of fasting and were most pronounced before breakfast. Increases in ketones appeared to be associated with changes in well-known metabolic determinants of ketone production. ClinicalTrials.gov identifier, NCT01947855. Boehringer Ingelheim & Eli Lilly and Company.

Iron-Catalyzed Ligand Free α-Alkylation of Methylene Ketones and β-Alkylation of Secondary Alcohols Using Primary Alcohols.

Herein, we demonstrate a general and broadly applicable catalytic cross coupling of methylene ketones and secondary alcohols with a series of primary alcohols to disubstituted branched ketones. A simple and nonprecious Fe2(CO)9 catalyst enables one-pot oxidations of both primary and secondary alcohols to a range of branched gem-bis(alkyl) ketones. A number of bond activations and formations selectively occurred in one pot to provide the ketone products. Coupling reactions can be performed in gram scale and successfully applied in the synthesis of an Alzehimer's drug. Alkylation of a steroid hormone can be achieved. A single catalyst enables sequential one-pot double alkylation to bis-hetero aryl ketones using two different alcohols. Preliminary mechanistic studies using an IR probe, deuterium labeling, and kinetic experiments established the participation of a borrowing-hydrogen process using Fe catalyst, and the reaction produces H2 and H2O as byproducts.

Lewis Base/Brønsted Acid Co-catalyzed Enantioselective Sulfenylation/Semipinacol Rearrangement of Di- and Trisubstituted Allylic Alcohols.

An enantioselective sulfenylation/semipinacol rearrangement of 1,1-disubstituted and trisubstituted allylic alcohols was accomplished with a chiral Lewis base and a chiral Brønsted acid as cocatalysts, generating various β-arylthio ketones bearing an all-carbon quaternary center in moderate to excellent yields and excellent enantioselectivities. These chiral arylthio ketone products are common intermediates with many applications, for example, in the design of new chiral catalysts/ligands and the total synthesis of natural products. Computational studies (DFT calculations) were carried out to explain the enantioselectivity and the role of the chiral Brønsted acid. Additionally, the synthetic utility of this method was exemplified by an enantioselective total synthesis of (-)-herbertene and a one-pot synthesis of a chiral sulfoxide and sulfone.