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A chromatography-free, asymmetric synthesis of the C2-symmetric P-chiral diphosphine t-Bu-SMS-Phos was developed using a chiral auxiliary-based approach in five steps from the chiral auxiliary in 36% overall yield. Separtion and recovery of the auxiliary were achieved with good yield (97%) to enable recycling of the chiral auxiliary. An air-stable crystalline form of the final ligand was identified to enable isolation of the final ligand by crystallization to avoid chromatography. This synthetic route was applied to prepare up to 4 kg of the final ligand. The utility of this material was demonstrated in the asymmetric hydrogenation of trifluoromethyl vinyl acetate at 0.1 mol % Rh loading to access a surrogate for the pharmaceutically relavent chiral trifluoroisopropanol fragment in excellent yield and enantiomeric excess (98.6%).

A practical and efficient synthesis of the FLAP inhibitor 1 was developed addressing multiple scale-up and safety concerns posed by the established synthesis and utilized a resolution strategy (replacing supercritical fluid chromatography (SFC) separation) for expedient access to the key structural component of 1: the challenging chiral quaternary center. Also highlighted are in situ IR monitoring, condensation to form the 1,2,4-oxadiazole ring, and an efficient Suzuki-Miyaura coupling.

An efficient asymmetric synthesis of 11-β-HSD inhibitor 1 has been accomplished in five linear steps and 53% overall yield, starting from the readily available 3-chloro-1-phenylpropan-1-one. The key feature of the synthesis includes an asymmetric methallylation of 3-chloro-1-phenylpropan-1-one catalyzed by the highly effective organocatalyst (S)-3,3'-F2-BINOL under solvent-free and metal-free conditions.

A practical and cost-effective synthesis of (2-aminopyrimidin-5-yl) boronic acid 1b has been developed. Key features of the synthesis include the inexpensive in situ protection of the amine via bis-silylation using TMSCl followed by metal–halogen exchange using n-BuLi and trapping with B(Oi-Pr)3. The water-soluble boronic acid is isolated by a well-designed acid–base sequence providing the target in 80% yield and high purity for the two-step process. The large-scale (15 kg) implementation of a Suzuki–Miyaura borylation to form the pinacol boronic ester is also described.

A practical and efficient synthesis of a complex chiral atropisomeric HIV integrase inhibitor has been accomplished. The combination of a copper-catalyzed acylation along with the implementation of the BI-DIME ligands for a ligand-controlled Suzuki cross-coupling and an unprecedented bis(trifluoromethane)sulfonamide-catalyzed tert-butylation renders the synthesis of this complex molecule robust, safe, and economical. Furthermore, the overall synthesis was conducted in an asymmetric and diastereoselective fashion with respect to the imbedded atropisomer.

A chromatography-free, asymmetric synthesis of the C2-symmetric P-chiral diphosphine t-Bu-SMS-Phos was developed using a chiral auxiliary-based approach in five steps from the chiral auxiliary in 36% overall yield. Separtion and recovery of the auxiliary were achieved with good yield (97%) to enable recycling of the chiral auxiliary. An air-stable crystalline form of the final ligand was identified to enable isolation of the final ligand by crystallization to avoid chromatography. This synthetic route was applied to prepare up to 4 kg of the final ligand. The utility of this material was demonstrated in the asymmetric hydrogenation of trifluoromethyl vinyl acetate at 0.1 mol % Rh loading to access a surrogate for the pharmaceutically relavent chiral trifluoroisopropanol fragment in excellent yield and enantiomeric excess (98.6%).

A practical noncryogenic process for the Aggarwal stereospecific boronate rearrangement with chiral secondary benzylic carbamates has been developed. The use of LDA instead of sec-BuLi combined with an in situ trapping of the unstable lithiated carbamate was critical to success. Furthermore, this new process increased the substrate scope to include the versatile aryl iodide and bromide substrates. The methodology was applied to a diverse array of substrates and was demonstrated on multikilogram scale.

Reported herein is a safe and economical synthesis of methyl 6-chloro-5-(trifluoromethyl)nicotinate, an intermediate in the synthesis of novel anti-infective agents. The key to this process is the trifluoromethylation of an aryl iodide using an inexpensive methyl chlorodifluoroacetate (MCDFA)/KF/CuI system, with an emphasis on the development work which led to this effective process.

A one-pot process has been developed for the synthesis of 8-arylquinolines via Pd-catalyzed borylation of quinoline-8-yl halides and subsequent Suzuki-Miyaura coupling with aryl halides using n-BuPAd(2) as ligand. Yields of up to 98% were obtained.

An operationally simple copper-BINAP-catalyzed, highly enantioselective propargylation of ketones is presented. The methodology was developed as an enantioselective process for methyl ethyl ketone and shown to be applicable to a wide variety of prochiral ketones. The resulting homopropargyl adducts are versatile latent carbonyls from which γ-butyrolactones, β-hydroxy methyl ketones, and β-hydroxycarboxylates are readily obtained.

Although TARC is widely used in semiconductor photolithography processes, the understandings of TARC related defects are still far from completeness. In this paper, the root causes and corrective actions of TARC related circle defect were studied. The results showed that the circle defect was induced by TARC bubbles and could be significantly decreased or totaly removed by using several different treatments. Among these treatments, the optimization of TARC coating process by adjusting the spin speed at the final dry step displayed more attractive results. In addition, the TARC thickness, profile, uniformity as well as the related wafer CD (critical dimension) uniformity by applying the new TARC coating recipe were carefully checked and did not show any deterioration.

A practical sequence involving a noncryogenic stereospecific boronate rearrangement followed by a robust formylation with an in situ generated DCM anion has been developed for the asymmetric construction of an all-carbon quaternary stereogenic center of a FLAP inhibitor. The key boronate rearrangement was rendered noncryogenic and robust by using LDA as the base and instituting an in situ trapping of the unstable lithiated benzylic carbamate with the boronic ester. A similar strategy was implemented for the DCM formylation reaction. It was found that the 1,2-boronate rearrangement for the formylation reaction could be temperature-controlled, thus preventing overaddition of the DCM anion and rendering the process reproducible. The robust stereospecific boronate rearrangement and formylation were utilized for the practical asymmetric synthesis of a chiral quaternary FLAP inhibitor.

Sixty-one women with newly diagnosed locoregional breast cancer (T1-3, N0-1, M0) having an initial Body Mass Index (BMI) between 20 and 35 kg/m2 who were receiving standard adjuvant treatment (chemotherapy, tamoxifen, and/or radiation) were asked to avoid weight gain (if initial BMIor = 25 kg/m2) or to lose up to 10 kg (if initial BMI 25-35 kg/m2) over one year. Women participated in twenty group sessions (10 weekly, 10 monthly) which involved a psychological supportive-expressive group intervention supplemented by individual weight goals, and nutrition and exercise programs. Fifty-five non-censored women (5 developed recurrence, 1 died of a subarachnoid hemorrhage) lost a mean of 0.53 +/- 3.72 kg. Weight loss was greatest in initially overweight women (BMIor = 25 kg/m2) who lost 1.63 +/- 4.11 kg (p = 0.01 compared to normal weight women) and in those not receiving chemotherapy who lost 2.15 +/- 2.83 kg (p = 0.0004 compared to those receiving chemotherapy). 70.9% met predefined criteria for success. Aerobic exercise increased significantly during the intervention (p = 0.00005) and was the strongest predictor of success (OR 1.73 for each additional 30 minutes of exercise weekly, p = 0.003). Changes in caloric intake were not significant, but fat intake decreased and carbohydrate and fibre intake increased significantly during the intervention. Eating behavior and psychological status improved significantly. Thus, this multidisciplinary weight management intervention successfully prevented weight gain in women with newly diagnosed locoregional breast cancer, and helped overweight women lose weight.

(S)-3,3′-F2-BINOL has been synthesized for the first time and demonstrated as a highly active organocatalyst for asymmetric methallylation of ketones. Up to 98:2 enantioselectivity and 99% yield were obtained with 5 mol % catalyst loading. The catalyst (S)-3,3′-F2-BINOL could be easily recovered and reused.

Prochiral aliphatic ketones as well as acetophenones and heterocyclic analogues are propargylated by trimethylsilylpropargyl boronate under optimized conditions to give the corresponding homopropargylic tertiary alcohols in general with

The method provides a general and efficient approach to biologically important 8-arylquinolines.

The high prevalence of diabetes mellitus in North American aboriginal populations may be due to recent changes in lifestyle, including the adoption of a high-fat, low-fiber diet. To determine whether fat or fiber intakes were associated with new cases of diabetes, we studied 72% (728/1018) of residents aged > 9 y from a remote aboriginal community in northern Ontario using the 75-g oral-glucose-tolerance test and 24-h dietary recall. The mean fat intake of this population (36% of energy) was typical for North America, but fiber intake (1.2 g/MJ) was very low. Logistic-regression analysis, adjusted for age, sex, and body mass index, showed that a 1-SD increase in fiber intake reduced the risk of having diabetes by 39% (P = 0.026) whereas the same increase in protein intake increased the risk by 38% (P = 0.027). There was no significant effect of energy, fat, starch, or simple sugars. These data support Trowell's original dietary-fiber hypothesis that "... dietary fiber depleted starchy foods are conducive to the development of diabetes mellitus in susceptible human genotypes."

OBJECTIVE To determine the true prevalence of impaired glucose tolerance (IGT), NIDDM, and associated risk factors by age and sex in an isolated native community. RESEARCH DESIGN AND METHODS A community-wide prevalence survey using a 75-g oral glucose tolerance test (OGTT) was undertaken in the remote native reserve of Sandy Lake, Ontario, Canada. Measurements for obesity included waist-to-hip circumference, BMI, and percentage body fat. RESULTS A total of 728 individuals were enrolled, representing a community participation rate of 72%. The overall crude prevalence of NIDDM was 17.2% (18.1% females and 16.0% males) and increased to 26.1% overall (28.0% females and 24.2% males) when age-standardized. The prevalence of IGT was higher in females compared with males (age-standardized prevalence of 19.8 vs. 7.1%, respectively). Females had a higher prevalence of obesity, IGT, and NIDDM occurring at younger ages. Measures of obesity and fasting insulin levels were significantly associated with NIDDM in the 18–49 age-group. CONCLUSIONS The prevalence rates of NIDDM in this study population are the highest reported to date in a Canadian native population and among the highest reported in the world. Females appear to be at much higher risk of developing obesity, IGT, and NIDDM and at a younger age. Due to the high prevalence rates of IGT and NIDDM in this young population, there is urgent need to develop culturally appropriate community-based public health intervention programs before the long-term complications of diabetes have a devastating effect on the residents.