Practical Synthesis of Terminal Vinyl Fluorides.

The synthesis of di- and trisubstituted vinyl fluorides with high isomeric purity remains a challenge for organic synthesis. While many methods exist to access these compounds, the separation of the desired isomer from the minor isomer and/or starting materials often is difficult. Herein, we report a practical method to access di- and trisubstituted vinyl fluorides via a selective Horner-Wadsworth-Emmons olefination/hydrolysis, which provides crystalline 2-fluoroacrylic acids in high (>98%) E-isomeric purity. A subsequent silver-catalyzed stereoretentive decarboxylation provides the title substances with high isomeric purity and without the need for tedious chromatography to remove the minor isomer. The process was amenable to a variety of aldehydes and ketones and provided a diverse array of di- and trisubstituted vinyl fluorides. The sequence was applied to the synthesis of antibacterial and anti-inflammatory compounds.

Effects of Ving Tsun sticking-hand training on upper-limb sensorimotor performance in community-dwelling middle-aged and older adults: A randomized controlled trial.

OBJECTIVE: To evaluate the effects of Ving Tsun (VT) sticking-hand training on upper-limb joint position sense and muscular performance in community-dwelling middle-aged and older adults. METHODS: Thirty-three adults were randomly allocated to either a VT group or a control group. The VT group received VT sticking-hand training twice per week for 3 months. Measurements were taken before and after the intervention period. The primary outcome was elbow-joint repositioning error, which was measured by an elbow-joint passive positioning and active repositioning test using a universal goniometer. Secondary outcomes were upper-limb muscles' peak force and time taken to reach peak force as measured by a hand-held dynamometer. RESULTS: No significant time, group or time-by-group interaction effects were found for elbow-joint repositioning error or upper-limb muscle peak force outcomes. Shoulder flexor time to peak force decreased by 33.8% from pre-test to post-test in the VT group (P = 0.007). Shoulder abductor, internal and external rotator, and elbow extensor times to peak force decreased by 30.0%-35.9% in the VT group (P < 0.05) and by 30.4%-37.1% in the control group (P < 0.05). CONCLUSIONS: VT sticking-hand training does not improve elbow-joint position sense or the maximum strength of upper-limb muscles in middle-aged and older adults. However, VT can improve shoulder flexor muscles' time to reach peak force in these populations. VT had no obvious effect on the time required to reach peak force in other shoulder muscles and elbow extensors.

A versatile catalyst system for enantioselective synthesis of 2-substituted 1,4-benzodioxanes.

We report the synthesis of enantiomerically enriched 1,4-benzodioxanes containing alkyl, aryl, heteroaryl, and/or carbonyl substituents at the 2-position. The starting 1,4-benzodioxines were readily synthesized via ring closing metathesis using an efficient nitro-Grela catalyst at ppm levels. Excellent enantioselectivities of up to 99:1 er were obtained by using the versatile catalyst system [Ir(cod)Cl]2/BIDIME-dimer in the asymmetric hydrogenation of 2-substituted 1,4-benzodioxines. Furthermore, DFT calculations reveal that the selectivity of the process is controlled by the protonation step; and coordinating groups on the substrate may alter the interaction with the catalyst, resulting in a change in the facial selectivity.

Copper-catalyzed asymmetric hydrogenation of 2-substituted ketones via dynamic kinetic resolution.

A new class of tunable heterophosphole dimeric ligands have been designed and synthesized. These ligands have enabled the first examples of Cu-catalyzed hydrogenation of 2-substituted-1-tetralones and related heteroaryl ketones via dynamic kinetic resolution, simultaneously creating two contiguous stereogenic centers with up to >99 : 1 dr and 98 : 2 er. The ligand-Cu complexes were isolated and characterized by single crystal X-ray, and DFT calculations revealed a novel heteroligated dimeric copper hydride transition state.

Bone Mineral Density, Balance Performance, Balance Self-Efficacy, and Falls in Breast Cancer Survivors With and Without Qigong Training: An Observational Study.

PURPOSE: A deterioration in bone strength and balance performance after breast cancer treatment can result in injurious falls. Therefore, interventions need to be developed to improve the bone strength and balance ability of breast cancer survivors. This cross-sectional exploratory study aimed to compare the bone mineral density (BMD), balance performance, balance self-efficacy, and number of falls between breast cancer survivors who practiced qigong, breast cancer survivors who did not practice qigong, and healthy individuals. METHODS: The study included 40 breast cancer survivors with more than 3 months of qigong experience, 17 breast cancer survivors with no qigong experience, and 36 healthy controls. All the participants underwent dual-energy X-ray absorptiometry scans to measure their lumbar spine, total hip, femoral neck, and total radius BMDs. The participants also underwent a timed one-leg stand test to measure their single-leg standing balance. The participants' balance self-efficacy was assessed using the activities-specific balance confidence scale, and the number of falls experienced by each participant was assessed in a face-to-face interview. RESULTS: The lumbar spine, total hip, femoral neck, and total radius BMDs were similar between the 3 groups ( P > .05). The breast cancer-qigong group outperformed the breast cancer-control group by 27.3% when they performed the one-leg stand test on a foam surface ( P = .025), and they also had a higher balance self-efficacy score ( P = .006). Nevertheless, the numbers of falls were comparable between the 3 groups ( P > .05). CONCLUSION: Qigong may be a suitable exercise for improving the balance performance and balance self-efficacy of breast cancer survivors.

Total Synthesis of (±)-Phomoidride†D.

Described herein is a synthetic strategy for the total synthesis of (±)-phomoidride D. This highly efficient and stereoselective approach provides rapid assembly of the carbocyclic core by way of a tandem phenolic oxidation/intramolecular Diels-Alder cycloaddition. A subsequent SmI2 -mediated cyclization cascade delivers an isotwistane intermediate poised for a Wharton fragmentation that unveils the requisite bicyclo[4.3.1]decene skeleton and sets the stage for synthesis completion.

Balance Performance in Irradiated Survivors of Nasopharyngeal Cancer with and without Tai Chi Qigong Training.

This cross-sectional exploratory study aimed to compare the one-leg-stance time and the six-minute walk distance among TC Qigong-trained NPC survivors, untrained NPC survivors, and healthy individuals. Twenty-five survivors of NPC with TC Qigong experience, 27 survivors of NPC without TC Qigong experience, and 68 healthy individuals formed the NPC-TC Qigong group, NPC-control group, and healthy-control group, respectively. The one-leg-stance (OLS) timed test was conducted to assess the single-leg standing balance performance of the participants in four conditions: (1) standing on a stable surface with eyes open, (2) standing on a compliant surface with eyes open, (3) standing on a stable surface with eyes closed, and (4) standing on a compliant surface with eyes closed. The six-minute walk test (6MWT) was used to determine the functional balance performance of the participants. Results showed that the NPC-control group had a shorter OLS time in all of the visual and supporting surface conditions than the healthy control group (P < 0.05). The OLS time of the TC Qigong-NPC group was comparable to that of the healthy control group in the somatosensory-challenging condition (condition 3) (P = 0.168) only. Additionally, there was no significant difference in the 6MWT distance among the three groups (P > 0.05). TC Qigong may be a rehabilitation exercise that improves somatosensory function and OLS balance performance among survivors of NPC.

Effects of a 6-month Tai Chi Qigong program on arterial hemodynamics and functional aerobic capacity in survivors of nasopharyngeal cancer.

PURPOSE: Survivors of nasopharyngeal cancer (NPC) often sustain cardiovascular complications after conventional cancer treatments. Tai Chi (TC) Qigong training may be a viable way to improve peripheral circulatory status and aerobic capacity in this population. The objective of this study was to evaluate the effects of a 6-month TC Qigong training program on blood flow velocities and resistance, palmar skin temperature, and functional aerobic capacity in survivors of NPC. METHODS: Twenty-five and 27 survivors of NPC volunteered to join the intervention group (mean age, 55.4 ± 7.5 years) and control group (mean age, 58.7 ± 9.5 years), respectively. The intervention group underwent a TC Qigong training program-the modified 18 Forms TC Internal Qigong-for 6 months, while the control group received no training. Peripheral arterial blood flow velocities and resistance, palmar skin temperature, and functional aerobic capacity were measured by a Doppler ultrasound machine, an infrared thermometer, and six-minute walk test, respectively. All outcomes were assessed at baseline, mid-intervention (3-month), post-intervention (6-month), and follow-up (12-month) periods. RESULTS: The TC Qigong group had higher diastolic blood flow velocity (p = 0.010), lower arterial blood flow resistance (p = 0.009), and higher palmar skin temperature (p = 0.004) than the control group after TC Qigong training. However, only the diastolic blood flow velocity was higher in the TC Qigong group than in the control group during the no-training follow-up period (p = 0.032). Additionally, an improvement in functional aerobic capacity was found in the intervention group after TC Qigong training (p < 0.008) but not in the control group over time (p > 0.008). CONCLUSIONS: TC Qigong training may improve peripheral circulatory status and functional aerobic capacity among people treated for NPC. However, this is only a pilot study and future definitive trials are needed to confirm the results. IMPLICATIONS FOR CANCER SURVIVORS: TC Qigong may have enormous potential as a rehabilitation intervention for survivors of NPC to improve arterial hemodynamics and functional aerobic capacity.

Ruthenium-catalyzed reductive coupling of 1,3-enynes and aldehydes by transfer hydrogenation: anti-diastereoselective carbonyl propargylation.

Under the conditions of ruthenium-catalyzed transfer hydrogenation employing isopropanol as a source of hydrogen, isopropoxy-substituted enyne 1 b and aldehydes 3 a-3 l engage in reductive coupling to provide products of propargylation 4 a-4 l with good to complete levels of anti-diastereoselectivity. The unprotected tertiary hydroxy moiety of isopropoxy enyne 1 b is required to enforce diastereoselectivity. Deuterium-labeling studies corroborate reversible enyne hydrometalation in advance of carbonyl addition. As demonstrated in the conversion of 4 f-h and 4 k to 5 f-h and 5 k, the isopropoxy group of the product is readily cleaved upon exposure to aqueous sodium hydroxide to reveal the terminal alkyne.

Direct, redox-neutral prenylation and geranylation of secondary carbinol C-H bonds: C4-regioselectivity in ruthenium-catalyzed C-C couplings of dienes to α-hydroxy esters.

The ruthenium catalyst generated in situ from Ru(3)(CO)(12) and tricyclohexylphosphine, PCy(3), promotes the redox-neutral C-C coupling of aryl-substituted α-hydroxy esters to isoprene and myrcene at the diene C4-position, resulting in direct carbinol C-H prenylation and geranylation, respectively. This process enables direct conversion of secondary to tertiary alcohols in the absence of stoichiometric byproducts or premetalated reagents, and is the first example of C4-regioselectivity in catalytic C-C couplings of 2-substituted dienes to carbonyl partners. Mechanistic studies corroborate a catalytic cycle involving diene-carbonyl oxidative coupling.

Alkyne-aldehyde reductive C-C coupling through ruthenium-catalyzed transfer hydrogenation: direct regio- and stereoselective carbonyl vinylation to form trisubstituted allylic alcohols in the absence of premetallated reagents.

Nonsymmetric 1,2-disubstituted alkynes engage in reductive coupling to a variety of aldehydes under the conditions of ruthenium-catalyzed transfer hydrogenation by employing formic acid as the terminal reductant and delivering the products of carbonyl vinylation with good to excellent levels of regioselectivity and with complete control of olefin stereochemistry. As revealed in an assessment of the ruthenium counterion, iodide plays an essential role in directing the regioselectivity of C-C bond formation. Isotopic labeling studies corroborate reversible catalytic propargyl C-H oxidative addition in advance of the C-C coupling, and demonstrate that the C-C coupling products do not experience reversible dehydrogenation by way of enone intermediates. This transfer hydrogenation protocol enables carbonyl vinylation in the absence of stoichiometric metallic reagents.

Amplification of anti-diastereoselectivity via Curtin-Hammett effects in ruthenium-catalyzed hydrohydroxyalkylation of 1,1-disubstituted allenes: diastereoselective formation of all-carbon quaternary centers.

Under the conditions of ruthenium-catalyzed transfer hydrogenation, 1,1-disubstituted allenes 1a-c and alcohols 2a-g engage in redox-triggered generation of allylruthenium-aldehyde pairs to form products of hydrohydroxyalkylation 3a-g, 4a-g, and 5a-g with complete branched regioselectivity. By exploiting Curtin-Hammett effects, good to excellent levels of anti-diastereoselectivity (4:1 to >20:1) are obtained. Thus, all carbon quaternary centers are formed in a diastereoselective fashion upon carbonyl addition from the alcohol oxidation level in the absence of premetalated nucleophiles or stoichiometric byproducts. Exposure of allene 1b to equimolar quantities of alcohol 2a and aldehyde 6b under standard reaction conditions delivers adducts 4a and 4b in a 1:1 ratio. Similarly, exposure of allene 1b to equimolar quantities of aldehyde 6a and alcohol 2b provides adducts 4a and 4b in an identical equimolar ratio. Exposure of allene 1b to d(2)-p-nitrobenzyl alcohol, deuterio-2a, under standard reaction conditions delivers the product of hydrohydroxyalkylation, deuterio-4a, which incorporates deuterium at the carbinol position (>95% (2)H) and the interior vinylic position (34% (2)H). Competition experiments involving exposure of allene 1b to equimolar quantities of benzylic alcohols 2a and deuterio-2a reveal no significant kinetic effect. The collective data corroborate rapid, reversible alcohol dehydrogenation, allene hydrometalation, and (E)-, (Z)-isomerization of the transient allylruthenium in advance of turnover-limiting carbonyl addition. Notably, analogous allene-aldehyde reductive C-C couplings employing 2-propanol as the terminal reductant display poor levels of anti-diastereoselectivity, suggesting that carbonyl addition is not turnover-limiting in reactions conducted from the aldehyde oxidation level.

Hydroacylation of 2-Butyne from the Alcohol or Aldehyde Oxidation Level via Ruthenium Catalyzed C-C Bond Forming Transfer Hydrogenation.

Under the conditions of ruthenium catalyzed transfer hydrogenation, 2-butyne couples to alcohols 1a-1j to deliver alpha,beta-unsaturated ketones 3a-3j in good to excellent isolated yields with complete E-stereoselectivity. Under identical conditions, aldehydes 2a-2j couple to 2-butyne to provide an identical set of alpha,beta-unsaturated ketones 3a-3j in good to excellent isolated yields with complete E-stereoselectivity. Nonsymmetric alkyne 4a couples to alcohol 1d or aldehyde 2d in good yield to deliver enone 3k as a 5:1 mixture of regioisomers. Thus, intermolecular alkyne hydroacylation is achieved from the alcohol or aldehyde oxidation level. In earlier studies employing the same ruthenium catalyst under slightly different conditions, alkynes were coupled to carbonyl partners from the alcohol or aldehyde oxidation level to furnish allylic alcohols. Therefore, under the conditions of C-C bond forming transfer hydrogenation, all oxidation levels of substrate (alcohol or aldehyde) and product (allylic alcohol or alpha,beta-unsaturated ketone) are accessible.