One-pot multicomponent coupling methods for the synthesis of diastereo- and enantioenriched (Z)-trisubstituted allylic alcohols.

(Z)-trisubstituted allylic alcohols are widespread structural motifs in natural products and biologically active compounds but are difficult to directly prepare. Introduced herein is a general one-pot multicomponent coupling method for the synthesis of (Z)-alpha,alpha,beta-trisubstituted allylic alcohols. (Z)-trisubstituted vinylzinc reagents are formed in situ by initial hydroboration of 1-bromo-1-alkynes. Addition of dialkylzinc reagents induces a 1,2-metalate rearrangement that is followed by a boron-to-zinc transmetalation. The resulting vinylzinc reagents add to a variety of prochiral aldehydes to produce racemic (Z)-trisubstituted allylic alcohols. When enantioenriched aldehyde substrates are employed, (Z)-trisubstituted allylic alcohols are isolated with high dr (>20:1 in many cases). For example, vinylation of enantioenriched benzyl-protected alpha- and beta-hydroxy propanal derivatives furnished the expected anti-Felkin addition products via chelation control. Surprisingly, silyl-protected alpha-hydroxy aldehydes also afford anti-Felkin addition products. A protocol for the catalytic asymmetric addition of (Z)-trisubstituted vinylzinc reagents to prochiral aldehydes with a (-)-MIB-based catalyst has also been developed. Several additives were investigated as inhibitors of the Lewis acidic alkylzinc halide byproducts, which promote the background reaction to form the racemate. Alpha-ethyl and alpha-cyclohexyl (Z)-trisubstituted allylic alcohols can now be synthesized with excellent levels of enantioselectivity in the presence of diamine inhibitors.

Addition/oxidative rearrangement of 3-furfurals and 3-furyl imines: new approaches to substituted furans and pyrroles.

Furans and pyrroles are important synthons in chemical synthesis and are commonly found in natural products, pharmaceutical agents, and materials. Introduced herein are three methods to prepare 2-substituted 3-furfurals starting from 3-furfural, 3-bromofuran, and 3-vinylfurans. Addition of a variety of organolithium, Grignard, and organozinc reagents (M-R) to 3-furfural provides 3-furyl alcohols in high yields. Treatment of these intermediates with NBS initiates a novel oxidative rearrangement that results in the installation of the R group in the 2 position of the 2-substituted 3-furfurals. Likewise, metalation of 3-bromofuran with n-BuLi and addition to benzaldehyde provides a furyl alcohol that is converted to 2-phenyl 3-furfural upon oxidative rearrangement. Enantioenriched disubstituted furans can be prepared starting with the Sharpless asymmetric dihydroxylation of 3-vinylfurans. The resulting enantioenriched diols undergo the oxidative rearrangement to furnish enantioenriched 2-substituted 3-furfurals with excellent transfer of asymmetry. This later method has been applied to the enantioselective preparation of an intermediate in Honda's synthesis of the natural product (-)-canadensolide. Mechanistic studies involving deuterium-labeled furyl alcohol suggest that the oxidative rearrangement proceeds through an unsaturated 1,4-dialdehyde intermediate. The alcohol then cyclizes onto an aldehyde, resulting in the elimination of water and rearomatization. On the basis of this proposed mechanism, we found that 3-furyl imines undergo the addition of organometallic reagents to provide furyl sulfonamides. Under the oxidative rearrangement conditions, 2-substituted 3-formyl pyrroles are formed, providing a novel route to these heterocycles. In contrast to the metalation of heterocycles, which often lead to mixtures of regioisomeric products, these new oxidative rearrangements of furyl alcohols and furyl sulfonamides generate only one regioisomer in each case.

Field Evaluations of Tracking/Locating Technologies for Prevention of Missing Incidents.

BACKGROUND: Persons with dementia are at risk of a missing incident, which is defined as an instance in which a demented person's whereabouts are unknown to the caregiver and the individual is not in an expected location. Since it is critical to determine the missing person's location as quickly as possible, we evaluated whether commercially available tracking technologies can assist in a rapid recovery. METHODS: This study examined 7 commercially available tracking devices: 3 radio frequency (RF) based and 4 global positioning system (GPS) based, employing realistic tracking scenarios. Outcome measures were time to discovery and degree of deviation from a straight intercept course. RESULTS/CONCLUSION: Across all scenarios tested, GPS devices were found to be approximately twice as efficient as the RF devices in locating a "missing person." While the RF devices showed reasonable performance at close proximity, the GPS devices were found to be more appropriate overall for tracking/locating missing persons over unknown and larger distances.

Pressure ulcer risk of patient handling sling use.

Patient handling slings and lifts reduce the risk of musculoskeletal injuries for healthcare providers. However, no published evidence exists of their safety with respect to pressure ulceration for vulnerable populations, specifically persons with spinal cord injury, nor do any studies compare slings for pressure distribution. High-resolution interface pressure mapping was used to describe and quantify risks associated with pressure ulceration due to normal forces and identify at-risk anatomical locations. We evaluated 23 patient handling slings with 4 nondisabled adults. Sling-participant interface pressures were recorded while participants lay supine on a hospital bed and while suspended during typical patient transfers. Sling-participant interface pressures were greatest while suspended for all seated and supine slings and exceeded 200 mm Hg for all seated slings. Interface pressures were greatest along the sling seams (edges), regardless of position or sling type. The anatomical areas most at risk while participants were suspended in seated slings were the posterior upper and lower thighs. For supine slings, the perisacral area, ischial tuberosities, and greater trochanters were most at risk. The duration of time spent in slings, especially while suspended, should be limited.

Generation and reactions of Pentacyclo[4.3.0.0(2,4).0(3,8).0(5,7)]non-4-ene.

The highly pyramidalized alkene, pentacyclo[4.3.0.0(2,4).0(3,8).0(5,7)]non-4-ene (9), has been generated via treatment of 4,5-diiodopentacyclo[4.3.0.0(2,4).0(3,8).0(5,7)]nonane (12) with n-butyllithium and tert-butyllithium. The title alkene has also been trapped as its Diels-Alder adduct with 1,3-diphenylisobenzofuran, 2,5-dimethylfuran, and spiro[2.4]hepta-4,6-diene. Products resulting from alkyllithium addition to the pyramidalized double bond of 9 have been isolated and fully characterized spectroscopically. The geometry, olefin strain energy, heat of hydrogenation, and relative HOMO/LUMO energies of 9 have been obtained by ab initio calculations at the MP2 and B3LYP levels using the 6-31G* basis set.