Synthesis, resolution, and applications of 2, 2'-bis(diphenylphosphino)-3,3'- binaphtho[2,1-b]furan

[structure: see text] A short five-step synthesis of (+/-)-2,2'-bis(diphenylphosphino)-3, 3'-binaphtho[2,1-b]furan (BINAPFu, 1) starting from 2-naphthoxyacetic acid is reported. The resolution of BINAPFu 1 was possible using our newly developed resolution procedure for phosphines wherein (1S)-camphorsulfonyl azide was used to prepare the bisphosphinimine of BINAPFu via the Staundinger reaction. BINAPFu consistently outperformed BINAP in an asymmetric Heck reaction between 2,3-dihydrofuran and phenyl triflate.     

Low temperature scanning force microscopy of the Si(111)-(7x7) surface

A low temperature scanning force microscope (SFM) operating in a dynamic mode in ultrahigh vacuum was used to study the Si(111)- (7x7) surface at 7.2 K. Not only the twelve adatoms but also the six rest atoms of the unit cell are clearly resolved for the first time with SFM. In addition, the first measurements of the short range chemical bonding forces above specific atomic sites are presented. The data are in good agreement with first principles computations and indicate that the nearest atoms in the tip and sample relax significantly when the tip is within a few A of the surface.     

Clarification of plasma from whole human blood using ultrasound

There has been interest for a number of years in the possibility of separating blood into cells and plasma by methods other than centrifugation, so that the plasma can be analysed on-line. Cells in whole blood normally occupy about 45% of the suspension volume. It has been shown with a number of different cell types, such as yeast and bacteria, that for concentrations of this order the cells are not as efficiently harvested by ultrasound as those for lower concentrations. In this study, removal of cells from 3-4 ml whole blood volumes has been examined in ultrasonic standing wave fields from tubular transducers driven at a frequency of 1.6 MHz. Samples of whole human blood (n = 11) from two volunteers have been processed by three tubular transducers where high levels of cell removal, 99.7% on average, have been demonstrated with high reproducibility between samples as well as for different transducers.     

Avoiding the classical resolution during the synthesis of MeO-BIPHEP and 3,3′-disubstituted derivatives

The Ullmann coupling of 1 (R = H) gives a 2:1 mixture of diastereomers 2 (R = H) in 81% yield that are easily separated by silica gel chromatography. This procedure avoids the generally cumbersome and sometimes difficult resolution step with DBTA. Similar Ullmann couplings and separation of the corresponding diastereomers are employed with other derivatives of 1 (R = OtBu, iPr, Ph, and mesityl) ultimately affording a new series of 3,3′-disubsituted-MeO-BIPHEP derivatives. The use of these new derivatives in palladium-catalyzed asymmetric Heck reaction, Pd-catalyzed polyene cyclizations and rhodium-catalyzed hydrogenations is also reported.     

Diastereospecific intramolecular Ullmann couplings: unique chiral auxiliary for the preparation of 3,3'-disubstituted MeO-BIPHEP derivatives

[reaction: see text] A chiral auxiliary is described that provides only one diastereomer during intramolecular Ullmann couplings. Treatment of five Ullmann coupling precursors with Cu powder in DMF at 115 degrees C provides 2,2',3,3',6,6'-hexasubstituted 1,1'-biphenyls as single diastereomers in yields ranging from 66% to 91%.     

Counter-current chromatography separation scaled up from an analytical column to a production column

An analytical separation was performed on an analytical J-type counter-current chromatography (CCC) instrument using a 5.4 ml column, with a 1 ml/min mobile phase flow rate. This separation had a resolution of 0.69 and was achieved in 10 min. The same separation was performed using two 2300 ml columns connected in series at a flow rate of 850 ml/min using a production scale J-type centrifuge. This production scale separation was also obtained in 10 min with a resolution of 0.71. This represents an 850 times increase in productivity. This paper presents these separations and the underlying scale up theory.     

Use of deuterium labeling studies to determine the stereochemical outcome of palladium migrations during an asymmetric intermolecular Heck reaction

A series of deuterium labeling experiments showed that Pd migrations during an intermolecular asymmetric Heck reaction between phenyl triflate and various deuterated 2,3-dihydrofurans (2b, 2c, 2d, 2e) occurs exclusively by either syn-1,2-dyotropic shifts or a syn-chain-walking mechanism; no evidence was observed to support anti-1,2-dyotropic shifts or anti-beta-H Pd eliminations during the formation of 6 and 7.