6 research outputs found
Nonacene Generated by On-Surface Dehydrogenation
The
on-surface synthesis of nonacene has been accomplished by dehydrogenation
of an air-stable partially saturated precursor, which could be aromatized
by using a combined scanning tunneling and atomic force microscope
as well as by on-surface annealing. This transformation allowed the
in-detail analysis of the electronic properties of nonacene molecules
physisorbed on Au(111) by scanning tunneling spectroscopy measurements.
The spatial mapping of molecular orbitals was corroborated by density
functional theory calculations. Furthermore, the thermally induced
dehydrogenation uncovered the isomerization of intermediate dihydrononacene
species, which allowed for their in-depth structural and electronic
characterization
Development of a Scalable, Chromatography-Free Synthesis of <i>t</i>‑Bu-SMS-Phos and Application to the Synthesis of an Important Chiral CF<sub>3</sub>‑Alcohol Derivative with High Enantioselectivity Using Rh-Catalyzed Asymmetric Hydrogenation
A chromatography-free,
asymmetric synthesis of the C2-symmetric
P-chiral diphosphine <i>t</i>-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%)
Process Development of the BACE Inhibitors BI 1147560 BS and BI 1181181 MZ
The development of large-scale syntheses of two beta-site
amyloid
precursor protein cleaving enzyme (BACE) inhibitors is described.
New methodologies were discovered to overcome safety and scalability
problems with existing procedures. The sterically hindered quaternary,
neopentyl stereocenter was formed in high diastereoselectivity by
the addition of a carbamoyl anion to an N-sulfinyl
ketimine. An aryl nitrile was installed by a palladium- and cyanide-free
electrophilic cyanation affected by transnitrilation of an arylmagnesium
derivative with dimethylmalononitrile. A safe route to an oxetanylmethylamine
side chain was devised based on diethyl malonate and dibenzylamine
starting materials. A mild enamine fluorination was developed for
the synthesis of a fluoroisobutylamine side chain
Process Development of the BACE Inhibitors BI 1147560 BS and BI 1181181 MZ
The development of large-scale syntheses of two beta-site
amyloid
precursor protein cleaving enzyme (BACE) inhibitors is described.
New methodologies were discovered to overcome safety and scalability
problems with existing procedures. The sterically hindered quaternary,
neopentyl stereocenter was formed in high diastereoselectivity by
the addition of a carbamoyl anion to an N-sulfinyl
ketimine. An aryl nitrile was installed by a palladium- and cyanide-free
electrophilic cyanation affected by transnitrilation of an arylmagnesium
derivative with dimethylmalononitrile. A safe route to an oxetanylmethylamine
side chain was devised based on diethyl malonate and dibenzylamine
starting materials. A mild enamine fluorination was developed for
the synthesis of a fluoroisobutylamine side chain
Process Development of the BACE Inhibitors BI 1147560 BS and BI 1181181 MZ
The development of large-scale syntheses of two beta-site
amyloid
precursor protein cleaving enzyme (BACE) inhibitors is described.
New methodologies were discovered to overcome safety and scalability
problems with existing procedures. The sterically hindered quaternary,
neopentyl stereocenter was formed in high diastereoselectivity by
the addition of a carbamoyl anion to an N-sulfinyl
ketimine. An aryl nitrile was installed by a palladium- and cyanide-free
electrophilic cyanation affected by transnitrilation of an arylmagnesium
derivative with dimethylmalononitrile. A safe route to an oxetanylmethylamine
side chain was devised based on diethyl malonate and dibenzylamine
starting materials. A mild enamine fluorination was developed for
the synthesis of a fluoroisobutylamine side chain
Process Development of the BACE Inhibitors BI 1147560 BS and BI 1181181 MZ
The development of large-scale syntheses of two beta-site
amyloid
precursor protein cleaving enzyme (BACE) inhibitors is described.
New methodologies were discovered to overcome safety and scalability
problems with existing procedures. The sterically hindered quaternary,
neopentyl stereocenter was formed in high diastereoselectivity by
the addition of a carbamoyl anion to an N-sulfinyl
ketimine. An aryl nitrile was installed by a palladium- and cyanide-free
electrophilic cyanation affected by transnitrilation of an arylmagnesium
derivative with dimethylmalononitrile. A safe route to an oxetanylmethylamine
side chain was devised based on diethyl malonate and dibenzylamine
starting materials. A mild enamine fluorination was developed for
the synthesis of a fluoroisobutylamine side chain