Copper-Catalyzed S_N2′-Selective Allylic Substitution Reaction of <i>gem</i>-Diborylalkanes

A Cu/(NHC)-catalyzed S_N2′-selective substitution reaction of allylic electrophiles with <i>gem</i>-diborylalkanes is reported. Different substituted <i>gem</i>-diborylalkanes and allylic electrophiles can be employed in this reaction, and various synthetic valuable functional groups can be tolerated. The asymmetric version of this reaction was initially researched with chiral N-heterocyclic carbene (NHC) ligands

Exploration of Biaryl Carboxylic Acids as Proton Shuttles for the Selective Functionalization of Indole C–H Bonds

A survey of diversely substituted 2-arylbenzoic acids were synthesized and tested for use as proton shuttle in the direct arylation of indoles with bromobenzenes. It was found that 3-ethoxy-2-phenylbenzoic acid gives superior yield and selectivity for this class of substrates

Data_Sheet_1_Clustering and prediction of disease progression trajectories in Huntington's disease: An analysis of Enroll-HD data using a machine learning approach.docx

IntroductionHuntington's disease (HD) is a rare neurodegenerative disease characterized by cognitive, behavioral and motor symptoms that progressively worsen with time. Cognitive and behavioral signs of HD are generally present in the years prior to a diagnosis; however, manifest HD is typically assessed by genetic confirmation and/or the presence of unequivocal motor symptoms. Nevertheless, there is a large variation in symptom severity and rate of progression among individuals with HD.MethodsIn this retrospective study, longitudinal natural history of disease progression was modeled in individuals with manifest HD from the global, observational Enroll-HD study (NCT01574053). Unsupervised machine learning (k-means; km3d) was used to jointly model clinical and functional disease measures simultaneously over time, based on one-dimensional clustering concordance such that individuals with manifest HD (N = 4,961) were grouped into three clusters: rapid (Cluster A; 25.3%), moderate (Cluster B; 45.5%) and slow (Cluster C; 29.2%) progressors. Features that were considered predictive of disease trajectory were then identified using a supervised machine learning method (XGBoost).ResultsThe cytosine adenine guanine-age product score (a product of age and polyglutamine repeat length) at enrollment was the top predicting feature for cluster assignment, followed by years since symptom onset, medical history of apathy, body mass index at enrollment and age at enrollment.ConclusionsThese results are useful for understanding factors that affect the global rate of decline in HD. Further work is needed to develop prognostic models of HD progression as these could help clinicians with individualized clinical care planning and disease management.</p

Copper-Catalyzed Cross-Coupling of Nonactivated Secondary Alkyl Halides and Tosylates with Secondary Alkyl Grignard Reagents

Practical catalytic cross-coupling of secondary alkyl electrophiles with secondary alkyl nucleophiles under Cu catalysis has been realized. The use of TMEDA and LiOMe is critical for the success of the reaction. This cross-coupling reaction occurs via an S_N2 mechanism with inversion of configuration and therefore provides a general approach for the stereocontrolled formation of C–C bonds between two tertiary carbons from chiral secondary alcohols

Copper-Catalyzed Cross-Coupling of Nonactivated Secondary Alkyl Halides and Tosylates with Secondary Alkyl Grignard Reagents

Practical catalytic cross-coupling of secondary alkyl electrophiles with secondary alkyl nucleophiles under Cu catalysis has been realized. The use of TMEDA and LiOMe is critical for the success of the reaction. This cross-coupling reaction occurs via an S_N2 mechanism with inversion of configuration and therefore provides a general approach for the stereocontrolled formation of C–C bonds between two tertiary carbons from chiral secondary alcohols

Copper-Catalyzed Cross-Coupling of Nonactivated Secondary Alkyl Halides and Tosylates with Secondary Alkyl Grignard Reagents

Practical catalytic cross-coupling of secondary alkyl electrophiles with secondary alkyl nucleophiles under Cu catalysis has been realized. The use of TMEDA and LiOMe is critical for the success of the reaction. This cross-coupling reaction occurs via an S_N2 mechanism with inversion of configuration and therefore provides a general approach for the stereocontrolled formation of C–C bonds between two tertiary carbons from chiral secondary alcohols

Stereoselective Synthesis of Monofluoroalkenylphosphine Oxides via Photoinduced Decarboxylative Coupling of α‑Fluoroacrylic Acids with P(O)H Compounds

Herein, a practical and efficient method for synthesizing monofluoroalkenyl phosphine oxides via photoinduced decarboxylative/dehydrogenative coupling of α-fluoroacrylic acids with phosphine oxides and phosphonates has been developed. Various α-fluoroacrylic acids and P(O)H compounds containing relevant functional groups, including tetrafluorobenzene and pentafluorobenzene, were converted into corresponding products with excellent E-stereoselectivity in satisfactory yields. This method can be extended to achieve the synthesis of monofluoroalkenyl silanes under similar conditions