A Formal Rearrangement of Allylic Silanols

We show that 1M aqueous HCl/THF or NaBH4/DMF allows for demercurative ring-opening of cyclic organomercurial synthons into secondary silanol products bearing terminal alkenes. We had previously demonstrated that primary allylic silanols are readily transformed into cyclic organomercurials using Hg(OTf)2/NaHCO3 in THF. Overall, this amounts to a facile two-step protocol for the rearrangement of primary allylic silanol substrates. Computational investigations suggest that this rearrangement is under thermodynamic control and that the di-tert-butylsilanol protecting group is essential for product selectivity

Catalytic Chemo‑, Regio‑, and Enantioselective Bromochlorination of Allylic Alcohols

Herein we describe a highly chemo-, regio-, and enantioselective bromochlorination reaction of allylic alcohols, employing readily available halogen sources and a simple Schiff base as the chiral catalyst. The application of this interhalogenation reaction to a variety of substrates, the rapid enantioselective synthesis of a bromochlorinated natural product, and preliminary extension of this chemistry to dibromination and dichlorination are reported

Enantiospecific Solvolytic Functionalization of Bromochlorides

Herein, we report that under mild solvolytic conditions, enantioenriched bromochlorides can be ionized, stereospecifically cyclized to an array of complex bromocyclic scaffolds, or intermolecularly trapped by exogenous nucleophiles. Mechanistic investigations support an ionic mechanism wherein the bromochloride serves as an enantioenriched bromonium surrogate. Several natural product-relevant motifs are accessed in enantioenriched form for the first time with high levels of stereocontrol, and this technology is applied to the scalable synthesis of a polycyclic brominated natural product. Arrays of nucleophiles including olefins, alkynes, heterocycles, and epoxides are competent traps in the bromonium-induced cyclizations, leading to the formation of enantioenriched mono-, bi-, and tricyclic products. This strategy is further amenable to intermolecular coupling between cinnamyl bromochlorides and a diverse set of commercially available nucleophiles. Collectively, this work demonstrates that enantioenriched bromonium chlorides are configurationally stable under solvolytic conditions in the presence of a variety of functional groups

Growth Retardation and Leaky SCID Phenotype of Ku70-Deficient Mice

Ku70, Ku80, and DNA-PKcs are subunits of the DNA-dependent protein kinase (DNA-PK), an enzyme implicated in DNA double-stranded break repair and V(D)J recombination. Our Ku70-deficient mice were about 50% the size of control littermates, and their fibroblasts were ionizing radiation sensitive and displayed premature senescence associated with the accumulation of nondividing cells. Ku70-deficient mice lacked mature B cells or serum immunoglobulin but, unexpectedly, reproducibly developed small populations of thymic and peripheral α/β T lineage cells and had a significant incidence of thymic lymphomas. In association with B and T cell developmental defects, Ku70-deficient cells were severely impaired for joining of V(D)J coding and recombination signal sequences. These unanticipated features of the Ku70-deficient phenotype with respect to lymphocyte development and V(D)J recombination may reflect differential functions of the three DNA-PK components