Synthesis of N-Substituted 3-Amino-4-halopyridines: A Sequential Boc-Removal/Reductive Amination Mediated by Brønsted and Lewis Acids.

N-Substituted 3-amino-4-halopyridines are valuable synthetic intermediates, as they readily provide access to imidazopyridines and similar heterocyclic systems. The direct synthesis of N-substituted 3-amino-4-halopyridines is problematic, as reductive aminations and base-promoted alkylations are difficult in these systems. A high yielding deprotection/alkylation protocol mediated by trifluoroacetic acid and trimethylsilyl trifluoromethanesulfonate is described, providing access to a wide scope of N-substituted 3-amino-4-halopyridines. This protocol furnishes many reaction products in high purity without chromatography. Similar reductive amination conditions were also established for deactivated anilines.

Ruthenium Hydride Catalyzed Silylvinylation of Internal Alkynes Using Ethylene as an Additive.

An efficient synthetic strategy for the regiospecific silylvinylation of internal alkynes is described. This transformation is catalyzed by RuHCl(CO)(SIMes)PPh3 and provides a net 5-exo-dig trans-silylvinylation of internal alkynes. Ethylene was used to decrease reaction times and displayed altered selectivity at increased pressure. Furthermore, alkyl-substituted alkynes were acceptable substrates at 80 psi of ethylene.

Stereo- and Regioselective Formation of Silyl-Dienyl Boronates.

The intramolecular trans-silylruthenation of internal alkynes and subsequent insertion of vinyl boronates is described. This approach provides complete regiocontrol through a stereoselective trans-5-exo-dig cyclization which affords a tetrasubstituted olefin as a vinylsilane and a highly functionalized Z,E diene motif.

Ruthenium catalyzed cycloisomerization of silicon-tethered 1,7-enynes to give exocyclic 1,3-dienes.

The cycloisomerization of vinyl silicon-tethered 1,7-enynes has been accomplished using catalytic Cp*Ru(COD)Cl. The products possess a new silane moiety and trisubstituted alkenes as part of the diene system. The reaction scope includes aryl, alkyl, vinyl, and cyclopropyl alkyne functionalities. Silicon was found not to be a mandatory component of the tether. The utility of the products was demonstrated through manipulation of the vinyl silane and Diels-Alder chemistry.

Rapid synthesis of 3,3' bis-arylated BINOL derivatives using a C-H borylation in situ Suzuki-Miyaura coupling sequence.

The increased interest in BINOL derived catalysts for asymmetric transformations has encouraged us to disclose a rapid and scalable method of preparing 3,3' bis-arylated BINOL derivatives 1 using a one-pot CH borylation/Suzuki-Miyaura coupling sequence. The use of an aldehyde additive was found to be crucial to the success of this in situ tandem approach. This method was applied to the preparation of 10 BINOL derivatives, each completed within 24 h. Notably, this approach requires only a single purification step.

Ethylene transposition: ruthenium hydride catalyzed intramolecular trans-silylvinylation of internal alkynes.

A highly selective intramolecular trans-silylvinylation of internal alkynes catalyzed by RuHCl(CO)(SIMes)(PPh3) has been accomplished. The use of methyl vinyl ketone as an additive increased the efficiency of this transformation. This process was used to successfully form five-, six-, and seven-membered oxasilacycles by a formal anti-exo-dig cyclization.

Copper- and palladium-catalyzed amidation reactions for the synthesis of substituted imidazo[4,5-c]pyridines.

Imidazo[4,5-c]pyridines were synthesized in three steps utilizing a palladium-catalyzed amidation/cyclization strategy. N-Aryl substrates were synthesized using copper-catalyzed amidation of 3-amino-N-Boc-4-chloropyridine. Complementary protocols for the selective chlorination of imidazo[4,5-c]pyridines at the C2 and C7 positions were also developed.

Synthesis of 2-amino-imidazo[4,5-b]pyridines.

The C2 amination of imidazo[4,5-b]pyridines was accomplished through C2 halogenation followed by substitution (SNAr) with functionalized primary and secondary amines. This regioselective sequence is operationally simple and provides an easy access to derivatives of protected imidazo[4,5-b]pyridines.

Total synthesis of pentosidine.

Pentosidine, a biologically important advanced glycation endproduct, has been accessed in a rapid, high-yielding manner. The synthesis was accomplished via a six-step sequence starting with 3-amino-2-chloropyridine and features a palladium-catalyzed tandem cross-coupling/cyclization to construct the imidazo[4,5-b]pyridine core.

Regiodivergent synthesis of functionalized indene derivatives via Pt-catalyzed Rautenstrauch reaction of propargyl carbonates.

A regiodivergent synthesis of functionalized indene derivatives from a Pt-catalyzed Rautenstrauch reaction of propargyl carbonate is described. A one-pot Rautenstrauch/Tsuji-Trost reaction delivering 2-indanones was realized efficiently using this methodology.

Synthesis of imidazo[4,5-b]pyridines and imidazo[4,5-b]pyrazines by palladium catalyzed amidation of 2-chloro-3-amino-heterocycles.

A facile synthesis of imidazo[4,5-b]pyridines and -pyrazines is described using a Pd-catalyzed amide coupling reaction. This reaction provides quick access to products with substitution at N1 and C2. A model system relevant to the natural product pentosidine has been demonstrated, as well as the total synthesis of the mutagen 1-Me-5-PhIP.

Enyne cross-metathesis with strained, geminally-substituted alkenes: direct access to highly substituted 1,3-dienes.

Angle strain in methylene cyclobutane was used to drive a cross-enyne metathesis with 1-alkynes, giving 1,1,3-trisubstituted 1,3-dienes in good isolated yields. An extensive survey of Grubbs' second-generation catalysts led to an optimized reaction conducted at 0 degrees C.

Alkenol-alkyne cross metathesis.

Allyl alcohols and their homologues were used in the enyne cross metathesis to prepare hydroxy-functionalized dienes. An isomerization was found to occur under prolonged heating, and a method for conversion to ( E)-diene product is also reported.

Tandem enyne metathesis and claisen rearrangement: a versatile approach to conjugated dienes of variable substitution patterns.

To extend the versatility of the ruthenium carbene-promoted enyne metathesis, it was combined with an Ireland ester enolate Claisen rearrangement. This reaction sequence provided conjugated dienes of higher substitution pattern than that obtained through a cross-enyne metathesis alone. The Ireland-Claisen was conducted across both acyclic and cyclic dienes produced from cross-metathesis and methylene-free enyne metathesis, respectively. In the case of cyclodienes, the Ireland-Claisen rearrangement produced s-trans locked dienes which underwent mode-selective ene reaction. The tandem, sequential use of the Ireland-Claisen rearrangement also proved suitable for chirality transfer originating from chiral propargylic alcohols. Last, the tandem metathesis/Ireland-Claisen was utilized to access 4-substituted-3,5-cyclohexadiene diol derivatives, which are valuable chiral intermediates for natural product synthesis. The combination of this pericyclic reaction with a catalytic metathesis reaction extends the versatility of cross-metathesis since additional diene motifs can be accessed.

Reconstructing psychopathy: clarifying the significance of antisocial and socially deviant behavior in the diagnosis of psychopathic personality disorder.

A survey of clinical views suggests that the significance of antisocial and socially deviant behavior in the diagnosis of psychopathic personality disorder is unclear. To investigate this issue, we evaluated Psychopathy Checklist-Revised ratings (PCL-R; Hare, 1991) using structural equation modeling. One model, referred to as the measurement model, included PCL-R ratings related to antisocial behavior as primary symptoms of psychopathy; a second, referred to as the causal model, included the same PCL-R ratings as secondary symptoms or consequences. Compared to the measurement models, the causal model included more PCL-R items, was more parsimonious, and had equal or superior fit indices. These findings suggest that antisocial behavior is best viewed as a secondary symptom or consequence of psychopathy, In addition, the findings have important implications for future research and clinical-forensic practice, especially concerning the assessment of risk for criminality and violence.