Organocatalytic Asymmetric Formation of Steroids

A novel and simple one‐step approach for the construction of optically active steroids in a highly stereoselective manner by using organocatalysis is presented. The reaction of (di)enals with cyclic dienophiles in the presence of a TMS‐protected prolinol catalyst leads to the construction of important 14 β‐steroids. This new reaction allows an easy access to optically active steroids with a variety of substituents in the A ring in high yields and up to greater than 99 % ee. The reaction has been extended to include the construction of B‐ and D ‐homosteroids as well as steroids containing heteroatoms in the B ring. The angular substituent at C13 can be varied and alkyl, ester, and sulfone functionalities are introduced with excellent stereoselectivities. Simple synthetic procedures provide access to a range of naturally occurring steroids such as estrone and related analogues.     

Facile Synthesis of Phosphaamidines and Phosphaamidinates using Nitrilium Ions as an Imine Synthon

Readily accessible nitrilium triflates are convenient imine building blocks for the expedient synthesis of a novel class of 1,3‐P,N ligands as demonstrated for the reaction with primary phosphanes. This procedure allows variation of all substituents. X‐ray crystal structures are reported for nitrilium ions, phosphaamidines, and three phosphaamidinate complexes. The lithium phosphaamidinate is N coordinated and its reaction with [AuCl(tht)] (tht=tetrahydrothiophene) gives a unique P‐bridged gold trimer, while a P,N‐bidentate complex results from [{RhCl(cod)}₂]. The nitrilium ion methodology allows extension of the 1,3‐P,N motive to bis(imino)phosphanes, which are the neutral phosphorus analogues of the valuable β‐diketiminate ligand.     

Synthesis of a Natural Product‐Like Compound Collection through Oxidative Cleavage and Cyclization of Linear Peptides

Massive efforts in molecular library synthesis have strived for the development of synthesis methodology which systematically delivers natural product‐like compounds of high spatial complexity. Herein, we present a conceptually simple approach that builds on the power of solid‐phase peptide synthesis to assemble precursor peptides (oligomers) designed to undergo oxidative cascade reactions. By harnessing the structural side‐chain diversity and inherent stereochemical features offered by readily available amino acids (monomers), a proof‐of‐concept collection of 54 skeletally and stereochemically diverse compounds was generated, and selected compounds were elaborated into isoform‐selective metalloprotease inhibitors.     

Nickel‐Catalyzed C?H Alkylations: Direct Secondary Alkylations and Trifluoroethylations of Arenes

A versatile nickel catalyst allowed for C H alkylations of unactivated arenes with challenging secondary alkyl bromides and chlorides. The high catalytic efficacy also set the stage for direct secondary alkylations of indoles as well as C H trifluoroethylations with ample substrate scope.     

Mono-Phosphazenyl Phosphines (R2N)3P=N–P(NR2)2 – Strong P-Bases,P-Donors,and P-Nucleophiles for the Construction of Chelates

We present a convenient three-step synthesis of amino substituted phosphazenyl phosphines of the general formula (R₂N)₃P=N–P(NR₂)₂ [NR₂ = N(CH₂)₄, N(CH₂)₅, N(CH₂)₆]. These easily accessible mixed valent compounds display a surprisingly high proton affinity and basicity in the same range as the corresponding Schwesinger diphosphazene (Me₂N)₃P=N–P=NEt(NMe₂)₂ (Et-P₂) and Verkade's proazaphosphatrane superbases. Within the central [P^III–N=P^V] scaffold, the phosphine P^III and not the phosphazene N^III atom is the center of highest proton affinity, basicity and donor strength. As P-bases, the title compounds display calculated proton affinities between 265.8 (NR₂ = NMe₂) and 274.7 kcal · mol^–1 [NR₂ = N(CH₂)₄] and pK_BH⁺ values between 26.4 (NR₂ = NMe₂) and 31.5 [NR₂ = N(CH₂)₄] on the acetonitrile scale. As P-nucleophiles, they are key intermediates in the synthesis of hyperbasic bis(diphosphazene) proton sponges, chiral bis(diphosphazene) proton pincers, bisphosphazides, and superbasic P₂-bisylides. Their Staudinger reactions as nucleophile towards 1,8-diazidonaphthalene leading to 1,8-naphthalene-bisphosphazides is described in detail. The donor strength of the title compounds towards fragments [Se] and [Ni(CO)₃] is in the same range as that of N-heterocyclic carbenes.     

RuII and RuIII Chloronitrile Complexes: Synthesis,Reaction Chemistry,Solid State Structure,and (Spectro)Electrochemical Behavior

The synthesis of [Ti₆O₄(OiPr)₈(O₂CPh)₈] ( 3 ) and [RuCl(N≡CR)₅][RuCl₄(N≡CR)₂] ( 4a , R = Me; 4b , R = Ph), [Ru(N≡CPh)₆][RuCl₄(N≡CPh)₂] ( 5 ) and [H₃O][RuCl₄(N≡CMe)₂] ( 7a ) is discussed. Crystallization of 5 from CH₂Cl₂ gave trans-[RuCl₂(N≡CPh)₄] ( 6 ). The solid-state structures of 3 , 4a , b , 5 , 6 and 7a are reported. Complex 4b forms a 3D network, while 6 displays a 2D structure, due to π-interactions between the benzonitrile ligands. The (spectro)electrochemical behavior of 4a , b and 6 was studied at 25 and –72 °C and the results thereof are compared with [NEt₄][RuCl₄(N≡CMe)₂] ( 7b ) and [RuCl(N≡CPh)₅][PF₆] ( 8 ). The electrochemical response of the cation and the anion in 4a , b are independent from each other. [RuCl(N≡CR)₅]⁺ possesses one reversible Ru^II/Ru^III process. However, [RuCl₄(N≡CMe)₂]^– was shown to be prone to ligand exchange and disproportionation upon formation of either a Ru^IV and Ru^II species at 25 °C, while at –72 °C the rapid conversion of the electrochemically formed species is hindered. In situ IR and UV/Vis/NIR studies confirmed the respective disproportionation reaction products of the aforementioned oxidation and reduction, respectively.     

Tuning PtII-Based Donor–Acceptor Systems through Ligand Design: Effects on Frontier Orbitals,Redox Potentials,UV/Vis/NIR Absorptions,Electrochromism, and Photocatalysis

Asymmetric platinum donor–acceptor complexes [(pimp)Pt(Q²⁻)] are presented in this work, in which pimp=[(2,4,6-trimethylphenylimino)methyl]pyridine and Q²⁻=catecholate-type donor ligands. The properties of the complexes are evaluated as a function of the donor ligands, and correlations are drawn among electrochemical, optical, and theoretical data. Special focus has been put on the spectroelectrochemical investigation of the complexes featuring sulfonyl-substituted phenylendiamide ligands, which show redox-induced linkage isomerism upon oxidation. Time-dependent density functional theory (TD-DFT) as well as electron flux density analysis have been employed to rationalize the optical spectra of the complexes and their reactivity. Compound 1 ([(pimp)Pt(Q²⁻)] with Q²⁻=3,5-di-tert-butylcatecholate) was shown to be an efficient photosensitizer for molecular oxygen and was subsequently employed in photochemical cross-dehydrogenative coupling (CDC) reactions. The results thus display new avenues for donor–acceptor systems, including their role as photocatalysts for organic transformations, and the possibility to introduce redox-induced linkage isomerism in these compounds through the use of sulfonamide substituents on the donor ligands.