C-heteroatom Bond Formation Research Articles

ChemInform Abstract: Unique Reactivity of Fluorinated Molecules with Transition Metals

AbstractReview: 235 refs.

ChemInform Abstract: Molecular Iodine Mediated Synthesis of Polysubstituted Oxazoles by Oxidative Domino Cyclization in Water.

A simple and efficient iodine-mediated domino protocol has been developed to construct polysubstituted oxazoles through the C-heteroatom bond formation in water from readily available β-ketoesters and primary amines in high yields. The reaction proceeds smoothly under metal and peroxide-free conditions.

Recent Advances in Chemistry of γ-Lactams: Part I. Synthesis Starting from Acyclic or Cyclic Precursors

γ-Lactams (pyrrolidin-2-ones) and products containing the γ-lactam core are important synthetic targets and often display interesting biological activities, so that the development of improved synthetic methodologies for their preparation has become the objective of many synthetic chemists. This review is presented in two parts: Part I highlights efficient synthetic strategies (issued between 2001 and 2013), which are classified according to the last step of the lactam ring formation, starting from acyclic or cyclic precursors, whereas Part II deals with functionalization of γ-lactam ring via C-C or C-Heteroatom bond formation. Enantioselective synthesis is thoroughly emphasized in both sections, also exploiting catalytic systems, since pure enantiomeric derivatives are important for biological testing. Keywords: Cyclization, enantioselectivity, lactams, stereoselectivity, synthetic methods.

Unique reactivity of fluorinated molecules with transition metals.

Organofluorine and organometallic chemistry by themselves constitute two potent areas in organic synthesis. Thus, the combination of both offers many chemical possibilities and represents a powerful tool for the design and development of new synthetic methodologies leading to diverse molecular structures in an efficient manner. Given the importance of the selective introduction of fluorine atoms into organic molecules and the effectiveness of transition metals in C-C and C-heteroatom bond formation, this review represents an interesting read for this aim.

Molecular iodine mediated synthesis of polysubstituted oxazoles by oxidative domino cyclization in water

A simple and efficient iodine-mediated domino protocol has been developed to construct polysubstituted oxazoles through the C-heteroatom bond formation in water from readily available β-ketoesters and primary amines in high yields.

Transition metal catalyzed nucleophilic allylic substitution: activation of allylic alcohols via π-allylic species

Modern organic synthesis now requires efficient atom economical synthetic methods operating under greener pathways to achieve C-C and C-heteroatom bond formation. Direct activation of allylic alcohols in the presence of transition metal catalysts leading to electrophilic π-allyl metal intermediates represents such a promising target in the field of nucleophilic allylation reactions. During the last decade, this topic of recognized importance has become an emerging area, and selected transition metals, sometimes associated with alcohol activators, have brought elegant solutions for performing allylic substitution directly from alcohols in a regio, stereo and enantioselective manner.

Recent advances and applications of iridium-catalysed asymmetric allylic substitution

Since their discovery in 1997, iridium-catalysed asymmetric allylic substitutions have been developed into a broadly applicable tool for the synthesis of chiral building blocks via C-C and C-heteroatom bond formation. The remarkable generality of these reactions and the high levels of regio- and enantioselectivity that are usually obtained in favour of the branched products have been made possible by a thorough investigation of the catalyst system and its mode of action. Therefore, today the Ir-catalysed asymmetric allylic substitution is a powerful reaction in the organic chemist's repertoire and has been used extensively for several applications. This article aims to provide an overview of the development of iridium catalysts derived from an Ir salt and a chiral phosphoramidite and their application to the enantioselective synthesis of natural products and biologically relevant compounds.

Allylic alcohols as synthetic enolate equivalents: Isomerisation and tandem reactions catalysed by transition metal complexes

Allylic alcohols can be isomerised into carbonyl compounds by transition metal complexes. In the last few years, catalyst design and development have resulted in highly efficient isomerisations under mild reaction conditions, including enantioselective versions. In addition, the isomerisation of allylic alcohols has been combined with C-C bond forming reactions when electrophiles such as aldehydes or imines were present in the reaction mixture. Also, C-F bonds can be formed when electrophilic fluorinating reagents are used. Thus, allylic alcohols can be treated as latent enol(ate)s. In this article, we highlight the latest developments concerning the isomerisation of allylic alcohols into carbonyl compounds, focusing in particular on tandem isomerisation/C-C or C-heteroatom bond formation processes. Significant attention is given to the mechanistic aspects of the reactions.

Hydrolases: catalytically promiscuous enzymes for non-conventional reactions in organic synthesis

During the last three decades the use of hydrolases for the catalysis of environmentally friendly organic processes under mild reaction conditions has been well documented. Hydrolases have shown themselves to be ideal tools for the acceleration of synthetic transformations because of their high stability, catalytic efficiency, commercial availability and broad substrate specificity in a wide spectrum of biocatalyzed processes. In recent years, novel examples have appeared related to non-conventional reactions catalyzed by hydrolytic enzymes. Amongst these, lipases and acylases have gained much attention as promiscuous biocatalysts showing good levels of reactivity in C-C bond formation, C-heteroatom bond formation, oxidative processes, and novel hydrolytic reactions. This critical review covers recent investigation in the field of catalytic promiscuity, and highlights the most surprising and uncommon activities that this class of enzymes shows in organic synthetic transformations (111 references).

Transition Metal Complex Catalysis in Fine Organic Synthesis. A Personal Account.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Transition Metal Complex Catalysis in Fine Organic Synthesis. A Personal Account

The development of catalytic systems for palladium catalyzed C-C and C-heteroatom bond formation is overviewed. Attention is focused on the issues relevant for environmental and technological safety of the processes: high catalytic efficiency, reactions in the absence of expensive non-recoverable phosphine ligands, the use of water and aqueous media, atom efficient transformations, etc.

Theoretical studies on C-heteroatom bond formation via reductive elimination from group 10 M(PH3)2(CH3)(X) species (X = CH3, NH2, OH, SH) and the determination of metal-X bond strengths using density functional theory.

Density functional calculations have been used to investigate C-C, C-N and C-O bond forming reactions via reductive elimination from Group 10 cis-M(PH3)2(CH3)(X) species (X = C-I3, NH2, OH). Both direct reaction from the four-coordinate species and a three-coordinate mechanism involving initial PH3 loss have been considered. For the four-coordinate pathway the ease of reductive elimination to give M(PH3)2 and CH3-X follows the trend M = Pd < Pt < Ni. The reaction of the cis-M(PH3)2(CH3)(NH2) species is promoted by the formation of methylamine adducts. Non-planar transition states are located and the C-heteroatom bond forming processes are characterised by migration of CH3 onto the cis-heteroatom ligand. For a given ligand, X, activation energies follow the trend M = Ni < Pd < Pt. Formation of the three-coordinate M(PH3)(CH3)(X) species is promoted by a labilisation of the cis-PH3 ligand in the four-coordinate reactants when X = NH2 or OH. For the three-coordinate pathway the energy change for reductive elimination to give M(PH3) and CH3-X again follows the trend M = Pd < Pt < Ni and in all cases the initial product is an M(PH3)(XCH3) adduct. The three-coordinate transition states again involve migration of the CH3 ligand onto the cis-X ligand and for X = NH2 or OH activation energies follow the trend Ni > Pd < Pt. For a given metal activation energies in both the four- and three-coordinate pathways increase along the series CH3 < NH2 < OH. These trends in activation energy can be rationalised in terms of the strength of M-CH3/M-X bonding as long as the extent of geometrical distortion required to obtain the transition state geometry is taken into account. Further calculations on cis-Pd(PH3)2(CH3)(SH) suggest that the more common experimental observation of C(sp3)-S compared to C(sp3)-O reductive elimination arises from the greater kinetic accessibility of the former process rather than an intrinsic thermodynamic preference for C-S bond formation. By comparison, the calculations indicate that C(sp3)-N reductive elimination should be feasible from Ni and Pd systems. DF calculations are shown to reproduce the relative homolytic bond strengths determined experimentally for Pt-X bonds. In the cis-M(PH3)2(CH3)(X) systems the M-CH3 homolytic bond strength increases down the group while for M-NH2 and M-OH bonds the trend is M = N approximately equal to Pd < Pt. M-NH2 and M-OH are considerably stronger than M-CH3 bonds and the presence of a heteroatom ligand serves to weaken M-CH3 bonds even further.

Palladium catalyzed C-C and C-heteroatom bond formation reactions

Abstract