Metallation acyclic systems

In 1982 the present author discovered cyclic orbital interactions in acyclic conjugation, and showed that the orbital phase continuity controls acyclic systems as well as the cyclic systems [23]. The orbital phase theory has thus far expanded and is still expanding the scope of its applications. Among some typical examples are included relative stabilities of cross vs linear polyenes and conjugated diradicals in the singlet and triplet states, spin preference of diradicals, regioselectivities, conformational stabilities, acute coordination angle in metal complexes, and so on. 

The reduction of vinyl halides most often is carried out via a metallation-protonation reaction. For instance, sodium in ethanol was employed by Barton et a/. for the reduction of a steroidal vinyl iodide (Scheme 44). A number of conditions for vinyl halide reduction to alkenes have been reported, representative examples of which include vinyl chloride and bromide reduction in acyclic systems with... 

Each section of this chapter is subdivided according to the type of species being metalated acyclic, carbocyclic or heterocyclic. The site of metalation is the criterion for classifying each species. Thus, the ortho metalation of anisole is classified as a carbocyclic system, whereas metalation of the N-methyl... 

The reaction of allylic organometallics with electrophilic reagents is a very important tool for the formation of carbon-carbon bonds in acyclic systems and for controlling their stereochemistry. Crotyl organometallic (2-butenylmetal) species undergo a 1,3-shift of the metal at room temperature. For the stereocontrolled use of allylmetals in synthesis, it is important to avoid their equilibration. 

Additions via Metalation of Acyclic Systems 2.143 Additions via Metalation c/Carbocyclic Systems... 

As the S=0 bond is an acceptor site for the Lewis acids [109], the conformation of the sulfinylimine moiety in the transition state influenced the stereochemical outcome of this reaction by intramolecular chelation with metal salts [108]. The potential of diastereo- and enantioselective reactions that form multiple carbon-carbon bonds in acyclic systems, including the formation of all-carbon quaternary stereocenters in a one-pot operation from easily accessible starting materials, has been further extended and has led to a unique approach to aldol products bearing all-carbon quaternary stereocenters in acyclic systems (Scheme 10.129) [110]. 

The nucleophile usually attacks the exo face of the allyl group (the one opposite the metal), and at the least hindered terminus of the allyl group (although this preference can be reversed with suitable ligands). The stereochemical consequences of this sequence have been used to define the relative stereochemistries of two chiral centers five carbons apart in an acyclic system, during the synthesis of... 

The progress has been much slower with acyclic systems. However, the trans-metallation of N-benzyl-N-Cbz- [350], N-Boc-N-methyl- [351], and N-Boc-N-tertbu-tylthiomethyl- [352] protected aminotins provided the corresponding amino-lithium derivatives that may be trapped with electrophiles with complete retention of configuration. This chemistry was applied to the preparation of /3-aminoalco-hols, N-methyl-/3-aminoalcohols and N-methyl-/3-amino acids. It can be noted that the preparation of enantio-enriched a- or /3-amino carbanions can be achieved starting from linear racemic precursors when the tin-to-lithium exchange is done in the presence of (-)-sparteine [353]. 

---