Synthon unstable

Synthetic Equivalent A reagent carrying out the function of a synthon which caimot itself be used, often because it is too unstable. 

Analysis It may be tempting to disconnect bond a but this would giye the unknown and presumably yery unstable PhC=0 synthon. The better disconnection is bond b giying two carbonjd compounds. 

Consonant with the present interest in chiral synthesis, two additional contributions can be cited. Sih al utilized a combined microbiological and organic chemical sequence in which key chirality establishing steps include the conversion of to chiral, but unstable, 18 by enzymic reduction using the fungus Diplodascus uninucleatus. Lower side-chain synthon was prepared by reduction of achiral with Pencillium decumbens. 

Both 2-azido [184] and 2-nitrophenyl isocyanides [185] are suitable synthons for the generation of the freely unstable 2-aminophenyl isocyanide and they have been used (Fig. 23) in the template-controlled preparation of NH,NH-stabilized benzim-idazolin-2-ylidene hgands. Both phenyl isocyanides coordinate readily to transition metal centers. The isocyanide ligand in complex 65 reacts with PPhs and the... 

We now turn to reagents which are important in context with the element/halogen exchange Compounds of the type 8 would be interesting reagents for nucleophilic halomethylation but are quite unstable due to carbene formation. Compound 9 would be an attractive synthetic equivalent for the synthons 8. As will be shown... 

Bis(phenylethynyl)-2,2 -bithiophene derivatives function as 1,6-diyne synthons for benzodithiophenes <1997HCA111>. Hence, treatment of 164 with chlorotris(triphenylphosphine)rhodium(l) provides an unstable... 

A new preparation of the C g ketone, an important synthon for the synthesis of vitamin A had also been published by Valla et al. [71]. Hence p-ionone and acetonitrile were condensed in the presence of KOH, to afford the nitrile (80%, E/Z isomers 80/20). A Reformatsky reaction of ethyl bromoacetate with the nitrile provided the ethyl P-ionylideneacetoacetate in 70% yield. Subsequent reduction with NaBH4, followed by esterification (MeSC Cl) and desulfonation of the unstable... 

Formaldehyde anion synthon ( CHO). The anion of 1 (n-BuLi, THF, 0°) is readily alkylated, particularly by primary halides. The products can he converted into aldehydes under very mild conditions. Oxidation with m-chloroperbenzoic acid gives an unstable sulfoxide, which undergoes an sila-Pummerer rearrangement to an acetal. Addition of water liberates the free aldehyde. Epoxides can also be used as electrophiles.2 3 Example ... 

An impressive number of alkaloids has been generated from the synthon (202), which is accessible by an acid catalyzed rearrangement of the appropriately substituted cyclopropyl-imine. The endocyclic enamine (202) should react with electrophiles on the /8-carbon in a process which simultaneously renders the a-carbon electrophilic and therefore susceptible to capture by nucleophilic reagents. The application of this methodology to the synthesis of ipalbidine (191a) and septicine (204) is shown in Scheme 30. Here, the unusual 3-phenylthio-2-pyrroline intermediate (203) serves as a relatively stable equivalent synthon of the unsubstituted 2-pyrroline analogue which is notoriously unstable (77ACR193). 

Isocyanides, formal divalent carbon functionalities, are ideal candidates for the development of MCRs. Their reaction with carbonyls and imines, through an a-addition process, generates a zwitterionic intermediate, which is then trapped by a nucleophile. The resulting double a-addition adduct is unstable and rapidly undergoes the Mumm rearrangement to afford the final product (Scheme 12.32). The venerable three-component Passerini reaction is the first MCR based on this type of reaction process [116]. It addresses the formation of a-acyloxycarboxamides, which constitute a class of very versatile synthons in organic chemistry. In the present context, this reaction was utilized by Schmidt and collaborators for the elaboration of intermediate 234 [117], a key fragment for the synthesis of the prolyl endopeptidase inhibitor Eurystatin A 231 (Scheme 12.33) [118]. 

Most hydroxy-substituted azaheteroaromatic compounds exist predominately in the NH/carbonyl tautomeric form, and such compounds have been widely discussed. By contrast, aza derivatives of cyclopentadienone, and of quinones, although they have received considerable attention in the last 30 years, have never previously been reviewed. In the present overview, we have attempted to collect the information on such derivatives, as well as including l-azetin-4-ones, i.e., of those azaheterocycles which contain in the ring at least one carbonyl group and one or two nitrogen atoms in the form of C=N or N=N bonds. Many of these compounds are unstable but their importance as reactive intermediates is established and many of them could be used as synthons in the preparation of pharmacologically active compounds. 

In chapter 6 we needed three types of synthon depending on the di-X relationship in the target molecule. For the 1,3-diX relationship we used just one synthon 2, for the 1,2-diX we used related synthons 5 and 8, and for the 1,1 -diX two more 11 and 14. The synthons for the 1,3-diX and 1,1 -diX relationships could be turned into reagents 3, 12 and 15 simply by using the natural electrophilic behaviour of the carbonyl group. The synthons 5 and 8 for the 1,2-diX relationship could not be turned into reagents so easily reagent 6 does not resemble synthon 5 while synthon 8 looks very unstable and such intermediates cannot be made. 

The iminium salts of 2,3-dihydropyridines are far more stable than the free bases and have been used extensively in the synthesis of alkaloids. N-Benzyl iminium salt 26, formed from the Polonovski-Potier reaction of V-oxide 25, was transformed into enol ether 27, which is a synthon for the unstable AT-benzvl-l, 2-dihvdropyridine 28 (Scheme 5) <2004LOC168>. The same transformation on a similar iminium salt has been used in the formation of macrocyclic marine alkaloids <1995TL2059>. Carbon nucleophiles, such as the silylenol ethers of esters, have been shown to undergo 1,2-addition rather than 1,4-addition to 2,3-dihydropyridinium salts <1999T14995>. 

Dent be tempted to try using fi hafoketones as equivalents for this synthon They are hard to make and highly unstable and they undergo rapid ElcB elimination (see Chapter 19). 

The notion of isomerism for synthons was defined in [18,21,16], in the present communication we shall study the synthons that are constructed over the same vertex set A. Therefore, they are automatically isomeric. The set of all synthons (nonisomorphic) constructed over the set A is called the family of isomeric synthons, and is denoted by 3F A). The synthons from a family will be advantageously classified in our forthcoming considerations as stable, unstable, and forbidden. This will be done by making use of the concept of valence states of vertices. 

The synthon SfAJ is unstable if and only if its certain vertex is in an unstable valence state and contains no vertex in forbidden valence state. 

Definition 2.4 A stable neighborhood of the synthon S(A), denoted by S(S(A)), is a set composed of stable synthons S (A) such that the internal vertices from each path of (S(A), S (A)) correspond merely to unstable synthons. 

Let us consider a stable synthon S (A) e S(S(A)), the transformation S(A) => S (A) is represented by a reaction graph either of the linear or cyclic form. In order to verify that the synthon S (A) belongs to the stable neighborhood of the stable synthon S(A) it is sufficient to verify that each connected subgraph of GR produces the unstable synthon. As this subgraph would be of linear form, at least one nonvirtual atom would gain or loose one valence electron and therefore its valence state would be unstable and the synthon S (A) produced should not be stable. 

All synthons 5(A) from FIS(A) can be divided into two groups and classified as stable and unstable. Following the idea of stable valence states (Sect. 3.1) we say that a synthon S(A) is stable if each of the atoms of S(A) is in a stable valence state in S(A). In all other cases the synthon is called unstable. However, the notion of the stable synthon is relative, and it does not mean that every stable synthon is a chemically stable compound . This notion just makes the model more flexible. For example, when working in carbene-chemistry we will consider carbene valence states — C—,C= of carbon as stable, otherwise, seen from an experimental chemist s point of view, they are considered as unstable. When considering only valence states without formal charge as stable then only the synthons 1, 7, and 11 in Scheme 7 are stable. 

Note that aldehydes can also be a source of acyl radicals ( 0=0) via reaction with transition metal salts such as Mn(III) acetate or Fe(II) compounds.Another useful variation employs imidoyl radicals as synthons for unstable aryl radicals. 

The Ni-catalyzed cross-coupling reaction of alkynyl Grignard reagents 60 with ( )- or (Z)-dichloroethene 61a,b has been applied to a simple procedure for the preparation of the protected fomi 62a,b of a highly unstable synthon, as hexa-3-ene-l,5-diyne [Eq. (23). Separation of the diastereomers 62a and 62b is facile since the former is an oil and the latter is a solid [35]. 

T.. ere is a problem with the aldehyde a synthon. We don t want to use an unstable 2-Ki .. -.dehyde so an allyl halide is best. The alkene must be cleaved by ozonolysis with reductive -up (Me2S) to stop oxidation of the aldehyde. 

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