Synthon stable

Figure lO.J-31. Disconnection of the strategic bond yields (charged) synthons. The synthons are then transformed into neutral, stable reactants. 

The addition of large enolate synthons to cyclohexenone derivatives via Michael addition leads to equatorial substitution. If the cyclohexenone conformation is fixed, e.g. as in decalones or steroids, the addition is highly stereoselective. This is also the case with the S-addition to conjugated dienones (Y. Abe, 1956). Large substituents at C-4 of cyclic a -synthons direct incoming carbanions to the /rans-position at C-3 (A.R. Battersby, 1960). The thermodynamically most stable products are formed in these cases, because the addition of 1,3-dioxo compounds to activated double bonds is essentially reversible. 

Most reactions leading to isoxazoles must involve at some stage cyclization of an intermediate which contains all five atoms of the isoxazole ring. In some cases the acyclic intermediates are short-lived and unisolable, in others they are stable and able to be isolated. In this section we discuss reactions which involve an isolable acyclic precursor. These reactions mostly utilize (CCCNO) synthons although a few examples of (OCCCN), (CCCON) and (CONCC) synthons are encountered. We are unaware of examples involving (CNOCC) synthons. 

Alternative conditions for reductive decyanations can be used. The allylic ether in compound 26, an intermediate in a total synthesis of (-)-roxaticin, was prone to reduction when treated with lithium in liquid ammonia. Addition of the substrate to an excess of lithium di-ferf-butylbiphenylide in THF at -78°C, and protonation of the alkyllithium intermediate provided the reduced product 27 in 63% yield, as a single diastereomer (Eq. 7). a-Alkoxylithium intermediates generated in this manner are configurationally stable at low temperature, and can serve as versatile synthons for carbon-carbon bond forming processes (see Sect. 4). 

Enantiopure a-amino aldehydes are valuable synthons in natural product synthesis [57]. However, problems are often encountered with their configurational instability [58]. Aziridine-2-carboxaldehydes are also a-amino aldehydes and accordingly have a potential synthetic value. We found that M-tritylaziridine-2-carboxaldehyde 56 is a perfectly stable compound and therefore comparable to Garner s aldehyde (ferf-butyl 2,2-dimethyl-4-(S)-formyl-oxazolidine-3-car-boxylate). Aldehyde 56 can readily be prepared from aziridine-2-carboxylic ester 12 by the sequence shown in Scheme 42 [59]. 

Today two directions of research are of interest On the one hand, investigations on the reactivity of basic systems are important to elucidate the typical" Si=E-multiple bond properties, in particular with respect to their use as synthons in organo silicon chemistry without being hampered in their synthetical potential by bulky substituents in this context, a comparison on their reactivity with the carbon analogues is still attractive. On the other hand, the isolation of new stable unsaturated silicon compounds and their structure determination continues to be of interest for quite a number of research groups worldwide. 

Although various compounds are known to act as synthetic equivalents to the formyl anion synthon,12 the advantages that appear to be associated with the use of 2-TST warrant comment. First, 2-TST is a readily available, relatively cheap, and storable reagent second, it reacts promptly and stereoselectively with aldehydes under neutral conditions third, it gives high yields of products that are stable to isolation and purification and nevertheless can be readily transformed into aldehydes. 

The p-functionalized 2-hydroxyphenyl isocyanide not only contains the isocyanide and the nucleophile within the same molecule, but both functional groups are also arranged in one plane for an intramolecular nucleophilic attack [176]. This arrangement, in addition to the aromaticity of the five-membered ring obtained after cyclization to the carbene ligand, particularly favors the intramolecular nucleophilic attack. In contrast to 2-hydroxyethyl isocyanide, free 2-hydroxyphenyl isocyanide is not stable [177]. The stable 2-trimethylsiloxyphenyl isocyanide [178] can serve as a synthon for 2-hydroxyphenyl isocyanide. Carbene complexes 63 with an NH,0-stabilized NHC ligand can be obtained from the complexes 62 with the... 

Trimethylsilyldiazomethane, as a stable and safe substitute for hazardous diazomethane, is useful both as a reagent for introducing a Cj-unit and as a C-N-N synthon for the preparation of azoles. Many methods are described in the literature for the preparation of trimethylsilyldiazomethane, including the trimethylsilylation of diazomethane (7-74S), the alkaline decomposition of N-nitroso-N-(trimethylsilylmethyl)amides (25-61%) and the diazo group transfer reaction of trimethylsilylmethyllithium with p-toluenesulfonyl azide (38%). The present modified diazo group transfer method appears to be the most practical, high-yield, and large scale procedure for the preparation of... 

The second important reaction path similar to AT synthesis starts with aminoguanidine derivatives (in this case part of a HP) and proceeds via condensation with a synthon Z (see principle in Scheme 8). In a first step l,2,4-triazolo-[4,3-a]pyrimidines (15) are formed these are often isolable and nearly always transformable into the more stable TPs by Dimroth rearrangement. 

Cyclopentadienones.2 Cyclopentadienones are generally not useful synthons because of their ready dimerization. A new synthesis of more stable substituted cyclopentadienones involves cyclization of two substituted alkynes with carbon monoxide by the [2 + 2 + 21cycloadditions shown in equations (I) and (II). 

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). 

For incorporating an iminoaza fragment into a peptide chain the hydrazone 40 might be converted into the synthon 43 (Scheme 18). Action of triphosgene on compound 40 produces an intermediate 42, which is not isolated. Addition of pentafluorophenol to 42 yields the stable activated synthon 43 (Scheme 18). 

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