Functionalisation follow

The disconnection of enantiopure carbocycles is never an easy task, but this is especially so when the target molecule possesses multiple ring systems comprised entirely of carbon and hydrogen atoms linked together via a bonds. When confronted with such structures it is often advisable (or even necessary) to retrosynthetically functionalise one or more of the ring systems present to permit a simplifying disconnection to be made. Once a hydroxyl, an amine, a carbonyl, or some other multiply bonded unit is positioned within a ring, this usually primes adjacent or nearby bonds for immediate disconnection, or for further functionalisation followed by disconnection. 

The presence of a tetrasubstituted C=C bond in the A-ring of (—)-silphiperfolene provides a logical starting point from where to commence retrosynthetic disassembly. It was Fraser-Reid s view that the option of further functionalisation followed by disconnection was the more... 

CNTs are used to obtain high performance vegetable oil-based polymer nanocomposites. Oxidative, acid and amine functionalisations followed by grafting of CNTs are the most widely used methods for this purpose. 

Despite the relative infancy in the development of solid phase reactions, a wide range of functionalised resins are commercially available. The main uses of these functionalised resins can be roughly classified as follows ... 

The use of a stereogenic carbon centre allowed an efficient asymmetric induction in the benzannulation reaction towards axial-chiral intermediates in the synthesis of configurationally stable ring-C-functionalised derivatives of al-locolchicinoids [51]. The benzannulation of carbene complex 52 with 1-pen-tyne followed by oxidative demetalation afforded a single diastereomer 53 (Scheme 33). 

H). On the other hand, the synthesis of unsymmetricaUy iV,iV -substituted congeners is less straightforward as a functionalised imidazole has to be isolated prior to alkylation or arylation. Two main methods are available for imidazole functionaU-sation deprotonation with metalUc Na or K leading to an imidazoUde (I) followed by reaction with RX or reaction of glyoxal with a primary amine, an ammonium salt and formaldehyde (J). Al-functionalised imidazole can then be alkylated or... 

Imidazolidine-2-thiones functionalised on the four-position can be obtained by reaction of HN(CH3)R with n-butyllithium, followed by addition of carbon disulfide. The lithium thicarbamate can then by further lithiated and cyclisation occurs upon reaction of this species with an imine (S) [22],... 

There has also been some interest in NHC-lanthanide complexes as polymerisation catalysts. Indenyl and fluorenyl functionalised NHC complexes of structures 14 and 15 (Fig. 4.5) were evaluated for isoprene polymerisation following activation... 

The remainder of the work on Ni(II) complexes involves the use of chelating ligands in which the carbene is functionalised with pendant heteroatom donor(s). The picolyl-functionalised NHC dicationic complex 29 (Fig. 4.11) was tested for ethylene polymerisation after treatment with MAO [34]. This complex was found to be highly active in a preliminary test (330 kg moF bar h" ), giving predominantly linear polyethylene. Unfortunately this work does not seem to have been followed up. The same system was active for norbomene polymerisation (TOF = 24 400 h" over 1 h). Maximum activity was achieved at 80°C whereafter thermal deactivation became significant, although the nature of this deactivation was not studied. The phenoxide-functionalised carbene complex 30 (Fig. 4.11) was also... 

Finally, the phosphine-functionalised carbene complex 40 (Fig. 4.14) has been tested following activation with [H(Et20)][B Ar "] [45], but again a very low activity was achieved (TON 129 after 2 h). The poor performance of these catalysts may also reflect their susceptibility to reductive elimination (of 2-acylimidazolium salt) and generation of Pd(0) [4, 5]. Interest in CO/aUcene seems to have dwindled recently, and as such no further reports on carbene complexes catalysing this reaction have appeared since 2003. 

Scheldt and co-workers have also accessed enolate equivalents from enals to furnish cyclopentanes 236 asymmetrically. Formation of the enolate equivalent from enals 235 with the NHC, followed by an intramolecular Michael reaction and 0-acylation, gives the lactone products 236, which are readily opened by either alcohols or amines to generate functionalised cyclopentane derivatives 237 in excellent ee. 

NHC-promoted enolate formation from an enal, followed by a desymmetrising aldol event to generate P-lactones and loss of CO, has been exploited by Scheidt and co-workers to generate functionalised cyclopentenes 240 in high ee from enal substrates 238 (Scheme 12.52) [94]. Interestingly, the use of alkyl ketones in this reaction manifold allows the isolation of the p-lactone intermediates with acyclic diketones, P-lactones 239 are formed with the R group anti- to the tertiary alkox-ide, while with cyclic diketones the P-lactone products have the R group with a syn relationship to the alkoxide [95]. 

Following the synthesis of the first methyl-palladium NHC complexes it was subsequently found that the complexes undergo a facile thermal decomposition process in which the NHC is lost as 2-methylimidazolium salt and the Pd is rednced to Pd(0) (Scheme 13.1) [15-17]. In ensuing studies investigating the reaction behavionr of a range of hydrocarbyl Pd and Ni carbene complexes, it was found that the decomposition reaction is ubiquitous. It occurs with varying ease, for mono-NHC, bis-NHC and donor functionalised-NHC complexes [16-23]. 

Solid-phase combinatorial synthesis of AT-acyl-L-HSL has also been reported. The procedure entails the DIC/HOBt catalysed acylation of methionine functionalised resin with a carboxylic acid followed by BrCN-mediated cyclisation process to produce HSL libraries with retention of stereochemistry (Scheme 5) [55]. 

The retrosynthesis involves the following transformations i) isomerisation of the endocyclic doble bond to the exo position ii) substitution of the terminal methylene group by a more stable carbonyl group (retro-Wittig reaction) iii) nucleophilic retro-Michael addition iv) reductive allylic rearrangement v) dealkylation of tertiary alcohol vi) homolytic cleavage and functionalisation vii) dehydroiodination viii) conversion of ethynyl ketone to carboxylic acid derivative ix) homolytic cleavage and functionalisation x) 3-bromo-debutylation xi) conversion of vinyl trimethylstannane to methyl 2-oxocyclopentanecarboxylate (67). 

Application of this work to a domino process using 51 involves Michael addition of P-ketoesters [91], p-diketones or P-ketosulfones [92] to a,P-unsaturated ketones followed by an intramolecular aldol reaction provides highly functionalised cyclohexanone building blocks with up to four contiguous chiral centres. Gryko has also reported examples of this domino Michael/intramolecular aldol reaction in the coupling of 1,3-diketones and methyl vinyl ketone using L-proUne as catalyst [93],... 

The corresponding imides (1.40), called fulgimides, are most readily synthesised by conversion of the fulgide into the succinamic acids by reaction with amines, followed by dehydration. Functionalisation of the anhydride can also be achieved by reaction of the fulgides with malononitrile in the presence of diethylamine and subsequent recyclisation with acetyl chloride to give (1.41) from the corresponding E-fulgide and (1.42) from the Z-isomer. 

An alternative approach to selective functionalisation of 75 <2002DEP10115921> involves a first nucleophilic substitution step, followed by reduction of the 7-8 double bond and concomitant removal of the 8-chloride. The reduced species is N-acetylated, and the key intermediate 79 can be functionalized at either of G-2 or of G-6 (Scheme 42). Phosphorus(lll) reduction is then used to remove the remaining chlorine, and the second aromatic ring is reinstated by peroxide oxidation. 

The six membered ring was formed by first functionalising the terminal double bond via selective hydroboration using 9-BBN, followed by oxidative work-up to yield the terminal alcohol. To ensure successful hydroboration, lead tetraacetate was added to 5. This removed all traces... 

There is much current interest in the development of simple and effective methods for the conversion of selectively functionalised carbohydrates into stereodefined cyclopentanols, and South African chemists have reported an excellent samarium diiodide-based process. Thus, dropwise addition of the iodoglucoside 1 to a refluxing solution of excess of samarium diiodide in THF/HMPA, and heating of the mixture under reflux for 2 hours followed by cooling, dilution with 1 1 hexane/ethyl acetate and quenching with 5% aqueous citric acid gave the pure cyclopentanol 2 in 70% yield after flash chromatography. 

There are relatively few synthetic routes to 2,7-naphthyridines almost all are multistage and rely on annulation of a second pyridine ring to a suitably functionalised pyridine precursor. French workers have described an efficient, one-pot synthesis of l,3,6,8-tetramethyl-2,7-naphthyridine 1 which involves treatment of a mixture of acetyl chloride (1.6 mol) and aluminium chloride (0.3 mol) with t-butanol or t-butyl chloride (0.1 mol) at 35°C for half an hour, followed by careful addition of the reaction mixture to liquid ammonia. This gave 37% of 2,4,6-trimethylpyridine and 63% of the naphthyridine 1 in a total yield of 91%. 

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