Functionalisation

The challenge of asymmetric and racemic a-functionalisation of carbonyls has led to the development of novel innovative solutions. As one option, organocatalysis and in particular, L-proline-catalysis has offered new technologies to access valuable a-functionalised products in a greener, more sustainable manner. 

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SYNTHESIS AND PROTOLYTIC PROPERTIES OF THE PERIODICALLY ORDERED MESOPOROUS ORGANOSILICAS WITH MCM-41-TYPE ARCHITECTURES FUNCTIONALISED... 

The presentation will focus on our work in functionalising these materials and modifying their physical properties to generate a range of materials with properties suitable for catalysis, and in some cases analytical applications. 

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 ... 

S.J. Shuttleworth, S.M. Allin and P.K. Sharma, Functionalised Polymers - Recent Developments and New Applications in Synthetic Organic Chemistry, Synthesis 1217-1239 7997. 

Israelachvili and his colleagues have used the SEA to study the interactions between surface layers of surfactant and of other molecules representing functionalised polymer chains, adhesion promoters or additives. Typically a monolayer of the molecule concerned is deposited onto cleaved mica sheets. The values of surface energies obtained from the JKR equation (Eq. 18) throw some interesting light on the nature and roughness of surface layers in contact. 

The required nitrite esters 1 can easily be obtained by reaction of an appropriate alcohol with nitrosyl chloride (NOCl). The 3-nitroso alcohols 2 formed by the Barton reaction are useful intermediates for further synthetic transformations, and might for example be converted into carbonyl compounds or amines. The most important application for the Barton reaction is its use for the transformation of a non-activated C-H group into a functional group. This has for example been applied for the functionalisation of the non-activated methyl groups C-18 and C-19 in the synthesis of certain steroids. ... 

J. H. Davis, Jr., Working Salts Syntheses and Uses of Ionic Liquids Containing Functionalised Ions,"... 

The 1,3-dipolar cycloadditions are a powerful kind of reaction for the preparation of functionalised five-membered heterocycles [42]. In the field of Fischer carbene complexes, the a,/ -unsaturated derivatives have been scarcely used in cyclo additions with 1,3-dipoles in contrast with other types of cyclo additions [43]. These complexes have low energy LUMOs, due to the electron-acceptor character of the pentacarbonyl metal fragment, and hence, they react with electron-rich dipoles with high energy HOMOs. 

The potential of Fischer carbene complexes in the construction of complex structures from simple starting materials is nicely reflected in the next example. Thus, the reaction of alkenylcarbene complexes of chromium and tungsten with cyclopentanone and cyclohexanone enamines allows the di-astereo- and enantioselective synthesis of functionalised bicyclo[3.2.1]octane and bicyclo[3.3.1]nonane derivatives [12] (Scheme 44). The mechanism of this transformation is initiated by a 1,4-addition of the C -enamine to the alkenylcarbene complex. Further 1,2-addition of the of the newly formed enamine to the carbene carbon leads to a metalate intermediate which can... 

Several examples of [5C+1S] cycloaddition reactions have been described involving in all cases a 1,3,5-metalahexatriene carbene complex as the C5-syn-thon and a CO or an isocyanide as the Cl-synthon. Thus,Merlic et al. described the photochemically driven benzannulation of dienylcarbene complexes to produce ortho alkoxyphenol derivatives when the reaction is performed under an atmosphere of CO, or ortho alkoxyanilines when the reaction is thermally performed in the presence of an isonitrile [111] (Scheme 63). In related works, Barluenga et al. carried out analogous reactions under thermal conditions [36a, c, 47a]. Interestingly, the dienylcarbene complexes are obtained in a first step by a [2+2] or a [3S+2C] process (see Sects. 2.3 and 2.5.1). Further reaction of these complexes with CO or an isonitrile leads to highly functionalised aromatic compounds (Scheme 63). 

J-Oxygen-functionalised sp3 organolithium compounds react with alkenyl-carbene complexes to generate the corresponding cyclic carbene complexes in a formal [3+3] process (see Sect. 2.8.1). In those cases where the organolithium derivative contains a double bond in an appropriate position, tricyclic ether derivatives are the only products isolated. These compounds derive from an intramolecular cyclopropanation of the corresponding cyclic carbene complex intermediate [89] (Scheme 83). 

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). 

Helquist s work on the use of diazomalonate in the synthesis of oxazoles has been extended to other diazocarbonyl compounds in our own laboratory.<92TL7769, 94T3761> Thus it was found that sulfonyl-, phosphonyl- and cyano-substituted diazoesters gave the corresponding 4-functionalised oxazoles 30 in acceptable yield (Scheme 20). In many cases the yield of oxazole was significantly improved by the use of rhodium(II) trifluoroacetamide as catalyst. The 4-cyano-oxazole 30 (R = Me, Z = CN) proved interesting in that it allowed the formation of a bis-oxazole 31 by a second rhodium catalysed reaction (Scheme 20). 

Degradation of bicyclic p-lactams has been used as a route to the monocyclic system. Highly functionalised P-lactams have been obtained in good yield by ozonolysis of A -cephems <96T10205> and enantiomerically pure 4-hydroxymethylazetidin-2-ones have been produced by degradation of a bicyclic oxazolidine, though in poor to moderate yield <96JCS(P1)227>. 

A novel route to functionalised 3-aminq)yridazines 77 is the reaction of 3-chloro-6-phenyl-1,2,4-triazine with C-nucleq)hiles. The mechanism proposed for this reaction is shown in Scheme 13 <96TL5795>. 

The cycloaddition of alkynes and alkenes to nitrile oxides has been used in the synthesis of functionalised azepine systems <96JHC259>, <96T5739>. The concomitantly formed isoxazole (dihydroisoxazole) ring is cleaved by reduction in the usual way. Other routes to 1-benzazepines include intramolecular amidoalkylation <96SC2241> and intramolecular palladium-catalysed aryl amination and aryl amidation <96T7525>. Spiro-substituted 2-benzazepines have been prepared by phenolic oxidation (Scheme 5) <96JOC5857> and the same method has been applied to the synthesis of dibenzazepines <96CC1481>. 

In other cyclisations to functionalised oxepanes, Rychnovsky and Dahanukar have shown that the epoxide 36 cyclises with BF3 etherate and TMSCN to form the oxepane 37 as single product <96TL339>, and Evans and Roseman have prepared a series of cyclic ethers by radical cyclisation of the acylselenides 38 (Scheme 8) <96JOC2252>. The major product was always the cw-isomer and the best yields were obtained with (TMSjaSiH. 

Functionalisation Through the C-7 Position of Zanamivir The Development of Long Acting Sialidase Inhibitors... 

The retention of potent enzyme inhibition and in vitro antiviral activity in the presence of functionalisation with relatively long hydrophobic chains at C-7 of zanamivir has been exploited in the development of di- and poly-valent structmes carrying zanamivir (reviewed in Sun 2007). Multivalent presentation of drug may... 

Brown JB (1999) Hydrogenation of functionalised carbon-carbon double bonds. In Jacobsen EN, Pfaltz A, Yamamoto H (eds) Comprehensive asymmetric catalysis, vol 1. Springer, Berhn Heidelberg New York, chap 5.1 Noyori R, Takaya H (1990) Acc Chem Res 23 345... 

Phospholes can readily be prepared on a large scale and are known with a vast range of substituants [6, 16b,c]. However, the synthesis of oligo(phosphole)s analogous to (C) (Fig. 1) is a real synthetic challenge since the low aromatic character of phosphole prevents the functionalisation of the P-Ca,a carbon atoms via electrophilic substitution and inhibits their preparation using electropolymerisation. As a consequence, no poly(phosphole)s have yet been reported, although bi- and tetra-phospholes have been prepared by stepwise routes (Scheme 2). 

More recently, P-cored derivative (116) was prepared from a straightforward combination of a Heck coupling, to afford an intermediate functionalised stil-bene phosphine oxide (114),a Horner-Wittig reaction yielding the phosphine oxide (115), and finally trichlorosilane reduction (Scheme 31) [89]. Using similar strategies, both the valence isoelectronic N- (117) and C- (118) cored dendrimers have been prepared (Scheme 31). 

Bauer RE, Grimsdale AC, Mullen K (2005) Functionalised Polyphenylene Dendrimers and Their Applications. 245 253-286 Beaulac R, see Bussito G (2004) 241 97-118... 

It might seem that allylic functionalisation can be used only on terminal alkenes such as (26) or trisubstituted alkenes, such as (31) when the orientation of addition is unambiguous. 

Early syntheses of lineatin reconnected the 1,5-di-functionalised part to give structures like (23) so that syntheses by 2 + 2 cycloaddition would ensure the correct stereochemistry. 

Development of (46) is easier because it needs only to be functionalised at the unique carbon atom between the... 

Woolfson and Mahmoud have classified the routes to preparation of decorated self-assembling peptide materials [53] as (1) co-assembly, where the functional part is already attached to a self-assembling component prior to assembly, and (2) postassembly, where a non-functionahsed self-assembled structure is modified by covalent or non-covalent means. This discussion adheres to this classification. A third route, beyond the scope of this review, is the use of structured peptides as templates for inorganic materials. Section 4.1 discusses functionalised self-assemblies formed from co-assembly-type approaches, while post-assembly modifications of self-assembled structures are considered in Sect. 4.2. 

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