Heck cyclisation

Many further important natural product syntheses are covered by the aforementioned review. Particularly noteworthy amongst them are Hudlicky s syntheses of conduramines [522] and (+)-lycoricidine [523] since they employ enantioselective microbial oxidations of halobenzenes as source of chirality. Racemic lycoricidine has also been prepared by Martin et al. this synthesis exhibits an interesting Heck cyclisation as key step in addition to the hetero Diels-... 

Chromans and isochromans can be obtained by the reductive Pd-catalysed Heck cyclisation of 4-(2-bromophenoxy)-2-methylbut-l-ene and 3-(2-bromobenzyloxy)-2-methylpropene respectively <07TL2307>. Bromopropyl derivatives of 3,5-dihydroxy-iodobenzene and of 3,5-dihydroxymethyliodobenzene undergo sequential intramolecular alkylations and an intermolecular Heck coupling on treatment with an acrylate under microwave irradiation and Pd-catalysis mediated by norbornene. The products are 5-alkenyl derivatives of pyrano[3,2-g]benzo-2/7-1 -pyrans and pyrano[4,3-/]bcnzo-l77-2-pyrans (Scheme 13) <07JOC775>. 

Using titanium tetrachloride, the two steps in situ are hydroamination then Heck cyclisation. ... 

Tietze and Schimpf have demonstrated that the Heck cyclisation of o-iodophenethylallylamines is a very viable route to 2,3,4,5-tetrahydro-lH-3-benzazepines <94AG(E)1089>. If the reaction is carried out using the propargylamine... 

An intramolecular Heck cyclisation of secondary ethers was revealed recently. The reaction starts from chiral secondary benzylic ethers and enan-tioenriched methylenecyclopentanes are obtained in high yield and enantiospecificity under catalysis of Ni(PCy3)2Cl2 (Scheme 14.34). The reaction using electrophilic substrates with pendant 1,2-disubstituted olefins... 

Scheme 14.34 Intramolecular Heck cyclisation of secondary ethers.

Wensbo, D., Armby, U. and Gronowitz, S. (1995) Indole-3-acetic acids and hetero analogues by one pot synthesis including Heck cyclisation. Tetrahedron, 51,10323 2. 

Gibson, S.E. and Middleton, R.J. (1995) Synthesis of 7-,8- and 9-membered rings via endo Heck cyclisations of amino acid derived substrates. J. Chem. Soc., Chem. Commun., 1743. ... 

Indole-fused, or indole-benzo-fused azepinone derivatives have attracted synthetic attention and examples include the preparation of 85 in 84% yield from 84 by intramolecular Heck coupling [01SL848], as well as the preparation of paullone 87 (a CDK inhibitor) by cyclisation of 86 under basic conditions borylation/Suzuki coupling technology was used to access 86 [02JOC1199]. Acid-catalysed cyclisation with polyphosphoric acid was used to prepare the racemic reduced azepino[4,5-6]indoles 92a,b from the precursors 91, which were obtained in turn from CDl-mediated coupling of 88 and 89, followed by reduction of the amide with lithium aluminium hydride [01H1455]. 

Chalcones can be prepared by a Heck reaction between an aryl iodide and an aryl vinyl ketone. Demethylation allows spontaneous cyclisation to the flavanone <03TL9107>. An arene-alkene photocyclisation is observed during the irradiation of dihydro-2-methyl-2-vinylnaphtho[l,2-6]pyran-4-one and benzotricyclo[5.3.1.0 ]undecenes 24 result <03TL2011>. 

A standard Heck reaction, as shown in the example below, involves the palladium-catalysed reaction of a halide with an alkene, most commonly an electron-deficient aUcene such as an acrylate, but other types can also be used. Heck-type cyclisation onto olefins is a useful reaction for ring synthesis. 

Reaction of aryl bromides under Heck conditions with 2-vinyloxyethanol and a Pd phosphine catalyst gives products 9 <04SLl56l> while Ru-catalysed cyclisation of 2-allyloxyethanol gives 10 <04SL1203>. Reaction of the corresponding substituted catechol with 1-... 

An efficient route to the synthesis of the cytotoxic pyrrolo[2,l-c][l,4]benzodiazepines 97-99 with conjugated C2-acrylyl substituents based on a Heck coupling of 96 to introduce this C2 side-chain. The route started from the nitro benzoic acid 93, and proceeded via standard transformations to 94, which was then cyclised to the 7-membered ring derivative 95 on oxidation of the primary alcohol to the aldehyde <04BMCL1547>. 

It is not clear whether the palladium-mediated cyclisations of anilino-acrylates and related sytems operate via a Heck sequence or via an electrophilic palladation of the enamine. 

A-Allyl ort/fo-haloarylamines can be cyclised under a variety of conditions to give either indoles or indolines, the latter being convertible into indoles by dehydrogenation or elimination of hydrogen halide from a suitable intermediate. An intramolecular Heck reaction gives the indole directly via migration of an initially formed exocyclic double bond into the heterocyclic ring the exo isomer is isolable if silver salts are added to the reaction mixture. ... 

There are also excellent total syntheses of spirotryprostatins which do not apply intermolecular functionalisation of the indole 3-position with a C5 prenyl-type precursor and are, therefore, not discussed in detail. Carreira and co-workers started from 3-diazo-2-oxindole, which was used in a Rh(I)-catalysed cyclopropanation of 1,3-pentadiene. The resulting cyclopropane was subjected to Mgl2-catalysed ring expansion and added to an imine affording the spiro[5.5] partial structure [130, 131]. Overman and Rosen built up the indole system by intramolecular Heck reaction of a functionalised iodoaniline [132,133]. In a model study building up the indole system, Cacchi and co-workers synthesised 3-prenylindoles via Pd-catalysed cyclisation of orf/io-alkynyltrifluoroacetanilides with prenyl esters [134]. 

The first asymmetric Heck reactions were reported by Shibasaki in 1989. Typical examples from this group include the desymmetrising cyclisation of vinyl... 

The asymmetric Heck reaction can be used to synthesise quaternary carbon centres. During studies towards the synthesis of 3,3-disubstituted oxindoles. Overman and coworkers have shown how the use of silver salts can change the sense of asymmetric induction of the cyclised product. Thus, the iodide (10.131) can be converted into the product (10.132) with the (S)-enantiomer predominating, when the reaction is run in the presence of silver salts. In the absence of silver salts, the (J )-enantiomer is the major product. 

In the presence of nucleophiles, Shibasaki and coworkers have extended their methodology to a Heck reaction/carbanion capture sequence, which gives good enantiomeric excess. For example, using nucleophile (10.148) provides the highest enantioselectivity in the cyclisation/nucleophilic capture of triflate (10.149). ... 

This transformation can also be achieved using malonates and P-keto ester nucleophiles. Tietze and Raschke have used a silane-terminated Heck reaction, in which the substrate (10.151) loses the silyl group to give the cyclised product (10.152). Incorporation of a nitrogen atom at the requisite position in the side chain allows the enantioselective synthesis of tetrahydroisoquinolines and benzazepines using this methodology. ... 

An asymmetric polyene cyclisation (asymmetric tandem Heck) has been reported in the synthesis of the pentacyclic polyketide (-l-)-xestoquinone. ... 

Mohanakrishnan, A.K. and Srinivasan, RC. (1996) Synthesis of 4-substituted-1,2,3,4-tetrahydro-/)-carbolines via intramolecular radical cyclisation and Heck reaction. Tetrahedron Lett., 37, 2659-62. 

Effect of ligands on palladinm-catalysed phenylative cyclisation reaction and competitive Mizoroki-Heck reaction Palladium-catalysed intramolecular ary-lative cyclisation reactions of A/-Allylacetamide 46 with bromobenzene afforded... 

More recently, the Heck reaction has been used in cascade cyclisations, and under enantioselective conditions. For example, the intramolecular synthesis of decalin derivative 9 has been achieved in good enantiomeric excess, using an optically pure phosphine (Binap) as part of the palladium catalyst. ... 

Because of their negligible vapor pressure, thermal stability and easy recyclability, neutral ILs have been referred to as environmentally benign solvents. These ILs have been employed as excellent and recyclable medium for a wide array of reactions e.g., Heck reaction [Park Alper, 2003], Bischler-Napierlaski cyclisation [fudeh et al, 2002], Beckmann rearrangement [Ren et al., 2001], addition of thiols to unsaturated ketones [Yadav et al., 2003], 1-proline catalysed aldol reaction [Loh et al., 2002], and Pechmann condensation of phenols and ethyl acetoacetate (EAA) catalyzed by POCI3 in [bmim]PF6 and [bmim]BF4 ILs [Potdar et al., 2005]. Other examples where ILs have been used as a reaction media include, but not limited to, Diels-Alder reactions [Reinhardt, 2009 Doherty, 2004 Song, 2001], Friedel-Crafts alkylation and acylation reactions [Xiao, 2006 Xiao Malhotra, 2005 ... 

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