Addition-cyclisation

Alumina catalyses addition of ethyl nitroacetate to 2,3-epoxyaldehydes, which occurs in two stages, the second of which involves the opening of an epoxide ring rapidly followed by a cyclisation that proceeds with inversion of configuration (e.g. equation 4.48) [171]. 

In this chapter we have surveyed those reactions which have been developed recently. It is hoped that this might stimulate investigation of other reactions, especially those for which environmentally undesirable reagents are currently in use on a commercial scale. 

Solid Supports and Catalysts in Organic Synthesis (ed K. Smith), Ellis Horwood Ltd., Chichester, 1992. 

Nauk SSSR, Ser. Khim, Nauk 1990, 103. 

Umezono, M. Kawai and Y. Izumi, J. Chem. Soc., Chem. Commun. 

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This sequence gives high yields when hydrogenation over Raney nickel is used. A quaternary ammonium hydroxide was used to catalyse the Michael addition. Cyclisation is spontaneous. 

The Pd-catalysed carbonylation of alkynyl epoxides 60 and alkynyldioxolanones 61 leads to the allenes 62 which can then be converted to the same pyranones through a tandem conjugate addition-cyclisation (Scheme 40) <00JCS(P1)3188>. Carbonylation of allenyl alcohols is catalysed by Ru3(CO)i2 and yields 5,6-dihydropyran-2-ones . 

Unexpectedly, and very pleasingly, even the construction of 7-membered rings proved possible. Two examples are shown in Scheme 30 illustrating both a direct cyclisation and an addition-cyclisation sequence [66]. The first derivative 54, being ultimately derived from tryptophan, can be obtained in principle as an optically pure substance. The second is a simple approach to very rare polycyclic structures such as 55, only one example of which was documented in the Beilstein data bank. 

As a result of acid-catalysed reactions during steam distillation, a number of terpenes and sesquiterpenes [66] of the native cold-pressed oils undergo transformation /9, 67-69]. This applies mainly to the pinenes, sabinene, thujene and some sesquiterpenes. While cold-pressed lime oils contain up to 2.3% of the reactive germacrenes, only traces of germacrene B can be found in distilled oils ]70]. When compared to their educts, the newly formed constiments, mainly alcohols, such as a-terpineol or fenchyl alcohol, possess completely different sensory properties. Additionally, cyclisations and hydratisations of aldehydes result in a reduced presence of these constituents in distilled products. Many compounds which characterise the flavour of distilled lime are formed during production. The extremely different composition of cold-pressed and distilled oils accounts for their completely different flavour profile and they, therefore, have to be considered as a reaction flavouring. 

Scheme 7.10 Indium-mediated tandem radical addition-cyclisation-trapping reactions in aqueous media.

Pyridine reacts with dimethyl acetylenedicarboxylate, firstly being A -alkylat-ed by the electrophilic alkyne to give a zwitterion which then adds as a nucleophile to a second equivalent of the alkyne, the process being completed by an intramolecular nucleophilic addition/cyclisation to the pyridine a-posi-tion the initial product tautomerises to a more stable final product. 

Synthesis of chiral heterocycles by domino organocatalytic processes has also been intensively studied. In particular, various benzo-fused heterocycles, such as chiral chromans, " thiochromanes, hydro-quinolines, dihydropyranes, or thiopyranes were investigated. These organocatalytic sequence were typically initiated by a hetero-Michael addition of a sulfur, oiqrgen or nitrogen nucleophile, which triggers the formation of an enolate/enamine that adds to the ortho electrophile terminating the cascade reaction. An elimination step or an additional cyclisation step follows (Scheme 8.25). 

The [Ir(ppy)2bpy] complex photo-catalyses inter- and intramolecular C-H functionalisation reactions of tertiary amines under the visible light irradiation. Oxygen behaves as a chemical switch, triggering different reaction pathways and leading to different products from the same starting material. In anaerobic conditions, the intermolecular addition of iV,iV-dimethyl-anilines to electron-deficient alkenes yields y-amino nitriles. Aerobic conditions, on the other hand, favour a radical addition/ cyclisation reaction, leading to tetrahydroquinoline derivatives. The intramolecular version of the radical addition produces unexpectedly indole-3-carboxaldehyde derivatives. ... 

Intermolecular variants involving addition-cyclisations have... 

This catalyst was also used by Ma et al. to promote a domino Michael addition-cyclisation process of aldehydes with a-keto-a,p-unsaturated esters, proceeding smoothly in water in the presence of AcOH as an additive.The corresponding chiral cyclic hemiacetals were formed in both high yields and diastereoselectivities and almost complete enantioselectivities, and were subsequently oxidised by treatment with PCC to furnish highly functionalised 3,4,5,6-tetrasubstituted dihydropyrones (Scheme 1.34). 

Scheme 1.35 Silylated biphenylprolinol-catalysed domino Michael addition-cyclisation reactions.

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