3- Chloro-4-iodo furans

Furthermore, the concept of a sequential nucleophilic addition in acidic medium can be transposed to the conversion of the ynone intermediates with iodine monochloride [197] and subsequent cyclization [198] into chloro iodo furans in a one-pot fashion. Therefore, after coupling of (hetero)aroyl chlorides 7 and THP-protected propargyl alcohols 54, NaCl, iodine monochloride, and PTSA were added to give after 4 h of stirring at room temperature the substituted 3-chloro-4-iodo furans 59 in moderate to decent yields (Scheme 34) [196]. 

Scheme 34 Coupling-transacetalization-addition-cyclocondensation three-component synthesis of 3-chloro-4-iodo furans 59...

Scheme 36 Suzuki coupling of the 3-chloro-4-iodo furan 59g...

Chloro-4-iodo furans 59 can be valuable building blocks for the synthesis of highly substituted furans as illustrated by the Suzuki coupling of chloro iodo furan 59g with boronic acid 60d (R = p-MeOCeHU) furnishing trisubstituted chloro furan 62 in 59% yield (Scheme 36). Expectedly, the coupling selectively occurs at the carbon-iodine bond. 

Synthetic procedures are available for the preparation of fluoro (e.g., 2-lithio-l-methyl-5-octylpyrrole with fV-fluoro-iV-(phenylsulfonyl)benzenesulfonamide <2003JFC(124)159>), chloro, bromo, and iodo compounds from the corresponding lithio derivatives, for example, 2-iodobenzo[A]furan via lithiation of the heterocycle then reaction with iodine <2002JOC7048>. Perchloryl fluoride (FCIO3), A-chlorosuccinimide, bromine, and iodine are examples of reagents which can be used to introduce fluorine, chlorine, bromine, and iodine, respectively. 

A carboxyl group is removed from a heterocyclic nucleus in much the same way as from an aromatic nucleus (method 13), i.e., by thermal decomposition. The pyrolysis is catalyzed by copper or copper salts and is frequently carried out in quinoline solution. The reaction is important in the synthesis of various alkyl and halo furans. Furoic acid loses carbon dioxide at its boiling point (205°) to give furan (85%). A series of halo furans have been made in 20-97% yields by pyrolysis of the corresponding halofuroic acids. The 5-iodo acid decarboxylates at a temperature of 140°, whereas the 3- and 5-chloro acids requite copper-bronze catalyst at 250°. ... 

The unsubstituted "1-norbomene" was nevertheless generated by alkyllithium-mediated iodo/lithium permutation from l-iodobicyclo[2.2.1]heptanes bearing at the 2-endo- or 2-exo-position a bromo or chloro substituent and ensuing lithium halide elimination. When the reaction is carried out in the presence of furan at -60 °C, always the same endo/exo mixture of Diels-Alder cycloadducts is obtained irrespective of what starting material is employed(Scheme 1-216). " This corroborates the intermediacy of the short-lived species 274. 

On the other hand, monosubstitution at C7 is the only route to products obtained in good yields in the reactions of 5-chloro-7-iodo or 5,7-dichloro-8-i-propoxyquinoline with the anions derived from CH3COR (R = Me, Et, t-Bu, 2-furanyl) (70 to 80% yields). Cychzation of these substituted compounds is possible to obtain furan derivatives (see Section 47.9). 

The compounds formed in the S,y l reaction of the enolate of a ketone or aldehyde (MeCOR, R = H, Me, i-Pr, t-Bu) with o-alkoxyhalobenzenes undergo spontaneous cyclodehydration after deblocking of the alkoxy function to afford benzo[h]furan 13 derivates quantitatively, as in the reaction with o-iodoani-sole (Scheme 3). This approach is also used in the synthesis of furo[3,2-/z]quinoHnes and furo[3,2-h] pyridines, which are quantitatively formed by acidic treatment of the products obtained in the SrjjI reaction of 5-chloro-7-iodo-8-i-propoxyquinoHne and 2-bromo-3-i-propoxypyridine, respectively, with the enolate ions of ketones ( CHjCOR, R = Me, Et, t-Bu, 2-furanyl, p-anisyl) ... 

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