Furans highly substituted

Furans. Highly substituted furans can be obtained by Rh2(OAc)4-catalyzed reaction of 2-diazo-l,3-dicarbonyls with arylacetylenes. A typical example5 is formulated. 

A high endo selectivity is observed in the reaction of (phenylsulfonyl)allene (112) with furan (157) (equation 113)108. The endo adduct 158 can be readily transformed into highly substituted cyclohexenol 160 upon treatment with n-butyllithium after hydrogenation of the ring double bond (equation 114)108. 

When a terminal alkyne is offered intramolecularly as in allenyne 108, the highly substituted phenols 110 were formed (Scheme 15.29) [65]. The reaction proceeds through an initial isomerization to the corresponding furan 109, which could be proved by the direct use of that furans [66-68],... 

When furan was substituted at C-2 by a pyridine function [e.g., 4 -(2, 6 -dimethyl)pyridyl] high yields (>90%) of the 5-bromo derivatives were... 

A related synthesis of highly substituted furans was reported by Schmalz and Zhang from cyclopropyl alkynyl ketones. The reaction scope included a great variety of nucleophiles such as several alcohols, indole or even acetic acid [140]. 

Phenol Synthesis A new method for obtaining arenes from easily available furans was reported by Hashmi et al. [19]. In this first paper, AuCl3 was used to produce a highly substituted phenol without side products. 

Iodine, NIS, PhSeCl, and AUCI3 have been shown to trigger the electrophilic 6(O) "-endo-dig cyclization of 2-(alk-l-ynyl)alk-2-en-l-ones (22) to produce highly substituted furans (23) (Scheme 3). Various nucleophiles, including functionally substituted alcohols, H2O, carboxylic acids, 1,3-diketones, and electron-rich arenes, and a range of cyclic and acyclic 2-(alk-l-ynyl)alk-2-en-l-ones readily participate in these cyclizations.40... 

Facile, regioselective ring opening-cross-metathesis reactions between unsymmet-rical norbornene derivatives and electron-rich alkenes in the presence of the second-generation Grubbs catalyst have been reported to generate highly substituted furans and pyrroles.114... 

PhsPAuOTf has been shown to catalyse the intermolecular addition of phenols and carboxylic acids to terminal alkenes, RCH2CH=CH2, at 85 °C in toluene with Markovnikov selectivity to produce RCH2CH(OR)Me.131 AUCI3 triggers the electrophilic 6(0)ir n-endo-dig cyclization of 2-(alk-l-ynyl)alk-2-en-l-ones to produce highly substituted furans in analogy with other electrophiles (see above Scheme 3).40... 

The cyclization of 2-(alk-l-ynyl)alk-2-en-l-ones (199) to afford highly substituted furans (200) can be readily induced in the presence of alcohols with a catalytic amount of Cu(I)Br in DMF at 80 °C. This catalyst is easy to handle, compared with the previously known system that employed the moisture-sensitive AUCI3.236... 

The gold-catalysed synthesis of highly substituted arenes or benzofurans from furans has proved to be a powerful tool for organic synthesis.76 Experimental evidence has now been provided for the formation of (47) via (46). 

The CIR is exceptionally well suited as an entry to multi-component syntheses of aromatic heterocycles and on this basis Muller and coworkers [91f, 92] designed a coupling-isomerization-Stetter-Paal-Knorr sequence as a diversity-oriented approach to highly substituted furans and pyrroles (Scheme 5.22). 

In addition to this latter work, a silver-catalyzed 1,2-alkyl/aryl shift is also possible with allenyl ketones (16), giving, as before, highly substituted furans (17, Scheme 5.9).44 Not surprisingly, Gevorgyan et al. observed that the migratory aptitude... 

Scheme 12.11. Highly substituted furan heterocycles by coinage metal catalysis.

Synthetically even more versatile trifunctional intermediates result from the addition of carbonyl compounds onto methyl 2-siloxycyclopropanecarboxylates 92). Benzo-phenone, titanium tetrachloride, and 162, for instance, provide an excellent yield of the a-hydroxyalkylated y-oxoester 174, which predominates in the equilibrium with its cyclic hemiacetal 176 (y-lactol). It can undergo elimination to the unsaturated ester 175, but as Scheme 7 illustrates, 174/176 can also serve as the starting material to several highly substituted furan(one) derivatives. 

Highly substituted furans play an important role in organic chemistry, both as key structural units in many natural products and important pharmaceuticals, and as useful building blocks in synthetic chemistry examples of their synthesis using gold catalysis have recently been reported.19... 

Preparation of highly substituted furans was reported by tandem ring-opening/cyclization reactions of alkynyl epoxy alcohols in moderate to good yields using alcohol as a nucleophile and Cu(OTf)2 as catalyst, as can be seen below <07S3295>. Silver-catalyzed reaction of similar substrates, 3-alkyne-l,2-diols, also furnished the corresponding... 

The addition of vinyl and aryl Grignard reagents to propargyl alcohols followed by reaction with a nitrile provides access to furans and butenolides in a one-pot procedure. These reactions are believed to involve a magnesium-chelate intermediate. Highly substituted furans can be prepared with control over the substitution pattern by the judicious choice of substrates and reagents (Scheme 26) <2000TL17>. 

A concise synthesis of highly substituted furans, pyrroles, butenolides, and 2-butene-4-lactam esters starts from alkynyl adducts of a Fischer carbene complex 21 (Scheme 27) < 1998JOC3164>. Incorporation of an aldehyde yields a reactive vinyl tungstencarbonyl complex 22 that can be oxidatively transformed to an ester group, furnishing the furan carboxylic ester 23. 

The reaction of dibenzoylacetylene and enol systems, such as acetylacetone, 5,5-dimethylcyclohexane-l,3-dione, 1-naphthol, 2-naphthol, 2,7-dihydroxynaphthalene, or 8-hydroxyquinoline in the presence of triphenylphosphine, leads to tetrasubstituted furans in 65-83% yield (Equation 115) <2002TL4503>. DABCO-catalyzed reaction of a-bromocarbonyl compounds with DMAD also yields highly substituted furans <2005JOC8204>. 

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. 

Diels-Alder reactions of oxazoles have proven to be quite versatile and continue to attract attention. Oxazoles have traditionally been used as the diene component and react with alkyne dienophiles to give furan products after extrusion of a nitrile molecule via a reverse-cycloaddition process. This method has been used to access highly substituted furans and has been utilized in numerous natural product syntheses. The reaction typically requires the use of high temperatures for efficient conversion. The furan intermediate 67 was obtained by a thermal intermole-cular Diels-Alder reaction between oxazole 66 and an acetylene. Furan 67 was a key intermediate for the synthesis of (—)-teubrevin G (Scheme 10) <2000JA9324>. Similarly, furan 68, obtained from a Diels-Alder reaction between 4-phenyloxazole and an acetylene, served as an intermediate in the total synthesis of the natural product cornexistin (Scheme 10) <20030L89>. 

The reaction was extended to more highly substituted silyloxy furans 17b and 17c furnishing the products with only slightly diminished enantioselectivities (Scheme 5.6). 

The procedure described here provides a direct synthesis of highly substituted furans (see Table). Reaction of keto carbenoids with acetylenes is normally an efficient method to prepare cyclopropenes. In numerous systems, however, the formation of furans was observed as a competing side reaction. Furan formation is particuiariy favored when the carbenoid is a pyruvate or contains two electron-withdrawing groups,and when eiectron-donating groups are present on the acetyiene. >8... 

Heterocycle synthesis. Highly substituted furans are obtained from 2-alkylidene-3-alkynones via conjugate addition to generate enols that show nucleophilicity at C-3." ... 

The asymmetric Michael addition of secondary enamines has been reviewed by d Angelo [179]. Some of the more selective examples of this type of reaction are listed in Table 5.8. It is significant that these Michael additions are highly regio-selective, reacting virtually exclusively at the more highly substituted carbon, which affords a,a-disubstituted (quaternary) cyclopentanones, cyclohexanones, furans,... 

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