Oxygen-containing heterocycle reaction

Sometimes, hydrogen sulfide converts an oxygen-containing heterocycle into a sulfur-containing one, and as furans and polycyclic furans are very common in nature such reactions may be the origin of the polycyclic thiophenes mentioned above. A typical example is the formation of the isothiazolin-3-thione (6) from the isoxazolin-3-thione (7) on treatment with hydrogen sulfide and hydrogen bromide.8... 

The key step in Biichi s total synthesis of loganin (5i)23 made use of the expansion of a four-membered ring to an oxygen-containing heterocycle by retro-aldol reaction. This strategy was later exploited by Tietze in his total synthesis of hydroxyloganin (54) as well as hydroxyloganic acid (55) 24). 

The formation of oxygen-containing heterocyclic compounds is also a consequence of the Maillard reaction. Amines and amino acids have a catalytic effect upon the formation of 2-furaldehyde (5), 5-(hydroxy-methyl)-2-furaldehyde (11),2-(2-hydroxyacetyl)furan (44),2 and 4-hy-droxy-5-methyl-3(2//)-furanone (111) (see Ref. 214). This catalytic effect can be observed with several other non-nitrogenous products, including maltol. The amino acid or amine catalysis has been attributed to the transient formation of enamines or immonium ions, or the 1,2-2,3 eno-lization of carbohydrates. Of interest is the detection of A -(2-furoyl-... 

Unlike carbocyclic and oxygen-containing heterocyclic systems, catalytic enantioselective synthesis of eight-membered ring amines proceeds efficiently and with excellent enantioselectivity. These catalytic ARCM reactions can be carried out in the absence of solvent as well. Representative data regarding cat-... 

Heating of carbohydrates produces a number of aromatic compounds Including aldehydes, ketones, and dicarbonyls as well as oxygen containing heterocyclic compounds such as furans, dihydrofuranones, and pyrans through caramelizatlon and dehydration reactions. 

Pyrans constitute another class of oxygen-containing heterocycles that have been prepared from Ni-catalyzed cycloaddition reactions. The coupling of diynes and aldehydes could be mediated by the combination of a Ni(0)... 

In connection with the aforementioned reaction, Shea et al. reported the synthesis of [5,8,5]- and [5,7,5]-tricyclic oxygen-containing heterocycles via tandem Nicholas [35] and Pauson-Khand [23,24] reactions of acyclic enynes [36]. A typical Nicholas/[2 + 2 + 1] sequence is depicted in Scheme 12. 

These non-classical Wittig reactions of esters have been used to prepare a number of oxygen-containing heterocycles.35 Phosphonate stabilized carbanions, for example, those derived from dimethyl methylphophonate, also react with esters to give, in this case, a P-keto phophonate which can react further with aldehydes and ketones. 

Considerably more important are reactions involving an endocyclic attack of C-nucleophiles. Besides rarer reactions with aromatic nucleophiles (the oxa analog of the Pictet-Spengler reaction) the use of vinylic nucleophiles especially provides an efficient route to critical , medium-sized oxygen-containing heterocycles. Thus, even nonactivated alkenes like (104) readily undergo acid-catalyzed cyclization in remarkable yields (Scheme 51). ... 

The intramolecular O—H insertion reaction of a carbene has been successful in the synthesis of the oxygen-containing heterocycle 216 in quantitative yield (85JOC5223). Carbene generated by photolysis of diazo precursor 217 in protic solvents gives 2-phenyl-2,5-dihydroisobenzofuran competitively with insertion into the O —H bonds of the solvent (90JOC2325). 

The transition-metal-catalyzed reaction of diazo compounds 702, which have a N—H or O—H bond at an appropriate position, gives nitrogen- and oxygen-containing heterocycles 703 (Scheme 2 1 8).293 Wang and Zhu demonstrated a convenient synthesis of the polyfunctionalized /Tfluoropyrroles by the rhodium-catalyzed intramolecular N—H insertion reaction.2933 The reaction of d-amino-y,y-difluoro-a-diazo-/Tketo esters 704 in the presence of Rh2(OAc)4 gave the... 

It was reported (94IC415) that the reactions of 2,2,3,3 tetrafluorobutyleneglycol triethylsilyl ether with 1,4-dibromotetrafluorobenzene, tetrabromoethane, and oxalyl fluoride form oxygen-containing heterocycles (Scheme 143). Adamson et al. (92JFC(58)300) showed that 1,2,3,4-tetrafluoroacridines 154 are formed in quantitative yields in reactions of pentafluorobenzaldehyde with substituted anilines at room temperature (Scheme 144). 2,3-Diphenyl-4,5,6,7-tetrafluorobenzofuran is formed in a reaction of hexafluorobenzene with phenyl benzyl ketone in the presence of sodium hydride (79BCJ2657) (Scheme 145). The reaction involves intramolecular nucleophilic cyclization of the generated O-nucleophile due to tautomerization of the intermediate ketone. 

Zeolites are known to catalyze the formation of various nitrogen-containing aromatic ring systems. Examples include the synthesis of pyridines by dehydrogenation / condensation / cyclization of C -Cg precursors [1], the formation of methylpyridines by high-temperature isomerization of anilines [2], the amination of oxygen-containing heterocyclic compounds [3] and the Fischer indole synthesis [4,5]. The latter synthesis consists (see Scheme 1) of a condensation towards a phenylhydrazone followed by an acid-catalyzed cyclization with elimination of ammonia. The two reaction steps are usually combined in a one-pot procedure. 

Cycloaddition reactions as an approach to nitrogen- and oxygen-containing heterocycles have dominated the literature this year and are the topic of the remainder of this section. The intramolecular cycloaddition of aryl oxaziridines to give fused isoxazolidines (71) proceeds in good yield, presumably via a nitrone intermediate. On the other hand the oxime (72) undergoes an intramolecular cycloaddition to give the isoxazolidine (73) and can either be... 

Ring-expansion reactions have been carried out in a dienone-phenol rearrangement of (7) to the oxygen-containing heterocycle (8) with 30% methanolic sulphuric acid," and in a stereospecific synthesis of a 4-thiacyclo-octene via a [2,3] sigmatropic shift (see last year s Report, p. 412). 

Hydroalkoxylation of alkynes, or the addition of alcohol to alkynes, is a fundamental reaction in organic chemistry that allows the preparation of enol ethers and a variety of oxygen-containing heterocycles such as furan, pyran, and benzofuran derivatives. Bergbreiter et al. found that a Mnear poly-(A-isopropylacrylamide) (PNIPAM) polymer exhibited inverse temperature solubility in water (i.e., soluble in cold water but insoluble in hot water). A recoverable homogeneous palladium catalyst was prepared based on the polymer. The PNIPAM-bound Pd(0) catalyst was effective for the reaction of 2-iodophenol with phenylacetylene in aqueous THE media to give the target product... 

FIGURE 10.12 Construction of large oxygen-containing heterocycles using reaction of 16 with salicylic acid and salicylaldehyde. 

There are several reactions (bromination, oxymercuration, epoxidation) of olefinic hydroxy and epoxy compounds in which the oxygen function can react intramolec-ularly with an intermediate formed at the double bond, leading to an oxygen-containing heterocyclic compound (tetrahydrofuran or tetrahydropyran) (Scheme 6). 

The proposed mechanism for the formation of the oxygen-containing heterocycles 21 and 22 is based on a seven-membered paUadacychc complex 23 (Scheme 13) in which the regiochemistry of the reaction is controlled by steric factors. 

Formation of six-membered cycles is the second most common case of heterocyclic Mizoroki-Heck reactions, with, as for the formation of five-membered rings, exo-cyclization reactions being largely favoured compared to c d( -cyclization reactions. As already noted for the five-membered cycles, there are more examples of iV-heterocyclic formation than of oxygen-containing heterocycles. 

---