Oxygen-containing heterocycle synthesis

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). 

Advances in the Synthesis of Oxygen-containing Heterocycles K. Fukui, Yuki Gosei Kagaku Kyokai Shi, 1966, 24, 741-754. 

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-... 

This section covers the synthesis of aziridines, oxiranes, /J-lactams and oxetanes. Aziridines are fairly important moieties in bioactive molecules and thus new routes for their synthesis are constantly being developed. /1-Lactams are probably the most important heterocyclic compounds that contain a single nitrogen atom, due to their importance in penicillin and cephalosporin chemistry. Their synthesis and chemistry has received much attention and much of this work has been reviewed544. The oxygen-containing heterocycles are much less commonly synthesized from double-bonded functional groups. 

The abundance of six-membered oxygen containing heterocycles in bioactive natural products continues to encourage the development of new and improved syntheses. There is a vast amount of new literature dedicated to the synthesis of pyrans and their benzo derivatives however, many traditional approaches are still of great value and this chapter should be read in conjunction with the corresponding chapters in the first and second editions of Comprehensive Heterocyclic Chemistry <1984CHEC, 1996CHEC-II>. 

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. 

Furfural (1), derived from annually renewable agricultural byproducts, is an important industrial chemical manufactured and used throughout the world. It is the feedstock for a number of derivative chemicals generically known as furans -the structural characteristic of which is the five-membered oxygen-containing heterocyclic ring. Furfuryl alcohol (2) is the most important derivative of commerce, where it is used primarily in synthesis of adhesive polymers. 

Oxazoles are well-investigated compounds. The occurrence, uses, and synthesis of oxazole derivatives have been the subjects of extensive reviews.5 The heterocyclic oxazole unit is seen with various substitution-patterns in a large number of naturally occurring compounds. Furthermore, oxazoles serve as synthetic intermediates leading to many other systems.5 6 7 In this context, oxazoles have seen, for example, numerous applications as "2-azadiene" components in 4+2 cycloadditions with several types of dienophiles. Further transformations of the products then lead to a number of other nitrogen- or oxygen-containing heterocyclic products.6... 

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... 

V. The Synthesis of Oxygen-Containing Heterocycles by Intramolecular Cyclizations in... 

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. 

Oxygen-containing Heterocycles Three-membered Rings. - The addition of oxygen to double bonds remains the most common method for epoxide synthesis, and several new variations on that theme have appeared this year. Thus, alkenes are converted into epoxides using a solution of elemental fluorine in an acetonitrile/water mixture with complete retention of olefin stereochemistry.1 Prat and Lett have re-examined the use of tungstic acid catalysed epoxidation in an attempt to define the scope and synthetic utility of the process. They have shown that reactivity increases with the nucleophilicity of the double bond and... 

Another multicomponent procedure used to construct oxygen containing heterocycles under MW conditions is the synthesis of pyrano[2,3-d]pyrimidine 56 [55]. 

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). 

FIGURE 10.13 Synthesis of large oxygen-containing heterocycles using reaction of 16 with bifunctional nucleophiles. 

Review article provides an overview of the synthesis of fluorinated nitrogen- and oxygen-containing heterocycles using RCM methodology. 

Hydroxylation of some substituted acetophenones under these conditions (Scheme 3.56) is especially useful for the synthesis of various oxygen-containing heterocyclic compounds [175-179]. Applications of this methodology in organic synthesis, especially in the chemistry of heterocyclic compounds, have been summarized in several reviews [166,180-182]. 

---