Heterocycles from acetals

Silylthioaldehydes 103, reactive dienophiles formed in situ from acetals according to a general method, are directly trapped with dienes to afford sulfur-containing heterocyclic compounds in good yield (Equation 2.29). Silylthioaldehydes are quite reactive in comparison with the aliphatic ones [102] which are rather inert in the cycloaddition reactions. 

In terms of economical synthetic approaches to indoles, the synthesis of this heterocycle from anilines and trialkylammonium chlorides was effected in an aqueous medium (H20-dioxane) at 180°C in the presence of a catalytic amount of ruthenium(III) chloride hydrate and triphenylphosphine together with tin(II)chloride <00TL1811>. Muchowski devised a novel synthetic route to indole-4-carboxaldehydes and 4-acetylindoles 86 via hydrolytic cleavage of W-alkyl-5-aminoisoquinolinium salts 85 to homophthaldehyde derivatives upon heating in a two phase alkyl acetate-water system containing an excess of a 2 1 sodium bisulfite-sodium sulfite mixture <00JHC1293>. 

The chromenes and benzofurans are rather simple compounds built from acetate and Isoprene metabolites. Heterocyclic ring formation gives rise to 2,2-dlmethyl chromene or 2-isoprophenyl benzofurans. The majority of known chromenes and benzofurans exhibit a methyl ketone moiety at a position para to the oxygen of the heterocyclic ring. Constituents esterified with phenolic acids or lacking methyl ketones are rare. 

Finally, we would like to report on four additional important flavor compounds that we have isolated and identified from our model mixture, two of which are, to the best of our knowledge, new to the literature. The components are illustrated in Table IV. Two aliphatic dithio-hemiacetals (methylthiomethanethiol and 1-methylthio-ethanethiol 1 7) as well as two heterocyclic dithiohemi-acetals (1-( 2-methyl-3-thienylthio)-ethanethiol 1 8 and 1-(2-methyl-3-furylthio)-ethanethiol J 9) were identified. 

Alkylmercaptomethyleneiminium salts as well as alkoxymethyleneiminium salts are transformed to amide thioacetals (443 equation 206) by alkali metal thiolates and thiols. - The action of alcoholic alkoxides on 2-alkoxy-2-dialkylaminocarbonitriles (444 equation 207) produces amide acetalsJ Spi-locyclic amide acetals (446 Scheme 82) were prepared from oxazolium salts (445) and substituted sal-icyl aldehydes. The addition of alcohols to the l,3-oxazolium-4-olate (447) affords heterocyclic amide acetals (448). ... 

The electrolysis of DMF in alcohols affords a product mixture in which amide acetals, e.g. (475) and (476) (equation 219), are present. The heterocyclic amide acetal (479 equation 220) was obtained by reaction of the ynamine (478) with the o-quinonimine derivative (477). ° An azomethine ylide, generated in situ from the iminium salts (480 equation 221), transforms m-nitrobenzaldehyde to the oxazolidine derivative (481). ... 

In the synthesis of various heterocycles from a-amino ketones, pyrazine formation can be a complicating side reaction due to the tendency of the a-amino ketone to dimerize. One way of avoiding this problem would be to generate the a-amino ketone in a protected form, specifically, as an a-amino acetal. Such derivatives allow the manipulation of the amino moiety as desired. Accordingly, the azirine intermediates derived from oxime tosylates by the Neber rearrangement are subsequently treated with acidic ethanol to furnish the corresponding a-amino acetals (equation 65). ° ... 

Intramolecular heterocyclization in polyacrylonitrile 86UK62. a-Isocyano acetates, synthesis of N-heterocycles from 85YGK764. Isonitrosotosyl malonates in synthesis of N-heterocycles 80H(14)1581. Lactams, regioselective formation from bridged bicyclic ketones 81T1283. Malononitrile derivatives, synthesis of N-heterocycles condensed from ... 

An intermolecular version of the Sakurai reaction has been developed. It proceeds at temperatures as low as —78°C, using substoichiometric amounts of the Lewis acid, to form five-or six-membered oxygenated heterocycles from cyclic allylsilox-anes and aldehydes through a chairlike transition state (eq 65). Acetals may also act as electrophiles in this kind of reaction. /3-Borylallylsilanes also undergo nucleophilic allylation to lead to the preparation of functionalized alkenylboranes, which may participate in further transformations. ... 

Why is this important There are many reactions in which lone pairs have an important role to play. For example, in an acetal hydrolysis, stabilization of the forming positive charge by an adjacent lone pair facilitates the elimination step of the mechanism. Let s consider what happens in this acetal hydrolysis where the acetal is a saturated heterocycle. From Chapter 11, you expect this to be the mechanism ... 

Irradiation acetic acid o-a-Chloro-N-heterocyclics from ethylene-N-chloramines... 

Hydrogen chloride acetic anhydride a-Oxo-N-heterocyclics from o-carboxy-N-oxides... 

Recently, a novel methodology has been developed to prepare densely functionalized heterocycles from the coupling of various Michael acceptors with readily available iminium ions (masked as N,0-acetals) via an intermolecular MBH-type reaction. An intramolecular MBH-type reaction was developed to construct a bicyclic pyrrolizidine ring. As shown Scheme 5.32, the total synthesis of ( + )-heliotridine, as this basic structure unit existed in many plants, was achieved. ... 

Potassium acetate a-Diketone monothioketals from a-hydroxymethyleneketones Spiro-1,3-S,S-heterocyclics from bis(thiolsulfonates)... 

Acetic anhydride (s. a. under CHfiOONa) o-Subst. N-heterocyclics from cyclic N-oxides s. 18, 833 s. a. Chem. Pharm. Bull. 21, 712 (1973)... 

Acetic acid I pyrrolidine 0-Heterocyclics from diols with cleavage of ketals... 

Without additional reagents N-Heterocyclic carbinol acetates from N-oxides... 

Let us summarize biosynthetically the flavan derivatives are hybrid substances. Their A ring is derived from acetate, their B ring and the C atoms 2, 3 and 4 of the heterocycle from phenylpropanes. The 15 C skeleton is probably synthesised from malonyl CoA and cinnamic acid CoA compounds, the reaction sequence being analogous to the acetate-malonate pathway. 

Combs et al. [73] reported the first examples of polymer-supported aryl-heteroaryl C-N cross-coupling reactions and dramatically decreased reaction times upon microwave irradiation. The methodology provides easy access to N-arylated heterocycles from heterocycles bearing an N-H bond and readily available arylboronic acids in the presence of copper(II) acetate and pyridine. 

The Curtius rearrangement in acetic anhydride of the azide (8) prepared from 4-carboxythiazole yields 4-acetamidothiazole (Scheme 8) (47). The same reaction starting with ethyl-2-methyl-4-thiazolyl carboxy-late, failed to give the 4-aminothiazole (48). Heterocyclizations are more convenient synthetic methods (Chapter II. Table 40). 

The direct combination of selenium and acetylene provides the most convenient source of selenophene (76JHC1319). Lesser amounts of many other compounds are formed concurrently and include 2- and 3-alkylselenophenes, benzo[6]selenophene and isomeric selenoloselenophenes (76CS(10)159). The commercial availability of thiophene makes comparable reactions of little interest for the obtention of the parent heterocycle in the laboratory. However, the reaction of substituted acetylenes with morpholinyl disulfide is of some synthetic value. The process, which appears to entail the initial formation of thionitroxyl radicals, converts phenylacetylene into a 3 1 mixture of 2,4- and 2,5-diphenylthiophene, methyl propiolate into dimethyl thiophene-2,5-dicarboxylate, and ethyl phenylpropiolate into diethyl 3,4-diphenylthiophene-2,5-dicarboxylate (Scheme 83a) (77TL3413). Dimethyl thiophene-2,4-dicarboxylate is obtained from methyl propiolate by treatment with dimethyl sulfoxide and thionyl chloride (Scheme 83b) (66CB1558). The rhodium carbonyl catalyzed carbonylation of alkynes in alcohols provides 5-alkoxy-2(5//)-furanones (Scheme 83c) (81CL993). The inclusion of ethylene provides 5-ethyl-2(5//)-furanones instead (82NKK242). The nickel acetate catalyzed addition of r-butyl isocyanide to alkynes provides access to 2-aminopyrroles (Scheme 83d) (70S593). 

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