Six-Membered Ring Systems: With O and/or S Atoms

Abstract The review covers work published in the calendar year 2011. Novel reaction chemistry and new ring synthetic methods for pyrans, [1]benzopyrans, dihydro[1]benzopyrans (chromenes, chromans), [2]benzopyrans, dihydro[2]benzopyrans (isochromenes, isochromans), pyranones, coumarins, chromones, xanthenes, xanthones, thiopyrans, dioxins, dioxanes, trioxanes, tetraoxanes, dithianes, trithianes, and oxathianes are reviewed.


INTRODUCTION
A large variety of publications involving O-and S-6-membered ring systems have appeared in 2017. The importance of these heterocyclic compounds is highlighted by the huge number of publications on the total synthesis of natural oxygen derivatives and of other communications dedicated to synthetic derivatives.
Reviews on stereoselective organocatalytic synthesis of tetrahydropyrans (17EJO4666), of tetrahydropyrans and their application in total synthesis of natural products (17CSR1661), on the synthesis of the less thermodynamically stable 2,6-trans-tetrahydropyrans (17S4899), on enantioselective synthesis of polyfunctionalized pyran and chromene derivatives (17TA1462), and on enantioselective and racemic total synthesis of camptothecins, including the formation of their pyran-2-one ring (17SL1134), have appeared.
Herein, we provide a personal overview of the most relevant transformations on O-and S-6-membered heterocycles, published in 2017.
Excellent enantioselectivity is achieved in the formal [3þ3] annulation reaction of d-acetoxy allenoates with 1C,3O-bisnucleophiles promoted by a tertiary amine organocatalyst to afford highly substituted 4H-pyrans (17OL1890, 17T3347). One-pot three-component reaction of aromatic aldehydes with malononitrile and b-keto esters carried out in the presence of hexamethylenetetramine in water gives access to polyfunctionalized 2-amino-4-aryl-4H-pyran-3-carbonitriles (17JHC1598, 17JHC1880). Further derivatives arise from the reaction of 2-tosyloxybenzaldehyde with malononitrile and cyclic and acyclic ketones in the presence of trimethylamine in ethanol, ammonium hydroxide in methanol, or under ultrasound irradiation (17JHC1442). Examples of 4-alkyl/aryl-2-amino-4H-pyran-3-carboxamides are produced from an ytterbium triflate-mediated threecomponent reaction of aliphatic/aromatic aldehydes with acetylacetone and cyanoacetamide. This reaction occurs at 50 C under solvent-free conditions and applying microwave and ultrasound irradiation, the first protocol being the most efficient (Scheme 7; 17TL1659).

Isochromenes and Isochromans
Under the dual catalysis of Cu(OTf) 2 and a chiral cationic rutheniumdiamine complex, a series of o-(alkynyl)aryl ketones underwent asymmetric hydrogenation to give polysubstituted 1H-isochromenes in high yields and enantioselectivity (17AGE4135). Further o-(alkynyl)aryl ketones undergo selective CeH functionalization and 6-endo-dig-oxo-cyclization reactions using different radical sources: in the presence of diphenylphosphine oxides and silver acetate as both catalyst and oxidant affords biphosphonylated isochromenes, while the presence of silver nitrate as both catalyst and nitrating reagent provides nitro-terminated isochromenes (Scheme 34; 17OL754).
The synthesis of 1,3-disubstituted 1H-isochromenes is achieved via tandem reactions of a wide range of o-alkynylbenzaldehydes with thiophenes mediated by a gold(III) catalyst in acetonitrile (17SC463), with
Palladium-mediated direct oxidative annulation of benzoic acids with phenols leads to a series of benzo[c]coumarins in moderate to good yields (17OL1326). More analogs arise from double CeH activation/oxygen insertion of 2-arylbenzaldehydes using a Cu(0)/Selectfluor catalytic system (17T154) and one-pot conversion of N-substituted 2-arylbenzamides in the presence of t-BuONO at 40 C, in metal-, oxidant-and solvent-free conditions (Scheme 56; 17JOC5769).
Benzo[c]coumarins and thieno[c]coumarins are accessed through the reaction of methyl anthranilates and methyl 2-aminothiophene carboxylate, respectively, with sodium nitrite in HCl to afford the corresponding diazonium salts, which undergo Meerwein reaction with benzoquinone and subsequent reduction of the obtained arylquinones using either sodium sulfide in aqueous ethanol or zinc powder in glacial acetic acid (17SC2399).
A variety of 3,4-disubstituted isocoumarins are available through rhodium(III)-catalyzed annulation reactions of aryl carboxylic acids with alkynes (17EJO341) and from palladum(II)-mediated reactions of 2-halobenzoates with ketones (17JOC8296). In the last case, the addition of iodide anions to the reaction mixture played an important role in the yield and selectivity when 2-bromobenzoates were used as starting materials (17JOC8296). Under Ru(II)/PEG-400 catalytic system, the reaction of Nmethoxy/benzyloxy aromatic amides with alkynes and using t-BuONO as oxygen source provided 3,4-disubstituted isocoumarins (Scheme 65; 17JOC5769).
A series of indole typeefused isocoumarins were synthesized through domino reactions of 2-amino-1,4-naphthoquinones with ninhydrin in the presence of PTSA in acetic acid (17H(94)237). It is through a Scheme 63 Scheme 64

Scheme 74
Scheme 75 derivatives in the presence of PTSA in refluxing water produces spiropyrroloquinoline xantheneetype derivatives (17JHC944).
Depending on the length and position of the spacer in the bis-aldehyde, a three-component reaction with malononitrile dimer and two equivalents of dimedone leads to bisxanthene derivatives 44 or 45 (Scheme 76; 17JHC2844).
A practical synthesis of peri-xanthenoxanthenes carried out in the presence of air as oxidant and potassium carbonate as base involves CeH/ CeO cyclization reactions of 2,2 0 -binaphthols performed with CuCl and N-methylimidazole as the catalytic system (Scheme 77)( 17OL2714). Under aerobic solvent-free conditions, a range of 9H-xanthen-9-ones arise from intramolecular oxidative dehydrogenative reaction of 2-aryloxybenzaldehydes promoted by carbon tetrabromide at 140 C. This reaction was applied to a 10-g scale-up for the synthesis of the parent xanthone (17OBC1589).
The reaction of a-substituted o-[(t-butylsulfanyl)methyl]styrenes with three equivalents of iodine and sodium bicarbonate in acetonitrile at 0 C gives access to isothiochromenes in moderate to good yields (17H(94) 2065). FriedeleCrafts acylation of alkyl/arylalkynes with 2-(methylthio) benzoyl chloride provides b-chlorovinyl ketones, which undergo intramolecular cyclization to afford 4H-thiochromen-4-ones in good yields (17OL312). Further derivatives arise from sequential nucleophilic addition, elimination and S N Ar reaction of b-chlorovinyl aromatic ketones, and sodium hydrogen sulfide carried out in the presence of cesium carbonate in DMSO (17S4309). The synthesis of cyclic sulfonamides 56 occurs via one-pot intramolecular Heck reaction of N-(o-bromoaryl)sulfonyl dihydropyrroles 55 followed by transfer hydrogenation sequence in the presence of ammonium formate (Scheme 82; 17TL4559).

Dithiin Analogs
Direct irradiation of bis-acrylates (R 1 ¼ Me) 57 in acetonitrile provides a mixture of isomers 58 and the cycloadduct cyclobutyl derivative 59. Photocycloaddition of bis-diene 60 and bis-triene 61 affords the two stereoisomeric cyclobutyl products 62-sym and 62-dis and 63-sym and 63dis, respectively. Under the same conditions, bis-sulfone 64 gives 65-sym isomer as major product and two new compounds, 65-sym' and the macrocycle 66. Using water as solvent and cyclodextrin or cucurbituril as host, the irradiation of bis-acrylates 57 (R 1 ¼ Me) also provides a mixture of isomers 58 and the cycloadduct cyclobutyl derivative 59. In these conditions, the acid derivatives 58 (R 1 ¼ H) led mainly to cycloadduct cyclobutyl derivative 59 and to the mixture of isomers 58, in minor amounts (Scheme 83; 17OBC4180).

Scheme 85
Scheme 86 Six-Membered Ring Systems: With O and/or S Atoms