Efficient synthesis of furan-2-ylacetates, 7-(alkoxycarbonyl)benzofurans, and 7-(alkoxycarbonyl)-2,3-dihydrobenzofurans based on cyclization reactions of free and masked dianions: a "cyclization/dehydrogenation" strategy

[reaction: see text] A variety of furan-2-ylacetates have been prepared by dehydrogenation of monocyclic 2-alkylidenetetrahydrofurans, which are readily available by cyclizations of open-chained 1,3-dicarbonyl dianions with 1-bromo-2-chloroethane. 5'H-[2,3']Bifuranyl-2'-ones are available based on sequential "cyclization/dehydrogenation" reactions of alpha-acetyl-gamma-butyrolactones. A variety of 7-(alkoxycarbonyl)benzofurans and 7-(alkoxycarbonyl)-2,3-dihydrobenzofurans were prepared by a cyclization/dehydrogenation strategy. These reactions rely on cyclizations of 2-oxocycloalkane-1-carboxylate-derived 1,3-dicarbonyl dianions ("free dianions") or 1,3-bis-silyl enol ethers ("masked dianions") with various 1,2-dielectrophiles.     

Synthesis of chromanes by sequential ‘[3+3]-cyclization/Williamson’ reactions of 1,3-bis(trimethylsilyloxy)-7-chlorohepta-1,3-dienes

Functionalized chromanes were prepared by sequential ‘[3+3]-cyclization/Williamson’ reactions of 1,3-bis(trimethylsilyloxy)-7-chlorohepta-1,3-dienes with 1,1,3,3-tetramethoxypropane, 3-silyloxyalk-2-en-1-ones, and 1,1-diacetylcyclopropane. The first step of the sequence involves [3+3] cyclizations of the starting materials to give 2-(3-chloropropyl)phenols. The subsequent cyclization proceeds by intramolecular nucleophilic substitution. 6-(2-Hydroxybenzoyl)chromanes were prepared based on sequential ‘[3+3]-cyclization/Williamson’ reactions of 1,3-bis(trimethylsilyloxy)-7-chlorohepta-1,3-dienes with 3-formylchromones.     

Domino reaction of 1,3-bis(trimethylsilyloxy)-1,3-dienes with oxalyl chloride: general and stereoselective synthesis of gamma-alkylidenebutenolides

The Lewis acid catalyzed cyclization of oxalyl chloride with 1,3-bis(trimethylsilyloxy)-1,3-dienes 3, derived from 1,3-dicarbonyl compounds 1, provides a new and general approach for the synthesis of gamma-alkylidenebutenolides 4, a pharmacologically and synthetically important class of substances. A variety of butenolides were efficiently prepared in good yields and with very good regio- and stereoselectivities. An up-scaling of the reaction was possible. The use of the Lewis acid trimethylsilyl-trifluoromethanesulfonate (TMSOTf) proved to be superior to other activation conditions. Sterically undemanding gamma-alkylidenebutenolides could be prepared alternatively by reaction of the corresponding 1,3-dicarbonyl dianions with N,N'-dimethoxy-N,N'-dimethylethanediamide (2d). In contrast to the dianion method, the Lewis acid catalyzed reaction also facilitated the cyclization of sterically hindered, base-labile, cyclic and functionalized substrates. From a methodology viewpoint, the dianion reaction represents the first cyclization of a bis-Weinreb amide and the first cyclization of an oxalic acid-synthon with an ambident dianion. The TMSOTf-catalyzed reactions are both the first cyclizations of 1,3bis(trimethylsilyloxy)-1,3-dienes with a C2 dielectrophile and the first cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-dienes with a carboxylic acid dichloride or a related dielectrophile.     

Enantioselective synthesis of 2-alkylidenetetrahydrofurans based on a ‘cyclization/enzymatic resolution’ strategy

Enantiomerically pure 2-alkylidenetetrahydrofurans have been prepared by TiCl₄ mediated enantiospecific reactions of 1,3-bis-silyl enol ethers with enantiomerically pure epichlorohydrin. In addition, the enzymatic kinetic resolution of 2-alkylidenetetrahydrofurans, using Candida antarctica lipase B (CAL-B), was studied. Enzymatic kinetic resolution of monocyclic 5-vinyl-2-alkylidenetetrahydrofuran with CAL-B afforded the enantiomerically pure ester with 97% ee. For a bicyclic 2-alkylidenetetrahydrofuran, this proceeded with excellent enantioselectivity (E >100) affording the enantiomerically pure acid with 98% ee. 2-Alkylidenetetrahydrofurans were prepared by [3+2] cyclization reactions of 1,3-dicarbonyl dianions (‘free dianions’) or 1,3-bis-silyl enol ethers (‘masked dianions’).     

Synthesis of (tetrahydrofuran-2-yl)acetates based on a ‘cyclization/hydrogenation/enzymatic kinetic resolution’ strategy

A variety of (tetrahydrofuran-2-yl)acetates and (pyrrolidin-2-yl)acetates have been prepared by hydrogenation of 2-alkylidenetetrahydrofurans and 2-alkylidenepyrrolidines, which are readily available by cyclization reactions of 1,3-dicarbonyl dianions (‘free dianions’) or 1,3-bis-silyl enol ethers (‘masked dianions’) with 1,2-dielectrophiles. The enzymatic kinetic resolution of (tetrahydrofuran-2-yl)acetates with recombinant esterase Est56 proceeded with excellent enantioselectivities (E>100).     

Synthesis and reactivity of 1-hydroxyspiro[2.5]cyclooct-4-en-3-ones

The first 1-hydroxyspiro[2.5]cyclooct-4-en-3-ones were prepared by cyclization of free and masked 1,3-dicarbonyl dianions with 1,1-diacetylcyclopropane. 1-Hydroxyspiro[2.5]cyclooct-4-en-3-ones represent precursors of unstable spiro[5.2]cycloocta-4,7-dien-6-ones and reactions with a number of nucleophiles were studied. The reactions are enhanced by dynamic spiro-activation.     

Chelation-control in the formal [3+3] cyclization of 1,3-bis-(silyloxy)-1,3-butadienes with 1-hydroxy-5-silyloxy-hex-4-en-3-ones. One-pot synthesis of 3-aryl-3,4-dihydroisocoumarins

The [3+3] cyclization of 1,3-bis(silyloxy)-1,3-butadienes with 1-hydroxy-5-silyloxy-hex-4-en-3-ones resulted in the one-pot formation of 3-aryl-3,4-dihydroisocoumarins. The reactions proceeded by regioselective cyclization to give 6-(2-aryl-2-chloroethyl)salicylates, which underwent a silica gel-mediated lactonization. The cyclizations of protected 1-amino-5-silyloxy-hex-4-en-3-ones proved to be not regioselective.     

[3+3] Cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes—a new approach to diverse CF3-substituted fluorenes,dibenzofurans, 9,10-dihydrophenanthrenes and 6H-benzo[c]chromenes

Trifluoromethyl-substituted fluorenes, dibenzofurans, 9,10-dihydrophenanthrenes and 6H-benzo[c]chromenes were prepared by formal [3+3] cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes. The reactions proceeded with very good regioselectivity. The product distribution depends on the type of 1,3-dielectrophile employed and can be explained by electronic reasons.     

Regioselective synthesis of amino- and nitroarenes based on [3+3] cyclocondensations of 1,3-bis(silyloxy)-1,3-butadienes

Functionalized amino- and nitro-substituted biaryls and dibenzo[b,d]pyrid-6-ones (6(5H)-phenanthridinones) were prepared by [3+3]cyclocondensation of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with nitro-substituted 1-aryl-1-silyloxy-1-en-3-ones and subsequent hydrogenation. 4-Nitro- and 4-aminophenols were prepared based on formal [3+3] cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with 3-ethoxy-2-nitro-2-en-1-ones.     

Synthesis of 3,4-benzo-7-hydroxy-2,9-diazabicyclo[3.3.1]non-7-enes by cyclization of 1,3-bis(silyl enol ethers) with quinazolines

A variety of functionalized 3,4-benzo-7-hydroxy-2,9-diazabicyclo[3.3.1]non-7-enes were prepared by one-pot cyclizations of 1,3-bis(silyl enol ethers) with quinazolines. The mechanism of the cyclization was studied by B3LYP/6-31G(d) density functional theory computations. The products could be functionalized by Suzuki cross-coupling reactions. The reaction of 1,3-bis(silyl enol ethers) with phthalazine afforded open-chain rather than cyclization products.     

Synthesis of functionalized diaryl selenides by the first [3+3] cyclocondensations of 1,3-bis(silyloxy)-1,3-butadienes with organoselenium compounds

Functionalized diaryl selenides were prepared by the first [3+3] cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with organoselenium compounds (i.e., 2-(phenylselanyl)-3-silyloxy-3-en-1-ones).     

Synthesis of of sterically encumbered biaryls based on a ‘copper(I)-catalyzed arylation/[3+3] cyclocondensation’ strategy

Sterically encumbered biaryls are prepared in two steps by combination of the CuI-proline-catalyzed arylation of acetylacetone with formal [3+3] cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-dienes. In addition, the synthesis of 4,6- and 5,6-diarylsalicylates based on [3+3] cyclizations is reported.     

Regioselective synthesis of functionalized 4-nitro- and 4-amino-phenols based on formal [3+3] cyclocondensations of 3-ethoxy-2-nitro-2-en-1-ones with 1,3-bis(silyloxy)-1,3-butadienes

Functionalized 4-nitro- and 4-aminophenols were regioselectively prepared based on [3+3] cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with 3-ethoxy-2-nitro-2-en-1-ones.     

Regioselective synthesis of 4-chlorophenols, 10-chloro-7-hydroxy-6H-benzo[c]chromen-6-ones, and 4-chloro-1-hydroxy-9H-fluoren-9-ones based on [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-dienes with 2-chloro-3-silyloxy-2-en-1-ones

A variety of 4-chlorophenols, 10-chloro-7-hydroxy-6H-benzo[c]chromen-6-ones, and 4-chloro-1-hydroxy-9H-fluoren-9-ones were prepared by formal [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-dienes with 2-chloro-3-(silyloxy)alk-2-en-1-ones.     

Synthesis of trifluoromethyl-substituted salicylates by cyclocondensation of 1,3-bis(silyloxy)-1,3-butadienes with 4,4-dimethylthio-1,1,1-trifluorobut-3-en-2-one

A formal [3+3] cyclocondensation of 1,3-bis(silyl enol ethers) with the little-known 4,4-dimethylthio-1,1,1-trifluorobut-3-en-2-one was studied. In contrast to 4,4-dimethoxy-1,1,1-trifluorobut-3-en-2-one, this α-oxoketene dithioacetal reacts with 1,3-bis(trimethylsilyloxy)-1,3-butadienes in the presence of TiCl₄ to give mainly 6-methylthio-4-(trifluoromethyl)salicylates via 1,2-addition. The scope and limitations of the reaction are discussed.     

Diacetoxylation of conjugated dienes with thallium(III) acetate in acetic acid

The reaction of conjugated dienes such as 1,3-butadiene, isoprene, 2,3-dimethyl-1,3-butadiene, 2,5-dimethyl-2,4-hexadiene, 1,3-cyclopentadiene, and 1,3-cyclohexadiene, with thallium(III)acetate in acetic acid at 10–65° for 0.5–15 hr affords an isomeric mixture of the corresponding diacetoxyalkenes (1,2- and 1,4-addition products) in 10–92% yields. The 1,2-addition products are predominantly formed in all cases examined except the case of 1,3-cyclopentadiene. The reaction is assumed to proceed through acetoxythallation and dethallation steps, the latter step being accompanied and/or followed by an attack of acetoxyl group. An initial attack of thallium moiety is proposed to occur mainly at C-1 and C-2 carbons in the cases of linear terminal dienes and cyclic dienes, respectively.     

Regioselective synthesis of sterically encumbered diaryl ethers based on one-pot cyclizations of 4-aryloxy-1,3-bis(trimethylsilyloxy)-1,3-dienes

Sterically encumbered diaryl ethers are prepared based on formal [3+3] cyclizations of novel 4-aryloxy-1,3-bis(trimethylsilyloxy)-1,3-dienes.     

Wide bite angle diphosphine rhodium complexes: Synthesis, structure, and catalytic 1,4-addition of arylboronic acids to enones

A rhodium complex [ClRh(CO)(L1)] featuring a wide bite angle diphosphine ligand (L1 = 1,3-bis(2-diphenylphosphinomethylphenyl)benzene) has been synthesized and structurally characterized. L1 supports a bite angle (P-M-P angle, β) of 171.4° in the trans-square planar complex. L1 was tested in Rh-catalyzed 1,4-addition reactions of arylboronic acids (six examples) to α,β-unsaturated ketones (five examples). In mixed aqueous/cyclohexane solution at 60 °C, addition reactions proceed in up to quantitative yield with a 1:1 arylboronic acid/enone ratio. Yields as high as 77% can be acquired even when one of the coupling partners is sterically encumbered 2,4,6-trimethylphenylboronic acid.     

Regioselective synthesis of diaryl sulfides by [3+3] cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-dienes

Functionalized and sterically encumbered diaryl sulfides were prepared based on [3+3] cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-dienes.     

Bis(ketenyl)benzenes: preparation,observation, and reaction with tetramethylpiperidin-1-yloxyl

1,2- and 1,3-Bis(ketenyl)benzenes formed by double dehydrochlorination and by double Wolff rearrangement, respectively, gave ketenyl IR absorption at 2115, and 2122, and 2116 cm^–1, respectively. Reaction of these bisketenes with the aminoxyl radical tetramethylpiperidin-1-yloxyl (TEMPO) gave the corresponding tetraadducts as mixtures of meso- and d,l-isomers. The kinetics of the reaction of 1,3-bis(ketenyl)benzene with TEMPO gave a rate constant comparable to that of the monoketene PhCH=C=O. The reactions proceed by the initial attack of TEMPO on the carbonyl carbon of one ketenyl group followed by fast capture of the intermediate radical by a second TEMPO, and then reaction of the remaining ketene.