The electroreductive coupling of coumarins with benzophenones in the presence of TMSCl gave adducts reacted at the 4-position of coumarins as trimethylsilyl ethers. From 3-methylcoumarin, 3,4-cis-adducts were formed stereoselectively. The de-trimethylsilylation of the adducts with 1 M HCl aq or TBAF in THF at 25 °C produced 4-(2-hydroxyphenyl)-5,5-diaryl-γ-butyrolactones. The γ-butyrolactones were further transformed to 2-(2,2-diaryl-2,3-dihydrobenzofuran-3-yl)acetic acids by treatment with 1 M HCl aq at reflux temperature. The de-trimethylsilylation of the adducts with 1 M HCl in MeOH afforded 2-(2,2-diaryl-2,3-dihydrobenzofuran-3-yl)acetic acid methyl esters. The de-trimethylsiloxylation of the adducts or dehydration of the γ-butyrolactones brought about 4-(diarylmethyl)coumarins.

The electroreductive coupling of 1,3-dimethyluracil, thymine, and 5-fluorouracil with aromatic ketones in the presence of TMSCl gave 6-substituted and cis-5,6-disubstituted 5,6-dihydro-1,3-dimethyluracils. The dehydrotrimethylsiloxylation of the adducts afforded 6-substituted and 5,6-fused 1,3-dimethyluracils. The detrimethylsilylation of the adducts with TBAF or 1 M HCl–MeOH gave 4,5,5-trisubstituted 3-methyloxazolizin-2-ones or 3-methyloxazolizin-2-imines in addition to simply desilylated alcohols. The cis-5,6-disubstituted 5,6-dihydro-1,3-dimethyluracils were isomerized to the corresponding trans-isomers by heating in the presence of cat. DMAP. The cis- and trans-5,6-disubstituted 5,6-dihydro-1,3-dimethyluracils were assigned by the coupling constants J5,6 of their 1H NMR spectra.

The electroreductive coupling of 1,3-dimethyluracils with benzophenones in the presence of TMSCl gave the adducts reacted at the 6-position of 1,3-dimethyluracils. From 1,3-dimethylthymine and 5-fluorouracil, the adducts were produced as 5,6-cis-isomers predominantly. Treatment of the adducts obtained from 1,3-dimethyluracil and thymine with refluxing p-TsOH/toluene gave 6-diarylmethyl-1,3-dimethyluracils, while the same treatment of the adducts obtained from 1,3-dimethyl-5-fluorouracil afforded fused tricyclic compounds. In addition, the electroreductive coupling of 1,3-dimethyluracil with alkyl phenyl ketones also gave adducts and they were transformed to 6-alkenyl-5,6-dihydro-1,3-dimethyluracils.

The reductive coupling of aliphatic esters with benzophenones by Zn–TiCl4 in THF gave two- and four-electron reduced products, diaryl(hydroxy)methyl ketones, and diarylmethyl ketones selectively by controlling the reaction conditions. In the reaction of aromatic esters with benzophenones, diarylmethyl ketones were obtained as the sole products. N-(Alkoxycarbonyl)-(S)-α-amino acid methyl esters gave optically active diphenylmethyl ketones by reduction with benzophenone. The obtained diphenylmethyl ketones were transformed to 4,5-cis-disubstituted oxazolidin-2-ones stereoselectively.

The electroreductive coupling of optically active N-E-crotonoyl- and N-cinnamoylimidazolidin-2-ones and oxazolidin-2-ones with diaryl ketones in the presence of chlorotrimethylsilane gave adducts with high diastereoselectivity. The adducts were readily transformed to optically active 4,5,5-trisubstituted γ-butyrolactones by treatment with TBAF.

The electroreductive coupling of 1-alkoxycarbonyl-3-methoxycarbonylindoles with aromatic ketones in the presence of chlorotrimethylsilane gave cis-adducts stereoselectively. The cis-adducts were readily transformed to trans-adducts by treatment with catalyst DBU. On the other hand, the electroreductive coupling of 1-methyl-3-methoxycarbonylindole with aliphatic ketones in isopropanol afforded trans-adducts exclusively. The adducts are the precursors for the synthesis of 2-substituted 3-methoxycarbonylindoles and indolines.

The electroreductive intramolecular coupling of aliphatic cyclic imides with α,β-unsaturated esters in the presence of chlorotrimethylsilane and subsequent desilylation with TBAF gave five- and six-membered cyclized esters and one-carbon elongated methyl ketones. These methyl ketones were formed by methyl-alkoxy exchange in intermediate silyl ketene acetals. The same methyl ketones were also obtained by the electroreductive intramolecular coupling of aliphatic cyclic imides with α,β-unsaturated methyl ketones. The cyclized methyl ketones were transformed to the known indolizidine and quinolizidine alkaloids, (±)-tashiromine and (±)-epilupinine.

The reductive coupling of aliphatic cyclic imides with benzophenones by Zn–TiCl4 in THF gave two- and four-electron reduced products selectively by controlling the reaction conditions. Although cyclic and acyclic products were formed as mixtures in most cases, cyclic dehydrated products could be selectively obtained by heating the product mixtures in the presence of cat. p-TsOH.

The reductive coupling of phthalimides with ketones and aldehydes by Zn-TiCl4 in THF gave two- and four-electron reduced products, 3-hydroxy-3-(1-hydroxyalkyl)isoindolin-1-ones and alkylideneisoindolin-1-ones, selectively by controlling the reaction conditions. Therefore, the one-pot synthesis of alkylideneisoindolin-1-ones from phthalimides was effected by this reaction. Although the alkylideneisoindolin-1-ones prepared from phthalimides and aldehydes were formed as mixtures of geometric isomers in most cases, the geometric ratios could be increased by reflux in cat. PPTS/toluene. After the isomerization, the E-isomers of N-methyl substituted alkylideneisoindolin-1-ones (X = Me, R1 = R, R2 = H) and the Z-isomers of N-unsubstituted alkylideneisoindolin-1-ones (X = H, R1 = H, R2 = R) were obtained preferentially.

The reductive coupling of N-methoxycarbonyl lactams with benzophenone by Zn-TiCl4 in THF gave cross-coupled products as cyclic α-diphenylidene-N-methoxycarbonylamines and ring-opening α,α-diphenyl-α-hydroxy-ω-(N-methoxycarbonyl)amino ketones selectively depending on the reduction conditions. The reductive coupling of N-methoxycarbonyl lactams with 9-fluorenone by Zn-TiCl4 gave cyclic α-(9H-fluoren-9-ylidene)-N-methoxycarbonylamines preferentially irrespective to the conditions.

The reductive coupling of 1,3-dimethyluracil with benzophenone by Zn–TiCl4 in THF gave unusual two-to-one adduct and its further reduced product. The reductive coupling of 1,3-dimethyl-5-fluorouracil with benzophenone by Zn–TiCl4 also gave two-to-one adduct. 1,3-Dimethylthymine was, however, completely inert under the same conditions.

The electroreductive intramolecular coupling of phthalimides with aromatic aldehydes in the presence of chlorotrimethylsilane and triethylamine led to five-, six-, and seven-membered cyclized products (58–84%). The electroreductive cyclization was applied to the total synthesis of lennoxamine.

The electroreductive intermolecular coupling of chiral α-imino N,N-dialkylamides derived from (S)-α-amino N,N-dialkylamides and aromatic aldehydes with ketones in the presence of chlorotrimethylsilane and triethylamine gave β-amino alcohols with moderate to good (R)-stereoselectivity.(S)-2-((R)-2-Hydroxy-2-methyl-1-phenylpropylamino)-N,N,3-trimethylbutanamideC17H28N2O2[α]D24=-76.0 (c 1.05, CHCl3)Source of chirality: (S)-valineAbsolute configuration: (S,R)(S)-2-((S)-2-Hydroxy-2-methyl-1-phenylpropylamino)-N,N,3-trimethylbutanamideC17H28N2O2[α]D23=+44.3 (c 1.40, CHCl3)Source of chirality: (S)-valineAbsolute configuration: (S,S)(S)-N,N-diethyl-2-((R)-2-hydroxy-2-methyl-1-phenylpropylamino)-3-methylbutanamideC19H32N2O2[α]D23=+84.8 (c 1.09, CHCl3)Source of chirality: (S)-valineAbsolute configuration: (S,R)(S)-2-((R)-2-Hydroxy-2-methyl-1-phenylpropylamino)-3-methyl-1-(piperidin-1-yl)butan-1-oneC20H32N2O2[α]D22=-73.7 (c 1.00, CHCl3)Source of chirality: (S)-valineAbsolute configuration: (S,R)(S)-2-((S)-2-Hydroxy-2-methyl-1-phenylpropylamino)-3-methyl-1-(piperidin-1-yl)butan-1-oneC20H32N2O2[α]D23=+57.7 (c 0.92, CHCl3).Source of chirality: (S)-valineAbsolute configuration: (S,S)(2S,3S)-2-((R)-2-Hydroxy-2-methyl-1-phenylpropylamino)-N,N,3-trimethylpentanamideC18H30N2O2[α]D23=+72.0 (c 1.00, CHCl3).Source of chirality: (S)-isoleucineAbsolute configuration: (S,S,R)(2S,3S)-2-((S)-2-Hydroxy-2-methyl-1-phenylpropylamino)-N,N,3-trimethylpentanamideC18H30N2O2[α]D23=+40.4 (c 1.05, CHCl3).Source of chirality: (S)-isoleucineAbsolute configuration: (S,S,S)(2S,3S)-N,N-Diethyl-2-((R)-2-hydroxy-2-methyl-1-phenylpropylamino)-3-methylpentanamideC20H34N2O2[α]D24=-73.1 (c 1.50, CHCl3).Source of chirality: (S)-isoleucineAbsolute configuration: (S,S,R)(2S,3S)-N,N-Diethyl-2-((S)-2-hydroxy-2-methyl-1-phenylpropylamino)-3-methylpentanamideC20H34N2O2[α]D24=+27.6 (c 1.14, CHCl3).Source of chirality: (S)-isoleucineAbsolute configuration: (S,S,S)(S)-2-((R)-2-Hydroxy-2-methyl-1-phenylpropylamino)-N,N,4-trimethylpentanamideC18H30N2O2[α]D21=-78.7 (c 1.01, CHCl3).Source of chirality: (S)-isoleucineAbsolute configuration: (S,R)(S)-2-((R)-2-Hydroxy-2-methyl-1-phenylpropylamino)-N,N-dimethyl-3-phenylpropanamideC21H28N2O2[α]D23=+12.0 (c 1.07, CHCl3).Source of chirality: (S)-phenylalanineAbsolute configuration: (S,R)(S)-2-((S)-2-Hydroxy-2-methyl-1-phenylpropylamino)-N,N-dimethyl-3-phenylpropanamideC21H28N2O2[α]D25=+109 (c 1.03, CHCl3).Source of chirality: (S)-phenylalanineAbsolute configuration: (S,S)(S)-Methyl 6-(dimethylamino)-5-((R)-2-hydroxy-2-methyl-1-phenylpropylamino)-6-oxohexanoateC19H30N2O4[α]D23=-58.7 (c 1.73, CHCl3).Source of chirality: (S)-glutamic acidAbsolute configuration: (S,R)(S)-Methyl 6-(dimethylamino)-5-((S)-2-hydroxy-2-methyl-1-phenylpropylamino)-6-oxohexanoateC19H30N2O4[α]D23=+31.4 (c 1.14, CHCl3).Source of chirality: (S)-glutamic acidAbsolute configuration: (S,S)(S)-N,N-Diethyl-2-((R)-2-hydroxy-1-(4-methoxyphenyl)-2-methylpropylamino)-3-methylbutanamideC20H34N2O3[α]D24=-90.0 (c 1.03, CHCl3).Source of chirality: (S)-valineAbsolute configuration: (S,R)(S)-N,N-Diethyl-2-((S)-2-hydroxy-1-(4-methoxyphenyl)-2-methylpropylamino)-3-methylbutanamideC20H34N2O3[α]D22=+56.0 (c 1.04, CHCl3).Source of chirality: (S)-valineAbsolute configuration: (S,S)(S)-N,N-Diethyl-2-((R)-2-hydroxy-1-(3-methoxyphenyl)-2-methylpropylamino)-3-methylbutanamideC20H34N2O3[α]D25=-85.0 (c 1.01, CHCl3).Source of chirality: (S)-valineAbsolute configuration: (S,R)(S)-N,N-Diethyl-2-((S)-2-hydroxy-1-(3-methoxyphenyl)-2-methylpropylamino)-3-methylbutanamideC20H34N2O3[α]D19=+49.6 (c 1.02, CHCl3).Source of chirality: (S)-valineAbsolute configuration: (S,S)(S)-N,N-Diethyl-2-((R)-2-hydroxy-1-(4-cyanophenyl)-2-methylpropylamino)-3-methylbutanamideC20H31N3O2[α]D23=-92.3 (c 1.11, CHCl3).Source of chirality: (S)-valineAbsolute configuration: (S,R)(S)-N,N-Diethyl-2-((S)-2-hydroxy-1-(4-cyanophenyl)-2-methylpropylamino)-3-methylbutanamideC20H31N3O2[α]D21=+42.0 (c 1.05, CHCl3).Source of chirality: (S)-valineAbsolute configuration: (S,S)(S)-N,N-Diethyl-2-((R)-2-hydroxy-2-methyl-1-(naphthalen-1-yl)propylamino)-3-methylbutanamideC23H34N2O2[α]D23=-7.4 (c 1.12, CHCl3).Source of chirality: (S)-valineAbsolute configuration: (S,R)(S)-N,N-Diethyl-2-((R)-2-hydroxy-2-methyl-1-(naphthalen-2-yl)propylamino)-3-methylbutanamideC20H34N2O3[α]D22=+95.8 (c 1.10, CHCl3).Source of chirality: (S)-valineAbsolute configuration: (S,R)(S)-N,N-Diethyl-2-((S)-2-hydroxy-2-methyl-1-(naphthalen-2-yl)propylamino)-3-methylbutanamideC20H34N2O3[α]D24=+57.6 (c 1.03, CHCl3).Source of chirality: (S)-valineAbsolute configuration: (S,S)(S)-2-((R)-(1-Hydroxycyclopentyl)(phenyl)methylamino)-N,N,3-trimethylbutanamideC19H30N2O2[α]D24=-54.4 (c 1.04, CHCl3).Source of chirality: (S)-valineAbsolute configuration: (S,R)(S)-2-((R)-(1-Hydroxycyclohexyl)(phenyl)methylamino)-N,N,3-trimethylbutanamideC20H32N2O2[α]D22=+35.1 (c 1.15, CHCl3).Source of chirality: (S)-valineAbsolute configuration: (S,S)(S)-N,N-Diethyl-2-((S)-2-hydroxy-2-methyl-1-phenylpropylamino)-3-methylbutanamideC19H32N2O2[α]D22=+35.6 (c 1.26, CHCl3).Source of chirality: (S)-valineAbsolute configuration: (S,S)(S)-2-((S)-2-Hydroxy-2-methyl-1-phenylpropylamino)-N,N,4-trimethylpentanamidC18H30N2O2[α]D24=+21.1 (c 0.90, CHCl3).Source of chirality: (S)-isoleucineAbsolute configuration: (S,S)(S)-N,N-Diethyl-2-((S)-2-hydroxy-2-methyl-1-(naphthalen-1-yl)propylamino)-3-methylbutanamideC23H34N2O2[α]D22=-22.0 (c 0.95, CHCl3).Source of chirality: (S)-valineAbsolute configuration: (S,S)

The electroreductive intramolecular coupling of aliphatic cyclic imides with ketones in isopropanol gave five- and six-membered cyclized products. Similarly, the electroreductive intramolecular coupling of aliphatic cyclic imides with O-methyloximes afforded five-, six-, and seven-membered cyclized products. These reactions provide a useful method to synthesize azabicyclo[n.m.0] compounds. The bicyclic products were stereoselectively transformed to the corresponding deoxylated compounds by reduction with NaB(CN)H3 or Et3SiH/BF3·Et2O.

The electroreductive intramolecular coupling of phthalimides with ketones in the presence of chlorotrimethylsilane gave five- and six-membered trans-cyclized products stereospecifically (>99%). Similar electroreductive intramolecular coupling of phthalimides with aldehydes afforded five-, six-, and seven-membered trans-cyclized products stereoselectively (75–93%). On the other hand, the reductive coupling of N-(oxoalkyl)phthalimides with samarium(II) iodide gave cis-cyclized products stereoselectively (88–>99%).

The electroreductive intramolecular coupling of phthalimides with α,β-unsaturated esters in the presence of chlorotrimethylsilane and subsequent desilylation of resulting silyl ketene acetals with TBAF gave five- and six-membered trans-cyclized products stereospecifically. The silyl ketene acetals were readily rearranged to benzoindole and tetrahydrobenzoquinoline by standing or treatment with a Lewis acid under open-air conditions. The electroreductive intermolecular coupling of N-methylphthalimide with methyl acrylate also proceeded.

The reduction of 1,2-bis(bromomethyl)benzene with zinc powder followed by cycloaddition with the chiral dienophile (4R,5S)-1-acryloyl-3,4-dimethyl-5-phenyl-2-imidazolidinone in the presence of BF3·Et2O under ultrasound irradiation gave the corresponding Diels–Alder cycloadduct in high yield (90%) and high diastereoselectivity (R:S = 87:13).(4S,5R)-1,5-Dimethyl-4-phenyl-3-((R)-1,2,3,4-tetrahydronaphthalene-2-carbonyl)imidazolidin-2-oneC22H24N2O3Ee >99%[α]D20=-41.2 (c 1.05, CHCl3)Source of chirality: (1S,2R)-(+)-norephedrineAbsolute configuration: (4S,5R,2′R)

The oxidative coupling of diaroylacetate derivatives prepared from (1R,1′R)-exo,exo′-3,3′-biisoborneol with NaH–Br2 gave the corresponding intramolecularly coupled products stereoselectively. The major (R,R)-isomers thus obtained were transformed to (−)-Sesamin and (−)-Eudesmin.Graphic(1R,1′R,2R,2′R,3S,3′S,4R,4′R)-3,3′-bi(2-acetoxy-1,7,7-trimethylbicyclo[2.2.1]heptanone)C24H38O4E.e. >99%[α]D20=+94.1 (c 1.07, CHCl3)Source of chirality: (1R)-camphorAbsolute configuration: 1R,1′R,2R,2′R,3S,3′S,4R,4′R(1R,1′R,2R,2′R,3S,3′S,4R,4′R)-3,3′-Bi(2-(3-(2H-benzo[d]1,3-dioxolan-5-yl)-3-oxopropanoyloxy)-1,7,7-trimethylbicyclo[2.2.1]heptanone)C40H46O10E.e. >99%[α]D25=+25.5 (c 1.21, CHCl3)Source of chirality: (1R)-camphorAbsolute configuration: 1R,1′R,2R,2′R,3S,3′S,4R,4′R(1R,1′R,2R,2′R,3S,3′S,4R,4′R)-3,3′-Bi-(2-(3-(3,4-dimethoxyphenyl)-3-oxopropanoyloxy)-1,7,7-trimethylbicyclo[2.2.1]heptanone)C42H54O10E.e. >99%[α]D25=+28.0 (c 1.33, CHCl3)Source of chirality: (1R)-camphorAbsolute configuration: 1R,1′R,2R,2′R,3S,3′S,4R,4′R(2S,3S,1R,4R,7R,8R,11R,12R,15R,16R)-11,12-(bis-2H-benzo[d]1,3-dioxolen-5-ylcarbonyl)-7,16,19,19,20,20-hexamethyl-9,14-dioxapentacyclo[14.2.1.1<4,7>.0<2,15>.0<3,8>]icosane-10,13-dioneC40H44O10E.e. >99%[α]D25=+25.5 (c 1.21, CHCl3)Source of chirality: (1R)-camphorAbsolute configuration: 1R,2S,3S,4R,7R,8R,11R,12R,15R,16R(2S,3S,1R,4R,7R,8R,11R,12R,15R,16R)-11,12-Bis[(3,4-dimethoxyphenyl)carbonyl]-7,16,19,19,20,20-hexamethyl-9,14-dioxapentacyclo[14.2.1.1<4,7>.0<2,15>.0<3,8>]icosane-10,13-dioneC42H52O10E.e. >99%[α]D25=+28.0 (c 1.33, CHCl3)Source of chirality: (1R)-camphorAbsolute configuration: 1R,2S,3S,4R,7R,8R,11R,12R,15R,16R

The oxidative coupling of sodium enolates of (4R,5S)-1-aroylacetyl-3,4-dimethyl-5-phenyl-2-imidazolidinones with Br2 as the oxidant affords the R,R-dimers stereoselectively. The R,R-selectivity can be explained by a radical coupling mechanism.Graphic(2R,3R)-2,3-Bis(2H-benzo[3,4-d]1,3-dioxolan-5-ylcarbonyl)-1,4-bis((4R,5S)-3,4-dimethyl-2-oxo-5-phenylimidazolidinyl)butane-1,4-dioneC42H38N4O10Ee >99%[α]D20 −174 (c 1.08, CHCl3)Source of chirality: (4R,5S)-3,4-dimethyl-5-phenyl-2-imidazolidinoneAbsolute configuration: 2R,3R(2R,3S)-2,3-Bis(2H-benzo[3,4-d]1,3-dioxolan-5-ylcarbonyl)-1,4-bis((4R,5S)-3,4-dimethyl-2-oxo-5-phenylimidazolidinyl)butane-1,4-dioneC42H38N4O10Ee >99%[α]D20 +236 (c 1.02, CHCl3)Source of chirality: (4R,5S)-3,4-dimethyl-5-phenyl-2-imidazolidinoneAbsolute configuration: 2R,3S(2R,3R)-1,4-Bis((4R,5S)-3,4-dimethyl-2-oxo-5-phenylimidazolidinyl)-2,3-bis[(3,4-dimethoxyphenyl)carbonyl]butane-1,4-dioneC44H46N4O10Ee >99%[α]D20 −175 (c 1.04, CHCl3)Source of chirality: (4R,5S)-3,4-dimethyl-5-phenyl-2-imidazolidinoneAbsolute configuration: 2R,3R(2R,3S)-1,4-Bis((4R,5S)-3,4-dimethyl-2-oxo-5-phenylimidazolidinyl)-2,3-bis[(3,4-dimethoxyphenyl)carbonyl]butane-1,4-dioneC44H46N4O10Ee >99%[α]D20 +179 (c 1.06, CHCl3)Source of chirality: (4R,5S)-3,4-dimethyl-5-phenyl-2-imidazolidinoneAbsolute configuration: 2R,3S(2R,3R)-2-(2H-benzo[3,4-d]1,3-dioxolan-5-ylcarbonyl)-1,4-bis((5S,4R)-3,4-dimethyl-2-oxo-5-phenylimidazolidinyl)-3-[(3,4-dimethoxyphenyl)carbonyl]butane-1,4-dioneC43H42N4O10Ee >99%[α]D20 −142 (c 1.05, CHCl3)Source of chirality: (4R,5S)-3,4-dimethyl-5-phenyl-2-imidazolidinoneAbsolute configuration: 2R,3R