Furans and their Benzo Derivatives: Synthesis

Friedrichsen, Willy

doi:10.1016/b978-008096518-5.00046-0

“…The control of enantio-and diastereoselectivity is applicable to the synthesis of cis-and trans-2,5-disubstituted dihydrofurans and cis-and trans-2,6-disubstituted dihydropyrans [28,29] with control of absolute and relative stereochemistry with readily available, enantioenriched allylic [30,31] and homoallylic alcohols [32,33] (Scheme 2). For example, 1 a and 1 e reacted with alkoxides derived from (R)-1-octen-3-ol and (S)-4-penten-2-ol, respectively, in the presence of catalysts derived from the two enantiomers of L 2 to form the branched allylic ethers 5, 5' and 6, 6' with excellent yields and regio-and diastereoselectivities.…”

Section: Angewandte Chemiementioning

confidence: 99%

Iridium‐Catalyzed Intermolecular Allylic Etherification with Aliphatic Alkoxides: Asymmetric Synthesis of Dihydropyrans and Dihydrofurans

Shu

¹

,

Hartwig

²

2004

View full text Add to dashboard Cite

Elimination and racemization limit the synthesis of sterically hindered ethers, [1] such as a-chiral ethers, by the Willamson synthesis. Enantioselective transition-metal-catalyzed allylic substitution [2][3][4][5][6] could be used to prepare these materials from achiral or racemic allylic electrophiles, but intermolecular enantioselective reactions of allylic acetates or carbonates with alkoxides are limited. Enantioselective reactions of phenoxides are well documented, [7][8][9] but no metal catalyzes intermolecular enantioselective allylations of alkoxides with broad scope. [10][11][12][13] Lee and Kim [14] as well as Evans and Leahy [15] demonstrated that zinc and copper alkoxides were more reactive for allylic substitution with achiral palladium and rhodium catalysts than alkali metal alkoxides. The palladium-catalyzed reactions generated achiral ethers, but the rhodium-catalyzed reactions formed branched chiral ethers. Reactions of primary alkoxides with optically active allylic acetates occurred with predominant retention of configuration, but reactions of secondary and tertiary alkoxides were conducted with racemic allylic electrophiles. Because the products from reactions of primary alkoxides can be formed by alkylation of an optically active alcohol, but products from reactions of secondary alkoxides cannot, a catalyst that forms optically active products from hindered alkoxides and allylic carbonates is synthetically valuable. We report herein enantioselective reactions of primary, secondary, and tertiary alkoxides with achiral allylic carbonates to form branched chiral allylic ethers in high yields and with high stereoselectivity in the presence of an iridium catalyst containing a phosphoramidite ligand (Scheme 1). [16][17][18][19][20][21][22] To optimize the conditions for the allylation of aliphatic alkoxides with iridium-phosphoramidite catalysts, we studied the reactions of cinnamyl carbonate with benzyloxides (Table 1). Careful selection of carbonate, alkoxide counterion, and nitrogen substituents in the ligand was essential for high yields. Cinnamyl carbonates with small alkyl groups underwent transesterification in competition with etherification, but tert-butyl cinnamyl carbonate (1 a) provided the

show abstract

“…The control of enantio-and diastereoselectivity is applicable to the synthesis of cis-and trans-2,5-disubstituted dihydrofurans and cis-and trans-2,6-disubstituted dihydropyrans [28,29] with control of absolute and relative stereochemistry with readily available, enantioenriched allylic [30,31] and homoallylic alcohols [32,33] (Scheme 2). For example, 1 a and 1 e reacted with alkoxides derived from (R)-1-octen-3-ol and (S)-4-penten-2-ol, respectively, in the presence of catalysts derived from the two enantiomers of L 2 to form the branched allylic ethers 5, 5' and 6, 6' with excellent yields and regio-and diastereoselectivities.…”

Section: Angewandte Chemiementioning

confidence: 99%

Iridium‐Catalyzed Intermolecular Allylic Etherification with Aliphatic Alkoxides: Asymmetric Synthesis of Dihydropyrans and Dihydrofurans

Shu

¹

,

Hartwig

²

2004

View full text Add to dashboard Cite

Elimination and racemization limit the synthesis of sterically hindered ethers, [1] such as a-chiral ethers, by the Willamson synthesis. Enantioselective transition-metal-catalyzed allylic substitution [2][3][4][5][6] could be used to prepare these materials from achiral or racemic allylic electrophiles, but intermolecular enantioselective reactions of allylic acetates or carbonates with alkoxides are limited. Enantioselective reactions of phenoxides are well documented, [7][8][9] but no metal catalyzes intermolecular enantioselective allylations of alkoxides with broad scope. [10][11][12][13] Lee and Kim [14] as well as Evans and Leahy [15] demonstrated that zinc and copper alkoxides were more reactive for allylic substitution with achiral palladium and rhodium catalysts than alkali metal alkoxides. The palladium-catalyzed reactions generated achiral ethers, but the rhodium-catalyzed reactions formed branched chiral ethers. Reactions of primary alkoxides with optically active allylic acetates occurred with predominant retention of configuration, but reactions of secondary and tertiary alkoxides were conducted with racemic allylic electrophiles. Because the products from reactions of primary alkoxides can be formed by alkylation of an optically active alcohol, but products from reactions of secondary alkoxides cannot, a catalyst that forms optically active products from hindered alkoxides and allylic carbonates is synthetically valuable. We report herein enantioselective reactions of primary, secondary, and tertiary alkoxides with achiral allylic carbonates to form branched chiral allylic ethers in high yields and with high stereoselectivity in the presence of an iridium catalyst containing a phosphoramidite ligand (Scheme 1). [16][17][18][19][20][21][22] To optimize the conditions for the allylation of aliphatic alkoxides with iridium-phosphoramidite catalysts, we studied the reactions of cinnamyl carbonate with benzyloxides (Table 1). Careful selection of carbonate, alkoxide counterion, and nitrogen substituents in the ligand was essential for high yields. Cinnamyl carbonates with small alkyl groups underwent transesterification in competition with etherification, but tert-butyl cinnamyl carbonate (1 a) provided the

show abstract

“…The furopyrazine ring was proposed by the isolation chemists to arise biosynthetically by Paal–Knorr (PK) reaction , of the diketopiperazine (DKP) 3 to give the 2,3-diaminofuran 4 that upon dehydrogenation gives hyrtioseragamine A ( 1 ) (Scheme A). We considered this proposal would be unfavorable; the PK synthesis of furans is endergonic, and the 2,3-diaminofuran 4 is electron-rich.…”

Section: Introductionmentioning

confidence: 99%

“…The furopyrazine ring was proposed by the isolation chemists to arise biosynthetically by Paal–Knorr (PK) reaction , of the diketopiperazine (DKP) 3 to give the 2,3-diaminofuran 4 that upon dehydrogenation gives hyrtioseragamine A ( 1 ) (Scheme A). We considered this proposal would be unfavorable; the PK synthesis of furans is endergonic, and the 2,3-diaminofuran 4 is electron-rich. Moreover, we are only aware of one report describing the synthesis of furopyrazines using the PK reaction. , In continuation of our interest in biomimetic alkaloid synthesis, an alternative biosynthetic proposal to the furo[2,3- b ]pyrazine unit present in the hyrtioseragamines was developed based on a reordering of the key oxidation events (Scheme B).…”

Section: Introductionmentioning

confidence: 99%

Bioinspired Synthesis of the Furopyrazine Alkaloid Hyrtioseragamine A

Kim

¹

,

Hume

²

,

Sperry

³

2021

View full text Add to dashboard Cite

A biosynthetic hypothesis proposed herein was used to guide the total synthesis of the marine-derived alkaloid hyrtioseragamine A. In the key biomimetic step, an enedione underwent acid-mediated isomerization–cyclodehydration to form the rare furopyrazine core of the natural product. The spectroscopic data for the synthetic sample is in full agreement with that described in the isolation report.

show abstract

Furans and their Benzo Derivatives: Synthesis

Cited by 34 publications

References 616 publications

Iridium‐Catalyzed Intermolecular Allylic Etherification with Aliphatic Alkoxides: Asymmetric Synthesis of Dihydropyrans and Dihydrofurans

Iridium‐Catalyzed Intermolecular Allylic Etherification with Aliphatic Alkoxides: Asymmetric Synthesis of Dihydropyrans and Dihydrofurans

Iridium‐Catalyzed Intermolecular Allylic Etherification with Aliphatic Alkoxides: Asymmetric Synthesis of Dihydropyrans and Dihydrofurans

Bioinspired Synthesis of the Furopyrazine Alkaloid Hyrtioseragamine A

Contact Info

Product

Resources

About