One-Pot Synthesis of Homoallylic Ketones from the Addition of Vinyl Grignard Reagent to Carboxylic Esters

Hansford, Karl A.; Dettwiler, James E.; Lubell, William D.

doi:10.1021/ol0359822

Cited by 45 publications

(28 citation statements)

References 77 publications

(32 reference statements)

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“…In contrast, when the synthesis of N-Pmc-thioacrylamide was attempted through addition of vinylmagnesium bromide to N-Pmc-isothiocyanate 1, to our surprise we recovered thioamide 2d as the sole isolable product. A review of the literature revealed a similar reaction as noted by Lubell and co-workers, 19 and was likely the result of addition of the vinyl nucleophile to isothiocyanate 1, followed by addition of a second equivalent of vinyl nucleophile in a conjugate fashion.…”

Section: Methodssupporting

confidence: 65%

Comprehensive and Facile Entry into Substituted Amidines via the Condensation of N-Pmc-Substituted Thioamides with Amines Using Mukaiyama Reagent as a Thiophile

Flemer¹,

Madalengoitia²

2011

Synthesis

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A convenient approach is presented for the preparation of substituted amidines through the fusion of N-Pmc-substituted thioamides with amines, facilitated by a variety of thiophilic reagents. Assorted thiophiles were evaluated for their effectiveness as condensation reagents between the two partners, with the Mukaiyama reagent emerging as the optimal candidate for this process. The scope and limitations of this method were explored, revealing interesting synthetic challenges and constraints. Many of these limitations were overcome through the application of alternative reaction pathways in the construction of troublesome products. Treatment of the resultant Pmc-amidines with trifluoroacetic acid and trimethylsilyl trifluoromethanesulfonate cleanly afforded the deprotected substituted amidines.

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Section: Methodssupporting

confidence: 65%

Comprehensive and Facile Entry into Substituted Amidines via the Condensation of N-Pmc-Substituted Thioamides with Amines Using Mukaiyama Reagent as a Thiophile

Flemer¹,

Madalengoitia²

2011

Synthesis

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“…We turned our attention to the use of a less sterically demanding nucleophile and applied the protocol reported by Lubell and co-workers, who developed a sequential addition of vinylmagnesium bromide on esters in the presence of a copper salt to afford the g,d-unsaturated ketones through collapse of the tetrahedral intermediate followed by selective 1,4-addition to the resulting vinyl ketone. [23] Ester 13 underwent twofold alkylation under Lubells conditions with a slight modification, delivering the desired g,d-unsaturated ketone 14 in 81 % yield with 10 equivalents of vinylmagnesium bromide and a stoichiometric amount of copper(I) cyanide. When the amounts of Grignard reagent and copper(I) cyanide were reduced, the yield of 14 decreased significantly and the product was accompanied by the formation of unidentified byproducts.…”

Section: Resultsmentioning

confidence: 99%

Catalytic Asymmetric Amination of N‐Nonsubstituted α‐Alkoxycarbonyl Amides: Concise Enantioselective Synthesis of Mycestericin F and G

Berhal

Takechi

Kumagai

et al. 2011

Chemistry A European J

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In an attempt to explore the synthetic utility of a ternary asymmetric catalyst comprising La(NO(3))(3)·6H(2)O, amide-based ligand (R)-L1, and D-valine tert-butyl ester H-D-Val-OtBu, we investigated a catalytic, asymmetric amination of functionalized N-nonsubstituted α-alkoxycarbonyl amides using di-tert-butyl azodicarboxylate as an electrophilic aminating reagent. A highly functionalized, cyclic N-nonsubstituted α-alkoxycarbonyl amide delivered the desired amination product in up to 96% enantiometric excess, with the requisite functionalities of the polar heads of sphingosines with the appropriate stereochemical arrangement. The rapid asymmetric assembly of these functional groups allowed a concise enantioselective synthetic route to sphingosines to be established with a broad flexibility towards derivative synthesis. These studies have culminated in an efficient catalytic enantioselective total synthesis of immunosuppressive fungal metabolites mycestericin F (3a) and G (3b).

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“…N -Pf-Amino ketones can be prepared by nucleophilic addition either to a carboxylic ester [ 18 ], an aldehyde [ 14 ], an oxazolidinone [ 19 ] or an isoxazolidide [ 10 ]. However, the most widely used routes, presumably because of their good yields compared to others, are via an aldehyde or an oxazolidinone.…”

Section: The Phenylfluorenyl Group In Synthesismentioning

confidence: 99%

The 9-Phenyl-9-fluorenyl Group for Nitrogen Protection in Enantiospecific Synthesis

Karppanen

Koskinen

2010

Molecules

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One of the biggest challenges in asymmetric synthesis is to prevent racemization of enantiopure starting materials. However, at least some of the enantiopurity is lost in most of the existing reactions used in synthetic organic chemistry. This translates into unnecessary material losses. Naturally enantiopure proteinogenic amino acids that can be transformed into many useful intermediates in drug syntheses, for example, are especially vulnerable to this. The phenylfluoren-9-yl (Pf) group, a relatively rarely used protecting group, has proven to be able to prevent racemization in α-amino compounds. This review article showcases the use of Pf-protected amino acid derivatives in enantiospecific synthesis.

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One-Pot Synthesis of Homoallylic Ketones from the Addition of Vinyl Grignard Reagent to Carboxylic Esters

Cited by 45 publications

References 77 publications

Comprehensive and Facile Entry into Substituted Amidines via the Condensation of N-Pmc-Substituted Thioamides with Amines Using Mukaiyama Reagent as a Thiophile

Comprehensive and Facile Entry into Substituted Amidines via the Condensation of N-Pmc-Substituted Thioamides with Amines Using Mukaiyama Reagent as a Thiophile

Catalytic Asymmetric Amination of N‐Nonsubstituted α‐Alkoxycarbonyl Amides: Concise Enantioselective Synthesis of Mycestericin F and G

The 9-Phenyl-9-fluorenyl Group for Nitrogen Protection in Enantiospecific Synthesis

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