Cyclopropanation Using an Iron‐Containing Methylene Transfer Reagent: 1,1‐Diphenylcyclopropane

Mattson, Matthew N.; O'Connor, Edward J.; Helquist, Paul

doi:10.1002/0471264180.os070.21

Cited by 3 publications

(4 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous cationic transition metal methylidene complexes have been reported. These cationic methylidenes are commonly made by α-abstraction of either a hydride or a halide from neutral transition metal alkyl precursors − or by acid treatment of an ether precursor. , Less common synthetic routes involve treatment of an iron thioether methylidene precursor or an osmium hydride , with cationic methylating reagents. To our knowledge, anionic transition metal methylidene complexes have yet to be reported.…”

Section: Resultsmentioning

confidence: 99%

Reactions of an Amphoteric Terminal Tungsten Methylidyne Complex

2001

View full text Add to dashboard Cite

Treatment of [Tp'(CO)(2)W triple bond C--PPh(3)][PF(6)] (Tp' = hydridotris(3,5-dimethylpyrazolylborate)) with Na[HBEt(3)] in THF forms the methylidyne complex Tp'(CO)(2)W triple bond C--H via formyl and carbene intermediates Tp'(CO)(C(O)H)W triple bond C- PPh(3) and Tp'(CO)(2)W=C(PPh(3))(H), respectively. Spectroscopic features reported for Tp'(CO)(2)W triple bond C--H include the W triple bond C stretch (observed by both IR and Raman spectroscopy) and the (183)W NMR signal (detected by a (1)H, (183)W 2D HMQC experiment). Protonation of the Tp'(CO)(2)W triple bond C--H methylidyne complex with HBF(4).Et(2)O yields the cationic alpha-agostic methylidene complex [Tp'(CO)(2)W=CH(2)][BF(4)]. The methylidyne complex Tp'(CO)(2)W triple bond C-H can be deprotonated with alkyllithium reagents to provide the anionic terminal carbide Tp'(CO)(2)W triple bond C--Li; a downfield resonance at 556 ppm in the (13)C NMR spectrum has been assigned to the carbide carbon. The terminal carbide Tp'(CO)(2)W triple bond C-Li adds electrophiles at the carbide carbon to generate Tp'(CO)(2)W triple bond C--R (R = CH(3), SiMe(3), I, C(OH)Ph(2), CH(OH)Ph, and C(O)Ph) Fischer carbynes. A pK(a) of 28.7 was determined for Tp'(CO)(2)W triple bond C--H in THF by titrating the terminal carbide Tp'(CO)(2)W triple bond C--Li with 2-benzylpyridine and monitoring its conversion to Tp'(CO)(2)W triple bond C--H with in situ IR spectroscopy. Addition of excess Na[HBEt(3)] to neutral Tp'(CO)(2)W triple bond C--H generates the anionic methylidene complex [Na][Tp'(CO)(2)W=CH(2)]. The synthetic methodology for generating an anionic methylidene complex by hydride addition to neutral Tp'(CO)(2)W triple bond C--H contrasts with routes that utilize alpha-hydrogen abstraction or hydride removal from neutral methyl precursors to generate methylidene complexes. Addition of PhSSPh to the anionic methylidene complex in solution generates the saturated tungsten product Tp'(CO)(2)W(eta(2)-CH(2)SPh) by net addition of the SPh(+) moiety.

show abstract

Section: Resultsmentioning

confidence: 99%

Reactions of an Amphoteric Terminal Tungsten Methylidyne Complex

2001

View full text Add to dashboard Cite

show abstract

“…19−21 Two methods have been reported to access the O-MTM derivatives of secondary alcohols: one is the Pummerer reaction with dimethyl sulfoxide 19,22,23 and the other is O-alkylation with chloromethyl methyl sulfide in the presence of NaH 24,25 or NaI. 26 Since chloromethyl methyl sulfide has a very unpleasant, penetrating odor and should be handled as a highly toxic carcinogen, 27 the Pummerer reaction with dimethyl sulfoxide is clearly the method of choice. According to a modification of the original procedure reported in 1978, 22 Pummerer reaction of 8 with DMSO (47 equiv), acetic anhydride (23 equiv), and acetic acid (12 equiv) delivered MTM ether 12 in 46% yield after chromatography, which was subjected to sulphonyl chloride treatment in order to get the pursued chloromethylation intermediate 10 that is difficult to monitor.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Then, a sequential methylthiomethyl (MTM) ether (also called O , S -acetal or thioacetal) formation and chlorination procedure were summoned to prepare the pursued 10 . − Two methods have been reported to access the O -MTM derivatives of secondary alcohols: one is the Pummerer reaction with dimethyl sulfoxide ,, and the other is O -alkylation with chloromethyl methyl sulfide in the presence of NaH , or NaI . Since chloromethyl methyl sulfide has a very unpleasant, penetrating odor and should be handled as a highly toxic carcinogen, the Pummerer reaction with dimethyl sulfoxide is clearly the method of choice.…”

Section: Resultsmentioning

confidence: 99%

Practical Synthesis of Tenofovir Alafenamide Fumarate Inspired by New Retrosynthetic Disconnection Featuring a Novel Carbon–Phosphorus Bond Construction Methodology

Liu

Chen

et al. 2023

Org. Process Res. Dev.

View full text Add to dashboard Cite

Tenofovir alafenamide fumarate (TAF) is rising as a mainstay antiretroviral agent for the treatment of HIV and chronic HBV infections. A de novo practical synthesis of TAF circumventing tenofovir (PMPA) has been accomplished on a 7 g scale. This reimagined synthesis of TAF, inspired by a hitherto uncharted retrosynthetic disconnection, centers on the P-alkylation of silylated diphenyl phosphonate 11 (as acceptor) with methylthiomethyl (MTM) ether derivative 12 (as donor) in the presence of NIS/TfOH combination as a promoter to construct the strategic carbon–phosphorus bond. This PMPA-free synthesis of TAF not only removes the intrinsic drawbacks encountered by the PMPA-dependent commercial process but also is beneficial to the diversification of the synthetic portfolio of TAF. Furthermore, this type of P-alkylation reaction with defined stereochemistry could be deployed for the late-stage modification of druglike molecules and natural products to access valuable phosphonate derivatives.

show abstract

“…Our first contribution to this area was the development of the sulfonium salt complex 3 as a truly practical, air- and water-stable reagent for cyclopropanation of alkenes (eq 1) . Thermal dissociation of dimethyl sulfide supposedly generates the carbene complex 2 .…”

Section: Introductionmentioning

confidence: 99%

Intramolecular C−H Insertion Reactions of (η⁵-Cyclopentadienyl)dicarbonyliron Carbene Complexes: Scope of the Reactions and Application to the Synthesis of (±)-Sterpurene and (±)-Pentalenene

et al. 2001

Self Cite

View full text Add to dashboard Cite

(eta(5)-Cyclopentadienyl)dicarbonyliron carbene complexes, [(eta(5)-C(5)H(5))(CO)(2)Fe=CHR](+)BF(4)(-), are generated as reactive intermediates from thioether derivatives, (eta(5)-C(5)H(5))(CO)(2)FeCH(R)SPh, by S-alkylation with trimethyloxonium tetrafluoroborate and loss of thioanisole. The carbene complexes undergo intramolecular C-H insertion into appropriately situated side chains to form cyclopentane derivatives. The reaction has been developed into a general procedure employing cycloalkanones as scaffolds bearing the iron carbene moieties and the side chains at C(2) and C(3), respectively. The products of the intramolecular insertion reactions are substituted bicyclo[n.3.0]alkanones. The scope and limitations of the reaction are described. The reaction is applied to a total synthesis of sterpurene and to a formal synthesis of pentalenene. Overall, this approach to cyclopentane annulation complements the related metal-catalyzed insertion reactions of diazocarbonyl compounds, which are also believed to occur via metal carbene complexes.

show abstract

Cyclopropanation Using an Iron‐Containing Methylene Transfer Reagent: 1,1‐Diphenylcyclopropane

Abstract: Cyclopropanation using an iron‐containing methylene transfer reagent: 1,1‐diphenylcyclopropane reactant: cyclopentadienyliron dicarbonyl dimer [C 5 H 5 (CO) 2 Fe] 2 , (0.50 mol equiv, 0.21 mol, 74.4 g; and ) intermediate: (η5‐… Show more

Cited by 3 publications

References 110 publications

Reactions of an Amphoteric Terminal Tungsten Methylidyne Complex

Reactions of an Amphoteric Terminal Tungsten Methylidyne Complex

Practical Synthesis of Tenofovir Alafenamide Fumarate Inspired by New Retrosynthetic Disconnection Featuring a Novel Carbon–Phosphorus Bond Construction Methodology

Intramolecular C−H Insertion Reactions of (η⁵-Cyclopentadienyl)dicarbonyliron Carbene Complexes: Scope of the Reactions and Application to the Synthesis of (±)-Sterpurene and (±)-Pentalenene

Contact Info

Product

Resources

About

Cyclopropanation Using an Iron‐Containing Methylene Transfer Reagent: 1,1‐Diphenylcyclopropane

Abstract: Cyclopropanation using an iron‐containing methylene transfer reagent: 1,1‐diphenylcyclopropane reactant: cyclopentadienyliron dicarbonyl dimer [C 5 H 5 (CO) 2 Fe] 2 , (0.50 mol equiv, 0.21 mol, 74.4 g; and ) intermediate: (η5‐… Show more

Cited by 3 publications

References 110 publications

Reactions of an Amphoteric Terminal Tungsten Methylidyne Complex

Reactions of an Amphoteric Terminal Tungsten Methylidyne Complex

Practical Synthesis of Tenofovir Alafenamide Fumarate Inspired by New Retrosynthetic Disconnection Featuring a Novel Carbon–Phosphorus Bond Construction Methodology

Intramolecular C−H Insertion Reactions of (η5-Cyclopentadienyl)dicarbonyliron Carbene Complexes: Scope of the Reactions and Application to the Synthesis of (±)-Sterpurene and (±)-Pentalenene

Contact Info

Product

Resources

About

Intramolecular C−H Insertion Reactions of (η⁵-Cyclopentadienyl)dicarbonyliron Carbene Complexes: Scope of the Reactions and Application to the Synthesis of (±)-Sterpurene and (±)-Pentalenene