Synthesis of (−)-malyngolide using reactions of alkylidenecarbenes

Ohira, Susumu; Ida, T.; Moritani, Masanori; Hasegawa, Taisuke

doi:10.1039/a705218i

Cited by 26 publications

(14 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another enantioselective transformation of this class was reported with the asymmetric arylative dearomatization of indoles through palladium‐phosphine‐catalyzed reductive Heck reaction using sodium formate in methanol . To date, the asymmetric reductive Heck reaction is rather limited to intramolecular reactions, which is particularly interesting for the synthesis of natural products . To the best of our knowledge, there are no examples that describe the “direct intermolecular” enantioselective reductive Heck reaction with a high ee , most likely because of the challenges involved in the asymmetric induction step.…”

Section: Introductionmentioning

confidence: 99%

Importance of the Reducing Agent in Direct Reductive Heck Reactions

et al. 2017

View full text Add to dashboard Cite

The role of the reductant in the palladium N‐heterocyclic carbene (NHC) catalyzed reductive Heck reaction and its effect on the mechanism of the reaction is reported. For the first time in this type of transformation, the palladium‐NHC‐catalyzed reductive Heck reaction was shown to proceed in the presence of LiOMe and iPrOH even at 10 °C to give the products very efficiently in excellent yields and with exceptional chemoselectivities. This study shows that the reaction proceeds through two distinct mechanisms that depend on the nature of the reducing agent. In the presence of a protic solvent or acidic medium the reaction undergoes protonation to yield the reduced product, whereas in the absence of proton source, it proceeds through the insertion of the reductant followed by reductive elimination. The kinetic data reveal that the oxidative addition is the rate‐determining step in the reaction. The reaction profiles show first‐order kinetics in aryl iodide and Pd and zero‐order kinetics in LiOMe, benzylideneacetone, and the excess amount of NHC ligand. In addition, the reaction progress kinetic analysis shows that neither catalyst decomposition nor product inhibition occurs during the reaction. DFT calculations of the key steps confirm that the oxidative addition step is the rate‐determining step in the reaction. Deuterium‐labeling experiments indicate that the product is formed by the protonation of the Pd−Calkyl bond of the intermediate formed after enone insertion into the Pd−CAr bond. Application of chiral NHC ligands in the asymmetric reductive Heck reaction only results in poor enantioselectivities (enantiomeric excess up to 20 %) and is also substrate specific. DFT calculations suggest that the migration of the aryl group to the alkene of the substrate is the enantioselectivity‐determining step of the reaction. It is further shown that if the steric bulk at the enone is small (a methyl group), the two transition state barriers from [PdII(L2)(ArI)(enone)] species Cre and Csi, which have the re and si face of the enone substrate coordinated to Pd, are very similar, in line with the experimental results. With a slightly larger group (an isopropyl substituent) a significant difference in energy barriers is calculated (2.6 kcal mol−1), and in the experiment this product is formed with a modest enantiomeric excess (up to 20 %).

show abstract

Section: Introductionmentioning

confidence: 99%

Importance of the Reducing Agent in Direct Reductive Heck Reactions

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Overview of Alkylidene Carbene-Generation Alkylidene carbenes (44) can be used in many synthetically valuable reactions including [1,2]-migration, ylide formation, alkyne cyclopropanation and [1,5]-C-H bond insertion. 28,29) Notably, [1,2]-migrations occurring with alkylidene carbenes (44) are useful for preparation of homologous alkynes (45), which are extensively used in organic synthesis 28,29) (Chart 12, Eq. 1).…”

Section: Allylic Rearrangement Of Cpsmentioning

confidence: 99%

“…Transformation of Ketones into Homologous Alkynes via CPs In continuation of our program of using CPs, we have recently reported novel synthetic methods for homologous alkynes (45) 13) or five-membered unsaturated cyclic compounds (47) 37) from carbonyl compounds (4 and 5) based on reactions of CPs (3) with trimethylsilyl azide (TMSN 3 ) in the presence of Bu 2 SnO as catalyst (the Wittenberger method), 38) as shown in Chart 14. In this two-step transformation, CPs (3) may form tetrazolylphosphates (48), which subsequently undergo successive fragmentation to generate alkylidene carbenes (44 and 46) that then undergo [1,2]-migration or [1,5]-C-H insertions to produce homologous alkynes (45) or five-membered cyclic compounds (47), respectively. The scope of these reactions, which occur under neutral conditions, could be extended towards a variety of alkynes and cyclopentene products that are not usually accessible from the corresponding carbonyl compounds via the lithium trimethyl silyldiazomethane [TMSC(Li) N 2 ] procedure [39][40][41] used currently in organic synthesis.…”

Section: Allylic Rearrangement Of Cpsmentioning

confidence: 99%

Development of New Synthetic Reactions Using Hetero-Heavy Atoms and Their Application to Synthesis of Biofunctional Molecules

Harusawa

2020

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Novel reactions using hetero-heavy atoms (P, S, Si, Se, and Sn) were developed and applied to the synthesis of biofunctional molecules and some medicine-candidates, in which the following items are covered. 1) Development of introduction of C 1-unit using cyanophosphates (CPs). 2) Carbene-generation under neutral condition from CPs and its application to organic synthesis. 3) [3,3]Sigmatropic rearrangement-ring expansion reactions of medium-sized cyclic thionocarbonates containing a sulfur atom and their application to natural product synthesis. 4) Stereoselective synthesis of novel β-imidazole C-nucleosides via diazafulvene intermediates and their application to investigating ribozyme reaction mechanism. 5) Developments of novel histamine H 3-and H 4-receptor ligands using new synthetic methods involving Se or Sn atoms.

show abstract

“…[21,22] A selective Wittig olefination between ketone 7 and the phosphonium salt 8 [23] afforded the anticipated diene derivative 9 (Scheme 2). Selective removal of the acetonide unit in 9 gave rise to the diol derivative 10, monoprotection of which afforded the diene alcohol 11 in good overall yield.…”

mentioning

confidence: 99%

“…Thus, diisopropylidenemannitol 6 was chosen as starting material and transformed into ketone 7 in nearly quantitative yield by a known sequence of reactions. [21,22] A selective Wittig olefination between ketone 7 and the phosphonium salt 8 [23] afforded the anticipated diene derivative 9 (Scheme 2). Selective removal of the acetonide unit in 9 gave rise to the diol derivative 10, monoprotection of which afforded the diene alcohol 11 in good overall yield.…”

mentioning

confidence: 99%

A Stereoselective Formal Synthesis of (−)‐Fumagillol

Bedel¹,

Haudrechy²,

Langlois³

2004

Eur J Org Chem

View full text Add to dashboard Cite

A novel formal synthesis of fumagillol, a direct precursor of the antiangiogenic sesquiterpene fumagillin, is described. The main features of the synthesis are a stereoselective Claisen−Ireland rearrangement, a ring-closing metathesis, a Fumagillin (1), isolated in 1951 by Elbe and Hanson [1] from the microbial organism Aspergillus fumigatus, is representative of a class of sesquiterpenes like ovalicin (2) [2] and FR 65814 (3), [3] which display various biological activities. Fumagillin (1) was originally described as an antimicrobial agent, but Folkman and co-workers [4] have more recently discovered that this compound is a potent and selective inhibitor of angiogenesis. The semisynthetic compound TNP-470 (4) [5,6] showed a better therapeutic index than fumagillin (1) and is one of the most promising drugs acting as an inhibitor of angiogenesis (Scheme 1). Scheme 1The recent discovery that methionine aminopeptidase II (MetAp-II) is selectively inhibited by fumagillin (1), [7] together with the X-ray structure of the covalent complex between fumagillin (1) and MetAp-II, [8] have increased interest in the synthesis of fumagillin (1) and of new fumagillin analogues.[9Ϫ11] [a]

show abstract

Synthesis of (−)-malyngolide using reactions of alkylidenecarbenes

Cited by 26 publications

References 33 publications

Importance of the Reducing Agent in Direct Reductive Heck Reactions

Importance of the Reducing Agent in Direct Reductive Heck Reactions

Development of New Synthetic Reactions Using Hetero-Heavy Atoms and Their Application to Synthesis of Biofunctional Molecules

A Stereoselective Formal Synthesis of (−)‐Fumagillol

Contact Info

Product

Resources

About