Vinyl Stannane Research Articles

Platinum Catalysed Hydrostannylation of Terminal Alkynes; Highly Selective Synthesis of Vinyl Stannanes

AbstractWe present the first study on the application of platinum complexes in the hydrostannylation of terminal alkynes. A range of platinum complexes were screened, with PtCl2/XPhos proving to provide the best selectivity for the β‐(E)‐vinyl stannane. The catalyst system is able to provide the corresponding vinyl stannane in selectivities which surpasses that which is typically afforded under palladium catalysis. Additionally, a telescoped hydrometallation/cross‐coupling sequence has been developed, allowing for application of the vinyl stannanes without excessive manipulation or purification of the intermediate stannane.magnified image

Cyclocarbonylation of Allenyl Glyoxylate Strategy to Build the Tricyclic Core of Cyclocalopin A.

An approach for the construction of the tricyclic framework of naturally occurring cyclocalopin A is described. The establishment of the crucial intermediate α-methylene bis-γ,δ-lactone involves a [2 + 2 + 1]-cyclocarbonylation of newly introduced allenyl glyoxylate via direct methods using Mo(CO)6 or sequential reaction pathways. The sequential reaction route involved a stannylative cyclization by Pd(0) catalyst, bromination of an vinyl stannane moiety, and final cyclocarbonylation by palladium catalysis to provide the bis-γ,δ-lactone. The feasibility of forming the spiro-system by an exo-selective [4 + 2]-cycloaddition was accomplished.

Iodoindenes: Synthesis and application to cross-coupling

An expeditious synthesis of 5-, 6-, and 7-iodoindenes from the corresponding aminoindan-1-ones in more than 70% yield employing readily available precursors and ubiquitous reagents is reported. The 4-iodoindene has been prepared analogously in 40% overall yield. A three-step sequence involves diazotization-iodination of aminoindan-1-one followed by the reduction and dehydration. The iodoindenes serve as effective substrates for the regioselective Stille coupling with vinyl stannanes but isomeric mixtures are produced during Sonogashira coupling with alkynes in the presence of triethylamine.

The synthesis of unnatural α-alkyl- and α-aryl-substituted serine derivatives.

The synthesis of α-aryl- and α-alkyl-substituted serine derivatives via [3,3]-sigmatropic rearrangement of allyl carbamates as a key step is reported. Allyl carbamates were obtained from the corresponding allyl alcohols. The former were prepared through three approaches. Aryl-substituted ones were synthesized via the Stille coupling reaction of aryl iodides with enantiomerically enriched vinyl stannanes. Conversely, alkyl-substituted allyl alcohols were prepared by an analogous strategy involving the Negishi coupling reaction of enantiomerically enriched vinyl iodides or by enzymatic kineric resolution of the corresponding racemic alcohols.

Stereoselective synthesis of the C14[sbnd]C23 fragment of biselyngbyolide A and B enabled by transition metal catalysis

Transition metal catalysis has enabled the highly stereoselective and protecting group-free synthesis of the C14C23 fragment of the apoptosis-inducing natural products biselyngbyolide A and B. A Pd-catalyzed Stille reaction between a vinyl stannane and a crotyl carbonate formed the skipped diene with complete control of the trisubstituted bond and excellent control over the branched/linear products. A Cu-catalyzed Stahl oxidation was used to form the requisite aldehyde needed for a Ag-catalyzed asymmetric allylation. The latter provided the final fragment with excellent stereochemical control.

Z-Selective Hydrostannylation of Terminal and Internal C–C Triple Bonds Initiated by the Trityl Cation

A metal-free method for the anti-addition of n-Bu3SnH across terminal and internal alkynes, including related α,β-unsaturated carboxyl compounds, is reported. The reaction is initiated by the trityl salt [Ph3C]+[B(C6F5)4]− and proceeds through β-tin-stabilized vinyl cations. Their reduction by hydride transfer from n-Bu3SnH explains the high Z-selectivity in the formation of the vinyl stannanes.

Total Syntheses of Disorazoles A₁ and B₁ and Full Structural Elucidation of Disorazole B₁.

Described herein are the first total syntheses of naturally occurring antitumor agents disorazoles A1 and B1 and the full structural assignment of the latter. The syntheses were achieved through convergent strategies employing enantioselective constructions of the required building blocks, including a novel Sharpless epoxidation/enzymatic kinetic resolution of stannane-containing substrates that led selectively to both enantiomeric forms of an epoxy vinyl stannane, and a series of coupling reactions, including a Wittig reaction, a Suzuki coupling, a Stille coupling, a Yamaguchi esterification and a Yamaguchi macrolactonization.

Toward Leiodermatolide: Synthesis of the Core Structure.

The macrocyclic core (35) of the marine natural product leiodermatolide (1) was synthesized from two key fragments, vinyl iodide 23 (C1-C11 part) and vinyl stannane 31 (C12-C18 part). A Stille coupling led to conjugated Z,Z-diene 32. The derived seco acid 34 was cyclized using a Yamaguchi macrolactonization. Key steps in the assembly of vinyl iodide 23 were a Paterson aldol reaction, and a Kumada coupling on a triflate derivative to create the C4-C5 trisubstituted double bond. The two stereocenters in fragment 31 were established by a Marshall-Tamaru reaction. The longest linear sequence comprises 20 steps.

ChemInform Abstract: Recent Advances in the Synthesis of Stannanes and the Scope of Their Posterior Chemical Transformations

AbstractReview: [64 refs.

ChemInform Abstract: Synthesis of Trisubstituted Alkenylstannanes Through Copper‐Catalyzed Three‐Component Coupling of Alkylboranes, Alkynoates, and Tributyltin Methoxide.

AbstractThe reaction of monosubstituted ethenes with (9‐BBN)2 and subsequent Cu‐catalyzed coupling of the resulting alkylborane with acetylenic esters and Bu3SnOMe offers a stereoselective synthesis of highly functionalized vinyl stannanes.

Design, Synthesis, and Biological Evaluation of Truncated Superstolide A

Design, Synthesis, and Biological Evaluation of Truncated Superstolide A

ChemInform Abstract: Stereospecific Preparation of (E)‐1,2‐Difluoro‐1,2‐disubstituted Alkenes.

Abstractvia Pd‐catalyzed coupling of (Z)‐vinyl stannanes (I) with aromatic iodides (II)

A stereoselective synthesis of the C9–C19 subunit of (+)-peloruside A

The stereoselective synthesis of a C9-C19 fragment of the potent antitumor agent peloruside A is disclosed. The C11 stereogenic centre was created by a vinylogous Mukaiyama aldol reaction following Carreira's protocol, with excellent stereocontrol. The C13 stereogenic centre was introduced by a substrate controlled reduction. The C15 stereocentre was fashioned using Noyori's asymmetric transfer hydrogenation while the Z-trisubstituted double bond was formed by a regioselective hydrostannation of an alkyne followed by methylation of the resultant vinyl stannane using Lipshutz's protocol. The C18 chiral centre was introduced by a chemoenzymatic route.

The stereospecific preparation of (E)-1,2-difluoro-1,2-disubstituted alkenes

(Z)-1,2-difluoro-2-substituted vinyl silanes were prepared stereospecifically from chlorotrifluoroethene, chlorotrimethylsilane and alkyl or aryllithium reagents. Subsequent exchange of the trimethylsilyl group via reaction of the vinylsilane with KF/n-Bu3SnCl/DMF stereospecifically afforded the corresponding (Z)-1,2-difluoro-2-substituted vinyl stannanes. Pd(PPh3)4/Cu(I)I/DMF coupling of the vinyl stannanes with substituted aromatic iodides stereospecifically provided the (E)-1,2-difluoro-1-substituted aryl-alkenes in excellent yield.

Stereocontrolled Synthesis of Substituted Chiral Piperidines viaOne-Pot Asymmetric 6π-Azaelectrocyclization: Asymmetric Syntheses of(−)-Dendroprimine, (+)-7-Epidendroprimine, (+)-5-Epidendroprimine, and (+)-5,7-Epidendroprimine

The asymmetric one-pot 6π-azaelectrocyclization of alkenyl vinyl stannane, ethyl (Z)-2-iodo-4-oxobutenoate, and (-)-7-isopropyl-cis-aminoindanol in the presence of a Pd(0) catalyst stereoselectively produced the tetracyclic aminoacetal compounds, resulting from the four-bond formation accompanying by controlling the stereochemistry at the two asymmetric centers. The produced cyclic aminoacetals can be regarded as synthetic precursors of substituted chiral piperidines, and the syntheses of 2,4- and 2,4,6-substituted piperidines were realized from the obtained aminoacetals by the stereoselective hydrogenation of the double bond conjugated with the C-4 ester group and alkylation at the aminoacetal moiety. In addition, the stereoselective synthesis of an indolizidine alkaloid, (-)-dendroprimine, and its three stereoisomers, (+)-7-epidendroprimine, (+)-5-epidendroprimine, and (+)-5,7-epidendroprimine, were achieved.

Design and Synthetic Investigation towardgem-difluoromethylenated Fostriecin Analogue

Fostriecin is a promising leading anticancer compound. The α,β-unsaturated lactone in Fostriecin is believed to be the critical pharmacophore, which can covalently bind to the Cys269 residue of the PP2A subunit via a Michael 1,4-conjugate addition. We reasoned that the introduction of strong electron-withdrawing gem-difluoromethylene to replace the methylene group at the γ position of the lactone ring would lead to fostriecin analogue 4 with enhanced enzymatic binding affinity. Ac- cordingly, the synthesis of fostriecin analogue 4 was investigated. The skeleton of target molecule 4 was established conver- gently from fragments a, b and c via an magnesium mediated chelation-controlled addition and Stille coupling using Pd(CH3CN)Cl2 as catalyst. The key steps of synthesizing fragment a included the coupling between alkenyl iodide 8 and ethyl bromodifluoroacetate in the presence of copper powder and the establishment of C-5 stereocenter via lipase AK cata- lyzed kinetic resolution. The construction of C-11 and C-9 stereocenters in fragment b were realized by the lipase AK cata- lyzed kinetic resolution and CBS asymmetric reduction of α,β-unsaturated ketone 23 (BH3•PhNEt2 as reductive agent), re- spectively. The connection of fragments a and b proceeded through the magnesium mediated chelation-controlled addition procedures: fragment a (vinyl stannane) was firstly converted to vinyl lithium reagent 27 by the treatment of BuLi (1.05 equiv.) at -78 ℃, then the i-PrMgCl (2.0 equiv.) solution in THF was added dropwise to produce the critical magne- sium-ate complex intermediate A, finally the addition of fragment b solution in THF to the magnesium-ate complex A gave the coupled product 29. The Stille coupling of fragment c with vinyl iodide 39 prepared from 29 in the presence of Pd(CH3CN)Cl2 gave target molecule skeleton 40 in 85% yield. Finally, the protected fostriecin analogue 42 was successfully synthesized by a longest linear steps of 18 steps in 1.28% overall yield. However, the deprotection of compound 42 failed to give the target molecular 4. This could be caused by the instability of the fluorinated lactone in which the strong electron- withdrawing gem-difluoromethylene group enhanced the polarization of the lactone function. Keywords Fostriecin; difluoromethylene; α,β-unsaturated δ-lactone; enzymatic kinetic resolution; 1,5-oxidative cycliza- tion; hydrolysis of fluorinated lactone

The stereocontrolled total synthesis of spirastrellolide A methyl ester. Expedient construction of the key fragments

Due to a combination of their promising anticancer properties, limited supply from the marine sponge source and their unprecedented molecular architecture, spirastrellolides represent attractive and challenging synthetic targets. A modular strategy for the synthesis of spirastrellolide A methyl ester, which allowed for the initial stereochemical uncertainties in the assigned structure was adopted, based on the envisaged sequential coupling of a series of suitably functionalised fragments; in this first paper, full details of the synthesis of these fragments are described. The pivotal C26-C40 DEF bis-spiroacetal was assembled by a double Sharpless asymmetric dihydroxylation/acetalisation cascade process on a linear diene intermediate, configuring the C31 and C35 acetal centres under suitably mild acidic conditions. A C1-C16 alkyne fragment was constructed by application of an oxy-Michael reaction to introduce the A-ring tetrahydropyran, a Sakurai allylation to install the C9 hydroxyl, and a 1,4-syn boron aldol/directed reduction sequence to establish the C11 and C13 stereocentres. Two different coupling strategies were investigated to elaborate the C26-C40 DEF fragment, involving either a C17-C25 sulfone or a C17-C24 vinyl iodide, each of which was prepared using an Evans glycolate aldol reaction. The remaining C43-C47 vinyl stannane fragment required for introduction of the unsaturated side chain was prepared from (R)-malic acid.

Convergent synthesis of 2 H-chromenes—a formal [3+3] cycloaddition by a one-pot, three-step cascade

In cases in which the palladium-catalyzed coupling of a bromoquinone with a vinyl stannane affords a vinyl quinone that enolizes, the resulting ortho-quinone methide undergoes an oxa-6π electrocyclization. Enolization is promoted by the presence of a polar additive. The net conversion is a formal [3+3] cycloaddition that gives 2 H-chromenes. Because the first two steps of the cascade are catalyzed, the overall conversion is an example of multicatalysis. Yields for the optimized, one-pot protocol are dramatically improved over the conventional stepwise process.

Formal synthesis of (+)-neooxazolomycin via a Stille cross-coupling/deconjugation route

A formal synthesis of neooxazolomycin is described via the preparation of Kende’s key intermediate in a longest linear sequence of 23 steps. This work is founded upon the union of three fragments: Moloney’s lactam-derived triflate, a vinyl stannane and a Julia–Kocienski sulfone and encompasses three key steps: (i) a Stille cross-coupling to combine the triflate and vinyl stannane, (ii) a base-promoted enone deconjugation to derive the dihydroxylation precursor and (iii) our previously reported Julia–Kocienski methodology to assemble the pentadienyl amine side chain with the sulfone precursor.

Stereocontrolled total synthesis of (+)-concanamycin F: the strategic use of boron-mediated aldol reactions of chiral ketones

A highly stereocontrolled total synthesis of the 18-membered macrolide (+)-concanamycin F, a potent inhibitor of vacuolar ATPases, is described that proceeds in 5.8% yield over 26 steps. The three key fragments, C1–C13 vinyl iodide, C14–C22 vinyl stannane and C23–C28 aldehyde, were efficiently constructed using asymmetric boron-mediated aldol reactions of appropriate chiral ketone building blocks. The nature of the silyl protection of the C7/C9 hydroxyls proved to be critical for achieving macrocyclisation, with TES ethers being superior to a cyclic silylene derivative. Following a Liebeskind-Stille cross-coupling reaction between the C1–C13 vinyl iodide and C14–C22 vinyl stannane fragments to assemble the (12 E,14 E)-diene, a modified Yamaguchi macrolactonisation delivered the requisite 18-membered macrocyclic core. This advanced intermediate was also obtained by an alternative sequence using an esterification step to connect the C1–C13 and C14–C22 fragments followed by a Pd-catalysed intramolecular Stille reaction to install the (12 E,14 E)-diene. Conversion of the resulting macrocyclic intermediate into a methyl ketone then enabled a highly diastereoselective Mukaiyama aldol coupling of the derived silyl enol ether with the C13–C28 aldehyde fragment to install the fully elaborated side chain, whereby subsequent global deprotection of the resulting β-hydroxyketone under suitable conditions (TASF followed by p-TsOH) afforded (+)-concanamycin F.