Sakurai Reaction Research Articles

Intramolecular Hosomi-Sakurai Reaction for the Synthesis of Benzoxasiloles.

A Lewis acid-catalyzed intramolecular Hosomi-Sakurai reaction of o-(allylsilyl)benzaldehyde/ketone has been developed. The reaction proceeds through simultaneous C-Si bond cleavage and C-C bond reconstruction. This protocol provides a rapid approach for the synthesis of allyl-substituted benzoxasiloles under mild conditions.

Synthesis of (–)-Aspidophytine

Key words Haplophyton cimicidum - (–)-aspidophytine - Stork–Danheiser transposition - Corey–Bakshi–Shibata reduction - Ireland–Claisen rearrangement - Malaprade–Lemieux–Johnson cleavage - iminium Hosomi–Sakurai reaction

Features of the intramolecular Hosomi–Sakurai reaction of allylic cyclopentenylsilane containing an enol ether moiety

A new intramolecular variant of the Hosomi–Sakurai reaction of 5-(2-methoxyvinyl)-4-((phenylthio)methyl)cyclopent-2-en-1-yl)trimethylsilane is presented, which is a by-process between hydrolysis to aldehyde and acetalization to dimethylacetal. The key steps are the generation of methoxy methylene carbocation from enol ether during acid catalysis and its subsequent attack on the allylsilane moiety with formation of norbornene derivative. In turn, the corresponding aldehyde undergoes Hosomi–Sakurai cyclization by interaction with BF3·Et2O in acetonitrile, as well as by reaction with TBAF in THF through various transition states, leading to epimeric alcohols of the same norbornene structure. At the same time, the starting enol ether by treatment with TBAF undergoes exclusively protodesilylation and hydrolysis, while with BF3·Et2O it gives mixtures of epimeric products of topology both bicyclo[2.2.1]heptane and bicyclo[3.2.0]heptane.

Asymmetric Addition of Allylsilanes to Aldehydes: A Cr/Photoredox Dual Catalytic Approach Complementing the Hosomi–Sakurai Reaction

The allylation of aldehydes is a fundamental transformation in synthetic organic chemistry. Among the multitude of available reagents, allylsilanes especially have been established as a preferred allyl source. As initially reported by Hosomi and Sakurai, these non-toxic and highly stable reagents add to carbonyls via an open transition state upon Lewis acid activation. Herein, we report a general strategy to access a variety of valuable homoallylic alcohols in opposite chemo- and diastereoselectivity to the established Hosomi–Sakurai conditions by switching to photocatalytic activation in combination with a closed transition state (chromium catalysis). Moreover, this dual catalytic approach displays a straightforward way to introduce excellent levels of enantioselectivity and its mild conditions allow for a broad substrate scope including chiral boron-substituted products as a highlight. To emphasize the synthetic utility, our method was applied as the key step in the synthesis of a bioactive compound and in the late-stage functionalization of steroid derivatives. Detailed mechanistic studies and DFT calculations hint toward an unprecedented photo-initiated chain being operative.

Trityl Cation-Catalyzed Hosomi-Sakurai Reaction of Allylsilane with β,γ-Unsaturated α-Ketoester to Form γ,γ-Disubstituted α-Ketoesters.

(Ph3C)[BPh(F)4]-catalyzed Hosomi-Sakurai allylation of allylsilanes with β,γ-unsaturated α-ketoesters has been developed to give γ,γ-disubstituted α-ketoesters in high yields with excellent chemoselectivity. Preliminary mechanistic studies suggest that trityl cation dominates the catalysis, while the silyl cation plays a minor role.

Annulation Tactics of cis-syn-cis Triquinanes by Allylsilanes: Application of Hosomi-Sakurai Reaction Conditions.

A stereoselective [3+2] cycloaddition approach to functionalized pentaquinanes starting from cis-syn-cis triquinanes, derived from Cookson's diones, is reported. This transformation involves generation of six new stereocenters in a single step leading to cis-anti-cis-syn-cis-anti-cis polyquinane systems. Our method prevents transannular cyclizations which are prevalent in these moieties. The structure and stereochemistry of target molecules are well-characterized based on NMR data and X-ray diffraction studies.

Access to Functionalized 3,5‐Disubstituted 1,2‐Dioxolanes under Mild Conditions through Indium(III) Chloride/Trimethylsilyl Chloride or Scandium(III) Triflate Catalysis

AbstractHerein we report the use of catalytic amount of scandium(III) triflate or indium(III) chloride (with trimethylsilyl chloride) for the functionalization of endoperoxyacetals through Sakurai or Mukaiyama reactions. These catalysts allow milder and more practical conditions than those previously reported with improvements in scope and reproducibility. This method allows a full catalytic sequence from cyclopropanols to produce desired functionalized 1,2‐dioxolanes.magnified image

Generation and Reactions of a Benzodehydrotropylium Ion–Co2(CO)6 Complex

A series of 7-methylenedehydrobenzo[7]annulen-5-ol hexacarbonyldicobalt complexes were generated by Hosomi–Sakurai reactions of allylsilanes containing o-alkynylarylaldehyde-Co2(CO)6 complexes. One of the cyclization products was converted into its corresponding dihydrobenzo[7]annulen-7-ol hexacarbonyldicobalt complex, an immediate precursor to a benzodehydrotropylium–Co2(CO)6. The cation was generated in situ and reacted with four nucleophiles, and its aromatic stabilization was determined by computational methods.

Scalable Synthesis of Biologically Relevant Spirocyclic Pyrrolidines.

Synthetic approaches toward multigram preparation of spirocyclic α,α-disubstituted pyrrolidines from readily available starting materials are discussed. It was shown that although a number of synthetic methodologies have been known to date, many of the title compounds remain hardly accessible. The most appropriate literature method (which relied on reaction of imines and allyl magnesium halide, followed by bromocyclization) was identified and optimized. It was found that the method is most fruitful for simple non-functionalized substrates. Two novel approaches based on the Sakurai or Petasis reactions of cyclic ketones, followed by hydroboration–oxidation at the allyl moiety thus introduced, were elaborated. The latter method had the largest scope and was beneficial for the substrates containing organosulfur or protected amino functions. For the synthesis of 4-azaspiro[2.4]heptane, an alternative synthetic scheme commencing from tert-butyl cyclopropanecarboxylate (instead of the corresponding ketone) was developed. It was shown that the whole set of the methodologies developed can be used for the synthesis of various spirocyclic α,α-disubstituted pyrrolidines—advanced building blocks of potential importance to medicinal and agrochemistry—at up to a 100 g scale.

A Stereoselective Synthesis of the ACE Inhibitor Trandolapril

A conceptually novel and stereoselective synthesis of the enantiopure octahydroindole building block and its conversion into the ACE inhibitor trandolapril was achieved. Key steps include the α-allylation of a protected l-pyroglutamic acid derivative, a highly diastereoselective Hosomi–Sakurai reaction and a Ru-catalyzed ring-closing metathesis of a 4,5-diallylated proline. This way, the synthesis of trandolapril was efficiently achieved in 25% overall yield (12 steps).

A highly efficient Hg(OTf)2-mediated Sakurai–Hosomi allylation of N-tert-butyloxycarbonylamino sulfones, aldehydes, fluoroalkyl ketones and α,β-unsaturated enones using allyltrimethylsilane

The cheap and easily available Hg(OTf)2 can efficiently mediate the Sakurai–Hosomi reaction of N-Boc amino sulfones, aldehydes, α-fluoroalkyl ketones and α,β-unsaturated enones using allyltrimethylsilane with the catalyst loading down to 0.5–5.0 mol%.

Catalytic enantioselective Hosomi-Sakurai reaction of α-ketoesters promoted by chiral copper(ii) complexes.

A catalytic enantioselective Hosomi-Sakurai reaction of α-ketoesters has been developed. A copper(ii) complex with a chiral bis(oxazoline) ligand bearing methanesulfonamide groups shows excellent catalytic activity to give α,α-disubstituted α-hydroxyesters in high yields with high enantioselectivities. This is the first successful method for the catalytic enantioselective 1,2-addition of α-ketoesters with allylic silanes.

Functionalisation of isoindolinones via a calcium catalysed Hosomi-Sakurai allylation.

A rapid and functionally tolerant calcium catalysed Hosomi-Sakurai reaction has been realised. Employing 1 mol% calcium, allylated isoindolinones can be synthesised in high yields and the reaction is shown to be tolerant to a range of medicinally relevant functional groups including heterocycles. The synthetic utility of the reaction has been shown, and a plausible reaction mechanism is provided.

Development of a reductive Hosomi-Sakurai reaction

Herein we present a full account on the reductive Hosomi-Sakurai reaction along with some insight into the reaction mechanism. Stereoselectivity appears to be highest when the crucial carbocation intermediate, derived by protonation of the homoallylic ether, is sufficiently stabilized to ensure that the hydride transfer becomes rate-determining. This hypothesis is supported by experiment and mechanistic analysis.

Synthesis of Arboridinine

Key words indole alkaloid - arboridinine - photocatalysis - silver-mediated cyclization - Hosomi–Sakurai reaction

A Stereoselective Reductive Hosomi-Sakurai Reaction.

A novel reductive variant of the classical Hosomi-Sakurai reaction is reported. This transformation hinges on a redox-neutral, stereoselective internal reduction event under mild conditions. This operationally simple reaction relies on readily available starting materials and leads to useful products in diastereoselectivities of up to 7:1. The versatility of this new method is demonstrated through the stereoselective one-step synthesis of an AChE inhibitor.

Synthesis of Enantioenriched Allylic Silanes via Nickel-Catalyzed Reductive Cross-Coupling.

An asymmetric Ni-catalyzed reductive cross-coupling has been developed to prepare enantioenriched allylic silanes. This enantioselective reductive alkenylation proceeds under mild conditions and exhibits good functional group tolerance. The chiral allylic silanes prepared here undergo a variety of stereospecific transformations, including intramolecular Hosomi-Sakurai reactions, to set vicinal stereogenic centers with excellent transfer of chirality.

P-1 分子内細見-櫻井反応を機軸とするアレロパシー活性テルペノイドの合成(ポスター発表の部)

P-1 分子内細見-櫻井反応を機軸とするアレロパシー活性テルペノイドの合成(ポスター発表の部)

Highly Enantioselective Addition of Allyltrimethylsilane to Aldehydes

Key words silylium Lewis acids - Hosomi–Sakurai reaction - aldehydes - allyltrimethylsilane - imidodiphosphorimidates - asymmetric catalysis

Extremely Active Organocatalysts Enable a Highly Enantioselective Addition of Allyltrimethylsilane to Aldehydes.

The enantioselective allylation of aldehydes to form homoallylic alcohols is one of the most frequently used carbon-carbon bond-forming reaction in chemical synthesis and, for several decades, has been a testing ground for new asymmetric methodology. However, a general and highly enantioselective catalytic addition of the inexpensive, nontoxic, air- and moisture-stable allyltrimethylsilane to aldehydes, the Hosomi-Sakurai reaction, has remained elusive. Reported herein is the design and synthesis of a highly acidic imidodiphosphorimidate motif (IDPi), which enables this transformation, thus converting various aldehydes with aromatic and aliphatic groups at catalyst loadings ranging from 0.05 to 2.0 mol % with excellent enantioselectivities. Our rationally constructed catalysts feature a highly tunable active site, and selectively process small substrates, thus promising utility in various other challenging chemical reactions.