Hiroyuki Kusama

Platinum(II)-Catalyzed Generation and [3+2] Cycloaddition Reaction of α,β-Unsaturated Carbene Complex Intermediates for the Preparation of Polycyclic Compounds

Pt(II)-catalyzed generation of unsaturated carbene complex intermediates from various propargyl ether derivatives based on electrophilic activation of alkynes was realized. These in situ generated unsaturated carbene complexes undergo [3+2] cycloaddition reaction with various vinyl ethers, leading to efficient formation of indoles, naphthols, and benzofuran fused with a five-membered ring in high yields.

Rhodium(I)-Catalyzed [4+1] Cycloaddition Reactions of α,β-Unsaturated Imines with Terminal Alkynes for the Preparation of Pyrrole Derivatives†

Vinylidene complexes have attracted much attention for being unique reactive intermediate and synthetically useful, and characteristic reactions have been developed using various kinds of transition-metal complexes. One of the main reactions involves the addition of heteroatom nucleophiles such as alcohols, carboxylates, and carbamates to give anti-Markovnikov addition products. However, the addition of the heteroatom of C=X bonds to the vinylidene carbon atom has rarely been achieved in spite of the high synthetic potential of the zwitterionic intermediates that are produced. Herein, we report a rhodium(I)-catalyzed [4+1] cycloaddition reaction between a,b-unsaturated imines and terminal alkynes for the preparation of synthetically useful, substituted pyrrole derivatives through the addition of the imine nitrogen atom to rhodium vinylidene intermediates. When a mixture of b-TMS-substituted a,b-unsaturated imine 1a and 1-octyne (2 a) was treated with a catalytic amount of [{RhCl(coe)2}2] and PCy3 in toluene at 110 8C for nine hours, pyrrole 3a (a formal [4+1] cycloaddition product) was obtained in good yield (Scheme 1). In this reaction [{RhCl(coe)2}2], as well as other phosphine ligands such as PPh3, P(iPr)3, 1,4-bis(diphenylphosphanyl)butane (dppb), and 1,1’-bis(diphenylphosphanyl)ferrocene (dppf) showed almost no activity. Also, [{RhOH(cod)}2] (cod = 1,5-cyclooctadiene), [Rh(cod)2]BF4, and [{IrCl(coe)2}2] in the presence of PCy3 did not show any activity either. Meanwhile, [{RhCl(cod)2}2]/PCy3 showed somewhat lower activity compared to [{RhCl(coe)2}2]/PCy3. The reaction is thought to proceed by the nucleophilic addition of the nitrogen atom of the imine 1a to the carbene carbon atom of the rhodium vinylidene complex A, which is generated in situ from the terminal alkyne, to afford a zwitterionic intermediate B (Scheme 2). This intermediate

Enantioselective preparation of 8-oxabicyclo[3.2.1]octane derivatives via asymmetric [3+2]-cycloaddition of platinum-containing carbonyl ylides with vinyl ethers.

A catalytic asymmetric synthesis of 8-oxabicyclo[3.2.1]octane derivatives was achieved through the [3+2]-cycloaddition of the platinum-containing carbonyl ylides generated from acyclic gamma,delta-ynones on treatment with 10 mol % of PtCl(2)-Walphos and AgSbF(6). Synthetically useful 8-oxabicyclo[3.2.1]octane derivatives were obtained in good yields and mostly in over 90% ees.

Gold‐Catalyzed Tandem Cyclization of Dienol Silyl Ethers for the Preparation of Bicyclo[4.3.0]nonane Derivatives

The reaction was thought to proceed through nucleophilic attack of the silyl enol ether moiety to the electrophilically activated alkyne followed by attack of the generated alkenyl metallic species A to the a,b-unsaturated silyloxonium moiety at the position b to the metal to give bicyclic carbene complex intermediate B, which gave the product through 1,2-hydrogen shift with regeneration of the catalyst. We then thought of the possibility of carrying out a similar geminal carbofunctionalization reaction by employing one-carbon-atom elongated substrates (3-siloxy-1,3-dien-8-ynes 3) with the expectation that 5-exo attack of the silyl enol ether moiety followed by ring closure (geminal carbo-functionalization) would give bicyclo[3.3.0]octane derivative D having a carbene complex moiety as a substituent on the bridgehead carbon atom. As there is no a-hydrogen atom at the carbene complex moiety, 1,2-hydrogen shift is not possible and the behavior of this intermediate is intriguing (Scheme 1). We now report that 1,2-alkyl migration occurred at the generated carbene moiety to give ring-expanded products by employing 3siloxy-1,3-dien-8-yne derivatives as substrates, to stereoselectively obtain synthetically useful bicyclo[4.3.0]nonane derivatives, whose configuration was different from that of the Diels–Alder adduct. We first examined the reaction of 3-siloxy-1,3-dien-8-yne 3a with the geometry of the silyl enol ether moiety as (Z) by using various electrophilic transition-metal catalysts. Although [W(CO)5(thf)] or [ReCl(CO)5] gave the products in reasonable yield (45 % and 78 %, respectively), the cationic gold catalyst gave the best result. Thus, treatment of 3a with 10 mol % of [AuClPPh3]/AgSbF6 [6] in the presence of molecular sieves (4 ) gave bicyclo[4.3.0]nonane derivative 4a, a formal [4+2] cycloadduct, as a single stereoisomer in 92% yield (Scheme 2). Interestingly, the configuration of the product was different from that of the thermal Diels– Alder adduct 5 obtained stereoselectively by heating a solution of (Z)-3 a in toluene for 1.5 h. Thus, two diastereoisomers of the same bicyclo[4.3.0]nonane derivative were obtained selectively by choosing Au-catalyzed or thermal conditions. Next, we examined the reaction of 3-siloxy-1,3-dien-8-yne derivative 3a with the geometry of the silyl enol ether moiety as (E) under thermal and Au-catalyzed conditions (Scheme 2). In this case, (E)-3a did not undergo thermal Scheme 1. Tandem cyclization of dienol silyl ethers.

Photochemically Promoted Transition Metal-Free Cross-Coupling of Acylsilanes with Organoboronic Esters

Intermolecular carbon-carbon bond formation between acylsilanes and organoboronic esters was achieved by photoirradiation under almost neutral, transition metal-free conditions. In this reaction, siloxycarbenes generated by photoisomerization of acylsilanes reacted with boronic esters to give the formal B-C bond insertion intermediates, which underwent unique rearrangement to afford the cyclic α-alkoxyboronic esters. Acidic treatment of the resulting crude products under air furnished the cross-coupled ketones in good yields.

Platinum(II)-catalyzed intermolecular [3 + 2] cycloaddition of propadienyl silyl ethers and alkenyl ethers.

A Pt(II)-catalyzed [3 + 2] cycloaddition reaction of silyl propadienyl ethers and alkenyl ethers has been developed as the first example of the utilization of allenes as a three-carbon unit in a transition-metal-catalyzed intermolecular cycloaddition reaction. Pt(II)-containing 1,3-dipole equivalents generated by electrophilic activation of silyl propadienyl ethers using a Pt(II) catalyst reacted with various electron-rich alkenes to give synthetically useful functionalized cyclopentene derivatives in high yield with wide generality.

Cobalt–Salen Complex-Catalyzed Oxidative Generation of Alkyl Radicals from Aldehydes for the Preparation of Hydroperoxides

Catalytic generation of alkyl radicals from aldehydes via oxidative deformylation was realized using a cobalt-salen complex with H2O2. The deformylation was thought to proceed through homolytic cleavage of peroxohemiacetal intermediates to provide even primary alkyl radicals under mild conditions. Variously substituted and functionalized hydroperoxides were obtained from corresponding aldehydes in good yield.

Synthetic Studies on and Mechanistic Insight into [W(CO)5(L)]-Catalyzed Stereoselective Construction of Functionalized Bicyclo[5.3.0]decane Frameworks

Stereoselective preparation of a variety of synthetically useful functionalized bicyclo[5.3.0]decane derivatives was achieved by tandem cyclization of 3-siloxy-1,3,9-triene-7-yne derivatives based on the electrophilic activation of alkynes catalyzed by [W(CO)(5)(L)]. The reaction proceeded smoothly under photoirradiation, and various substrates were cyclized to give the corresponding bicyclic compounds with up to four chiral centers stereospecifically. Reactions of siloxydienes with a silyl substituent as an equivalent of a hydroxyl group also proceeded with wide generality to afford silyl-substituted bicyclo[5.3.0]decanes, which were highly useful as synthetic intermediates. Stereochemical studies concerning the silyl enol ether moiety suggested that two types of reaction pathway for the formation of seven-membered rings were present. The reaction of (Z)-enol silyl ethers proceeded through Cope rearrangement of cis-divinylcyclopropane intermediates, and that of (E)-enol silyl ethers by 1,4-addition of the dienyl tungsten species at the position δ to the metal atom. In the reactions of siloxydiene derivatives with silyl substituents, all possible diastereomers could be synthesized stereoselectively by changing the geometry of the silyl enol ether and enyne moieties.

Total Synthesis of (±)‐Englerin A Using An Intermolecular [3+2] Cycloaddition Reaction of Platinum‐Containing Carbonyl Ylide

Total synthesis of (±)-Englerin A has been achieved starting from γ,δ-ynone 5 in 14 steps. The key feature of this synthesis is the highly efficient and stereoselective preparation of 8-oxabicyclo[3.2.1]octane derivative 6, a core skeleton of Englerin A, based on an inverse electron-demand [3+2] cycloaddition reaction of the platinum-containing carbonyl ylide, which was developed in our laboratory.

Tungsten(0)‐ and Rhenium(I)‐Catalyzed Tandem Cyclization of Acetylenic Dienol Silyl Ethers Based on Geminal Carbo‐Functionalization of Alkynes

Tungsten(0)- and rhenium(I)-catalyzed reactions of acetylenic dienol silyl ethers based on the concept of geminal carbo-functionalization of alkynes are reported. Treatment of 3-siloxy-1,3-diene-7-ynes with catalytic amounts of [W(CO)(6)] or [ReCl(CO)(5)] under photoirradiation conditions gives synthetically useful bicyclo[3.3.0]octane derivatives in good yields. Extremely high catalytic activity is noted for the rhenium(I) complex. The reaction has been extended to substrates containing a nitrogen atom in their tethers. In this case, two kinds of synthetically useful heterocyclic compounds-the 2-azabicyclo[3.3.0]octane derivatives 9 and the monocyclic dihydropyrroles 10, with allenyl substituents-are obtained, and selective preparation of either product can be achieved through the use of an appropriate combination of the nitrogen substituent and the type of the rhenium(I) catalyst. The 2-azabicyclo[3.3.0]octane derivatives 9 are obtained selectively by carrying out treatment of N-Ns derivatives in the presence of [ReCl(CO)(4)(PPh(3))], whereas the dihydropyrrole derivatives 10 are obtained by treatment of N-Mbs derivatives with [ReCl(CO)(5)]/AgSbF(6) . Finally, we have applied this geminal carbo-functionalization to one-carbon-elongated substrates containing N-Ts moieties in their tethers. Selective 5-exo cyclization is achieved in the presence of gold(I) or rhenium(I) catalysts, whereas 6-endo cyclization is observed on use of [W(CO)(6)].