Efficient Generation and Synthetic Applications of Alkyl-Substituted Siloxycarbenes: Suppression of Norrish-Type Fragmentations of Alkanoylsilanes by Triplet Energy Transfer.

Acylsilanes have been known to undergo isomerization to siloxycarbenes under photoirradiation and the thus generated carbenes can be utilized for various synthetic reactions. But this carbene formation is not necessarily efficient with some alkanoylsilanes because Norrish-type fragmentations compete, which limit the synthetic utility of alkanoylsilanes as carbene precursors. In this study, generation of siloxycarbenes from alkanoylsilanes by visible-light-induced energy transfer was examined by using an Ir complex, [Ir{dF(CF3 )ppy}2 (dtbpy)]PF6 , and was successfully applied to the C-C coupling reactions with boronic esters or aldehydes. This methodology efficiently suppressed undesired Norrish-type reactions and broadened synthetic utility of alkanoylsilanes.

Lewis Acid-Assisted Photoinduced Intermolecular Coupling between Acylsilanes and Aldehydes: A Formal Cross Benzoin-Type Condensation.

Intermolecular carbon-carbon bond-forming reaction between readily available acylsilanes and aldehydes was achieved under photoirradiation conditions with assistance of a catalytic amount of Lewis acid. Nucleophilic addition of photochemically generated siloxycarbenes to aldehydes followed by 1,4-silyl migration afforded synthetically useful α-siloxyketones. Electrophilic activation of aldehydes by Lewis acid is highly important to realize this reaction efficiently, otherwise the yield of the desired coupling products were significantly decreased. Noteworthy is that a formal cross benzoin-type reaction using acylsilanes was achieved under Lewis acidic conditions. This is the first example of Lewis acid-catalyzed reaction of photochemically generated siloxycarbenes with electrophiles.

Total Synthesis of (±)-Integrifolin.

The total synthesis of (±)-integrifolin has been achieved for the first time through the stereoselective preparation of the bicyclo[5.3.0]decane skeleton based on the tungsten-catalyzed cyclization of acyclic trienynes under photoirradiation conditions. Further key transformations of the cyclized product are the Tamao oxidation through cyclic silyl ether, the introduction of two oxygen functionalities by the oxidation of the diene and the construction of three exo-methylene moieties.

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.

Generation of (amino)(boryloxy)carbenes from carbamoylboranes and their coupling reaction with aldehydes.

Carbamoylboranes were found to react with various aldehydes under heating conditions to give α-hydroxycarboxamides in good yields. A DFT study supports the mechanism, which involves thermally generated (amino)(boryloxy)carbene intermediates. To our knowledge, this is the first report on the generation of (amino)(boryloxy)carbene intermediates from carbamoylboranes and its application to carbon-carbon bond-forming reactions.

Photoinduced Intramolecular Cyclization of Acylsilanes Bearing a Boronate Moiety: Construction of a Highly Strained trans-Fused Bicyclo[3.3.0]octane Skeleton.

A reliable strategy for the construction of trans-fused bicyclo[n.3.0] skeletons was explored by utilizing photoinduced cyclization of acylsilanes bearing a boronate. The substrates having an acylsilane and a boronate in a 1,2-trans relationship were prepared via hydroboration of cycloalkene derivatives. The desired cyclization was efficiently promoted by photoirradiation to give the trans-fused bicyclo[n.3.0] derivatives as a single diastereomer. It is noteworthy that this methodology enables the efficient construction of a highly strained trans-5-5 ring system.

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 generation and [3+2] cycloaddition reaction of α,ß-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.

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)].

Visible-Light-Induced In Situ Generation of Fischer-Type Copper Carbene Complexes from Acylsilanes and Its Application to Catalytic [4 + 1] Cycloaddition with Siloxydienes.

A novel methodology for in situ generation of Fischer-type metal-carbene complexes was developed. Photoirradiation to a mixture of an acylsilane and a cationic copper complex cleanly gave a Fischer-type copper-siloxycarbene complex, which was detected by spectroscopic methods. This carbene complex reacted with siloxydienes in a [4 + 1] cycloaddition manner to give cyclopentene derivatives. It is noteworthy that this reaction proceeds with a catalytic amount of copper through in situ generation of a Fischer-type copper-siloxycarbene complex 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% ee's.

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.

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.

Theoretical study of the cycloaddition reaction of a tungsten-containing carbonyl ylide.

The [3+2] cycloaddition reaction of a tungsten-containing carbonyl ylide with methyl vinyl ether and the insertion reactions of the nonstabilized carbene complex intermediates produced have been investigated through the use of B3LYP density functional theory. The [3+2] cycloaddition reaction of the tungsten-containing carbonyl ylide has been proven to proceed concertedly, reversibly, and with high endo selectivity. The intermolecular Si-H insertion reactions of the carbene complex intermediates have been proven to be favored over the intramolecular C-H insertion, in good agreement with experimental results. Moreover, the kinetic endo/exo ratio of the [3+2] cycloaddition reaction has been shown to determine the endo/exo selectivity of the Si-H insertion products. In addition, secondary orbital interactions involving the benzene ring and the carbonyl ligand on the metal center have turned out to strongly influence the high endo selectivity of the [3+2] cycloaddition reaction with methyl vinyl ether.

Efficient control of pi-alkyne and vinylidene complex pathways for the W(CO)5(L)-catalyzed synthesis of two types of nitrogen-containing bicyclic compounds.

When omega-acetylenic dienol silyl ethers containing NMs part in the tether were treated with a catalytic amount of W(CO)6 under photoirradiation, 2-azabicyclo[3.3.0]octanes were obtained in good yield via pi-alkyne complexes. On the other hand, treatment of the same substrates with a catalytic amount of W(CO)6 in the presence of n-Bu3N under the same reaction conditions gave 3-azabicyclo[3.3.0]octanes in good yield exclusively via vinylidene complexes. Thus, the pi-alkyne and vinylidene complex pathways are easily controlled by using a catalytic amount of W(CO)5(L) and an amine.

Chelation-assisted electrocyclic reactions of 3-alkenyl-2,2'-bipyridines: an efficient method for the synthesis of 5,6-dihydro-1,10-phenanthroline and 1,10-phenanthroline derivatives.

An efficient method for the synthesis of substituted 5,6-dihydro-1,10-phenanthrolines and 1,10-phenanthrolines has been developed by means of the chelation-assisted photochemical electrocyclic reactions of 3-alkenyl-2,2'-bipyridines.

Pt(II)- or Au(III)-catalyzed [3+2] cycloaddition of metal-containing azomethine ylides: highly efficient synthesis of the mitosene skeleton.

[reaction: see text] Only 1-3 mol % of PtCl(2) or AuBr(3) was sufficient to promote generation and [3+2] cycloaddition of transition-metal-containing azomethine ylides derived from N-(o-alkynylphenyl)imines bearing an internal alkyne moiety. A highly efficient method for the preparation of synthetically useful tricyclic indole derivatives having a substituent at the 3-position of the indole nucleus was established by this method.

Intermolecular 1,5-dipolar cycloaddition reaction of tungsten-containing vinylazomethine ylides leading to seven-membered heterocycles.

Intermolecular 1,5-dipolar cycloaddition reaction of tungsten-containing vinylazomethine ylide, generated from o-(alk-3-en-1-ynyl)phenylbenzaldimines and tungsten carbonyl complex, with ketene acetals proceeds efficiently to give azepino[1,2-a]indole derivatives in good yield. Formation of [5+2] or [3+2] cycloadducts can be controlled by an appropriate choice of dipolarophile.

Synthesis of isochromene esters utilizing 1,6-addition of nucleophiles to benzopyranylidenetungsten(0) complexes.

[reaction: see text] A concise method for the preparation of isochromene carboxylates has been developed by the regioselective 1,6-addition of various nucleophiles such as Grignard reagents, alkoxide, and cyanide onto benzopyranylidenetungsten(0) complexes, followed by iodine oxidation of the addition intermediates.