Construction of fully substituted carbon centers containing a heteroatom and a CF3 group via in situ generated p-quinone methides.

1,6-Conjugate additions of in situ generated δ-CF3-δ-substituted p-quinone methides have been achieved with a variety of heteronucleophiles under mild conditions, which led to facile and practical construction of fully substituted carbon centers including a heteroatom and a CF3 group. In particular, it was revealed that some amines themselves worked for efficient cleavage of the TBS protective group, and addition of a catalytic amount of an appropriate Brønsted acid was found to sometimes improve the progress of the desired process.

Base-Mediated Claisen Rearrangement of CF3-Containing Bisallyl Ethers.

We have previously clarified that the strongly electron-withdrawing CF3 group nicely affected the base-mediated proton shift of CF3-containing propargylic or allylic alcohols to afford the corresponding α,ß-unsaturated or saturated ketones, respectively, which was applied this time to the Claisen rearrangement after O-allylation of the allylic alcohols with a CF3 group, followed by isomerization to the corresponding allyl vinyl ethers via the proton shift, enabling the desired rearrangement in a tandem fashion, or in a stepwise manner, the latter of which was proved to have attained an excellent diastereoselectivity with the aid of a palladium catalyst.

Facile preparation and conversion of 4,4,4-trifluorobut-2-yn-1-ones to aromatic and heteroaromatic compounds.

The concise preparation of 4,4,4-trifluorobut-2-yn-1-ones by the oxidation of the readily accessible corresponding propargylic alcohols as well as their utilization as Michael acceptors for the construction of aromatic and heteroaromatic compounds are reported.

Syntheses of α-CF3-α-quaternary ketones via p-quinone methides and their derivatization to compounds with successively congested stereogenic centers.

New and successful results for the construction of new and structurally interesting compounds are reported via N-heterocyclic carbene (NHC)-catalyzed 1,6-conjugate additions of a variety of aldehydes to δ-CF3-δ-substituted p-quinone methides generated in situ, and the products are used for the 1,2-addition reactions of appropriate metal nucleophiles, enabling us to furnish highly diastereoselective products with a unique successive quaternary carbon-tertiary alcohol framework (up to dr = >99 : 1).

Ring-Opening Functionalization of Simple gem-Difluorocyclopropanes by Single-Electron Oxidants.

It was reported for the first time that single-electron oxidants such as CAN or K2S2O8 affected facile ring opening of simple gem-difluorocyclopropanes to afford 1,3-dibromo-2,2-difluoropropanes in good yields by the action of KBr, and the appropriate choice of conditions allowed to incorporate not only second halogen atoms but also hydroxy or acetamido groups at the C1 position in the difluoropropane structures in a regiospecific fashion after initiation of the reaction by the introduction of the first bromine atom at the C3 position.

Fluorine-Containing Dibenzoanthracene and Benzoperylene-Type Polycyclic Aromatic Hydrocarbons: Synthesis, Structure, and Basic Chemical Properties.

Intramolecular photocyclization of stilbene derivatives (Mallory reaction) is one of the efficient methods for building polycyclic aromatic hydrocarbon (PAH) frameworks, and is also expected to be applicable to synthesis of fluorine-containing PAHs (F-PAHs). In this study, dibenzoanthracene-type (4a) and benzoperylene-type (4b) F-PAHs were synthesized using the Mallory reaction of the 1,4-distyrylbenzene-type π-conjugated molecule (3a), which was prepared by addition-defluorination of available octafluorocyclopentene (OFCP) and aryllithium in three steps. The structure of 4a originating from π⁻π interaction was characterized by X-ray crystallographic analysis. The absorption maxima of UV-Vis spectra and emission maxima of photoluminescence spectra of the PAHs were positioned at a longer wavelength compared to those of the corresponding unsubstituted PAHs, presumably due to the electron-withdrawing nature of perfluorocyclopentene (PFCP) units. The effect of PFCP units in F-PAHs was also studied by time-dependent density functional theory (TD-DFT) calculation.

Base-promoted isomerization of CF3-containing allylic alcohols to the corresponding saturated ketones under metal-free conditions.

Following to the computational expectation, our previously reported intriguing 1,3-proton shift of 4,4,4-trifluorobut-2-yn-1-ols was successfully extended to the 4,4,4-trifluorobut-2-en-1-ol system under metal-free conditions to afford the corresponding saturated ketones in high to excellent chemical yields using such a convenient and easy-to-handle base as DBU at the toluene refluxing temperature, and utilization of the corresponding optically active substrates unambiguously demonstrated that this transformation proceeded in a highly stereoselective fashion.

Diastereoselective Mannich reactions of pseudo-C2-symmetric glutarimide with activated imines.

As an extension of the boron enolate-based aldol reactions, the oxazolidinone-installed bisimide 1a from 3-(trifluoromethyl)glutaric acid was employed for Mannich reactions with tosylated imines 2 as electrophiles to successfully obtain the corresponding adducts in a stereoselective manner.

Stereoselective synthesis of 6/7/6-fused heterocycles with multiple stereocenters via an internal redox reaction/inverse electron-demand hetero-Diels-Alder reaction sequence.

A highly stereoselective synthesis of fused heterocycles with multiple stereocenters via an internal redox reaction/inverse electron-demand hetero-Diels-Alder (IEDHDA) reaction sequence is described. The present reaction sequence has three interesting features: (1) complete control of two potentially competitive processes, i.e., hetero-Diels-Alder reaction and [1,5]-hydride shift; (2) one-shot construction of the complicated 6/7/6-fused heterocyclic structure having multiple stereocenters; and (3) high control of its stereoselectivity. When alkenylidene barbiturates with an allyl benzyl ether moiety were treated with a catalytic amount of Sc(OTf)3 and 2,2'-bipyridine, the internal redox reaction/IEDHDA reaction proceeded successively to afford 6/7/6-fused heterocycles in good chemical yields with good to excellent diastereoselectivities.

Synthesis of Polysubstituted Naphthalenes by a Hydride Shift Mediated C-H Bond Functionalization/Aromatization Sequence.

A synthetic strategy for forming multisubstituted naphthalenes based on hydride shift mediated C(sp3)-H bond functionalization was developed. This strategy consists of three successive transformations: (1) an intramolecular hydride shift mediated C(sp3)-H bond functionalization; (2) a decarboxylative fragmentation; and (3) an oxidation reaction. When benzylidene malonates having a 2-alkoxyethyl group at the ortho position were treated with a catalytic amount of Al(OTf)3, the hydride shift/cyclization reaction proceeded smoothly to afford tetralin derivatives in good chemical yields. The resulting tetralins were easily converted into naphthalenes by exposing them to modified Krapcho decarboxylation reaction conditions (LiCl, DMSO, and heating under an O2 atmosphere). The one-pot operation of these two reactions was also realized.

Silyl-Group Boosted Internal Redox Reaction: Hydride Shift from an Aliphatic Secondary Position for the Formation of Six- and Seven-Membered Carbocycles.

We report a hydride shift/cyclization reaction at the aliphatic secondary position (methylene group). The key to accomplishing this reaction was the employment of benzylidene malonate having a silyl group ß to the hydride donor carbon. When the corresponding malonates were treated with a catalytic amount of Al(OTf)3, the [1,5]-hydride shift from the simple aliphatic secondary position proceeded smoothly to afford silyl-group substituted tetralin derivatives in excellent chemical yields (up to 98%). This reaction system was applied to the formation of seven-membered carbocycles via the [1,6]-hydride shift mediated process.

Divergent synthesis of multi-substituted phenanthrenes via an internal redox reaction/ring expansion sequence.

We report an effective synthetic route to multi-substituted phenanthrenes via an internal redox reaction/ring expansion sequence. The interesting feature of the present system is that it allows for the divergent synthesis of the target skeleton depending on the selected Lewis acid catalyst. When benzylidene malonates with a cyclic structure at the ortho-position were treated with BF3·OEt2, three sequential processes (internal redox reaction/elimination of the alkoxy group/ring expansion) proceeded to give phenanthrene derivatives in which the alkoxycarbonyl (CO2R) group and the alkyl (R) group were in close proximity to each other, in good chemical yields. In sharp contrast, treatment with Bi(OTf)3 exclusively led to the formation of another type of phenanthrene, whose R group was positioned distal to the CO2R group.

Regioselective carbon-carbon bond formation of 5,5,5-trifluoro-1-phenylpent-3-en-1-yne.

The regioselective carbon-carbon bond formation was studied using 5,5,5-trifluoro-1-phenylpent-3-en-1-yne as a model substrate, and predominant acceptance of electrophiles ß to a CF3 group as well as a deuterium trap experiment of the lithiated species led to the conclusion that the obtained regioselectivity is kinetically determined for the reactions with electrophiles, under equilibration of the possible two anionic species.

Synthetic utilization of 2-chloro-1,1,1,2-tetrafluoroethane.

ß-Substituted α-fluoro-α,ß-unsaturated carboxylic acids have been successfully synthesized, usually in a (Z)-stereospecific manner by way of a stepwise or a one-pot three-step procedure starting from 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124), one of the major byproducts of the industrial process for tetrafluoroethene formation from chlorofluoromethane (HCFC-22).

Clarification of the Reactivity of 1,3,3,3-Tetrafluoropropene Oxides.

Our computation has successfully clarified the reluctant behavior of trans- and cis-1,3,3,3-tetrafluoropropene oxides 1c toward nucleophiles and led to the expectation that these epoxides would react under the Brønsted acid activation conditions. Actually, this was the case, and these epoxides smoothly opened with CF3SO3H, whose elimination after the protection of the resultant OH group afforded the enol benzoates as the enolate precursors, which nicely allowed us to construct the corresponding aldol products by reactions with various aldehydes.

Construction of trifluoromethylated quaternary stereocenters via p-quinone methides.

Development of a new synthetic method for the construction of quaternary centers with a trifluoromethyl group was realized by way of 1,6-addition of various nucleophiles including active methylene compounds to highly reactive δ-trifluoromethylated p-quinone methides generated in situ from the corresponding tertiary carbonates with a catalytic amount of an appropriate base.

Stereoselective aldol reactions using pseudo C2 symmetric 1-benzyl-4-(trifluoromethyl)piperidine-2,6-dione.

Crossed aldol reactions of the CF3-containing pseudo C2 symmetric cyclic imide 3 were carried out by way of the corresponding boron bisenolate to stereoselectively furnish the desired products 4 and this procedure allowed the preferential construction of the diastereomers of the compounds previously obtained from the acyclic counterpart 1.

Stereodivergent construction of aminodiols with a CF3 group.

A stereodivergent synthesis of various 2-amino-1,3-diols and 3-amino-1,2-diols from a single intermediate, 2,3-epoxyketones, is described.