Ruthenium-Catalyzed Dimerization of 1 , 1-Diphenylpropargyl Alcohol to a Hydroxybenzocyclobutene and Related Reactions

Propargyl alcohol is a useful synthon in synthetic organic chemistry. We found that the ruthenium(II) complex [Cp*RuCl(diene)] (Cp* = η-C5Me5; diene = isoprene or 1,5-cyclooctadiene (cod)) catalyzes dimerization of 1,1-diphenylprop-2-yn-1-ol (1,1-diphenylpropargyl alcohol, 1a) at room temperature to afford an alkylidenebenzocyclobutenyl alcohol 2a quantitatively. Meanwhile, a stoichiometric reaction of the related hydrido complex [Cp*RuH(cod)] with 1a at 50 ◦C led to isolation of a ruthenocene derivative 4 bearing a cyclopentadienyl ring generated by dehydrogenative trimerization of 1a. Detailed structures of 2a and 4 were determined by X-ray crystallography. The reaction mechanisms for the formation of 2a and 4 were proposed.


Ruthenium-Catalytic Dimerization of 1,1-Arylpropargyl Alcohol
The addition of the ruthenium(II) complex [Cp*RuCl(diene)] (diene = isoprene or 1,5-cyclooctadiene (cod)) to 50 equiv.of 1,1-diphenylpropargyl alcohol 1a in THF at room temperature resulted in full conversion of the alcohol.A subsequent chromatographic workup afforded a novel alkylidenebenzocyclobutenyl alcohol 2a in 97% yield (Scheme 1).The p-methoxyphenyl analogue 1b was also converted to 2b.The products 2 were characterized by X-ray analysis of 2a as well as 1 H and 13 C{ 1 H} NMR spectroscopy.Figure 1 clearly shows the benzocyclobutene framework of 2a.The C-C bond distances in the six-membered ring of the benzocyclobutene core fall in the range of 1.383(2)-1.398(2)Å, indicating the delocalization of the double bonds.Meanwhile, the short C2-C15 and C16-C17 distances (1.337(2) Å) as well as the long C15-C16 distance (1.456(2) Å) in 2 are in agreement with the butadiene skeleton derived from dimerization of 1.The hydroxy groups is preserved throughout the reaction despite of their ease of dehydration in the coordination sphere [20].The 1 H NMR spectrum of 2a displays three mutually coupled vinyl resonances at δ 6.27, 6.32, and 6.45; these signals are assigned to the H14, H12, and H13 atoms shown in Figure 1, respectively, by HMQC and HMBC experiments.

Ruthenium-Catalytic Dimerization of 1,1-Arylpropargyl Alcohol
The addition of the ruthenium(II) complex [Cp*RuCl(diene)] (diene = isoprene or 1,5cyclooctadiene (cod)) to 50 equiv.of 1,1-diphenylpropargyl alcohol 1a in THF at room temperature resulted in full conversion of the alcohol.A subsequent chromatographic workup afforded a novel alkylidenebenzocyclobutenyl alcohol 2a in 97% yield (Scheme 1).The p-methoxyphenyl analogue 1b was also converted to 2b.The products 2 were characterized by X-ray analysis of 2a as well as 1 H and 13 C{ 1 H} NMR spectroscopy.Figure 1 clearly shows the benzocyclobutene framework of 2a.The C-C bond distances in the six-membered ring of the benzocyclobutene core fall in the range of 1.383(2)-1.398(2)Å, indicating the delocalization of the double bonds.Meanwhile, the short C2-C15 and C16-C17 distances (1.337(2) Å) as well as the long C15-C16 distance (1.456(2) Å) in 2 are in agreement with the butadiene skeleton derived from dimerization of 1.The hydroxy groups is preserved throughout the reaction despite of their ease of dehydration in the coordination sphere [20].The 1 H NMR spectrum of 2a displays three mutually coupled vinyl resonances at δ 6.27, 6.32, and 6.45; these signals are assigned to the H14, H12, and H13 atoms shown in Figure 1, respectively, by HMQC and HMBC experiments.The catalytic formation of 2 should entail the orthometalation of one of the aryl group in 1 in addition to the C-C bond formation.We confirmed that a potential intermediate enyne 3 [21], which would be formed by head-to-head dimerization of 1a [22,23], does not undergo the C-H cleavage reaction under the present dimerization conditions (Scheme 2).The result may also exclude the involvement of analogous orthometalation of the terminal monoyne 1 in the catalysis, although a related C-H cleavage reaction of 1a on an osmium complex was known [24].On the other hand, a Inorganics 2017, 5, 80 2 of 8

Ruthenium-Catalytic Dimerization of 1,1-Arylpropargyl Alcohol
The addition of the ruthenium(II) complex [Cp*RuCl(diene)] (diene = isoprene or 1,5cyclooctadiene (cod)) to 50 equiv.of 1,1-diphenylpropargyl alcohol 1a in THF at room temperature resulted in full conversion of the alcohol.A subsequent chromatographic workup afforded a novel alkylidenebenzocyclobutenyl alcohol 2a in 97% yield (Scheme 1).The p-methoxyphenyl analogue 1b was also converted to 2b.The products 2 were characterized by X-ray analysis of 2a as well as 1 H and 13 C{ 1 H} NMR spectroscopy.Figure 1 clearly shows the benzocyclobutene framework of 2a.The C-C bond distances in the six-membered ring of the benzocyclobutene core fall in the range of 1.383(2)-1.398(2)Å, indicating the delocalization of the double bonds.Meanwhile, the short C2-C15 and C16-C17 distances (1.337(2) Å) as well as the long C15-C16 distance (1.456(2) Å) in 2 are in agreement with the butadiene skeleton derived from dimerization of 1.The hydroxy groups is preserved throughout the reaction despite of their ease of dehydration in the coordination sphere [20].The 1 H NMR spectrum of 2a displays three mutually coupled vinyl resonances at δ 6.27, 6.32, and 6.45; these signals are assigned to the H14, H12, and H13 atoms shown in Figure 1, respectively, by HMQC and HMBC experiments.The catalytic formation of 2 should entail the orthometalation of one of the aryl group in 1 in addition to the C-C bond formation.We confirmed that a potential intermediate enyne 3 [21], which would be formed by head-to-head dimerization of 1a [22,23], does not undergo the C-H cleavage reaction under the present dimerization conditions (Scheme 2).The result may also exclude the involvement of analogous orthometalation of the terminal monoyne 1 in the catalysis, although a related C-H cleavage reaction of 1a on an osmium complex was known [24].On the other hand, a The catalytic formation of 2 should entail the orthometalation of one of the aryl group in 1 in addition to the C-C bond formation.We confirmed that a potential intermediate enyne 3 [21], which would be formed by head-to-head dimerization of 1a [22,23], does not undergo the C-H cleavage reaction under the present dimerization conditions (Scheme 2).The result may also exclude the involvement of analogous orthometalation of the terminal monoyne 1 in the catalysis, although a related C-H cleavage reaction of 1a on an osmium complex was known [24].On the other hand, a labeling experiment using 1a-d 1 with a deuterium at the acetylenic position revealed that the hydrogen atom derived from the aromatic C-H bond cleavage is selectively incorporated into the vinyl group adjacent to the C(OH)Ph 2 moiety in 2a (Scheme 3).
Inorganics 2017, 5, 80 3 of 8 labeling experiment using 1a-d1 with a deuterium at the acetylenic position revealed that the hydrogen atom derived from the aromatic C-H bond cleavage is selectively incorporated into the vinyl group adjacent to the C(OH)Ph2 moiety in 2a (Scheme 3).On the basis of these observations, we propose the mechanism for the catalytic dimerization of 1a (Scheme 4).Two molecules of 1a first bind to the ruthenium atom to form a ruthenacycle A [8,9,25].Subsequent σ-bond metathesis in A would result in the formation of the vinyl intermediate B, which would then undergo E-Z isomerization.Reductive elimination from the hydrido(vinyl) complex C affords the dimerization product 2a.The mechanism is consistent with the deuterium labeling experiment illustrated in Scheme 3. In related reactions of propargylic alcohols without 1-aryl substituents, Dixneuf and co-workers obtained alkylidenecyclobutene derivatives by a threecomponent dehydrative condensation of propargylic alcohols and carboxylic acid with a Cp*Ru catalyst [26].They isolated a cyclobutadiene complex, which may be derived from reductive elimination form A, as the reaction intermediate.Trost and co-workers also described a ruthenacycle similar to A as a key intermediate in CpRu-catalyzed reactions of propargylic alcohols [27,28].On the other hand, Chan and co-workers synthesized indene derivatives by the iron-catalyzed selfcondensation of 1-arylpropargyl alcohols involving aromatic C-H bond cleavage [29].

Reaction of a (Hydrido)ruthenium Complex with 1,1-Diphenylpropargyl Alcohol
In order to gain further insight into the mechanism of the catalytic dimerization of 1a shown in Scheme 1, we examined the reaction of 1a with a related hydrido complex.When the hydrido On the basis of these observations, we propose the mechanism for the catalytic dimerization of 1a (Scheme 4).Two molecules of 1a first bind to the ruthenium atom to form a ruthenacycle A [8,9,25].Subsequent σ-bond metathesis in A would result in the formation of the vinyl intermediate B, which would then undergo E-Z isomerization.Reductive elimination from the hydrido(vinyl) complex C affords the dimerization product 2a.The mechanism is consistent with the deuterium labeling experiment illustrated in Scheme 3. In related reactions of propargylic alcohols without 1-aryl substituents, Dixneuf and co-workers obtained alkylidenecyclobutene derivatives by a threecomponent dehydrative condensation of propargylic alcohols and carboxylic acid with a Cp*Ru catalyst [26].They isolated a cyclobutadiene complex, which may be derived from reductive elimination form A, as the reaction intermediate.Trost and co-workers also described a ruthenacycle similar to A as a key intermediate in CpRu-catalyzed reactions of propargylic alcohols [27,28].On the other hand, Chan and co-workers synthesized indene derivatives by the iron-catalyzed selfcondensation of 1-arylpropargyl alcohols involving aromatic C-H bond cleavage [29].

Reaction of a (Hydrido)ruthenium Complex with 1,1-Diphenylpropargyl Alcohol
In order to gain further insight into the mechanism of the catalytic dimerization of 1a shown in Scheme 1, we examined the reaction of 1a with a related hydrido complex.When the hydrido On the basis of these observations, we propose the mechanism for the catalytic dimerization of 1a (Scheme 4).Two molecules of 1a first bind to the ruthenium atom to form a ruthenacycle A [8,9,25].Subsequent σ-bond metathesis in A would result in the formation of the vinyl intermediate B, which would then undergo E-Z isomerization.Reductive elimination from the hydrido(vinyl) complex C affords the dimerization product 2a.The mechanism is consistent with the deuterium labeling experiment illustrated in Scheme 3. In related reactions of propargylic alcohols without 1-aryl substituents, Dixneuf and co-workers obtained alkylidenecyclobutene derivatives by a three-component dehydrative condensation of propargylic alcohols and carboxylic acid with a Cp*Ru catalyst [26].They isolated a cyclobutadiene complex, which may be derived from reductive elimination form A, as the reaction intermediate.Trost and co-workers also described a ruthenacycle similar to A as a key intermediate in CpRu-catalyzed reactions of propargylic alcohols [27,28].On the other hand, Chan and co-workers synthesized indene derivatives by the iron-catalyzed self-condensation of 1-arylpropargyl alcohols involving aromatic C-H bond cleavage [29].
Inorganics 2017, 5, 80 3 of 8 labeling experiment using 1a-d1 with a deuterium at the acetylenic position revealed that the hydrogen atom derived from the aromatic C-H bond cleavage is selectively incorporated into the vinyl group adjacent to the C(OH)Ph2 moiety in 2a (Scheme 3).On the basis of these observations, we propose the mechanism for the catalytic dimerization of 1a (Scheme 4).Two molecules of 1a first bind to the ruthenium atom to form a ruthenacycle A [8,9,25].Subsequent σ-bond metathesis in A would result in the formation of the vinyl intermediate B, which would then undergo E-Z isomerization.Reductive elimination from the hydrido(vinyl) complex C affords the dimerization product 2a.The mechanism is consistent with the deuterium labeling experiment illustrated in Scheme 3. In related reactions of propargylic alcohols without 1-aryl substituents, Dixneuf and co-workers obtained alkylidenecyclobutene derivatives by a threecomponent dehydrative condensation of propargylic alcohols and carboxylic acid with a Cp*Ru catalyst [26].They isolated a cyclobutadiene complex, which may be derived from reductive elimination form A, as the reaction intermediate.Trost and co-workers also described a ruthenacycle similar to A as a key intermediate in CpRu-catalyzed reactions of propargylic alcohols [27,28].On the other hand, Chan and co-workers synthesized indene derivatives by the iron-catalyzed selfcondensation of 1-arylpropargyl alcohols involving aromatic C-H bond cleavage [29].

Reaction of a (Hydrido)ruthenium Complex with 1,1-Diphenylpropargyl Alcohol
In order to gain further insight into the mechanism of the catalytic dimerization of 1a shown in Scheme 1, we examined the reaction of 1a with a related hydrido complex.When the hydrido

Reaction of a (Hydrido)ruthenium Complex with 1,1-Diphenylpropargyl Alcohol
In order to gain further insight into the mechanism of the catalytic dimerization of 1a shown in Scheme 1, we examined the reaction of 1a with a related hydrido complex.When the hydrido complex [Cp*RuH(cod)] was treated with a slight excess of 1a at 50 • C, a novel ruthenocene complex 4 was obtained in moderate yield (Scheme 5).The 1 H NMR spectrum of 4 exhibits two mutually coupled doublets at δ 3.56 and 4.24 with a 1H intensity each, which are assignable to the newly formed cyclopentadienyl ligand.Figure 2 depicts the crystal structure of 4 featuring a fused bicyclic hemiketal skelton derived from dehydrative condensation of three molecules of 1a.The two cyclopentadinyl rings in 4 are slightly tilted with a dihedral angle of 12.9 • .The Cp-fused six-membered ring adopts a half-chair conformation with an axial hydroxy group, and two vicinal phenyl groups in the ring lie in the anti configuration.
Inorganics 2017, 5, 80 4 of 8 complex [Cp*RuH(cod)] was treated with a slight excess of 1a at 50 °C, a novel ruthenocene complex 4 was obtained in moderate yield (Scheme 5).The 1 H NMR spectrum of 4 exhibits two mutually coupled doublets at δ 3.56 and 4.24 with a 1H intensity each, which are assignable to the newly formed cyclopentadienyl ligand.Figure 2 depicts the crystal structure of 4 featuring a fused bicyclic hemiketal skelton derived from dehydrative condensation of three molecules of 1a.The two cyclopentadinyl rings in 4 are slightly tilted with a dihedral angle of 12.9°.The Cp-fused sixmembered ring adopts a half-chair conformation with an axial hydroxy group, and two vicinal phenyl groups in the ring lie in the anti configuration.The mechanism for the formation of 4 remains open to speculation; however, the reaction apparently involves 1,2-migration of the phenyl group in the propragylic alcohol.A plausible route is suggested in Scheme 6. Formation of the ruthenacycle A as in the dimerization of 1a (Scheme 4) would be followed by protonation of the hydrido ligand and enyne metathesis to yield the sevenmembered ruthenacycle B. Subsequent 1,2-migration of the phenyl group to the electrophilic carbene atom [30]  Inorganics 2017, 5, 80 4 of 8 complex [Cp*RuH(cod)] was treated with a slight excess of 1a at 50 °C, a novel ruthenocene complex 4 was obtained in moderate yield (Scheme 5).The 1 H NMR spectrum of 4 exhibits two mutually coupled doublets at δ 3.56 and 4.24 with a 1H intensity each, which are assignable to the newly formed cyclopentadienyl ligand.Figure 2 depicts the crystal structure of 4 featuring a fused bicyclic hemiketal skelton derived from dehydrative condensation of three molecules of 1a.The two cyclopentadinyl rings in 4 are slightly tilted with a dihedral angle of 12.9°.The Cp-fused sixmembered ring adopts a half-chair conformation with an axial hydroxy group, and two vicinal phenyl groups in the ring lie in the anti configuration.The mechanism for the formation of 4 remains open to speculation; however, the reaction apparently involves 1,2-migration of the phenyl group in the propragylic alcohol.A plausible route is suggested in Scheme Formation of ruthenacycle A as in the dimerization of 1a (Scheme 4) would be followed by protonation of the hydrido ligand and enyne metathesis to yield the sevenmembered ruthenacycle B. Subsequent 1,2-migration of the phenyl group to the electrophilic carbene atom [30]   The mechanism for the formation of 4 remains open to speculation; however, the reaction apparently involves 1,2-migration of the phenyl group in the propragylic alcohol.A plausible route is suggested in Scheme 6. Formation of the ruthenacycle A as in the dimerization of 1a (Scheme 4) would be followed by protonation of the hydrido ligand and enyne metathesis to yield the seven-membered ruthenacycle B. Subsequent 1,2-migration of the phenyl group to the electrophilic carbene atom [30] would generate C. Rearrangement of C leads to ring contraction to afford the ruthenabenzene D, which would undergo reductive elimination.Ring closure of the resultant ruthenocene E gives rise to the formation of the hemiketal 4 as the final product.
would generate C. Rearrangement of C leads to ring contraction to afford the ruthenabenzene D, which would undergo reductive elimination.Ring closure of the resultant ruthenocene E gives rise to the formation of the hemiketal 4 as the final product.