Laina M. Geary
- Courses4
- Reviews9
- School: University of Nevada
- Campus: Reno
- Department: Chemistry
- Email address: Join to see
- Phone: Join to see
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Location:
1664 N Virginia St
Reno, NV - 89557 - Dates at University of Nevada: June 2015 - December 2019
- Office Hours: Join to see
Biography
University of Nevada Reno - Chemistry
Experience
University of Texas at Austin
Banting (NSERC) Postdoctoral Fellow
All projects use transfer hydrogenation to simplify and improve the overall efficiency of C-C bond formation.
1. Development of diastereoselective ruthenium(II) catalyzed propargylation via 1,3-enynes.
2. Development of diastereo- and enantioselective iridium catalyzed propargylation of carbonyl compounds.
* 1,3-Enynes and propargyl chlorides as allenylmetal precursors.
3. Development of ruthenium(0) catalyzed transformations.
* n-Prenylation and geranylation of activated ketones from mandelates and 1,3-dienes;
* [4+2] Cycloadditions between 1,2-glycols and diene to give bridgehead 1,2-diols.
* Synthesis of polycyclic aromatic heterocycles (polyacenes) via the Ru(0) catalyzed [4+2].
* Synthesis of macrocyclic diones via sequential Ru(0) [4+2] cycloaddition and oxidative cleavageUniversity of Nevada Reno
Assistant Professor
Research in the Geary laboratory will focus on the development and application of transition metal chemistry in catalysis and synthetic chemistry to the formation of carbon-carbon bonds. The research will be divided into three general themes.
The first will focus on the catalytic generation of reactive intermediates. By avoiding stoichiometric, preformation of highly reactive intermediates, we aim to direct the reactivity of these species in a controlled and selective manner. A second area of focus will be on rendering traditional, stoichiometric organic reactions into catalytic processes. A third area of focus is the invention of new catalytic reactions for the construction of carbon-carbon bonds. These are not mutually exclusive concepts, and the interplay between two or more areas will drive the research program. The study of reaction mechanism will be central to all projects and will lead to both a deeper understanding of chemical processes and lead to the discovery of new chemistry.
One key concept in the design of projects involves the availability of the starting materials. The degrees of separation between the commodity or feedstock chemical and the starting material for the C-C bond forming reaction should be kept to a minimum, and are ideally zero. This necessitates the conceptualization of targets and goals from the very beginning, and provides a focus for the idealization of chemistries developed. The terms atom economy, step economy, and redox economy frequently appear in the literature, and serve to emphasize the importance of chemoselectivity in any transformation. High chemoselectivity is a standing goal to maximize the functional group compatibility and minimize substrate preactivation. Students will get training in organic synthesis, organometallic chemistry, and asymmetric catalysis within the broad goal of simplicity to complexity via C-C bond formation.
Education
University of Manitoba
Ph.D.
Organic Chemistry
Thesis: A diversity-oriented approach to the palladium-catalyzed modular assembly of conjugated compounds and heterocycles: high-value compounds from trichloroethyleneUniversity of Manitoba
B.Sc.(Hons)
Chemistry
Publications
Enantioselective Carbonyl Propargylation by Iridium-Catalyzed Transfer Hydrogenative Coupling of Alcohols and Propargyl Chlorides
Angew. Chem., Int. Ed.
It takes alkynes! Exposure of propargyl chlorides to primary benzylic alcohols in the presence of [Ir(cod){(R)-segphos}]OTf (cod=1,5-cyclooctadiene, segphos=5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole, Tf=trifluoromethanesulfonyl) results in hydrogen exchange to give allenyliridium–aldehyde pairs that combine to form products of propargylation with high ee value (see scheme). The reaction can also be conducted using aldehydes.
Enantioselective Carbonyl Propargylation by Iridium-Catalyzed Transfer Hydrogenative Coupling of Alcohols and Propargyl Chlorides
Angew. Chem., Int. Ed.
It takes alkynes! Exposure of propargyl chlorides to primary benzylic alcohols in the presence of [Ir(cod){(R)-segphos}]OTf (cod=1,5-cyclooctadiene, segphos=5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole, Tf=trifluoromethanesulfonyl) results in hydrogen exchange to give allenyliridium–aldehyde pairs that combine to form products of propargylation with high ee value (see scheme). The reaction can also be conducted using aldehydes.
Benzannulation via Ruthenium Catalyzed Diol-Diene [4+2] Cycloaddition: One- and Two-Directional Syntheses of Fluoranthenes and Acenes
Journal of the American Chemical Society
A new benzannulation protocol is described and applied to the synthesis of polycyclic aromatic hydrocarbons. Ruthenium(0)-catalyzed diol–diene [4+2] cycloaddition delivers cyclohex-1-ene-4,5-diols, which are subject to aromatization upon dehydration or Nicholas diol deoxydehydration. Employing diol and tetraol reactants, benzannulation can be conducted efficiently in one- and two-directional modes, respectively, as illustrated in the construction of substituted fluoranthenes and acenes.
Enantioselective Carbonyl Propargylation by Iridium-Catalyzed Transfer Hydrogenative Coupling of Alcohols and Propargyl Chlorides
Angew. Chem., Int. Ed.
It takes alkynes! Exposure of propargyl chlorides to primary benzylic alcohols in the presence of [Ir(cod){(R)-segphos}]OTf (cod=1,5-cyclooctadiene, segphos=5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole, Tf=trifluoromethanesulfonyl) results in hydrogen exchange to give allenyliridium–aldehyde pairs that combine to form products of propargylation with high ee value (see scheme). The reaction can also be conducted using aldehydes.
Benzannulation via Ruthenium Catalyzed Diol-Diene [4+2] Cycloaddition: One- and Two-Directional Syntheses of Fluoranthenes and Acenes
Journal of the American Chemical Society
A new benzannulation protocol is described and applied to the synthesis of polycyclic aromatic hydrocarbons. Ruthenium(0)-catalyzed diol–diene [4+2] cycloaddition delivers cyclohex-1-ene-4,5-diols, which are subject to aromatization upon dehydration or Nicholas diol deoxydehydration. Employing diol and tetraol reactants, benzannulation can be conducted efficiently in one- and two-directional modes, respectively, as illustrated in the construction of substituted fluoranthenes and acenes.
Direct, Redox Neutral Prenylation and Geranylation of Secondary Carbinol C-H Bonds: C4 Regioselectivity in Ruthenium-Catalyzed C-C Couplings of Dienes to alpha-Hydroxy Esters
Journal of the American Chemical Society
The ruthenium catalyst generated in situ from Ru3(CO)12 and tricyclohexylphosphine, PCy3, promotes the redox-neutral C–C coupling of aryl-substituted α-hydroxy esters to isoprene and myrcene at the diene C4-position, resulting in direct carbinol C–H prenylation and geranylation, respectively. This process enables direct conversion of secondary to tertiary alcohols in the absence of stoichiometric byproducts or premetalated reagents, and is the first example of C4-regioselectivity in catalytic C–C couplings of 2-substituted dienes to carbonyl partners. Mechanistic studies corroborate a catalytic cycle involving diene–carbonyl oxidative coupling.
Enantioselective Carbonyl Propargylation by Iridium-Catalyzed Transfer Hydrogenative Coupling of Alcohols and Propargyl Chlorides
Angew. Chem., Int. Ed.
It takes alkynes! Exposure of propargyl chlorides to primary benzylic alcohols in the presence of [Ir(cod){(R)-segphos}]OTf (cod=1,5-cyclooctadiene, segphos=5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole, Tf=trifluoromethanesulfonyl) results in hydrogen exchange to give allenyliridium–aldehyde pairs that combine to form products of propargylation with high ee value (see scheme). The reaction can also be conducted using aldehydes.
Benzannulation via Ruthenium Catalyzed Diol-Diene [4+2] Cycloaddition: One- and Two-Directional Syntheses of Fluoranthenes and Acenes
Journal of the American Chemical Society
A new benzannulation protocol is described and applied to the synthesis of polycyclic aromatic hydrocarbons. Ruthenium(0)-catalyzed diol–diene [4+2] cycloaddition delivers cyclohex-1-ene-4,5-diols, which are subject to aromatization upon dehydration or Nicholas diol deoxydehydration. Employing diol and tetraol reactants, benzannulation can be conducted efficiently in one- and two-directional modes, respectively, as illustrated in the construction of substituted fluoranthenes and acenes.
Direct, Redox Neutral Prenylation and Geranylation of Secondary Carbinol C-H Bonds: C4 Regioselectivity in Ruthenium-Catalyzed C-C Couplings of Dienes to alpha-Hydroxy Esters
Journal of the American Chemical Society
The ruthenium catalyst generated in situ from Ru3(CO)12 and tricyclohexylphosphine, PCy3, promotes the redox-neutral C–C coupling of aryl-substituted α-hydroxy esters to isoprene and myrcene at the diene C4-position, resulting in direct carbinol C–H prenylation and geranylation, respectively. This process enables direct conversion of secondary to tertiary alcohols in the absence of stoichiometric byproducts or premetalated reagents, and is the first example of C4-regioselectivity in catalytic C–C couplings of 2-substituted dienes to carbonyl partners. Mechanistic studies corroborate a catalytic cycle involving diene–carbonyl oxidative coupling.
2-Substituted Benzo[b]furans from (E)-1,2-Dichlorovinyl Ethers and Organoboron Reagents: Scope and Mechanistic Investigations into the One-Pot Suzuki Coupling/Direct Arylation
European Journal of Organic Chemistry
2-Substituted benzo[b]furans can easily be assembled from simple phenols, boronic acids or other organoboron reagents, and trichloroethylene. The overall process requires only two synthetic steps, with the key step being a one-pot sequential Suzuki cross-coupling/direct arylation reaction. The method tolerates many useful functional groups and does not require the installation of any other activating functionality. The modular nature of the process permits the rapid synthesis of many analogues using essentially the same chemistry, of particular value in drug development. Results of kinetic isotope effect studies and investigations into the regioselectivity of the process indicate that the direct arylation step most likely does not involve an electrophilic palladation. The most likely mechanism lies somewhere on the continuum between a C–H bond metathesis and an assisted palladation or concerted metallation-deprotonation pathway.
Enantioselective Carbonyl Propargylation by Iridium-Catalyzed Transfer Hydrogenative Coupling of Alcohols and Propargyl Chlorides
Angew. Chem., Int. Ed.
It takes alkynes! Exposure of propargyl chlorides to primary benzylic alcohols in the presence of [Ir(cod){(R)-segphos}]OTf (cod=1,5-cyclooctadiene, segphos=5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole, Tf=trifluoromethanesulfonyl) results in hydrogen exchange to give allenyliridium–aldehyde pairs that combine to form products of propargylation with high ee value (see scheme). The reaction can also be conducted using aldehydes.
Benzannulation via Ruthenium Catalyzed Diol-Diene [4+2] Cycloaddition: One- and Two-Directional Syntheses of Fluoranthenes and Acenes
Journal of the American Chemical Society
A new benzannulation protocol is described and applied to the synthesis of polycyclic aromatic hydrocarbons. Ruthenium(0)-catalyzed diol–diene [4+2] cycloaddition delivers cyclohex-1-ene-4,5-diols, which are subject to aromatization upon dehydration or Nicholas diol deoxydehydration. Employing diol and tetraol reactants, benzannulation can be conducted efficiently in one- and two-directional modes, respectively, as illustrated in the construction of substituted fluoranthenes and acenes.
Direct, Redox Neutral Prenylation and Geranylation of Secondary Carbinol C-H Bonds: C4 Regioselectivity in Ruthenium-Catalyzed C-C Couplings of Dienes to alpha-Hydroxy Esters
Journal of the American Chemical Society
The ruthenium catalyst generated in situ from Ru3(CO)12 and tricyclohexylphosphine, PCy3, promotes the redox-neutral C–C coupling of aryl-substituted α-hydroxy esters to isoprene and myrcene at the diene C4-position, resulting in direct carbinol C–H prenylation and geranylation, respectively. This process enables direct conversion of secondary to tertiary alcohols in the absence of stoichiometric byproducts or premetalated reagents, and is the first example of C4-regioselectivity in catalytic C–C couplings of 2-substituted dienes to carbonyl partners. Mechanistic studies corroborate a catalytic cycle involving diene–carbonyl oxidative coupling.
2-Substituted Benzo[b]furans from (E)-1,2-Dichlorovinyl Ethers and Organoboron Reagents: Scope and Mechanistic Investigations into the One-Pot Suzuki Coupling/Direct Arylation
European Journal of Organic Chemistry
2-Substituted benzo[b]furans can easily be assembled from simple phenols, boronic acids or other organoboron reagents, and trichloroethylene. The overall process requires only two synthetic steps, with the key step being a one-pot sequential Suzuki cross-coupling/direct arylation reaction. The method tolerates many useful functional groups and does not require the installation of any other activating functionality. The modular nature of the process permits the rapid synthesis of many analogues using essentially the same chemistry, of particular value in drug development. Results of kinetic isotope effect studies and investigations into the regioselectivity of the process indicate that the direct arylation step most likely does not involve an electrophilic palladation. The most likely mechanism lies somewhere on the continuum between a C–H bond metathesis and an assisted palladation or concerted metallation-deprotonation pathway.
Palladium-Catalyzed Modular Assembly of Electron-Rich Alkenes, Dienes, Trienes, and Enynes from (E)-1,2-Dichlorovinyl Phenyl Ether
Journal of Organic Chemistry
We have devised a modular construction of electron-rich alkene derivatives from trichloroethylene (TCE). The three C−Cl bonds of TCE have sufficiently different reactivities that they can be sequentially and selectively functionalized. Following the substitution of one chlorine by phenol to generate (E)-1,2-dichlorovinyl ether, the C1-Cl group next participates in palladium-catalyzed cross-coupling reactions with a variety of organometallic reagents. Subsequently, the C2-Cl group can engage in cross-couplings, while the C2-H may be deprotonated and quenched with an electrophile. Thus, isomerically pure tri- and tetrasubstituted electron-rich alkenes may be accessed in as few as two steps from simple and inexpensive starting materials. This method is ideally suited for diversity-oriented synthesis of highly conjugated molecules of interest as chromophores or as potential molecular electronics. It also gives access to diverse building blocks for further synthetic elaboration into high-value compounds.
Enantioselective Carbonyl Propargylation by Iridium-Catalyzed Transfer Hydrogenative Coupling of Alcohols and Propargyl Chlorides
Angew. Chem., Int. Ed.
It takes alkynes! Exposure of propargyl chlorides to primary benzylic alcohols in the presence of [Ir(cod){(R)-segphos}]OTf (cod=1,5-cyclooctadiene, segphos=5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole, Tf=trifluoromethanesulfonyl) results in hydrogen exchange to give allenyliridium–aldehyde pairs that combine to form products of propargylation with high ee value (see scheme). The reaction can also be conducted using aldehydes.
Benzannulation via Ruthenium Catalyzed Diol-Diene [4+2] Cycloaddition: One- and Two-Directional Syntheses of Fluoranthenes and Acenes
Journal of the American Chemical Society
A new benzannulation protocol is described and applied to the synthesis of polycyclic aromatic hydrocarbons. Ruthenium(0)-catalyzed diol–diene [4+2] cycloaddition delivers cyclohex-1-ene-4,5-diols, which are subject to aromatization upon dehydration or Nicholas diol deoxydehydration. Employing diol and tetraol reactants, benzannulation can be conducted efficiently in one- and two-directional modes, respectively, as illustrated in the construction of substituted fluoranthenes and acenes.
Direct, Redox Neutral Prenylation and Geranylation of Secondary Carbinol C-H Bonds: C4 Regioselectivity in Ruthenium-Catalyzed C-C Couplings of Dienes to alpha-Hydroxy Esters
Journal of the American Chemical Society
The ruthenium catalyst generated in situ from Ru3(CO)12 and tricyclohexylphosphine, PCy3, promotes the redox-neutral C–C coupling of aryl-substituted α-hydroxy esters to isoprene and myrcene at the diene C4-position, resulting in direct carbinol C–H prenylation and geranylation, respectively. This process enables direct conversion of secondary to tertiary alcohols in the absence of stoichiometric byproducts or premetalated reagents, and is the first example of C4-regioselectivity in catalytic C–C couplings of 2-substituted dienes to carbonyl partners. Mechanistic studies corroborate a catalytic cycle involving diene–carbonyl oxidative coupling.
2-Substituted Benzo[b]furans from (E)-1,2-Dichlorovinyl Ethers and Organoboron Reagents: Scope and Mechanistic Investigations into the One-Pot Suzuki Coupling/Direct Arylation
European Journal of Organic Chemistry
2-Substituted benzo[b]furans can easily be assembled from simple phenols, boronic acids or other organoboron reagents, and trichloroethylene. The overall process requires only two synthetic steps, with the key step being a one-pot sequential Suzuki cross-coupling/direct arylation reaction. The method tolerates many useful functional groups and does not require the installation of any other activating functionality. The modular nature of the process permits the rapid synthesis of many analogues using essentially the same chemistry, of particular value in drug development. Results of kinetic isotope effect studies and investigations into the regioselectivity of the process indicate that the direct arylation step most likely does not involve an electrophilic palladation. The most likely mechanism lies somewhere on the continuum between a C–H bond metathesis and an assisted palladation or concerted metallation-deprotonation pathway.
Palladium-Catalyzed Modular Assembly of Electron-Rich Alkenes, Dienes, Trienes, and Enynes from (E)-1,2-Dichlorovinyl Phenyl Ether
Journal of Organic Chemistry
We have devised a modular construction of electron-rich alkene derivatives from trichloroethylene (TCE). The three C−Cl bonds of TCE have sufficiently different reactivities that they can be sequentially and selectively functionalized. Following the substitution of one chlorine by phenol to generate (E)-1,2-dichlorovinyl ether, the C1-Cl group next participates in palladium-catalyzed cross-coupling reactions with a variety of organometallic reagents. Subsequently, the C2-Cl group can engage in cross-couplings, while the C2-H may be deprotonated and quenched with an electrophile. Thus, isomerically pure tri- and tetrasubstituted electron-rich alkenes may be accessed in as few as two steps from simple and inexpensive starting materials. This method is ideally suited for diversity-oriented synthesis of highly conjugated molecules of interest as chromophores or as potential molecular electronics. It also gives access to diverse building blocks for further synthetic elaboration into high-value compounds.
Ring expansion of cyclic 1,2-diols to form medium sized rings via ruthenium catalyzed transfer hydrogenative [4+2] cycloaddition
Chemical Communications
A new method for the ring expansion of cyclic diols is described. Using improved conditions for the ruthenium(0) catalyzed cycloaddition of cyclic 1,2-diols with 1,3-dienes, fused [n.4.0] bicycles 3a–3r (n = 3–6) are formed, which upon exposure to iodosobenzene diacetate engage in oxidative cleavage to form the 9–12 membered rings 4a–4r.
Enantioselective Carbonyl Propargylation by Iridium-Catalyzed Transfer Hydrogenative Coupling of Alcohols and Propargyl Chlorides
Angew. Chem., Int. Ed.
It takes alkynes! Exposure of propargyl chlorides to primary benzylic alcohols in the presence of [Ir(cod){(R)-segphos}]OTf (cod=1,5-cyclooctadiene, segphos=5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole, Tf=trifluoromethanesulfonyl) results in hydrogen exchange to give allenyliridium–aldehyde pairs that combine to form products of propargylation with high ee value (see scheme). The reaction can also be conducted using aldehydes.
Benzannulation via Ruthenium Catalyzed Diol-Diene [4+2] Cycloaddition: One- and Two-Directional Syntheses of Fluoranthenes and Acenes
Journal of the American Chemical Society
A new benzannulation protocol is described and applied to the synthesis of polycyclic aromatic hydrocarbons. Ruthenium(0)-catalyzed diol–diene [4+2] cycloaddition delivers cyclohex-1-ene-4,5-diols, which are subject to aromatization upon dehydration or Nicholas diol deoxydehydration. Employing diol and tetraol reactants, benzannulation can be conducted efficiently in one- and two-directional modes, respectively, as illustrated in the construction of substituted fluoranthenes and acenes.
Direct, Redox Neutral Prenylation and Geranylation of Secondary Carbinol C-H Bonds: C4 Regioselectivity in Ruthenium-Catalyzed C-C Couplings of Dienes to alpha-Hydroxy Esters
Journal of the American Chemical Society
The ruthenium catalyst generated in situ from Ru3(CO)12 and tricyclohexylphosphine, PCy3, promotes the redox-neutral C–C coupling of aryl-substituted α-hydroxy esters to isoprene and myrcene at the diene C4-position, resulting in direct carbinol C–H prenylation and geranylation, respectively. This process enables direct conversion of secondary to tertiary alcohols in the absence of stoichiometric byproducts or premetalated reagents, and is the first example of C4-regioselectivity in catalytic C–C couplings of 2-substituted dienes to carbonyl partners. Mechanistic studies corroborate a catalytic cycle involving diene–carbonyl oxidative coupling.
2-Substituted Benzo[b]furans from (E)-1,2-Dichlorovinyl Ethers and Organoboron Reagents: Scope and Mechanistic Investigations into the One-Pot Suzuki Coupling/Direct Arylation
European Journal of Organic Chemistry
2-Substituted benzo[b]furans can easily be assembled from simple phenols, boronic acids or other organoboron reagents, and trichloroethylene. The overall process requires only two synthetic steps, with the key step being a one-pot sequential Suzuki cross-coupling/direct arylation reaction. The method tolerates many useful functional groups and does not require the installation of any other activating functionality. The modular nature of the process permits the rapid synthesis of many analogues using essentially the same chemistry, of particular value in drug development. Results of kinetic isotope effect studies and investigations into the regioselectivity of the process indicate that the direct arylation step most likely does not involve an electrophilic palladation. The most likely mechanism lies somewhere on the continuum between a C–H bond metathesis and an assisted palladation or concerted metallation-deprotonation pathway.
Palladium-Catalyzed Modular Assembly of Electron-Rich Alkenes, Dienes, Trienes, and Enynes from (E)-1,2-Dichlorovinyl Phenyl Ether
Journal of Organic Chemistry
We have devised a modular construction of electron-rich alkene derivatives from trichloroethylene (TCE). The three C−Cl bonds of TCE have sufficiently different reactivities that they can be sequentially and selectively functionalized. Following the substitution of one chlorine by phenol to generate (E)-1,2-dichlorovinyl ether, the C1-Cl group next participates in palladium-catalyzed cross-coupling reactions with a variety of organometallic reagents. Subsequently, the C2-Cl group can engage in cross-couplings, while the C2-H may be deprotonated and quenched with an electrophile. Thus, isomerically pure tri- and tetrasubstituted electron-rich alkenes may be accessed in as few as two steps from simple and inexpensive starting materials. This method is ideally suited for diversity-oriented synthesis of highly conjugated molecules of interest as chromophores or as potential molecular electronics. It also gives access to diverse building blocks for further synthetic elaboration into high-value compounds.
Ring expansion of cyclic 1,2-diols to form medium sized rings via ruthenium catalyzed transfer hydrogenative [4+2] cycloaddition
Chemical Communications
A new method for the ring expansion of cyclic diols is described. Using improved conditions for the ruthenium(0) catalyzed cycloaddition of cyclic 1,2-diols with 1,3-dienes, fused [n.4.0] bicycles 3a–3r (n = 3–6) are formed, which upon exposure to iodosobenzene diacetate engage in oxidative cleavage to form the 9–12 membered rings 4a–4r.
Ruthenium-Catalyzed Reductive Coupling of 1,3-Enynes and Aldehydes by Transfer Hydrogenation: anti-Diastereoselective Carbonyl Propargylation
Chemistry: A European Journal
Under the conditions of ruthenium-catalyzed transfer hydrogenation employing isopropanol as a source of hydrogen, isopropoxy-substituted enyne 1 b and aldehydes 3 a–3 l engage in reductive coupling to provide products of propargylation 4 a–4 l with good to complete levels of anti-diastereoselectivity. The unprotected tertiary hydroxy moiety of isopropoxy enyne 1 b is required to enforce diastereoselectivity. Deuterium-labeling studies corroborate reversible enyne hydrometalation in advance of carbonyl addition. As demonstrated in the conversion of 4 f–h and 4 k to 5 f–h and 5 k, the isopropoxy group of the product is readily cleaved upon exposure to aqueous sodium hydroxide to reveal the terminal alkyne.
Enantioselective Carbonyl Propargylation by Iridium-Catalyzed Transfer Hydrogenative Coupling of Alcohols and Propargyl Chlorides
Angew. Chem., Int. Ed.
It takes alkynes! Exposure of propargyl chlorides to primary benzylic alcohols in the presence of [Ir(cod){(R)-segphos}]OTf (cod=1,5-cyclooctadiene, segphos=5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole, Tf=trifluoromethanesulfonyl) results in hydrogen exchange to give allenyliridium–aldehyde pairs that combine to form products of propargylation with high ee value (see scheme). The reaction can also be conducted using aldehydes.
Benzannulation via Ruthenium Catalyzed Diol-Diene [4+2] Cycloaddition: One- and Two-Directional Syntheses of Fluoranthenes and Acenes
Journal of the American Chemical Society
A new benzannulation protocol is described and applied to the synthesis of polycyclic aromatic hydrocarbons. Ruthenium(0)-catalyzed diol–diene [4+2] cycloaddition delivers cyclohex-1-ene-4,5-diols, which are subject to aromatization upon dehydration or Nicholas diol deoxydehydration. Employing diol and tetraol reactants, benzannulation can be conducted efficiently in one- and two-directional modes, respectively, as illustrated in the construction of substituted fluoranthenes and acenes.
Direct, Redox Neutral Prenylation and Geranylation of Secondary Carbinol C-H Bonds: C4 Regioselectivity in Ruthenium-Catalyzed C-C Couplings of Dienes to alpha-Hydroxy Esters
Journal of the American Chemical Society
The ruthenium catalyst generated in situ from Ru3(CO)12 and tricyclohexylphosphine, PCy3, promotes the redox-neutral C–C coupling of aryl-substituted α-hydroxy esters to isoprene and myrcene at the diene C4-position, resulting in direct carbinol C–H prenylation and geranylation, respectively. This process enables direct conversion of secondary to tertiary alcohols in the absence of stoichiometric byproducts or premetalated reagents, and is the first example of C4-regioselectivity in catalytic C–C couplings of 2-substituted dienes to carbonyl partners. Mechanistic studies corroborate a catalytic cycle involving diene–carbonyl oxidative coupling.
2-Substituted Benzo[b]furans from (E)-1,2-Dichlorovinyl Ethers and Organoboron Reagents: Scope and Mechanistic Investigations into the One-Pot Suzuki Coupling/Direct Arylation
European Journal of Organic Chemistry
2-Substituted benzo[b]furans can easily be assembled from simple phenols, boronic acids or other organoboron reagents, and trichloroethylene. The overall process requires only two synthetic steps, with the key step being a one-pot sequential Suzuki cross-coupling/direct arylation reaction. The method tolerates many useful functional groups and does not require the installation of any other activating functionality. The modular nature of the process permits the rapid synthesis of many analogues using essentially the same chemistry, of particular value in drug development. Results of kinetic isotope effect studies and investigations into the regioselectivity of the process indicate that the direct arylation step most likely does not involve an electrophilic palladation. The most likely mechanism lies somewhere on the continuum between a C–H bond metathesis and an assisted palladation or concerted metallation-deprotonation pathway.
Palladium-Catalyzed Modular Assembly of Electron-Rich Alkenes, Dienes, Trienes, and Enynes from (E)-1,2-Dichlorovinyl Phenyl Ether
Journal of Organic Chemistry
We have devised a modular construction of electron-rich alkene derivatives from trichloroethylene (TCE). The three C−Cl bonds of TCE have sufficiently different reactivities that they can be sequentially and selectively functionalized. Following the substitution of one chlorine by phenol to generate (E)-1,2-dichlorovinyl ether, the C1-Cl group next participates in palladium-catalyzed cross-coupling reactions with a variety of organometallic reagents. Subsequently, the C2-Cl group can engage in cross-couplings, while the C2-H may be deprotonated and quenched with an electrophile. Thus, isomerically pure tri- and tetrasubstituted electron-rich alkenes may be accessed in as few as two steps from simple and inexpensive starting materials. This method is ideally suited for diversity-oriented synthesis of highly conjugated molecules of interest as chromophores or as potential molecular electronics. It also gives access to diverse building blocks for further synthetic elaboration into high-value compounds.
Ring expansion of cyclic 1,2-diols to form medium sized rings via ruthenium catalyzed transfer hydrogenative [4+2] cycloaddition
Chemical Communications
A new method for the ring expansion of cyclic diols is described. Using improved conditions for the ruthenium(0) catalyzed cycloaddition of cyclic 1,2-diols with 1,3-dienes, fused [n.4.0] bicycles 3a–3r (n = 3–6) are formed, which upon exposure to iodosobenzene diacetate engage in oxidative cleavage to form the 9–12 membered rings 4a–4r.
Ruthenium-Catalyzed Reductive Coupling of 1,3-Enynes and Aldehydes by Transfer Hydrogenation: anti-Diastereoselective Carbonyl Propargylation
Chemistry: A European Journal
Under the conditions of ruthenium-catalyzed transfer hydrogenation employing isopropanol as a source of hydrogen, isopropoxy-substituted enyne 1 b and aldehydes 3 a–3 l engage in reductive coupling to provide products of propargylation 4 a–4 l with good to complete levels of anti-diastereoselectivity. The unprotected tertiary hydroxy moiety of isopropoxy enyne 1 b is required to enforce diastereoselectivity. Deuterium-labeling studies corroborate reversible enyne hydrometalation in advance of carbonyl addition. As demonstrated in the conversion of 4 f–h and 4 k to 5 f–h and 5 k, the isopropoxy group of the product is readily cleaved upon exposure to aqueous sodium hydroxide to reveal the terminal alkyne.
Modular Construction of 2-Substituted Benzo[b]furans from 1,2-Dichlorovinyl Ethers
Organic Letters
(E)-1,2-Dichlorovinyl ethers and amides are easily accessible from trichloroethylene via nucleophilic addition across in situ synthesized dichloroacetylene. A one-pot, sequential Suzuki−Miyaura coupling/intramolecular direct arylation between dichlorovinyl ethers and organoboronic acids provides easy access to a variety of benzofurans in only two steps from inexpensive commercially available compounds. The method is extendable to the preparation of indoles from the analogous dichlorovinyl amides.
Enantioselective Carbonyl Propargylation by Iridium-Catalyzed Transfer Hydrogenative Coupling of Alcohols and Propargyl Chlorides
Angew. Chem., Int. Ed.
It takes alkynes! Exposure of propargyl chlorides to primary benzylic alcohols in the presence of [Ir(cod){(R)-segphos}]OTf (cod=1,5-cyclooctadiene, segphos=5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole, Tf=trifluoromethanesulfonyl) results in hydrogen exchange to give allenyliridium–aldehyde pairs that combine to form products of propargylation with high ee value (see scheme). The reaction can also be conducted using aldehydes.
Benzannulation via Ruthenium Catalyzed Diol-Diene [4+2] Cycloaddition: One- and Two-Directional Syntheses of Fluoranthenes and Acenes
Journal of the American Chemical Society
A new benzannulation protocol is described and applied to the synthesis of polycyclic aromatic hydrocarbons. Ruthenium(0)-catalyzed diol–diene [4+2] cycloaddition delivers cyclohex-1-ene-4,5-diols, which are subject to aromatization upon dehydration or Nicholas diol deoxydehydration. Employing diol and tetraol reactants, benzannulation can be conducted efficiently in one- and two-directional modes, respectively, as illustrated in the construction of substituted fluoranthenes and acenes.
Direct, Redox Neutral Prenylation and Geranylation of Secondary Carbinol C-H Bonds: C4 Regioselectivity in Ruthenium-Catalyzed C-C Couplings of Dienes to alpha-Hydroxy Esters
Journal of the American Chemical Society
The ruthenium catalyst generated in situ from Ru3(CO)12 and tricyclohexylphosphine, PCy3, promotes the redox-neutral C–C coupling of aryl-substituted α-hydroxy esters to isoprene and myrcene at the diene C4-position, resulting in direct carbinol C–H prenylation and geranylation, respectively. This process enables direct conversion of secondary to tertiary alcohols in the absence of stoichiometric byproducts or premetalated reagents, and is the first example of C4-regioselectivity in catalytic C–C couplings of 2-substituted dienes to carbonyl partners. Mechanistic studies corroborate a catalytic cycle involving diene–carbonyl oxidative coupling.
2-Substituted Benzo[b]furans from (E)-1,2-Dichlorovinyl Ethers and Organoboron Reagents: Scope and Mechanistic Investigations into the One-Pot Suzuki Coupling/Direct Arylation
European Journal of Organic Chemistry
2-Substituted benzo[b]furans can easily be assembled from simple phenols, boronic acids or other organoboron reagents, and trichloroethylene. The overall process requires only two synthetic steps, with the key step being a one-pot sequential Suzuki cross-coupling/direct arylation reaction. The method tolerates many useful functional groups and does not require the installation of any other activating functionality. The modular nature of the process permits the rapid synthesis of many analogues using essentially the same chemistry, of particular value in drug development. Results of kinetic isotope effect studies and investigations into the regioselectivity of the process indicate that the direct arylation step most likely does not involve an electrophilic palladation. The most likely mechanism lies somewhere on the continuum between a C–H bond metathesis and an assisted palladation or concerted metallation-deprotonation pathway.
Palladium-Catalyzed Modular Assembly of Electron-Rich Alkenes, Dienes, Trienes, and Enynes from (E)-1,2-Dichlorovinyl Phenyl Ether
Journal of Organic Chemistry
We have devised a modular construction of electron-rich alkene derivatives from trichloroethylene (TCE). The three C−Cl bonds of TCE have sufficiently different reactivities that they can be sequentially and selectively functionalized. Following the substitution of one chlorine by phenol to generate (E)-1,2-dichlorovinyl ether, the C1-Cl group next participates in palladium-catalyzed cross-coupling reactions with a variety of organometallic reagents. Subsequently, the C2-Cl group can engage in cross-couplings, while the C2-H may be deprotonated and quenched with an electrophile. Thus, isomerically pure tri- and tetrasubstituted electron-rich alkenes may be accessed in as few as two steps from simple and inexpensive starting materials. This method is ideally suited for diversity-oriented synthesis of highly conjugated molecules of interest as chromophores or as potential molecular electronics. It also gives access to diverse building blocks for further synthetic elaboration into high-value compounds.
Ring expansion of cyclic 1,2-diols to form medium sized rings via ruthenium catalyzed transfer hydrogenative [4+2] cycloaddition
Chemical Communications
A new method for the ring expansion of cyclic diols is described. Using improved conditions for the ruthenium(0) catalyzed cycloaddition of cyclic 1,2-diols with 1,3-dienes, fused [n.4.0] bicycles 3a–3r (n = 3–6) are formed, which upon exposure to iodosobenzene diacetate engage in oxidative cleavage to form the 9–12 membered rings 4a–4r.
Ruthenium-Catalyzed Reductive Coupling of 1,3-Enynes and Aldehydes by Transfer Hydrogenation: anti-Diastereoselective Carbonyl Propargylation
Chemistry: A European Journal
Under the conditions of ruthenium-catalyzed transfer hydrogenation employing isopropanol as a source of hydrogen, isopropoxy-substituted enyne 1 b and aldehydes 3 a–3 l engage in reductive coupling to provide products of propargylation 4 a–4 l with good to complete levels of anti-diastereoselectivity. The unprotected tertiary hydroxy moiety of isopropoxy enyne 1 b is required to enforce diastereoselectivity. Deuterium-labeling studies corroborate reversible enyne hydrometalation in advance of carbonyl addition. As demonstrated in the conversion of 4 f–h and 4 k to 5 f–h and 5 k, the isopropoxy group of the product is readily cleaved upon exposure to aqueous sodium hydroxide to reveal the terminal alkyne.
Modular Construction of 2-Substituted Benzo[b]furans from 1,2-Dichlorovinyl Ethers
Organic Letters
(E)-1,2-Dichlorovinyl ethers and amides are easily accessible from trichloroethylene via nucleophilic addition across in situ synthesized dichloroacetylene. A one-pot, sequential Suzuki−Miyaura coupling/intramolecular direct arylation between dichlorovinyl ethers and organoboronic acids provides easy access to a variety of benzofurans in only two steps from inexpensive commercially available compounds. The method is extendable to the preparation of indoles from the analogous dichlorovinyl amides.
Diastereo- and Enantioselective Iridium-Catalyzed Carbonyl Propargylation from the Alcohol or Aldehyde Oxidation Level: 1,3-Enynes as Allenylmetal Equivalents
Angew. Chem., Int. Ed.
Axial to axial to point chirality transfer: Exposure of conjugated enynes to alcohols in the presence of an iridium catalyst modified by a segphos ligand results in the generation of aldehyde–allenyliridium pairs and formation of enantiomerically enriched products of carbonyl anti-(α-methyl)propargylation (see scheme). An identical set of products are obtained from aldehydes under related transfer hydrogenation conditions by employing formic acid as a reductant.
Enantioselective Carbonyl Propargylation by Iridium-Catalyzed Transfer Hydrogenative Coupling of Alcohols and Propargyl Chlorides
Angew. Chem., Int. Ed.
It takes alkynes! Exposure of propargyl chlorides to primary benzylic alcohols in the presence of [Ir(cod){(R)-segphos}]OTf (cod=1,5-cyclooctadiene, segphos=5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole, Tf=trifluoromethanesulfonyl) results in hydrogen exchange to give allenyliridium–aldehyde pairs that combine to form products of propargylation with high ee value (see scheme). The reaction can also be conducted using aldehydes.
Benzannulation via Ruthenium Catalyzed Diol-Diene [4+2] Cycloaddition: One- and Two-Directional Syntheses of Fluoranthenes and Acenes
Journal of the American Chemical Society
A new benzannulation protocol is described and applied to the synthesis of polycyclic aromatic hydrocarbons. Ruthenium(0)-catalyzed diol–diene [4+2] cycloaddition delivers cyclohex-1-ene-4,5-diols, which are subject to aromatization upon dehydration or Nicholas diol deoxydehydration. Employing diol and tetraol reactants, benzannulation can be conducted efficiently in one- and two-directional modes, respectively, as illustrated in the construction of substituted fluoranthenes and acenes.
Direct, Redox Neutral Prenylation and Geranylation of Secondary Carbinol C-H Bonds: C4 Regioselectivity in Ruthenium-Catalyzed C-C Couplings of Dienes to alpha-Hydroxy Esters
Journal of the American Chemical Society
The ruthenium catalyst generated in situ from Ru3(CO)12 and tricyclohexylphosphine, PCy3, promotes the redox-neutral C–C coupling of aryl-substituted α-hydroxy esters to isoprene and myrcene at the diene C4-position, resulting in direct carbinol C–H prenylation and geranylation, respectively. This process enables direct conversion of secondary to tertiary alcohols in the absence of stoichiometric byproducts or premetalated reagents, and is the first example of C4-regioselectivity in catalytic C–C couplings of 2-substituted dienes to carbonyl partners. Mechanistic studies corroborate a catalytic cycle involving diene–carbonyl oxidative coupling.
2-Substituted Benzo[b]furans from (E)-1,2-Dichlorovinyl Ethers and Organoboron Reagents: Scope and Mechanistic Investigations into the One-Pot Suzuki Coupling/Direct Arylation
European Journal of Organic Chemistry
2-Substituted benzo[b]furans can easily be assembled from simple phenols, boronic acids or other organoboron reagents, and trichloroethylene. The overall process requires only two synthetic steps, with the key step being a one-pot sequential Suzuki cross-coupling/direct arylation reaction. The method tolerates many useful functional groups and does not require the installation of any other activating functionality. The modular nature of the process permits the rapid synthesis of many analogues using essentially the same chemistry, of particular value in drug development. Results of kinetic isotope effect studies and investigations into the regioselectivity of the process indicate that the direct arylation step most likely does not involve an electrophilic palladation. The most likely mechanism lies somewhere on the continuum between a C–H bond metathesis and an assisted palladation or concerted metallation-deprotonation pathway.
Palladium-Catalyzed Modular Assembly of Electron-Rich Alkenes, Dienes, Trienes, and Enynes from (E)-1,2-Dichlorovinyl Phenyl Ether
Journal of Organic Chemistry
We have devised a modular construction of electron-rich alkene derivatives from trichloroethylene (TCE). The three C−Cl bonds of TCE have sufficiently different reactivities that they can be sequentially and selectively functionalized. Following the substitution of one chlorine by phenol to generate (E)-1,2-dichlorovinyl ether, the C1-Cl group next participates in palladium-catalyzed cross-coupling reactions with a variety of organometallic reagents. Subsequently, the C2-Cl group can engage in cross-couplings, while the C2-H may be deprotonated and quenched with an electrophile. Thus, isomerically pure tri- and tetrasubstituted electron-rich alkenes may be accessed in as few as two steps from simple and inexpensive starting materials. This method is ideally suited for diversity-oriented synthesis of highly conjugated molecules of interest as chromophores or as potential molecular electronics. It also gives access to diverse building blocks for further synthetic elaboration into high-value compounds.
Ring expansion of cyclic 1,2-diols to form medium sized rings via ruthenium catalyzed transfer hydrogenative [4+2] cycloaddition
Chemical Communications
A new method for the ring expansion of cyclic diols is described. Using improved conditions for the ruthenium(0) catalyzed cycloaddition of cyclic 1,2-diols with 1,3-dienes, fused [n.4.0] bicycles 3a–3r (n = 3–6) are formed, which upon exposure to iodosobenzene diacetate engage in oxidative cleavage to form the 9–12 membered rings 4a–4r.
Ruthenium-Catalyzed Reductive Coupling of 1,3-Enynes and Aldehydes by Transfer Hydrogenation: anti-Diastereoselective Carbonyl Propargylation
Chemistry: A European Journal
Under the conditions of ruthenium-catalyzed transfer hydrogenation employing isopropanol as a source of hydrogen, isopropoxy-substituted enyne 1 b and aldehydes 3 a–3 l engage in reductive coupling to provide products of propargylation 4 a–4 l with good to complete levels of anti-diastereoselectivity. The unprotected tertiary hydroxy moiety of isopropoxy enyne 1 b is required to enforce diastereoselectivity. Deuterium-labeling studies corroborate reversible enyne hydrometalation in advance of carbonyl addition. As demonstrated in the conversion of 4 f–h and 4 k to 5 f–h and 5 k, the isopropoxy group of the product is readily cleaved upon exposure to aqueous sodium hydroxide to reveal the terminal alkyne.
Modular Construction of 2-Substituted Benzo[b]furans from 1,2-Dichlorovinyl Ethers
Organic Letters
(E)-1,2-Dichlorovinyl ethers and amides are easily accessible from trichloroethylene via nucleophilic addition across in situ synthesized dichloroacetylene. A one-pot, sequential Suzuki−Miyaura coupling/intramolecular direct arylation between dichlorovinyl ethers and organoboronic acids provides easy access to a variety of benzofurans in only two steps from inexpensive commercially available compounds. The method is extendable to the preparation of indoles from the analogous dichlorovinyl amides.
Diastereo- and Enantioselective Iridium-Catalyzed Carbonyl Propargylation from the Alcohol or Aldehyde Oxidation Level: 1,3-Enynes as Allenylmetal Equivalents
Angew. Chem., Int. Ed.
Axial to axial to point chirality transfer: Exposure of conjugated enynes to alcohols in the presence of an iridium catalyst modified by a segphos ligand results in the generation of aldehyde–allenyliridium pairs and formation of enantiomerically enriched products of carbonyl anti-(α-methyl)propargylation (see scheme). An identical set of products are obtained from aldehydes under related transfer hydrogenation conditions by employing formic acid as a reductant.
Successive C-C Coupling of Dienes to Vicinally Dioxygenated Hydrocarbons: Ruthenium Catalyzed [4+2] Cycloaddition across the Diol, Hydroxycarbonyl or Dione Oxidation Levels
Journal of the American Chemical Society
The ruthenium(0) catalyst generated from Ru3(CO)12 and tricyclohexylphosphine or BIPHEP promotes successive C-C coupling between dienes and vicinally dioxygenated hydrocarbons from the diol, hydroxyketone and dione oxidation levels to form products of [4+2] cycloaddition. A mechanism involving diene-carbonyl oxidative coupling followed by intramolecular carbonyl addition of the resulting allylruthenium intermediate is postulated.
Possible Matching Profiles
The following profiles may or may not be the same professor:
- Laina M Geary (80% Match)
Assistant Professor Chemistry
University Of Nevada, Reno - University Of Nevada, Reno
