Thesis advisor: Amir H. Hoveyda / Chapter 1. The development of chiral monodentate N-heterocyclic carbenes (NHCs) is presented. Structurally varied twenty-eight new chiral imidazolinim salts, NHC precursors, were synthesized and characterized. Chapter 2. The first example of Cu-catalyzed enantioselective conjugate additions of alkyl- and arylzinc reagents to unactivated cyclic enones is presented. Transformations are promoted in the presence of 2.5-15 mol % of a readily available chiral NHC-based Cu complex, affording the desired products bearing all-carbon quaternary stereogenic centers in 67-98% yield and in up to 97% ee. Catalytic enantioselective reactions can be carried out on a benchtop, with undistilled solvent and commercially available (not further purified) Cu salts. Chapter 3. A new class of enantioselective conjugate addition (ECA) reactions that involve aryl- or alkenylsilylfluoride reagents and are catalyzed by chiral non-C2-symmetric Cu-based NHC complexes are presented. Transformations have been designed based on the principle that a catalytically active chiral NHC-Cu-aryl or NHC-Cu-alkenyl complex can be accessed from reaction of a Cu-halide precursor with in situ-generated aryl- or alkenyl-tetrafluorosilicate. Reactions proceed in the presence of 1.5 equivalents of the aryl- or alkenylsilane reagents and 1.5 equivalents of tris(dimethylamino)sulfonium difluorotrimethylsilicate. Desired products are isolated in 63-97% yield and 73.5:26.5-98.5:1.5 enantiomeric ratio (47%-97% ee). Chapter 4. An efficient Cu-catalyzed protocol for enantioselective addition of a dimethylphenylsilanyl group to a wide range of cyclic and acyclic unsaturated ketones, esters, acrylonitriles and dienones is presented. Reactions are performed in the presence of 1-5 mol % of commercially available and inexpensive CuCl, a readily accessible monodentate imidazolinium salt as well as commercially available (dimethylphenylsilyl)pinacolatoboron. Cu-catalyzed 1,4- and 1,6-conjugate additions afford the enantiomerically enriched silanes in 72%-98% yield and 90:10->99:1 enantiomeric ratio (er) with up to >25:1 of Z:E selectivity. Chapter 5. A Cu-catalyzed method for enantioselective boronate conjugate additions to trisubstituted alkenes of acyclic a,b-unsaturated carboxylic esters, ketones, and thioesters is presented. All transformations are promoted by 5 mol % of a chiral monodentate NHC-Cu complex, derived from a readily available C1-symmetric imidazolinium salt, and in the presence of commercially available bis(pinacolato)diboron. Reactions are efficient (typically, 60% to >98% yield after purification) and deliver the desired boryl carbonyls in up to >98:2 enantiomer ratio (er). In addition, metal-free, nucleophilic activation of a B-B bond has been exploited in the development of a highly efficient method for conjugate additions of commercially available bis(pinacolato)diboron to cyclic or acyclic a,b-unsaturated carbonyls. Reactions are readily catalyzed by 2.5-10 mol % of a simple NHC. A variety of cyclic and acyclic unsaturated ketones and esters can serve as substrates. Transformations deliver boryl carbonyls bearing tertiary as well as quaternary B-substituted carbons in up to >98% yield. / Thesis (PhD) — Boston College, 2010. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Marc L. Snapper / Chapter 1. A Practical Synthesis of 3-Acyl Cyclobutanones by [2 + 2] Annulation. Mechanism and Utility of the Zn(II)-Catalyzed Condensation of alpha-Chloroenamines with Electron-Deficient Alkenes. We have developed a catalytic method for the synthesis of highly functionalized 3-acyl cyclobutanones which are useful building blocks for a variety of natural products. Methods for cyclobutanone synthesis have traditionally been limited to Lewis-acid promoted rearrangement of oxaspiropentanes or cyclizations of ketene and syntheses involving keteneiminium salts have required stoichiometric quantities of a Lewis acid. Furthermore, the mechanism for these types of cyclizations remains unknown. This portion of my research focused on an efficient, catalytic method for the synthesis of 3- acyl cyclobutanones and providing insight into the mechanism for cycloaddition. Chapter 2. Enantioselective Synthesis of Boron-Substituted Quaternary Carbons by NHC-Cu-Catalyzed Boronate Conjugate Additions to Unsaturated Carboxylic Esters, Ketones, or Thioesters. We have developed an enantioselective NHC-Cu-catalyzed conjugate addition of boronate esters to acyclic, trisubstituted alpha, beta-unsaturated carbonyl compounds. Enantioselective conjugate addition of a boronic acid pinacol ester through the use of bis(pinacolato)diboron [B2(pin)2,] to alpha, beta-unsaturated aliphatic and aryl esters promoted by 5 mol % of an NHC-Cu catalyst afforded tertiary beta-boryl carbonyls in high efficiency and enantioselectivity. Trisubstituted alpha, beta-unsaturated esters and thioesters were found to be reactive substrates in the presence of a stoichiometric quantity of methanol. Chapter 3. Metal-Free Catalytic C-Si Bond Formation in an Aqueous Medium and C-B Bond Formation in a Protic Medium. Enantioselective NHC-Catalyzed Silyl and Boryl Conjugate Additions to Cyclic and Acyclic alpha, beta-Unsaturated carbonyls. We have developed a method for enantioselective metal-free silyl conjugate additions through the use of dimethylphenylsilyl) boronic acid pinacol ester [PhMe2SiB(pin)] catalyzed by chiral N-heterocyclic carbenes (NHCs) in basic aqueous thf. Optimization of metal-free conditions demonstrated that the presence of water was required for high efficiency. alpha, beta-Unsaturated cyclic ketones and lactones were examined as substrates, and acyclic ketones, esters and aldehydes were also competent substrates for silyl conjugate addition. beta-Silyl carbonyls were isolated in up to >98% yield and >98:2 er. Chapter 4. Elucidation of Mechanism for Enantioselective NHC-Catalyzed Silyl Conjugate Addition. We propose a catalytic cycle for NHC-catalyzed enantioselective silyl conjugate addition. Mechanistic studies of NHC-catalyzed enantioselective silyl conjugate additions are presented. Optimization of conditions for an inefficient alpha, beta-unsaturated electron-deficient ketone provided insight into the roles for dbu and water. Kinetic data indicate that conjugate addition is first order in PhMe2SiB(pin) and carbene, and DFT calculations support the formation of an NHC-silyl anion as a reactive intermediate in the catalytic cycle. / Thesis (PhD) — Boston College, 2012. / Discipline: Chemistry.

Thesis advisor: Amir H. Hoveyda / Chapter 1 Catalytic Enantioselective Addition of Organoaluminum Reagents Catalytic methods involving the enantioselective addition of both commercially available as well as in situ generated organoaluminum reagents are reviewed. An overview of additions to aldehydes, ketones, and imines is provided as well as the difficulties and limitations of such transformations. Furthermore, additions to unsaturation adjacent to a leaving group to form a new stereogenic center are examined. Finally, conjugate addition reactions wherein an organoaluminum reagent is added to an olefin adjacent to a carbonyl or nitro group are discussed. Chapter 2 Synthesis of Quaternary Carbon Stereogenic Centers through Enantioselective Cu-Catalyzed Allylic Substitution with Alkenylaluminum Reagents A method for the formation of 1,4-diene containing quaternary stereogenic centers through catalytic enantioselective allylic substitution is disclosed. The addition of alkyl- and aryl-substituted alkenylaluminum reagents to trisubstituted allylic phosphates is promoted by 0.5–2.5 mol % of a sulfonate-containing bidentate N-heterocyclic carbene–copper complex. Products containing a quaternary stereogenic center as well as a newly formed terminal olefin are obtained in up to 97% yield and 99:1 er with high site selectivity (>98:2 SN2’:SN2). The requisite nucleophiles are generated in situ through hydroalumination of terminal alkynes. The utility of the method is demonstrated through a concise synthesis of natural product bakuchiol. Chapter 3 A Multicomponent Ni-, Zr-, Cu-Catalyzed Strategy for Enantioselective Synthesis of Alkenyl-Substituted Quaternary Carbons Despite the widespread use of conjugate addition in organic synthesis, few reports pertain to the addition of nucleophiles to acyclic systems and none in which the nucleophile is an alkene. Herein, we report the first examples of enantioselective conjugate addition of alkenylmetal reagents to trisubstituted enones to form all-carbon quaternary stereogenic centers. Alkenylaluminum nucleophiles are prepared through a site-selective Ni-catalyzed hydroalumination of terminal alkynes and the requisite E-trisubsituted enones are the products of a regioselective Zr-catalyzed carboalumination/acylation of a terminal alkyne. Products are obtained in up to 97% yield and 99:1 er. A model for enantioselectivity, supported by DFT calculations, is proposed. Chapter 4 Formation of Tertiary Centers through Catalytic Enantioselective Conjugate Addition of Alkenylaluminum Reagents to Acyclic Enones We have developed an enantioselective NHC–Cu catalyzed synthesis of tertiary centers in acyclic systems using in situ generated alkenylaluminum reagents, as current methods typically rely on Rh-catalysis at high temperatures with alkenyl boronic acids in protic solvents. Moreover, most examples include chalcone-derived substrates, which, while more reactive, often preclude further functionalization. With the current method, we are able to couple a variety of alkenyl nucleophiles with α,β-unsaturated ketones. E- or Z-silylalkenylaluminum reagents, derived from hydroalumination of silyl-protected alkynes, lead to products in good yields and high enantioselectivities. Additionally, both the α- and β-alkenylaluminum reagents participate in the reaction. Chapter 5 Development of N-Heterocyclic Carbene–Cu Catalyzed Allylic Substitution of Diboryl Methane to Morita-Baylis-Hillman Derived Allylic Phosphates We have developed a method for the coupling of a geminyl diboron reagent with Morita-Baylis-Hillman derived trisubstituted ester-containing allylic phosphates. With 10 mol % of an in situ generated NHC–Cu complex and 1.5 equivalents of the boron reagent, we are able to form the desired product in high regio- and enantioselectivity with a 2,5-ditert-butyl containing carbene. Simple aryl substituents as well as those containing a halogen or an electron-withdrawing group furnish the desired products in up to 85% yield and 98:2 er. Alkyl-containing substrates are also competent reaction partners, although longer chain aliphatics results in slightly diminished enantioselectivity. We are pursuing the application of this method to the synthesis of α-methylene lactones which can be further functionalized to natural products like tubulin polymerization inhibitor (–)-steganone and glaucoma medication (+)-pilocarpine. / Thesis (PhD) — Boston College, 2016. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

by Tat-Ming Tso. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (p. 43-45). / Chapter Chapter 1 --- INTRODUCTION --- p.1 / Chapter §1.1 --- Introduction --- p.1 / Chapter §1.2 --- Preconditioned Conjugate Gradient Method --- p.3 / Chapter §1.3 --- Outline of Thesis --- p.3 / Chapter Chapter 2 --- CIRCULANT AND NON-CIRCULANT PRECONDITIONERS --- p.5 / Chapter §2.1 --- Circulant Matrix --- p.5 / Chapter §2.2 --- Circulant Preconditioners --- p.6 / Chapter §2.3 --- Circulant Preconditioners from Kernel Function --- p.8 / Chapter §2.4 --- Non-circulant Band-Toeplitz Preconditioners --- p.9 / Chapter Chapter 3 --- B-SPLINES --- p.11 / Chapter §3.1 --- Introduction --- p.11 / Chapter §3.2 --- New Version of B-splines --- p.15 / Chapter Chapter 4 --- CIRCULANT PRECONDITIONERS CONSTRUCTED FROM B-SPLINES --- p.24 / Chapter Chapter 5 --- NUMERICAL RESULTS AND CONCLUDING REMARKS --- p.28 / Chapter Chapter 6 --- APPLICATIONS TO SIGNAL PROCESSING --- p.37 / Chapter §6.1 --- Introduction --- p.37 / Chapter §6.2 --- Preconditioned regularized least squares --- p.39 / Chapter §6.3 --- Numerical Example --- p.40 / REFERENCES --- p.43

Elliptic partial differential equations that are used to model physical phenomena give rise to large sparse linear systems. Such systems can be symmetric positive definite and can be solved by the preconditioned conjugate gradients method. In this thesis, we develop support graph preconditioners for symmetric positive definite matrices that arise from the finite element discretization of elliptic partial differential equations. An object oriented code is developed for the construction, integration and application of these preconditioners. Experimental results show that the advantages of support graph preconditioners are retained in the proposed extension to the finite element matrices.

The Alexander terrane is an allochthonous terrane within the North American Cordillera. New structural mapping and geochronology within the southern Alexander terrane in the vicinity of Porcher Island provides evidence for two major tectonic events. The oldest is Late Silurian to Early Devonian magmatism and deformation assigned to the Klakas orogeny. The area has subsequently been affected by mid-Cretaceous conjugate shear zones potentially associated with tectonic escape. Northwest-striking sinistral shear zones characterize mid-Cretaceous deformation in the western Coast Belt south of Prince Rupert in north coastal British Columbia. Structurally focused mapping and geochronology has revealed a component of lateral extension to this deformation. General flow characteristics of the shear zones are identified by comparison of fabric patterns to published models for fabric development in shear zones. U-Pb ages from synkinematic dykes constrain motion on northwest-striking sinistral transpressional shear zones, including the Useless, Barrett and Salt Lagoon shear zones, to ca. 104 – 96 Ma, and dextral transpression on the north-striking Telegraph Passage shear zone to ca. 97.6 ± 0.2 Ma. The geometry, kinematics, and coeval nature of these shear zones suggests that they formed in part as a ductile conjugate set. The presence of similarly-oriented conjugate shear bands in the apex zone between sinistral and dextral shear zones further reinforces this interpretation. The orientation of these conjugate sets indicates a component of north-northwest east-southeast extension. The conjugate shear zones merge together into the Grenville Channel shear zone, a sinistral transpressional shear zone with high strike-parallel stretch. A U-Pb age of 103 ± 32 Ma from a synkinematic dyke in the Grenville Channel shear zone coincides with a previously published Lu-Hf age of 102.6 ± 3.7 Ma on synkinematic garnet. Overall, structural and geochronological data from Porcher Island and surrounding area in north coastal British Columbia indicate that mid-Cretaceous deformation was characterized by ENE-WSW (orogen normal) shortening and NNW-SSE (orogen parallel) extension. This local strain regime is consistent with large-scale mid-Cretaceous tectonic escape as proposed for the northern Cordillera at that time, expressed in coeval sinistral faulting in the Coast Belt and dextral faulting in the northern Omineca belt. The Late Silurian to Early Devonian Ogden Channel complex is a mafic to intermediate metaplutonic-metamorphic complex within the southern Alexander terrane on southern Porcher Island and adjacent Pitt Island in north coastal British Columbia. Lithological characteristics of the complex suggest that it represents the mid-crustal roots of a volcanic arc. An age of 413.3 ± 2.5 Ma from a comparatively weakly deformed quartz diorite dyke indicates that the synkinematic Ogden Channel complex is at least in part Early Devonian in age, corresponding to the Klakas orogeny that affected the Alexander terrane in southeast Alaska. Crosscutting relationships indicate that individual intrusions within the Ogden Channel complex were emplaced syn- to post-kinematically with respect to southwest-vergent sinistral reverse deformation (present coordinates). The structural and lithological characteristics of the Ogden Channel complex are consistent with the interpretation that this part of the Alexander terrane was located in the upper plate of a northeast-dipping subduction zone, which culminated in the Klakas orogeny.

A set of studies centered around the reactions of the active methine compound 1-carbomethoxy-5-dicyanomethyl-1,3-cyclohexadiene (the "ring-opened adduct"), obtained by base-induced ring-opening of the Diels-Alder adduct of 5,5-dicyanocyclopentadiene and methyl acrylate, has been carried out. A plan was devised for the anionic (at the dicyanomethyl carbon) ring-opened adduct whereby its reaction with electrophiles, for example Michael reactions with double-bond acceptors, would generate reactive intermediates that would undergo cyclization by tandem conjugate addition to the a,ß,?,d-unsaturated ring p-system to generate bicyclic compounds. In practice, reaction with di-<i>tert</i>-butyl methylidenemalonate, methyl vinyl ketone, and cyclopentenone generated intermediates that exhibited greater tandem reactivity than was anticipated: the bicyclic enolates were found to cyclize further by Thorpe-Ziegler-like reaction with the proximal nitrile to generate, after facile acid hydrolysis, substituted known tricyclic skeleta termed homobrendanes, specifically, tricyclo[5. 2. 1. 0^4,8]decenes. An attempt was made to generalize the reaction to other substrates, among them singly-activated Michael acceptors and 1,2-heteroatom electrophiles, but the generalization of the homobrendane forming reaction did not meet with success. Attempted functional group manipulations to probe the conversion of the homobrendane derived from di-<i>tert</i>-butyl methylidenemalonate to the homobrendane natural product 2-isocyanoallopupukeanane revealed the unreactivity of the skeletal double-bond toward electrophiles and the high reactivity of the ring ketone toward nucleophiles, among them mCPBA which brought about Baeyer-Villiger reaction, and chloride and hydroxide, which brought about addition/elimination reactions to cleave the last-formed homobrendane ring. <br /> The ring-opened adduct was also envisaged as a potential substrate in intramolecular Heck reactions. To this end, Heck substrates were generated from the ring-opened adduct anion and iodo- and bromo-benzyl halides. A key observation at this stage pertained to the unexpected acidity of the ring-opened adduct C5 proton, which could be deprotonated by DBU to bring about allylic isomerization, a finding that would provide a key insight to the pattern of reactivity later evidenced with alkyl propiolates. Optimization of the Heck substrate-generating reaction was followed by Heck reactions under Jeffery's conditions, which generated angular tricycles as intended, accompanied by aromatic compounds generated by base-induced HCN elimination/rearrangement and dehydrogenation. The Jeffery's conditions were optimized to limit the production of aromatics. <br /> The possibility of ring-opened adduct-derived vinyl silane intermediates undergoing cationic cyclizations led to a minor study based upon the bromination of allylsilanes and the elimination of TMSBr from 1,2-dibromo-3-trimethylsilyl compounds, accessible compounds unaccounted for in the review literature. It was determined that the combination of HBr and Br₂ (perhaps as HBr₃) was required to eliminate TMSBr, in contravention of the textbook account of electrophilic substitutions being the inherent reactions of allylsilanes and Br₂. <br /> Unexpected tandem reactivity was observed in the reactions of the anionic ring-opened adduct and alkyl propiolates under catalytic DBU conditions. Rather than tandem cyclization or simple adduct formation, the allenolate intermediates were determined to undergo extremely facile formal allenolate Cope rearrangements involving the ?,d-double-bond of the parent ring. Excess base intercepted the allenolate by deprotonating ring C5 and effecting 1,2-vinyl transfer by 3-<i>exo</i>-trig addition-elimination. The chemistry of the highly delocalized side-chain carbanion in the Cope product was studied in detail.

Alkylidene Meldrum’s acids are very reactive acceptors in conjugate additions, and are known to be significantly more electrophilic than other α,β-unsaturated carbonyl electrophiles. They also offer advantages in terms of ease of preparation, purification and storage. Despite this, they are relatively underused in organic synthesis, and have been treated as something of a curiousity in the literature. The goal of my research was to demonstrate the utility of these molecules in new reactions that are not readily available to other electrophiles. To facilitate this work, new conditions for the Knoevenagel condensation of aldehydes with Meldrum’s acid were developed. This allowed access to a broader range of monosubstituted alkylidenes than was previously possible from any single method. In a reaction that exploits the acylating ability of Meldrum’s acid, a domino addition of phenols to alkylidene Meldrum’s acids was developed. Here, Yb(OTf)3 catalyzed the addition of a phenol to the alkylidene as well as acylation through activation of the electrophile. The unique properties of these acceptors permitted synthesis of 3,4-dihydrocoumarins and coumarins through C-alkylation/O-acylation, and also 4-chromanones and chromones through O-alkylation/C-acylation. The predictable and general reversal of chemoselectivity is dependent on the number of substituents on the alkylidene. The same properties that make alkylidene Meldrum’s acids strong electrophiles also make them excellent dienophiles. A one-pot Diels-Alder/Friedel-Crafts process was used as an entry into the 6-5-6-tricyclic skeleton of a family of natural products that have been of interest in our group. The modular nature of the reaction allowed structural variation at nearly every position around both 6-membered rings. An attempted extension of this work into the synthesis of ergot alkaloids provided insight into the factors affecting Friedel-Crafts acylation of 4-substituted indoles. These results provided a highly regioselective entry into 4,5-fused indole ring systems. The electrophilicity of alkylidene Meldrum’s acids was combined with Lewis acid activation for development of a mild conjugate allylation reaction. The use of allyltriphenyltin as nucleophile for addition to monosubstituted alkylidenes avoided many of the practical disadvantages of working with trialkylstannanes. By employing such a relatively weak allylating agent, functional group compatibility was maximized to include groups susceptible to nucleophilic allylation. Additions to chiral, non-racemic alkylidenes were highly diastereoselective. It was also shown that functionalized all-carbon quaternary stereocentres can be formed by this process.

A set of studies centered around the reactions of the active methine compound 1-carbomethoxy-5-dicyanomethyl-1,3-cyclohexadiene (the "ring-opened adduct"), obtained by base-induced ring-opening of the Diels-Alder adduct of 5,5-dicyanocyclopentadiene and methyl acrylate, has been carried out. A plan was devised for the anionic (at the dicyanomethyl carbon) ring-opened adduct whereby its reaction with electrophiles, for example Michael reactions with double-bond acceptors, would generate reactive intermediates that would undergo cyclization by tandem conjugate addition to the a,ß,?,d-unsaturated ring p-system to generate bicyclic compounds. In practice, reaction with di-<i>tert</i>-butyl methylidenemalonate, methyl vinyl ketone, and cyclopentenone generated intermediates that exhibited greater tandem reactivity than was anticipated: the bicyclic enolates were found to cyclize further by Thorpe-Ziegler-like reaction with the proximal nitrile to generate, after facile acid hydrolysis, substituted known tricyclic skeleta termed homobrendanes, specifically, tricyclo[5. 2. 1. 0^4,8]decenes. An attempt was made to generalize the reaction to other substrates, among them singly-activated Michael acceptors and 1,2-heteroatom electrophiles, but the generalization of the homobrendane forming reaction did not meet with success. Attempted functional group manipulations to probe the conversion of the homobrendane derived from di-<i>tert</i>-butyl methylidenemalonate to the homobrendane natural product 2-isocyanoallopupukeanane revealed the unreactivity of the skeletal double-bond toward electrophiles and the high reactivity of the ring ketone toward nucleophiles, among them mCPBA which brought about Baeyer-Villiger reaction, and chloride and hydroxide, which brought about addition/elimination reactions to cleave the last-formed homobrendane ring. <br /> The ring-opened adduct was also envisaged as a potential substrate in intramolecular Heck reactions. To this end, Heck substrates were generated from the ring-opened adduct anion and iodo- and bromo-benzyl halides. A key observation at this stage pertained to the unexpected acidity of the ring-opened adduct C5 proton, which could be deprotonated by DBU to bring about allylic isomerization, a finding that would provide a key insight to the pattern of reactivity later evidenced with alkyl propiolates. Optimization of the Heck substrate-generating reaction was followed by Heck reactions under Jeffery's conditions, which generated angular tricycles as intended, accompanied by aromatic compounds generated by base-induced HCN elimination/rearrangement and dehydrogenation. The Jeffery's conditions were optimized to limit the production of aromatics. <br /> The possibility of ring-opened adduct-derived vinyl silane intermediates undergoing cationic cyclizations led to a minor study based upon the bromination of allylsilanes and the elimination of TMSBr from 1,2-dibromo-3-trimethylsilyl compounds, accessible compounds unaccounted for in the review literature. It was determined that the combination of HBr and Br₂ (perhaps as HBr₃) was required to eliminate TMSBr, in contravention of the textbook account of electrophilic substitutions being the inherent reactions of allylsilanes and Br₂. <br /> Unexpected tandem reactivity was observed in the reactions of the anionic ring-opened adduct and alkyl propiolates under catalytic DBU conditions. Rather than tandem cyclization or simple adduct formation, the allenolate intermediates were determined to undergo extremely facile formal allenolate Cope rearrangements involving the ?,d-double-bond of the parent ring. Excess base intercepted the allenolate by deprotonating ring C5 and effecting 1,2-vinyl transfer by 3-<i>exo</i>-trig addition-elimination. The chemistry of the highly delocalized side-chain carbanion in the Cope product was studied in detail.

Alkylidene Meldrum’s acids are very reactive acceptors in conjugate additions, and are known to be significantly more electrophilic than other α,β-unsaturated carbonyl electrophiles. They also offer advantages in terms of ease of preparation, purification and storage. Despite this, they are relatively underused in organic synthesis, and have been treated as something of a curiousity in the literature. The goal of my research was to demonstrate the utility of these molecules in new reactions that are not readily available to other electrophiles. To facilitate this work, new conditions for the Knoevenagel condensation of aldehydes with Meldrum’s acid were developed. This allowed access to a broader range of monosubstituted alkylidenes than was previously possible from any single method. In a reaction that exploits the acylating ability of Meldrum’s acid, a domino addition of phenols to alkylidene Meldrum’s acids was developed. Here, Yb(OTf)3 catalyzed the addition of a phenol to the alkylidene as well as acylation through activation of the electrophile. The unique properties of these acceptors permitted synthesis of 3,4-dihydrocoumarins and coumarins through C-alkylation/O-acylation, and also 4-chromanones and chromones through O-alkylation/C-acylation. The predictable and general reversal of chemoselectivity is dependent on the number of substituents on the alkylidene. The same properties that make alkylidene Meldrum’s acids strong electrophiles also make them excellent dienophiles. A one-pot Diels-Alder/Friedel-Crafts process was used as an entry into the 6-5-6-tricyclic skeleton of a family of natural products that have been of interest in our group. The modular nature of the reaction allowed structural variation at nearly every position around both 6-membered rings. An attempted extension of this work into the synthesis of ergot alkaloids provided insight into the factors affecting Friedel-Crafts acylation of 4-substituted indoles. These results provided a highly regioselective entry into 4,5-fused indole ring systems. The electrophilicity of alkylidene Meldrum’s acids was combined with Lewis acid activation for development of a mild conjugate allylation reaction. The use of allyltriphenyltin as nucleophile for addition to monosubstituted alkylidenes avoided many of the practical disadvantages of working with trialkylstannanes. By employing such a relatively weak allylating agent, functional group compatibility was maximized to include groups susceptible to nucleophilic allylation. Additions to chiral, non-racemic alkylidenes were highly diastereoselective. It was also shown that functionalized all-carbon quaternary stereocentres can be formed by this process.