Publications by authors named "Maciej A Walczak"

27 Publications

  • Page 1 of 1

Ligand-Free Copper(I)-Mediated Cross-Coupling Reactions of Organostannanes with Sulfur Electrophiles.

J Org Chem 2020 09 9;85(18):11942-11951. Epub 2020 Sep 9.

Department of Chemistry, University of Colorado, Boulder, Colorado 80309, United States.

The synthesis of aryl thioether through the cross-coupling of C-S bond is a highly attractive area of research due to the prevalence of aryl thioether in bioactive natural products, functional materials, agrochemicals, and pharmaceutically active compounds. Herein, we report a ligand-free Cu(I) mediated electrophilic thiolation of organostannanes with sulfur electrophiles. A selective transfer of alkyl groups was achieved in reactions with alkyl carbastannatranes affording congested thioethers. This study offers a unified method to access diaryl and aryl alkyl thioethers and was demonstrated in the context of late-stage modifications..
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http://dx.doi.org/10.1021/acs.joc.0c01399DOI Listing
September 2020

Stereochemistry of Transition Metal Complexes Controlled by the Metallo-Anomeric Effect.

J Am Chem Soc 2020 09 19;142(35):15127-15136. Epub 2020 Aug 19.

Department of Chemistry, University of Colorado, Boulder, Colorado 80309, United States.

The use of stereoelectronic interactions to control reactivity and selectivity has a long history in chemistry. The anomeric effect, one of the fundamental concepts in organic chemistry, describes the preferences of a substituent at the anomeric carbon in glycosides to adopt axial configuration when the anomeric group is an electronegative element such as oxygen or a halogen. The origin of the anomeric effect has been the subject of intense debate. Explanations capitalizing on either the delocalization of the endocyclic oxygen lone pair into the antibonding σ* orbital or the minimization of the dipole-dipole interactions are currently the two leading theoretical models. Although the majority of experimental and theoretical studies have focused on the elements from groups 6 and 7, little is known about conformational preferences of tetrahydropyran rings substituted with a transition metal at the anomeric carbon and the role of these interactions in stereoselective synthesis. Here, we report studies on conformational and configurational preferences of organometallic complexes stabilized by vicinal heteroatoms. We provide computational evidence that late transition metals adopt the axial position in heterocycles or synclinal geometry in acyclic systems. Furthermore, the anomeric preferences of late transition metals correlate with the oxidation state of the metal and can be explained by hyperconjugative interactions between endocyclic heteroatom and the σ* acceptor orbitals of the C-M bond. In a broader context, this discovery provides insight into the role of previously unanticipated stereoelectronic effects that can be harnessed in the design of stereoselective reactions, including chemical glycosylation and enantioselective catalysis.
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http://dx.doi.org/10.1021/jacs.0c06882DOI Listing
September 2020

Catalytic and Photochemical Strategies to Stabilized Radicals Based on Anomeric Nucleophiles.

J Am Chem Soc 2020 06 10;142(25):11102-11113. Epub 2020 Jun 10.

Department of Chemistry, University of Colorado, Boulder, Colorado 80309, United States.

Carbohydrates, one of the three primary macromolecules of living organisms, play significant roles in various biological processes such as intercellular communication, cell recognition, and immune activity. While the majority of established methods for the installation of carbohydrates through the anomeric carbon rely on nucleophilic displacement, anomeric radicals represent an attractive alternative because of their functional group compatibility and high anomeric selectivities. Herein, we demonstrate that anomeric nucleophiles such as C1 stannanes can be converted into anomeric radicals by merging Cu(I) catalysis with blue light irradiation to achieve highly stereoselective C(sp)-S cross-coupling reactions. Mechanistic studies and DFT calculations revealed that the C-S bond-forming step occurs via the transfer of the anomeric radical directly to a sulfur electrophile bound to Cu(II) species. This pathway complements a radical chain observed for photochemical metal-free conditions where a disulfide initiator can be activated by a Lewis base additive. Both strategies utilize anomeric nucleophiles as efficient radical donors and achieve a switch from an ionic to a radical pathway. Taken together, the stability of glycosyl nucleophiles, a broad substrate scope, and high anomeric selectivities observed for the thermal and photochemical protocols make this novel C-S cross coupling a practical tool for late-stage glycodiversification of bioactive natural products and drug candidates.
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http://dx.doi.org/10.1021/jacs.0c03298DOI Listing
June 2020

Copper-Catalyzed Oxidative Acetalization of Boronic Esters: An Umpolung Strategy for Cyclic Acetal Synthesis.

J Org Chem 2020 06 9;85(12):8230-8239. Epub 2020 Jun 9.

Department of Chemistry, University of Colorado, Boulder, Colorado 80309, United States.

A protocol for the acetalization of boronic esters is described. The reaction is catalyzed by copper, and the conditions proved to be mild and were amenable to a variety of functional groups. We expanded the Chan-Lam coupling to include C(sp) nucleophiles and converted them into corresponding acetals. This method allows for the orthogonal acetalization of substrates with reactive, acid-sensitive functional groups.
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http://dx.doi.org/10.1021/acs.joc.0c00720DOI Listing
June 2020

Total synthesis of micrococcin P1 and thiocillin I enabled by Mo(vi) catalyst.

Chem Sci 2019 Feb 3;10(7):1971-1975. Epub 2018 Dec 3.

Department of Chemistry , University of Colorado , Boulder , CO 80309 , USA . Email:

Thiopeptides are a class of potent antibiotics with promising therapeutic potential. We developed a novel Mo(vi)-oxide/picolinic acid catalyst for the cyclodehydration of cysteine peptides to form thiazoline heterocycles. With this powerful tool in hand, we completed the total syntheses of two representative thiopeptide antibiotics: micrococcin P1 and thiocillin I. These two concise syntheses (15 steps, longest linear sequence) feature a C-H activation strategy to install the trisubstituted pyridine core and thiazole groups. The synthetic material displays promising antimicrobial properties measured against a series of Gram-positive bacteria.
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http://dx.doi.org/10.1039/c8sc04885aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383332PMC
February 2019

Acyl Glycosides through Stereospecific Glycosyl Cross-Coupling: Rapid Access to C(sp)-Linked Glycomimetics.

ACS Cent Sci 2018 Dec 4;4(12):1652-1662. Epub 2018 Dec 4.

Department of Chemistry, University of Colorado, Boulder, Colorado 80309, United States.

Replacement of a glycosidic bond with hydrolytically stable C-C surrogates is an efficient strategy to access glycomimetics with improved physicochemical and pharmacological properties. We describe here a stereoretentive cross-coupling reaction of glycosyl stannanes with C(sp)- and C(sp)-thio(seleno)esters suitable for the preparation -acyl glycosides as synthetic building blocks to obtain C(sp)-linked and fluorinated glycomimetics. First, we identified a set of standardized conditions employing a Pd(0) precatalyst, CuCl additive, and phosphite ligand that provided access to -acyl glycosides without deterioration of anomeric integrity and decarbonylation of the acyl donors (>40 examples). Second, we demonstrated that C(sp)-glycomimetics could be introduced into the anomeric position via a direct conversion of C1 ketones. Specifically, the conversion of the carbonyl group into a CF mimetic is an appealing method to access valuable fluorinated analogues. We also illustrate that the introduction of other carbonyl-based groups into the C1 position of mono- and oligosaccharides can be accomplished using the corresponding acyl donors. This protocol is amenable to late-stage glycodiversification and programmed mutation of the C-O bond into hydrolytically stable C-C bonds. Taken together, stereoretentive anomeric acylation represents a convenient method to prepare a diverse set of glycan mimetics with minimal synthetic manipulations and with absolute control of anomeric configuration.
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http://dx.doi.org/10.1021/acscentsci.8b00628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311691PMC
December 2018

Stereoretentive C( sp)-S Cross-Coupling.

J Am Chem Soc 2018 12 11;140(51):18140-18150. Epub 2018 Dec 11.

Department of Chemistry , University of Colorado , Boulder , Colorado 80309 , United States.

We report a stereoretentive cross-coupling reaction of configurationally stable nucleophiles with disulfide and N-sulfenylsuccinimide donors promoted by Cu(I). We demonstrate the utility of this method in the synthesis of thioglycosides derived from simple alkyl and aryl thiols, thioglycosides, and in the glycodiversification of cysteine residues in peptides. These reactions operate well with carbohydrate substrates containing common protective groups and reagents with free hydroxyl and secondary amide functionalities under standardized conditions. Competition experiments in combination with computational DFT studies established that the putative anomeric intermediate is an organocopper species that is configurationally stable and resistant to epimerization due to its short lifetime. The subsequent reductive elimination from the Cu(III) intermediate is rapid and stereoretentive. Taken together, the glycosyl cross-coupling is ideally suited for late stage glycodiversification and bioconjugation under highly controlled installation of the aliphatic carbon-sulfur bonds.
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http://dx.doi.org/10.1021/jacs.8b11211DOI Listing
December 2018

Stereoselective oxidative glycosylation of anomeric nucleophiles with alcohols and carboxylic acids.

Nat Commun 2018 09 7;9(1):3650. Epub 2018 Sep 7.

Department of Chemistry and Biochemistry, University of Colorado Boulder, Boulder, CO, 80309, USA.

Oligosaccharides, one of the most abundant biopolymers, are involved in numerous biological processes. Although many efforts have been put in preparative carbohydrate chemistry, achieving optimal anomeric and regioselectivities remains challenging. Herein we describe an oxidative glycosylation method between anomeric stannanes and oxygen nucleophiles resulting in the formation of a C-O bond with consistently high anomeric control for glycosyl donors bearing a free C2-hydroxyl group. These reactions are promoted by hypervalent iodine reagents with catalytic or stoichiometric amounts of Cu or Zn salts. The generality of this transformation is demonstrated in 42 examples. Mechanistic studies indicate that the oxidative glycosylation is initiated by the hydroxyl-guided delivery of the hypervalent iodine and tosylate into the anomeric position, and results in excellent 1,2-trans selectivity. The unique mechanistic paradigm, high selectivities, and mild reaction conditions make this method suitable for the synthesis of oligosaccharides and for integration with other methodologies such as automated synthesis.
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http://dx.doi.org/10.1038/s41467-018-06016-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128909PMC
September 2018

Rethinking Carbohydrate Synthesis: Stereoretentive Reactions of Anomeric Stannanes.

Chemistry 2019 Mar 13;25(13):3147-3155. Epub 2018 Dec 13.

Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO, 80309, United States.

In this Concept article, recent advances are highlighted in the synthesis and applications of anomeric nucleophiles, a class of carbohydrates in which the C1 carbon bears a carbon-metal bond. First, the advantages of exploiting the carboanionic reactivity of carbohydrates and the methods for the synthesis of mono- and oligosaccharide stannanes are discussed. Second, recent developments in the glycosyl cross-coupling method resulting in the transfer of anomeric configuration from C1 stannanes to C-aryl glycosides are reviewed. These highly stereoretentive processes are ideally suited for the preparation of carbohydrate-based therapeutics and were demonstrated in the synthesis of antidiabetic drugs. Next, the application of the glycosyl cross-coupling method to the preparation of Se-glycosides and to glycodiversification of small molecules and peptides are highlighted. These reactions proceed with exclusive anomeric control for a broad range of substrates and tolerate carbohydrates with free hydroxyl groups. Taken together, anomeric nucleophiles have emerged as powerful tools for the synthesis of oligosaccharides and glycoconjugates and their future applications will open new possibilities to incorporate saccharides into small molecules and biologics.
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http://dx.doi.org/10.1002/chem.201803082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265906PMC
March 2019

Asymmetric Synthesis of Chiral 1,2-Amino Alcohols and Morpholin-2-ones from Arylglyoxals.

J Org Chem 2018 09 6;83(17):10487-10500. Epub 2018 Aug 6.

Department of Chemistry and Biochemistry , University of Colorado , Boulder , Colorado 80309 , United States.

Chiral 1,2-amino alcohols are privileged scaffolds with important applications as drug candidates and chiral ligands. Although various methods for the preparation of this structural motif have been reported, these methods are limited because of the use of precious metals and ligands. Here, we report a practical and high yielding synthesis of chiral 1,2-amino alcohols using arylglyoxals and pseudoephedrine auxiliary. This reaction is catalyzed by a Brønsted acid and provides morpholinone products in high yields and selectivities. The morpholine ring was converted into 1,2-amino alcohols in a two-step protocol.
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http://dx.doi.org/10.1021/acs.joc.8b01516DOI Listing
September 2018

Direct Dehydrative Glycosylation of C1-Alcohols.

Chem Asian J 2018 Oct 1;13(20):2978-2990. Epub 2018 Oct 1.

Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO, 80309, USA.

Due to the central role played by carbohydrates in a multitude of biological processes, there has been a sustained interest in developing effective glycosylation methods to enable more thorough investigation of their essential functions. Among the myriad technologies available for stereoselective glycoside bond formation, dehydrative glycosylation possesses a distinct advantage given the unique properties of C1-alcohols such as straightforward preparation, stability, and a general reactivity compatible with a diverse set of reaction conditions. In this Focus Review, a survey of direct dehydrative glycosylations of C1-alcohols is provided with an emphasis on recent achievements, pervading limitations, mechanistic insights, and applications in total synthesis.
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http://dx.doi.org/10.1002/asia.201800971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326538PMC
October 2018

Stereoretentive Intramolecular Glycosyl Cross-Coupling: Development, Scope, and Kinetic Isotope Effect Study.

Org Lett 2018 08 17;20(15):4627-4631. Epub 2018 Jul 17.

Department of Chemistry and Biochemistry , University of Colorado , Boulder , Colorado 80309 , United States.

A series of cyclic C-glycosides were synthesized using the palladium-catalyzed stereoretentive intramolecular glycosylation of aryl iodides by employing a bulky phosphine ligand. A variety of functional groups are tolerated in the reaction, and enantioenriched anomeric nucleophiles could be coupled without erosion of optical purity. This study offers a unified method to access both cis- and trans-fused rings by capitalizing on the stereoretentive nature of the Stille reaction. In addition, competition experiments for intermolecular and intramolecular cross-couplings revealed secondary KIEs of 1.43 and 0.81, respectively, suggesting a profoundly different steric congestion at the transition state.
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http://dx.doi.org/10.1021/acs.orglett.8b01927DOI Listing
August 2018

Stereoretentive Reactions at the Anomeric Position: Synthesis of Selenoglycosides.

Angew Chem Int Ed Engl 2018 06 14;57(24):7091-7095. Epub 2018 May 14.

Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO, 80309, USA.

Reported is the stereospecific cross-coupling of anomeric stannanes with symmetrical diselenides, resulting in the synthesis of selenoglycosides with exclusive anomeric control. The reaction proceeds without the need for directing groups and is compatible with free hydroxy groups as demonstrated in the preparation of glycoconjugates derived from mono-, di-, and trisaccharides and peptides (35 examples). Given its generality and broad substrate scope, the glycosyl cross-coupling method presented herein can find use in the synthesis of selenium-containing glycomimetics and glycoconjugates.
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http://dx.doi.org/10.1002/anie.201802847DOI Listing
June 2018

Glycosyl Cross-Coupling with Diaryliodonium Salts: Access to Aryl C-Glycosides of Biomedical Relevance.

Org Lett 2018 04 12;20(7):1936-1940. Epub 2018 Mar 12.

Department of Chemistry and Biochemistry , University of Colorado , Boulder , Colorado 80309 , United States.

A stereospecific cross-coupling reaction of anomeric nucleophiles with diaryliodonium triflates resulting in the synthesis of aryl C-glycosides is reported. This process capitalizes on a stereoretentive reaction of configurationally stable C1 stannanes and is promoted by a palladium catalyst in the presence of a bulky phosphine ligand that suppresses the undesired β-elimination. The utility of this reaction has been demonstrated in the preparation of a series of C-glycosides derived from common saccharides resulting in exclusive transfer of anomeric configuration from the anomeric nucleophile to the product, and in the synthesis of empagliflozin, a commercial antidiabetic drug.
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http://dx.doi.org/10.1021/acs.orglett.8b00475DOI Listing
April 2018

Constrained saccharides: a review of structure, biology, and synthesis.

Nat Prod Rep 2018 03 7;35(3):220-229. Epub 2018 Mar 7.

Department of Chemistry and Biochemistry, University of Colorado 215 UCB, Boulder, CO 80309, USA.

Review primarily covers from 1995-2018Carbohydrate function, recognized in a multitude of biological processes, provides a precedent for developing carbohydrate surrogates that mimic the structure and function of bioactive compounds. In order to constrain highly flexible oligosaccharides, synthetic tethering techniques like those exemplified by stapled peptides are utilized to varying degrees of success. Naturally occurring constrained carbohydrates, however, exist with noteworthy cytotoxic and chemosensitizing properties. This review highlights the structure, biology, and synthesis of this intriguing class of molecules.
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http://dx.doi.org/10.1039/c7np00050bDOI Listing
March 2018

Glycosyl Cross-Coupling of Anomeric Nucleophiles: Scope, Mechanism, and Applications in the Synthesis of Aryl C-Glycosides.

J Am Chem Soc 2017 12 30;139(49):17908-17922. Epub 2017 Nov 30.

Department of Chemistry and Biochemistry, University of Colorado , Boulder, Colorado 80309, United States.

Stereoselective manipulations at the C1 anomeric position of saccharides are one of the central goals of preparative carbohydrate chemistry. Historically, the majority of reactions forming a bond with anomeric carbon has focused on reactions of nucleophiles with saccharide donors equipped with a leaving group. Here, we describe a novel approach to stereoselective synthesis of C-aryl glycosides capitalizing on the highly stereospecific reaction of anomeric nucleophiles. First, methods for the preparation of anomeric stannanes have been developed and optimized to afford both anomers of common saccharides in high anomeric selectivities. We established that oligosaccharide stannanes could be prepared from monosaccharide stannanes via O-glycosylation with Schmidt-type donors, glycal epoxides, or under dehydrative conditions with C1 alcohols. Second, we identified a general set of catalytic conditions with Pd(dba) (2.5 mol%) and a bulky ligand (JackiePhos, 10 mol%) controlling the β-elimination pathway. We demonstrated that the glycosyl cross-coupling resulted in consistently high anomeric selectivities for both anomers with mono- and oligosaccharides, deoxysugars, saccharides with free hydroxyl groups, pyranose, and furanose substrates. The versatility of the glycosyl cross-coupling reaction was probed in the total synthesis of salmochelins (siderophores) and commercial anti-diabetic drugs (gliflozins). Combined experimental and computational studies revealed that the β-elimination pathway is suppressed for biphenyl-type ligands due to the shielding of Pd(II) by sterically demanding JackiePhos, whereas smaller ligands, which allow for the formation of a Pd-F complex, predominantly result in a glycal product. Similar steric effects account for the diminished rates of cross-couplings of 1,2-cis C1-stannanes with aryl halides. DFT calculations also revealed that the transmetalation occurs via a cyclic transition state with retention of configuration at the anomeric position. Taken together, facile access to both anomers of various glycoside nucleophiles, a broad reaction scope, and uniformly high transfer of anomeric configuration make the glycosyl cross-coupling reaction a practical tool for the synthesis of bioactive natural products, drug candidates, allowing for late-stage glycodiversification studies with small molecules and biologics.
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http://dx.doi.org/10.1021/jacs.7b08707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581190PMC
December 2017

Size Matters: Chemical Synthesis of a Homogenous Arabinogalactan 92-mer.

Chembiochem 2017 09 9;18(18):1789-1791. Epub 2017 Aug 9.

Department of Chemistry and Biochemistry, University of Colorado, 215 UCB, Boulder, CO, 80309, USA.

31+30+31: Ye and colleagues have synthesized a branched 92-mer of arabinogalactan-a major component of the cell wall of M. tuberculosis-by linking a linear oligogalactan 30-mer with two d-arabinofuranose 31-mers. Their approach capitalizes on sequential, one-pot glycosylation reactions that result in a rapid increase in molecular complexity and efficient synthesis of a branched oligosaccharide.
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http://dx.doi.org/10.1002/cbic.201700311DOI Listing
September 2017

Dehydrative glycosylation with cyclic phosphonium anhydrides.

Org Biomol Chem 2016 Dec;15(1):51-55

Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.

Cyclic phosphonium anhydrides generated from bis-phosphine oxides and trifluoromethanesulfonic anhydride are shown as general coupling reagents in a dehydrative glycosylation reaction of C1-hemiacetals. This reaction protocol is characterized by a broad substrate scope and high yields, including reactions of O-, C-, N-, and S-based nucleophiles with furanose, pyranose, and deoxysugar donors.
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http://dx.doi.org/10.1039/c6ob01812bDOI Listing
December 2016

Highly Stereospecific Cross-Coupling Reactions of Anomeric Stannanes for the Synthesis of C-Aryl Glycosides.

J Am Chem Soc 2016 09 13;138(37):12049-52. Epub 2016 Sep 13.

Department of Chemistry and Biochemistry, University of Colorado , Boulder, Colorado 80309, United States.

We demonstrate that configurationally stable anomeric stannanes undergo a stereospecific cross-coupling reaction with aromatic halides in the presence of a palladium catalyst with exceptionally high levels of stereocontrol. In addition to a broad substrate scope (>40 examples), this reaction eliminates critical problems inherent to nucleophilic displacement methods and is applicable to (hetero)aromatics, peptides, pharmaceuticals, common monosaccharides, and saccharides containing free hydroxyl groups.
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http://dx.doi.org/10.1021/jacs.6b07891DOI Listing
September 2016

Ring-strain-enabled reaction discovery: new heterocycles from bicyclo[1.1.0]butanes.

Acc Chem Res 2015 Apr 16;48(4):1149-58. Epub 2015 Mar 16.

†Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States.

Mechanistically as well as synthetically, bicyclo[1.1.0]butanes represent one of the most fascinating classes of organic compounds. They offer a unique blend of compact size (four carbon atoms), high reactivity (strain energy of 66 kcal/mol), and mechanistic pathway diversity that can be harvested for the rapid assembly of complex scaffolds. The C(1)-C(3) bond combines the electronic features of both σ and π bonds with facile homolytic and heterolytic bond dissociation properties and thereby readily engages pericyclic, transition-metal-mediated, nucleophilic, and electrophilic pathways as well as radical acceptor and donor substrates. Despite this multifaceted reaction profile and recent advances in the preparation of bicylo[1.1.0]butanes, the current portfolio of synthetic applications is still limited compared with those of cyclopropanes and cyclobutanes. In this Account, we describe our work over the past decade on the exploration of substituent effects on the ring strain and the reactivity of bicyclo[1.1.0]butanes, particularly in the context of metal-mediated processes. We first describe Rh(I)-catalyzed cycloisomerization reactions of N-allyl amines to give pyrrolidine and azepine heterocycles. The regioselectivity of the C,C-bond insertion/ring-opening step in these reactions is controlled by the phosphine ligand. After metal carbene formation, an intramolecular cyclopropanation adds a second fused ring system. A proposed mechanism rationalizes why rhodium(I) complexes with monodentate ligands favor five-membered heterocycles, as opposed to Rh(I)-bidentate ligand catalysts, which rearrange N-allyl amines to seven-membered heterocycles. The scope of Rh(I)-catalyzed cycloisomerization reactions was extended to allyl ethers, which provide a mixture of five- and seven-membered cyclic ethers regardless of the nature of the phosphine additive and Rh(I) precatalyst. The chemical diversity of these cycloisomerization products was further expanded by a consecutive one-pot metathesis reaction. Rh(I)-catalyzed cycloisomerizations of propargyl amides, ethers, and electron-deficient bicyclo[1.1.0]butanes diverged mechanistically and often led to a significant number of decomposition products. In these cases, Pt(II) emerged as a superior, more alkynophilic late transition metal with its own mechanistic peculiarities. While monosubstituted bicyclo[1.1.0]butanes led to the formation of tetrahydropyridines, 1,3-disubstituted and electron-deficient bicyclo[1.1.0]butanes reacted distinctly differently with Pt(II) and ultimately provided a complementary set of nitrogen- and oxygen-containing cyclic scaffolds. The metal-catalyzed ring transformations of bicyclo[1.1.0]butanes presented herein suggest additional strategies for new reaction discoveries that can access a wide variety of novel cyclic frameworks from relatively simple starting materials. In addition, these case studies highlight the considerable potential for future applications in natural products, medicinal, and diversity-oriented synthesis based on the wealth of mechanistic pathways available to these strained small-ring carbocycles.
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http://dx.doi.org/10.1021/ar500437hDOI Listing
April 2015

Building biologics by chemical synthesis: practical preparation of di- and triantennary N-linked glycoconjugates.

J Am Chem Soc 2013 Mar 19;135(12):4700-3. Epub 2013 Mar 19.

Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10065, USA.

A unified strategy for the syntheses of bi- and triantennary fully sialylated N-glycans is described. The synthesis capitalizes on a global glycosylation strategy that delivers the desired undeca- and tetradecasaccharide in excellent yields. Finally, conjugation of the glycan to PSMA oligopeptide is described.
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http://dx.doi.org/10.1021/ja401385vDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632434PMC
March 2013

Solving the convergence problem in the synthesis of triantennary N-glycan relevant to prostate-specific membrane antigen (PSMA).

J Am Chem Soc 2012 Oct 21;134(39):16430-3. Epub 2012 Sep 21.

Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10065, USA.

The first total synthesis of triantennary, fully sialylated N-glycan of complex type is described. Two strategies for installation of sialylated antennae are explored, and both approaches converge on a global glycosylation step that delivers the desired tetradecasaccharide in good yields.
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http://dx.doi.org/10.1021/ja307628wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3470013PMC
October 2012

An ESR analysis of the mechanism of pericyclic reactions of bicyclobutane.

Org Biomol Chem 2009 Jun 6;7(11):2363-6. Epub 2009 Apr 6.

Department of Chemistry & Center for Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, PA, USA.

Experimental and simulated ESR data are in good agreement with a biradical mechanism for the intramolecular pericyclic reactions of bicyclo[1.1.0]butanes.
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http://dx.doi.org/10.1039/b815469bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737485PMC
June 2009

Formal Alder-ene reaction of a bicyclo[1.1.0]butane in the synthesis of the tricyclic quaternary ammonium core of daphniglaucins.

Tetrahedron Lett 2008 Jun;49(41):5986-5989

Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.

A tricyclic substructure of the tetracyclic nitrogen core of the daphniglaucins was formed by an oxidative activation of the allyl side chain of a bicyclo[1.1.0]butylmethylamine, a spontaneous intramolecular formal Alder-ene reaction, and a selective cyclization of a triol intermediate.
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http://dx.doi.org/10.1016/j.tetlet.2008.07.179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2575373PMC
June 2008

Rhodium(I)-catalyzed cycloisomerizations of bicyclobutanes.

J Am Chem Soc 2008 Jun 8;130(22):6924-5. Epub 2008 May 8.

Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, USA.

The selection of rhodium precatalyst and phosphine ligand determines the course of the cycloisomerization of N-allylated bicyclo[1.1.0]butylalkylamines. Cyclopropane-fused pyrrolidines and azepines are obtained with high levels of stereo- and regiocontrol. Novel azatricyclo[6.1.0.0(1,5)]nonanes are the result of a tandem cycloisomerization-ring closing metathesis sequence. Allylic ethers lead to furans and oxepanes.
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http://dx.doi.org/10.1021/ja802906kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754197PMC
June 2008

Pericyclic cascade reactions of (bicyclo[1.1.0]butylmethyl)amines.

Angew Chem Int Ed Engl 2006 Jun;45(25):4172-5

Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.

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http://dx.doi.org/10.1002/anie.200600723DOI Listing
June 2006

Diversity-oriented synthesis of azaspirocycles.

Org Lett 2004 Aug;6(17):3009-12

Department of Chemistry, Center for Chemical Methodologies & Library Development, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.

Multicomponent condensation of N-diphenylphosphinoylimines, alkynes, zirconocene hydrochloride, and diiodomethane provides a rapid access to omega-unsaturated dicyclopropylmethylamines. These novel building blocks are converted into heterocyclic 5-azaspiro[2.4]heptanes, 5-azaspiro-[2.5]octanes, and 5-azaspiro[2.6]nonanes by means of selective ring-closing metathesis, epoxide opening, or reductive amination. The resulting functionalized pyrrolidines, piperidines, and azepines are scaffolds of considerable relevance for chemistry-driven drug discovery.
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http://dx.doi.org/10.1021/ol0487783DOI Listing
August 2004