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The first catalytic asymmetric ring-closing metathesis method for the synthesis of N-containing heterocycles is reported; this is accomplished through Mo-catalyzed kinetic resolution or desymmetrization of unsaturated amines. Importantly, this catalytic asymmetric method delivers medium-ring unsaturated amines (including eight-membered rings) in high yield, with exceptional enantioselectivity and without the need for solvents. These enantioselective reactions can be effected by catalysts prepared in situ from commercially available reagents.

Tungsten NArR alkylidene complexes have been prepared that contain the electron-withdrawing ArR groups 2,4,6-X3C6H2 (ArX3, X = Cl, Br), 2,6-Cl2-4-CF3C6H2 (ArCl2CF3), and 3,5-(CF3)2C6H3 (Ar(CF3)2). Reported complexes include W(NArR)2Cl2(dme) (dme = 1,2-dimethoxyethane), W(NArR)2(CH2CMe3)2, W(NArR)(CHCMe3)(OTf)2(dme), and W(NArR)(CHCMe3)(ODBMP)2 (DBMP = 4-Me-2,6-(CHPh2)C6H2). The W(NArR)(CHCMe3)(ODBMP)2 complexes were explored as initiators for the polymerization of 2,3-dicarbomethoxynorbornadiene (DCMNBD).

The origins of the unexpected finding that Ru catechothiolate complexes, in contrast to catecholate derivatives, promote exceptional Z-selective olefin metathesis reactions are elucidated. We show that species containing a catechothiolate ligand, unlike catecholates, preserve their structural integrity under commonly used reaction conditions. DFT calculations indicate that, whereas alkene coordination is the stereochemistry-determining step with catecholate complexes, it is through the metallacyclobutane formation that the identity of the major isomer is determined with catechothiolate systems. The present findings suggest that previous models for Z selectivity, largely based on steric differences, should be altered to incorporate electronic factors as well.

Imido alkylidene complexes of Mo and W and oxo alkylidene complexes of W that contain thiophenoxide ligands of the type S-2,3,5,6-Ph4C6H (STPP) and S-2,6-(mesityl)2C6H3 (SHMT = S-hexamethylterphenyl) have been prepared in order to compare their metathesis activity with that of the analogous phenoxide complexes. All thiolate complexes were significantly slower (up to ∼10× slower) for the metathesis homocoupling of 1-octene or polymerization of 2,3-dicarbomethoxynorbornene, and none of them was Z-selective. The slower rates could be attributed to the greater σ-donating ability of a thiophenoxide versus the analogous phenoxide and consequently a higher electron density at the metal in the thiophenoxide complexes.

The first general enantioselective allenyl addition to a range of aromatic and aliphatic aldehyde derived imines is presented.

The enantioselective boryl conjugate addition of bis(pinacolato)diboron to cyclic and linear α,β-unsaturated ketones leads to corresponding boron-substituted chiral ketones (III) and (V).

The title reaction proceeds in very short reaction times with high chemoselectivity to give the allene in mostly 98% vs.

A broadly applicable method for catalytic enantioselective allylic substitution of easily accessible di- or trisubstituted allylic phosphates and alkenyl-boron reagents, resulting in formation of tertiary C—C bonds, is presented.

The availability of enantiomerically enriched carbonyl-containing compounds is essential to the synthesis of biologically active molecules. Since catalytic enantioselective conjugate addition (ECA) reactions directly generate the latter valuable class of molecules, the design and development of such protocols represents a compelling objective in modern chemistry. Herein, we disclose the first solution to the problem of ECA of alkenyl groups to acyclic trisubstituted enones, an advance achieved by adopting an easily modifiable and fully catalytic approach. The requisite alkenylaluminum reagents are synthesized with exceptional site- and/or stereoselectivity by a Ni-catalyzed hydroalumination process, and the necessary enones are prepared through a site- and stereoselective zirconocene-catalyzed carboalumination/acylation reaction. The all-catalytic procedure is complete within four hours, furnishing the desired products in up to 77 % overall yield and 99:1 enantiomeric ratio.

A broadly applicable Ru-catalyzed protocol for Z-selective ring-opening/cross-metathesis (ROCM) is disclosed. In addition to reactions relating to terminal alkenes of different sizes, the first examples of Z-selective ROCM processes involving heteroaryl olefins, 1,3-dienes, and O- and S-substituted alkenes as well as allylic and homoallylic alcohols are reported. Z-Selective transformations with an α-substituted allylic alcohol are shown to afford congested Z alkenes with high diastereoselectivity. Transformations are performed in the presence of 2.0–5.0 mol % of a recently disclosed Ru-based dithiolate complex that can be easily prepared in a single step from commercially available starting materials. Typically, transformations proceed at ambient temperature and are complete within eight hours; products are obtained in up to 97 % yield, >98:2 Z/E, and >98:2 diastereomeric ratio. The present investigations reveal a mechanistically significant attribute of the Ru-based dithiolates that arises from electrostatic interactions with anionic S-based ligands.

There have been numerous significant advances in catalytic olefin metathesis (OM) during the past two decades. Such progress has transformed this important set of reactions to strategically pivotal processes that generate stereochemical identity while delivering molecules that cannot be easily prepared by alternative routes. In this Perspective, an analysis of the origin of the inception of bidentate benzylidene ligands for Ru-based OM catalysts is first presented. This is followed by an overview of the intellectual basis that culminated in the development of Mo-based diolates and stereogenic-at-Ru complexes for enantioselective OM. The principles accrued from the study of the latter Ru carbenes and Mo alkylidenes and utilized in the design of stereogenic-at-Mo, -W, and -Ru species applicable to enantioselective and Z-selective OM are then discussed. The influence of the recently introduced catalytic OM protocols on the design of synthesis routes leading to complex organic molecules is probed. The impact of a better understanding of the mechanistic nuances of OM toward the discovery of stereoselective catalysts is reviewed as well.

The first synthesis of (±)-tetrapetalone A-Me aglycon is described. Key bond-forming reactions include Nazarov cyclization, a ring-closing metathesis promoted with complete diastereoselectivity by a chiral molybdenum-based complex, tandem conjugate reduction/intramolecular aldol cyclization, and oxidative dearomatization.

A practical catalytic method for enantioselective addition of an allene unit to aldimines is disclosed. Transformations are promoted by an in-situ-generated B-based catalyst that is derived from a simple, robust, and readily accessible (in multigram quantities) chiral aminoalcohol. A range of aryl-, heteroaryl-, and alkyl-substituted homoallenylamides can be obtained in 66–91% yield and 84:16 to >99:1 enantiomeric ratio through reactions performed at ambient temperature and in the presence of 0.1–3.0 mol% of the chiral catalyst and a commercially available allenylboron reagent. The catalytic protocol does not require strict anhydrous conditions, can be performed on gram scale, and promotes highly selective addition of an allenyl unit (vs a propargyl group). The utility of the approach is demonstrated through development of succinct approaches to syntheses of anisomycin and epi-cytoxazone.

Investigations detailed herein provide insight regarding the mechanism of stereochemical inversion of stereogenic-at-Ru carbene complexes through a nonolefin metathesis-based polytopal rearrangement pathway. Computational analyses (DFT) reveal that there are two key factors that generate sufficient energy barriers that are responsible for the possibility of isolation and characterization of high-energy, but kinetically stable, intermediates: (1) donor-donor interactions that involve the anionic ligands and the strongly electron donating carbene groups and (2) dipolar effects arising from the syn relationship between the anionic groups (iodide and phenoxide). We demonstrate that a Brønsted acid lowers barriers to facilitate isomerization, and that the positive influence of a proton source is the result of its ability to diminish the repulsive electronic interactions originating from the anionic ligands. The implications of the present studies regarding a more sophisticated knowledge of the role of anionic units on the efficiency of Ru-catalyzed olefin metathesis reactions are discussed. The electronic basis for the increased facility with which allylic alcohols participate in olefin metathesis processes will be presented as well. Finally, we illustrate how a better understanding of the role of anionic ligands has served as the basis for successful design of Ru-based Z-selective catalysts for alkene metathesis.

Optically pure (R)-5,5‘,6,6‘,7,7‘,8,8‘-octahydro-1,1‘-bi-2-naphthol was derivatized with mesityl and benzhydryl groups in the 3 and 3‘ positions to give R-H2Mes2Bitet and R-H2Benz2Bitet, respectively. Addition of R-K2Benz2Bitet to Mo(NAr)(CHCMe2Ph)(OTf)2(dme) yielded Mo(NAr)(CHCMe2Ph)(R-Benz2Bitet)(THF) (7), while addition of R-K2Mes2Bitet to Mo(NAr)(CHCMe2Ph)(OTf)2(dme) in THF gave Mo(NAr)(CHCMe2Ph)(R-Mes2Bitet)(THF) (8). Four complexes that contained the 2,6-dichlorophenylimido ligand were prepared by similar procedures, namely, Mo(NArCl)(CHCMe3)(S-Biphen)(THF) (9), Mo(NArCl)(CHCMe3)(R-Trip2BINO)(THF) (10), Mo(NArCl)(CHCMe3)(R-Mes2Bitet)(THF) (11), and Mo(NArCl)(CHCMe3)(R-Benz2Bitet)(THF) (12). X-ray studies of 8, 9, and 12 revealed them to be typical distorted trigonal bipyramids with THF and one biphenolate oxygen occupying axial positions. In 9 and 12 the alkylidene orientation was found to be syn, while in 8 the alkylidene orientation was found to be anti. Catalysts 7, 8, 9, 10, 11, and 12 were all ...

Enantiomerically pure molybdenum imido alkylidene complexes were prepared that contain binaphtholate ligands substituted in the 3 and 3‘ positions with either phenyl (4; Mo(NAr)(CHCMe2Ph)[Ph](THF)) or 2,4,6-trimethylphenyl groups (5; Mo(NAr)(CHCMe2Ph)[Mes](THF); Ar = 2,6-i-Pr2C6H3). Compound 5 was found to be an anti trigonal bipyramidal complex in an X-ray study. Asymmetric metatheses employing complex 5 were found to proceed to high conversion and to give high product % ee, while reactions that employed complex 4 were found to give lower conversion and lower % ee. One ring-closing reaction with 5 was shown to take place at a rate that was proportional to catalyst and substrate. Molybdacyclobutane complexes were observed in solution during ring-closing reactions. The molybdacyclobutane complex generated by treating 5 with ethylene was found to be a trigonal bipyramidal species which decomposed to yield some propylene; the metal-containing product or products of decomposition could not be identified. Moly...

Glass-bound Ru-based catalysts! Ru-containing glass pellets efficiently promote olefin metathesis reactions and are easily employed in syntheses of compound libraries. These robust catalysts are active in air and commercially available solvents, can be recycled up to 16 times, and removed from reaction mixtures with a simple pair of tweezers (minimal solvent waste).

Kinetic, structural, and stereochemical data regarding the mechanism of Ti-catalyzed addition of cyanide to imines in the presence of Schiff base peptide ligands are disclosed. The reaction is first order in the Ti-ligand complex; kinetic studies reveal DeltaS(dagger) = -45.6 +/- 4.1 cal K(-1) mol(-1), indicating a highly organized transition structure for the turnover-limiting step of the catalytic cycle. A mechanistic model consistent with the kinetic and stereochemical data is presented, where the Ti center is coordinated to the Schiff base unit of the ligand and the AA2 moiety of the peptidic segment of the chiral ligand associates and delivers HNC to the activated bound substrate. Thus, these studies illustrate that these non-C2-symmetric catalysts likely operate in a bifunctional fashion.

Two new biphenolate ligands were prepared starting from 3,3‘-di-tert-butyl-5,5‘,6,6‘-tetramethyl-2,2‘-dimethoxy-1,1‘-biphenyl via deprotonation of the 6 and 6‘ methyl group with KO-t-Bu/n-BuLi, reaction with dichlorodimethylsilane or chlorotrimethylsilane, and deprotection with boron tribromide. Molybdenum imido alkylidene complexes were prepared by treating Mo(NAr)(CHCMe2Ph)(OTf)2(DME) with the dipotassium salt of each biphenolate. X-ray crystallographic studies of syn-Mo(NAr)(CHCMe2Ph)[(rac)-Me2SiBiphen] and syn-Mo(NAr)(CHCMe2Ph)[(rac)-TMS2Biphen] revealed a significantly different geometry of the biphenolate ligands compared to previously structurally characterized four-coordinate biphenolate molybdenum imido alkylidene complexes. The enantiopure complexes were shown to catalyze asymmetric olefin metathesis with an enantioselectivity comparable to that of Mo(NAr)(CHCMe2Ph)[(S)-Biphen].

A cross-metathesis reaction was achieved between acid- and base-sensitive functionalized olefins and electron-deficient olefins or allylsilane by using the recyclable ruthenium catalyst V at room temperature. The cross-metathesis products are isolated in moderate to good yield. Ratios of E and Z cross-metathesis products depend upon substituents on the electron-deficient coupling partner.

[reaction: see structure] The first examples of efficient electrophilic Zr-catalyzed carbomagnesations are disclosed, where in contrast to previous catalytic carbomagnesations the alkyl moiety of the electrophile is transferred (vs that of the Grignard reagent). The identity of the Grignard reagent is manipulated so that Zr-Mg exchange is facilitated, leading to the formation of alkylmagnesium halide products.

No glove box required! A new chiral catalyst for olefin metathesis is prepared from commercially available materials and is equally or more effective and selective than the previous systems. The new user-friendly catalyst can be prepared in situ (see scheme, Ar=aryl, Tf=trifluoromethanesulfonyl), isolation not needed, outside of a glove box, and delivers reactivity and enantioselectivity levels formerly available only through multiple catalysts.

Highest enantioselectivities so far with dialkylzinc reagents! Quaternary carbon centers are formed enantioselectively through a Cu-catalyzed allylic substitution reaction that is promoted by pyridinyl peptide-based ligands in the presence of dialkylzinc reagents. The modularity of this new class of chiral ligands is exploited for reactivity and selectivity optimization.

This describes the synthesis of several Ru catalysts which can be used for ROCM (see scheme) and ROMP reactions.

Citation Mann, Tyler J., Alexander W. H. Speed, Richard R. Schrock, and Amir H. Hoveyda. “Catalytic Z-Selective Cross-Metathesis with Secondary Silyland Benzyl-Protected Allylic Ethers: Mechanistic Aspects and Applications to Natural Product Synthesis.” Angewandte Chemie International Edition 52, no. 32 (August 5, 2013): 8395-8400. As Published http://dx.doi.org/10.1002/anie.201302538 Publisher Wiley Blackwell

The title reaction allows a new, efficient, and widely applicable method to prepare ketones bearing an all-carbon quaternary stereogenic center at β position.

Chiral Mo-based complexes 1 – 3 promote the catalytic enantioselective ring-closing metathesis of various polyenes to afford unsaturated furans, pyrans and siloxanes efficiently and in high ee (70–98% ee). The structural modularity of this class of chiral catalysts plays a critical role in these studies. Modification of the diolate or imido moities of these chiral catalysts gives rise to a range of complexes that can be screened for higher reactivity and/or enantioselectivity.

Two 3,3‘-dialkyl-5,5‘,6,6‘-tetramethyl-1,1‘-biphenyl-2,2‘-diols (where alkyl = t-Bu, adamantyl) were prepared in two steps and resolved as the menthol phosphate derivative. Addition of the dipotassium salt of each biphenolate to various Mo(N-Aryl)(CHR)(OTf)2(DME) complexes produced racemic and enantiopure compounds of the type Mo(N-aryl)(CHR)(biphenolate). X-ray crystallographic studies of syn-Mo(N-2,6-i-Pr2C6H3)(CHCMe2Ph)[(S)-Biphen] and syn-Mo(N-2-CF3C6H4)(CHCMe3)[(S)-Biad](pyridine) proved the absolute stereochemistry of the biphenolate ligands. Neophylidene and neopentylidene complexes were found to have predominantly the syn conformation in solution. The [syn]/[anti] equilibrium constant for Mo(N-Aryl)(CHR)[Biphen] complexes increased in magnitude with decreasing size of the arylimido ligand, and decreased upon reducing the steric bulk of the alkylidene substituent. The rates of exchange of syn and anti isomers, as determined by single-parameter line shape analysis and by spin saturation transfer, we...

Several highly active, recoverable and recyclable Ru-based metathesis catalysts are presented. The crystal structure of Ru complex 5, bearing a 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene and styrenyl ether ligand is disclosed. The heterocyclic ligand significantly enhances the catalytic activity, and the styrenyl ether allows for the easy recovery of the Ru complex. Catalyst 5 promotes ring-closing metathesis (RCM) and the efficient formation of various trisubstituted olefins at ambient temperature in high yield within 2 h; the catalyst is obtained in >95% yield after silica gel chromatography and can be used directly in subsequent reactions. Tetrasubstituted olefins can also be synthesized by RCM reactions catalyzed by 5. In addition, the synthesis and catalytic activities of two dendritic and recyclable Ru-based complexes are disclosed (32 and 33). Examples involving catalytic ring-closing, ring-opening, and cross metatheses are presented where, unlike monomer 5, dendritic 33 can be readily recovered.

Disubstituted aryl olefins undergo efficient alkylations in the presence of 5 mol % Cp2ZrCl2, n-BuMgCl, and alkyl tosylates or alkyl bromides. In one class of reactions (Table 1), the resulting alkyl zirconocene (initial alkylation product) undergoes β-hydride abstraction with a hydrogen atom from within the substrate to afford allylic alkylation products (Scheme 5). In another category of reactions, where cyclic allylic ethers (chromenes) are used (Table 2), Zr-alkoxide elimination occurs after the C−C bond formation to effect a net allylic substitution. It is proposed that these reactions involve the nucleophilic attack of substrate-derived zirconates or zirconocene−Grignard reagents on various tosylates and bromides. There is little or no competitive electrophile alkylation by the n-alkyl Grignard reagent. Several mechanistic and synthetic aspects of these Zr-catalyzed C−C bond forming reactions are examined and discussed.

Addition of the dipotassium salt of 2,2‘-bis-p-tolylsulfonamido-1,1‘-binaphthyl (K2[BINA(NTs)2]) to Mo(NAr)(CHCMe2Ph)(OTf)2(dme) (Ar = 2,6-i-Pr2C6H3; OTf = OSO2CF3), Mo(N-2-CF3C6H4)(CHCMe2Ph)(OTf)2(dme), and Mo(N-2-CF3C6H4)(CH-t-Bu)(OTf)2(dme) gave Mo(NAr)(CHCMe2Ph)[BINA(NTs)2] (1a), Mo(N-2-CF3C6H4)(CHCMe2Ph)[BINA(NTs)2] (1b), and Mo(N-2-CF3C6H4)(CH-t-Bu)[BINA(NTs)2] (1c), respectively. The X-ray crystal structure of 1c showed that one sulfonyl oxygen is coordinated to the molybdenum. Related complexes, Mo(NAr)(CHCMe2Ph)[BINA(N−i-Pr)2] (2) and Mo(NAr)(CHCMe2Ph)[BINA(NTMS)2] (3), were prepared similarly. The pseudotetrahedral nature of 2 was confirmed in an X-ray study. None of these complexes reacts readily with ethylene, styrene, benzaldehyde, or diallyl ether.

The Zr-catalyzed kinetic resolution of aliphatic allylic ethers derived from five-, six-, seven-, and eight-membered ring allylic alcohols is reported. The level of resolution efficiency varies as a function of ring size and substitution pattern of the pendant alkene. The metal-catalyzed transformation of the above unsaturated ethers to dihydrofurans is also disclosed. Seven- and eight-membered ring substrates are readily converted to furans in the presence of 10 mol % Ru catalyst 16. In contrast, the less reactive cyclopentenol systems demand the more potent Mo-based metathesis catalyst 3. The selectivity and reactivity patterns in the Zr-catalyzed process and the Ru- or Mo-catalyzed reactions differ from the previously reported reactions of the related styrenyl ethers.

A new class of chiral Mo-based complexes 2a and 2b, bearing functionalized chiral binol ligands, is disclosed. Mo complex 2a promotes the asymmetric ring-closing metathesis (ARCM) of various dienes and trienes to afford six-membered carbo- and heterocycles efficiently and in high optical purity. The binol-based chiral Mo catalysts complement the previously reported biphen-based complexes, which are particularly effective in the enantioselective synthesis of five-membered rings by ARCM. Studies regarding catalytic kinetic resolutions and asymmetric desymmetrizations are described. It is possible to obtain optically pure products in high yield from catalytic reactions without the use of solvent (cf. eq 1). The structural attributes of these complexes are detailed on the basis of the data available from an X-ray structure and variable-temperature 1H NMR studies. The results of this investigation indicate the following: (i) The anti-Mo·THF complex exists as a mixture of diastereomers, whereas the syn isomer ...

There have been recent attempts to use the principles of combinatorial chemistry and high-throughput screening strategies for catalyst identification. With the technology available that allows the synthesis of large libraries, scientists of varied backgrounds have implemented screening efforts to identify active and selective catalysts. Within this context, several techniques have come to light in the past year: infrared thermography is used to identify optimal catalysts by monitoring the change in temperature for exothermic reactions; fluorescence and colored-dye assays, a familiar tool to biologists, is being applied to the identification of catalysts that exhibit the highest activity. Whereas none of these screening methods provide a general solution to the problem of screening large combinatorial libraries (there is likely to be no general solution), each advance represents an important intellectual and technological step forward.

A Ru carbene (8, Scheme 2) that contains an internal metal−oxygen chelate is an active metathesis catalyst and is readily obtained by the sequential treatment of Cl2Ru(PPh3)3 with (2-isopropoxyphenyl)diazomethane and PCy3. This Ru-carbene complex offers excellent stability to air and moisture and can be recycled in high yield by silica gel column chromatography. The structures of this and related complexes have been unambiguously established by NMR and single-crystal X-ray diffraction studies.

Are there more efficient ways to discover new catalysts? Classical efforts, while very successful, have been typically quite linear in design. In contrast, early efforts using diversity-based techniques such as parallel synthesis and screening (right) to rapidly identify and optimize new catalysts are beginning to yield some promising results.

Abstract: A large variety of metal-based chiral complexes have been developed in the past twenty five years that allow for the effective catalytic resolution of an impressive range of racemic compounds. After the initial discovery of Ti-catalyzed kinetic resolution of allylic alcohols by Sharpless and coworkers in the early eighties, a number of other transformations have emerged that may be used for catalytic resolution. Amongst them are the Ru-catalyzed hydrogenation, the Zr-catalyzed carbomagnesation, the Mn-catalyzed epoxidation, the Co-catalyzed epoxide hydrolysis, and the Ti-catalyzed reduction of C=N and C=0 bonds. Most recently, the Mo-catalyzed ring-closing metathesis has been utilized to catalytically resolve organic molecules in an efficient manner. This article provides a brief overview of these and other major developments in metal-catalyzed kinetic resolution; strengths and weaknesses of various methods are discussed, and different protocols that afford identical or similar optically pure or enriched compounds are compared. Where possible, the available mechanistic paradigms that affords a rationale as to the observed stereochemical outcomes are provided.

The first enantioselective total synthesis of the antihypertensive agent (S,R,R,R)-nebivolol (3) is described. The synthesis includes the efficient (EBTHI)Zr-catalyzed kinetic resolutions of cycloheptenyl styrenyl ethers 8 and 16, which are subsequently treated with 4 mol % Mo(CHCMe2Ph)(N(2,6-(i-Pr)2C6H3))(OCMe(CF3)2)2 to afford chiral nonracemic 2-substituted chromenes (R,R)-9 and (S,R)-17. Since the present retrosynthetic analysis dissects the molecule into two chromene fragments, both the (R) and (S) antipodes of (EBTHI)Zr catalyst are required. Accordingly, Buchwald's efficient resolution process is used to resolve rac-(EBTHI)ZrCl2 (from catalytic hydrogenation of commercially available rac-(EBI)ZrCl2), such that the two requisite transition metal chiral catalysts are obtained by a single process. Other noteworthy features of the synthesis include a highly efficient, regio- and stereoselective Pd-catalyzed opening of cyclic allylic epoxide 7 with diaryloxystannane 15 and a photochemical modification o...

Combinatorial chemistry and high-throughput strategies can be used to identify effective small-molecule chiral catalysts. Infrared thermography has been used recently as the means to identify the most active catalyst.

An efficient metal-catalyzed process that converts styrenyl ethers to 2-substituted chromenes is described. This class of reactions may be carried out on either terminal or disubstituted styrenyl substrates. Depending on the level of substitution of the olefins, the Ru−carbene catalyst may initiate reaction either by interaction with the styrenyl or the carbocyclic alkene. Metal-catalyzed rearrangements, carried out under an atmosphere of ethylene, afford excellent yields of monomeric products. With disubstituted styrene ethers, the presence of ethylene is also critical to reaction efficiency. Mechanistic data that rationalize these observations are provided. Although Ru complexes (PCy3)2Cl2RuCHCHCPh2 or (PCy3)2Cl2RuCHPh effectively serve as catalysts, with the more functionalized substrates, higher yields are obtained when Mo(CHCMe2Ph)(N(2,6-(i-Pr)2C6H3))(OCMe(CF3)2)2 is used. A variety of starting materials for the metal-catalyzed chromene synthesis (disubstituted styrenes) are available in the opticall...

Studies on the directed regio- and stereoselective Ni-catalyzed allylic substitution reactions involving methyl- and phenylmagnesium bromides and various acyclic and cyclic allylic ethers are reported. In the presence of a properly positioned internal Lewis base, CC bonds can be formed catalytically and with excellent levels of selectivity. Internal chelation allows Ni-catalyzed CC bond forming reactions that are otherwise non-selective, sluggish, or do not occur at all, to proceed to completion readily, in excellent yields, at ambient temperature and with high regio- and stereocontrol. Directed alkene isomerization highlights an especially attractive feature of the metal-catalyzed alkylation strategy: because the initial product contains a prostereogenic site that remains within reach of the internal Lewis base, it can be subjected to additional directed stereoselective manipulations.

A concise and stereoselective route for the synthesis of the carbohydrate moiety of the antifungal agent Sch 38516 is described. The synthesis scheme includes a dipolar cycloaddition, which is rendered diastereoselective through the use of a readily available and easily removable chiral auxiliary.

The first enantioselective total synthesis of antifungal agent Sch 38516, also known as fluvirucin B1, is described. The synthesis includes a convergent asymmetric preparation of amine 17 and acid 18, which are then united to afford diene 62. Metal-catalyzed transformations play a crucial role in the synthesis of the latter moiety. Of particular note are the diastereo- and enantioselective Zr-catalyzed alkylations, a tandem Ti- and Ni-catalyzed process that constitutes a hydrovinylation reaction, and a Ru-catalyzed alcohol oxidation to afford carboxylic acid 18. The requisite carbohydrate 38 is synthesized in a highly diastereo- and enantioselective fashion. Optical purity of the carbohydrate moiety arises from the use of the asymmetric dihydroxylation method of Sharpless; diastereochemical control is achieved through a selective dipolar [3 + 2] cycloaddition with a readily available amine serving as the chiral auxiliary. Union of the appropriately outfitted carbohydrate 71 and diene 62 through an efficie...