Epoxidation, Cyclopropanation, and Electrophilic Addition Reactions

Organometallics 2010, 29, 4793–4803 DOI: 10.1021/om901017d

4793

Epoxidation, Cyclopropanation, and Electrophilic Addition Reactions at the meta Position of Phenol and meta-Cresol§ Victor E. Zottig,† Michael A. Todd,† Adam C. Nichols-Nielander,† Daniel P. Harrison,† Michal Sabat,† William H. Myers,‡ and W. Dean Harman*,† †

Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904, and ‡Department of Chemistry, University of Richmond, Richmond, Virginia 23173 Received November 24, 2009 Scheme 1

Introduction In solution, phenol exists as an equilibrium mixture of three tautomers. While the enolic form normally dominates, complexation of the C2 and C3 carbons to {Os(NH3)5}2þ enhances the equilibrium population of the 2H and 4H isomers to the point that the three tautomers are virtually isoergic.1 When the Os(II) complex is replaced with the more π-basic complex {TpW(NO)(PMe3)}, the 2H-phenol species becomes dominant.2

Phenols are well known to undergo reactions with electrophiles regioselectively at the ortho and para positions. For example, while there are numerous ways to prepare catechol and p-dihydroquinone from phenol,3,4 no direct methods exist to oxidize phenol to resorcinol, and the bromination of phenol results in either o- or p-bromophenol or polybrominated products.3,5,6 We sought to determine whether it would be possible to direct electrophiles to a meta position of phenol by effectively locking it in its 2H-tautomeric form with tungsten (Scheme 1). Previous studies with osmium and molybdenum complexes have determined that 1,2-η2-1,3dienes react with electrophiles at the uncoordinated terminal alkene carbon (i.e., C4), and provided that the influence of the metal was stronger than that of the cross-conjugated carbonyl, it would be possible to effect electrophilic addition to the uncoordinated meta carbon of a 2H-phenol (Scheme 1). From this point, decomplexation and proton loss could lead to a 3-substituted phenol, or alternatively,

nucleophilic addition to the resulting allyl could lead to 3,4disubstituted enones.7

Results and Discussion The phenol complex 1 can be prepared from phenol and TpW(NO)(PMe3)(η2-benzene)8 as a mixture of two diastereomers (Scheme 2). The addition of base catalyzes the interconversion of these two forms, and one (oxygen distal to the phosphine) was found to selectively precipitate from solution. Using this procedure, a 2:1 mixture of diastereomers was converted to pure 1 in 81% yield (3-6 g scale).9 In a similar manner, the meta-cresol analogue 2 was prepared in 74% yield (3 g scale). Attempts to generate the ortho-cresol analogue were unsuccessful, but para-cresol was successfully coordinated.10

Part of the Dietmar Seyferth Festschrift. *Corresponding author. E-mail: [email protected]. (1) Kopach, M. E.; Harman, W. D.; Hipple, W. G. J. Am. Chem. Soc. 1992, 114, 1737. (2) Todd, M. A.; Grachan, M. L.; Sabat, M.; Myers, W. H.; Harman, W. D. Organometallics 2006, 25, 3948. (3) Preethi, M. E. L.; Revathi, S.; Sivakumar, T.; Manikandan, D.; Divakar, D.; Rupa, A. V.; Palanichami, M. Catal. Lett. 2008, 120, 56. (4) Behrman, E. J. Org. React. 1988, 35. (5) Venkateswarlu, K.; Suneel, K.; Das, B.; Reddy, K. N.; Reddy, T. S. Synth. Commun. 2009, 39, 215. (6) Adams, R.; Marvel, C. S. Org. Synth. 1921, 1. (7) Todd, M. A.; Sabat, M.; Myers, W. H.; Smith, T. M.; Harman, W. D. J. Am. Chem. Soc. 2008, 130, 6906.

(8) Welch, K. D.; Harrison, D. P.; Lis, E. C.; Liu, W.; Salomon, R. J.; Harman, W. D.; Myers, W. H. Organometallics 2007, 26, 2791. (9) Todd, M. A.; Sabat, M.; Myers, W.; Harman, W. D. J . Am. Chem. Soc. 2007, 129, 11010. (10) Limited attempts to carry out reactions with the para-cresol analogue, similar to those reported herein for 1 or 2, were unsuccessful.

r 2010 American Chemical Society

Published on Web 03/31/2010

§

pubs.acs.org/Organometallics

4794

Organometallics, Vol. 29, No. 21, 2010 Scheme 2

Zottig et al. Scheme 4

Scheme 3 Scheme 5

The 2H-phenol complex 1 is expected to have two nucleophilic sites on the organic ligand (O and C3), and its corresponding reaction with triflic acid resulted in the formation of two new products. One (O-1H) resembled the starting material but with many of its 1H NMR resonances shifted significantly downfield compared to its predecessor. Multiplets at 3.20 and 4.18 ppm were reminiscent of the H6 and H3 protons for the analogous TpW(NO)(PMe3)(5,6-η22H-anisolium) complex.11 Meanwhile, the minor product (11) Keane, J. M.; Chordia, M. D.; Mocella, C. J.; Sabat, M.; Trindle, C. O.; Harman, W. D. J. Am. Chem. Soc. 2004, 126, 6806.

(C-1H) showed signals at 4.40 (d), 5.96 (t), and ∼6.3 ppm, similar to that observed for allylic protons of other π-allyl complexes of {TpW(NO)(PMe3)}.12 Unfortunately, these complexes have limited thermal stability and could not be equilibrated, separated, or fully characterized before their decomposition. However, one of the decomposition products (3) was ultimately identified as that resulting from PMe3 addition to C4 of the purported complex C-1H (Scheme 3). Compound 3 could ultimately be prepared in good yield from the direct reaction of 1 and [HPMe3]OTf, and a single crystal obtained from this reaction mixture ultimately led to the confirmation of its molecular structure. In an analogous manner, thiophenol could be added across C3 and C4 of the phenol complex 1 to generate 4, provided that the product was isolated as its conjugate acid (4H). Complex 4H has two diastereotopic methylene groups and a broad singlet at 4.17 ppm identified as H4. While this (12) Lis, E. C.; Delafuente, D. A.; Lin, Y.; Mocella, C. J.; Todd, M. A.; Liu, W.; Sabat, M.; Myers, W. H.; Harman, W. D. Organometallics 2006, 25, 5051.

Article

Organometallics, Vol. 29, No. 21, 2010

4795

Figure 1. Molecular structures of disubstituted cyclohexenone complexes 7, 10, and 11.

reaction goes to completion according to a 31P NMR spectrum of the reaction mixture (CH2Cl2), when the product 4H was isolated and returned to solution, significant amounts of O-1H (∼40%) and free thiophenol were formed, indicating that the addition of thiophenol to the protonated phenol complex was reversible. A similar set of experiments indicated that the addition of HPPh3þ to 1 was possible (in situ combination of 1, PPh3, and diphenylammonium triflate (DPhAT)), but that this addition product too was highly susceptible to elimination of HPPh3þ, and these complexes were not further pursued. The reactivity of phenol complex 1 with electrophilic halogen sources was similar to that with Brønsted acids. For example, a solution of [PPh3Me]Br was treated with phenyliodobis(trifluoroacetate) (PIFA) at -40 ( 2 °C to generate a source of “Brþ” in situ. This mixture was then added to a solution of 1 and followed by the addition of methanol. The product 6, a brominated methoxycyclohexenone, was isolated in 74% yield.7 When a similar reaction sequence was carried out with Selectfluor, a mild “Fþ” source, and methanol, the fluorinated methoxycyclohexenone complex 5 was produced (79%).7 Coupling data (e.g., JCF = 174 Hz; HMBC, HSQC) for 5 indicated that the electrophilic reagent adds to the C3 position of the phenol ring, and NOE and COSY data confirmed a syn relationship between the halogen and the methoxy group. Whereas the bromo analogue 6 rapidly decomposed when subjected to trace amounts of water, the fluorinated congener 5 was found to be stable to both water and air. Significantly, the phenol complex 1 and the meta-cresol analogue 2 undergo reactions with 3-chloroperbenzoic acid (mCPBA) followed by the addition of various nucleophiles to form δ-hydroxyenone complexes (7-12) in yields ranging from 67% to 83%. Spectroscopic and crystallographic data indicate that in every case the N, O, or S nucleophile adds to C4 syn to the hydroxy group at C5. The presence of a methyl group at C3 in the meta-cresol cases does not appear to interfere with either the regio- or the stereochemistry of the addition sequence.

Suspecting that the reaction of 1 or 2 with mCPBA and a nucleophile to generate the hydroxyenone complexes 7-12 occurs by way of an epoxide intermediate, we endeavored to find reaction conditions suitable to isolate this purported intermediate. Unfortunately, all attempts to recover an epoxide from 1 and mCPBA failed. Alternative approaches to epoxide formation were explored with 1 including DMDO, Shi’s protocol, Davis’s oxaziridine, and Jacobsen’s conditions, but all were found to be ineffective. However, expanding the search to reactions with the meta-cresol complex (2) brought success with the preparation of 15 in 91% yield (3 g) using DMDO (generated in situ) as the oxidant. Also, 15 could be prepared from the Shi protocol or mCPBA, but in more modest yields. Spectroscopic features for the epoxide 15 are generally similar to other enone complexes (e.g., 11, 12); however, H6 of the epoxide is significantly shifted upfield (3.39 ppm) compared to the corresponding proton of diol 11 (H4, 4.68 ppm). In addition, C6 and C1 are shifted upfield by >10 ppm (13C NMR) for the epoxide (cf. C4, C5 of 11). In a similar reaction to the epoxide formation, both the phenol (1) and the meta-cresol (2) complexes were found to react with CH2I2 in a Simmons-Smith reaction to form the oxonorcarene complexes 13 and 14. Single crystals were obtained of the methyl analogue (14), and its molecular structure was successfully determined by X-ray diffraction (Figure 2). With a conjugated epoxide complex in hand, we set out to explore the effect the metal has on the opening of the epoxide ring. While vinyl epoxides readily undergo palladium-catalyzed reactions with nucleophiles (vide infra),13-15 well-characterized examples of transition metal complexes of vinyl epoxides are all but unknown.16 Treating the epoxide with (13) Trost, B. M.; Sudhakar, A. R. J. Am. Chem. Soc. 1988, 110, 7933. (14) Trost, B. M.; Molander, G. A. J. Am. Chem. Soc. 1981, 103, 5969. (15) Trost, B. M.; Sudhakar, A. R. J. Am. Chem. Soc. 1987, 109, 3792. (16) Franck-Neumann, M.; Gateau, C.; Miesch-Gross, L. Tetrahedron Lett. 1997, 38, 8077.

4796


Zottig et al. Scheme 7

Figure 2. ORTEP diagram for oxonorcarene complex 14. Scheme 6

Scheme 8

water and trace acid cleanly generates the cis-diol 11, the same species generated directly from mCPBA and 2. When epoxide 15 is combined with aniline, or indoline, cis-amino alcohols 16 and 17 are formed, respectively. These reactions were found to be dramatically catalyzed by the addition of the Brønsted acid DPhAT. In contrast, when the epoxide is treated with 5 equiv of morpholine (0.7 M), a new complex, 18, gradually forms over a period of several hours with spectroscopic features that differed somewhat from expectation. In particular, a methine resonance (HSQC) at 6.04 ppm and a downfield-shifted methyl group (2.07 ppm) signaled the presence of an additional CdC bond. A complete spectroscopic analysis (HSQC, HMBC, COSY) reveals that the product 18 (81%) is the result of addition of morpholine and the elimination of water to give a 4H-phenol complex (Scheme 7). A similar result occurs when epoxide 15 is treated with other amine bases.17 For example, the reaction of benzylamine and 15 generates complex 19 in 79% yield. At first, we expected that such a product resulted from the addition of the amine to C4 followed by an E1cb-type dehydration (Scheme 8, path I). However, repeated attempts to stop the reaction prior to elimination were unsuccessful, regardless of the number of equivalents of amine, temperature of the (17) Other amines that successfully add are piperidine, allylamine, heptylamine, and furfurylamine.

reaction, or presence of a Brønsted acid. Furthermore, when the amino alcohol 17 derived from aniline and epoxide 15 was combined with an excess of morpholine or KHMDS no elimination occurred. These observations led us to propose an alternative reaction mechanism in which the elimination happened prior to the addition at C4 (Scheme 8, path II). Consistent with this proposal, when the epoxide is treated with the base KHMDS in the absence of suitable nucleophile, elimination occurs to generate the 4-hydroxy-4H-phenol complex 20 in good yield. When 20 was then treated with morpholine, the appearance of 18 was observed after 1 h (complete conversion by 20 h). From a synthetic standpoint, the reactions outlined in Scheme 7 are noteworthy in several aspects. They represent an epoxide undergoing an SN1-type ring-opening, but with the nucleophile adding to the less substituted carbon, and syn to the oxygen leaving group, in both aspects the opposite of what is typically observed in organic chemistry. In the presence of palladium, vinyl epoxides normally undergo reaction with amines to form 1,4-amino alcohols.14 However, in an elegant report by Trost et al. a vinyl epoxide was incorporated in the synthesis of several oxazolidinones using isocyanates.13 In that study, the stereochemistries of the resulting heterocycles were found to be largely independent of the stereochemistries of the epoxide precursors, and a mechanism passing though a palladium π-allyl intermediate

Article


4797

Scheme 9

Figure 3. POV-ray diagram of complex 22.

was invoked, not unlike that presented in Scheme 8. Taking a cue from the Trost report, we combined epoxide 15 with tosyl isocyanate. Following precedent, the bicyclic oxazolidinone complex 21 was formed in good yield (Scheme 9). COSY, NOESY, and X-ray data confirm that the bicyclic ligand in 21 has a cis ring fusion. In a similar reaction, when the phenol complex 1 was combined with mCPBA followed by the lithium enolate of dimethyl malonate (prepared in situ), the bicyclic lactone 22 was formed in 50% yield. The other primary reaction manifold for η2-phenol complexes is electrophilic addition at C4. In particular, earlier reports with pentaammineosmium(II) indicated a rich reactivity with Michael acceptors adding to the ortho or para position of several phenols, including estradiol. The present tungsten system also demonstrates such reactivity, but in order to access the phenolic form required for ortho/para addition of electrophiles, base must be added.2 Thus, addition of base to 1 shifts the site of electrophilic addition from C3 to C4/C2.

There are numerous examples of hexahapto-coordinated phenols with metal fragments including {IrCp*}2þ,18 {Ir(H)2(PR3)}þ,19 {RuCp*}þ,20,21 {FeCp}þ,22 {Mn(CO)3}þ,23,24 (18) White, C.; Thompson, S. J.; Maitlis, P. M. J. Organomet. Chem. 1977, 127, 415. (19) Torres, F.; Sola, E.; Martin, M.; Ochs, C.; Picazo, G.; Lopez, J. A.; Lahoz, F. J.; Oro, L. A. Organometallics 2001, 20, 2716. (20) Chaudret, B.; He, X.; Huang, Y. J. Chem. Soc., Chem. Commun. 1989, 1844. (21) Koelle, U.; Wang, M. H.; Raabe, G. Organometallics 1991, 10, 2573. (22) Helling, J. F.; Hendrickson, W. A. J. Organomet. Chem. 1979, 168, 87. (23) Lee, S.-G.; Kim, J.-A.; K, C. Y.; Yoon, T.-S.; Kim, N.-J.; Shin, W. Organometallics 1995, 14, 1023. (24) Seo, H.; Lee, S.-G.; Mok, D.; Hong, B. K.; Hwang, S.; Chung, D. S.; Chung, Y. K. Organometallics 2002, 21, 3417. (25) Heppert, J. A.; Boyle, T. J.; Takusagawa, F. Organometallics 1989, 8, 461. (26) Zhao, Z.; Messinger, J.; Schon, U.; Wartchow, R.; Butenschon, H. Chem. Commun. 2006, 3007. (27) Li, Z.; Harman, W. D.; Lay, P. A.; Taube, H. Inorg. Chem. 1994, 33, 3635.

{Cr(CO)3},25,26 and {Os(NH3)3}2þ.27 Upon coordination to an electron-deficient metal fragment, such as Cr(CO)3, arenes, including phenol, are activated toward nucleophilic addition by virtue of the electron-withdrawing power of the metal fragment.28 The addition of basic nucleophiles (e.g., MeMgBr) to η6-phenol complexes of {Mn(CO)3}þ, {FeCp}þ, and {Cr(CO)3}, however, results in the deprotonation of the hydroxyl group, producing a change in hapticity from hexato pentahapto, along with a formal reduction of the metal center.22-25,29,30 Thus, the chemistry of η6-phenol complexes is dominated by an η5-oxocyclohexadienyl intermediate. Many of these complexes exhibit similar reactivity to uncoordinated phenol and react with electrophiles at oxygen.25,26,29 Several systems, however, show reactivity beyond oxygen alkylation. For example, the addition of nucleophiles to (η5-C6H5O)Mn(CO)3 results in C2 addition to form a metalstabilized phenolate complex.23,24 The only known η4-phenol complex appears to be Fe(CO)3(η4-C6H6O).31-35 The phenol ligand is isolated as the 2,4-cyclohexadienone tautomer. These complexes react readily with strong nucleophiles, such as phenyl lithium, and are subsequently quenched with an electrophile. The addition of the nucleophile occurs at the ipso carbon, anti to the metal fragment. Acid facilitates the elimination of the oxygen-containing group to complete the substitution.31 Alternatively, the electrophile can be added first, to generate the pentahapto complex. Nucleophilic addition can then occur at the ipso carbon, to generate the same complex as discussed above.32-35 In a few cases direct addition of the nucleophile to the meta position was observed, where the addition occurred anti to the iron fragment.33,36 It appears that no other transition metal complex derived from phenol lends itself to electrophilic addition to the meta position of phenol or nucleophilic addition to the para position of a phenol ring. However, phenolic oxidations at C4 have been (28) Suresh, C. H.; Koga, N.; Gadre, S. R. Organometallics 2000, 19, 3008. (29) Holden, M. S.; Brosius, A. D.; Hilfiker, M. A.; Humbert, E. J. Tetrahedron Lett. 2000, 41, 6275. (30) Bhasin, K. K.; Balkeen, W. G.; Pauson, P. L. J. Organomet. Chem. 1981, 204, C25. (31) Cowles, R. J. H.; Johnson, B. F. G.; Lewis, J.; Parkins, A. W. J. Chem. Soc., Dalton Trans. 1972, 1768. (32) Owen, D. A.; Stephenson, G. R. Tetrahedron Lett. 1990, 31, 3401. (33) Stephenson, G. R.; Howard, P. W.; Owen, D. A.; Whitehead, A. J. J. Chem. Soc., Chem. Commun. 1991, 641. (34) Iwakoshi, M.; Ban, S. H.; Hayashi, Y.; Narasaka, K. Chem. Lett. 1998, 395. (35) Owen, D. A.; Malkov, A. V.; Palotai, I. M.; Roe, C.; Sandoe, E. J.; Stephenson, G. R. Chem.;Eur. J. 2007, 13, 4293. (36) Ban, S. H.; Hayashi, Y.; Narasaka, K. Chem. Lett. 1998, 393.

4798


Zottig et al.

carbon, and halogens. When the meta position is substituted, an epoxide can be isolated that readily undergoes nucleophilic addition at the para carbon with weakly basic nucleophiles. These nucleophiles add exclusively syn to the epoxide oxygen. Thus, tandem addition of electrophile and nucleophile generates substituted functionalized cyclohexenone ligands from phenols with unconventional substitution patterns and stereochemistries. More basic nucleophiles induce dehydration across C2 and C3 to form several 4-substituted 4H-phenol complexes.

Scheme 10

Experimental Section

37

accomplished using phenyliodonium acetate. Also related to this work is the seminal report by Mayer et al. demonstrating nucleophilic addition of amines to an osmium(IV) anilido complex.38 As several of the complexes generated from the phenol complexes 1 and 2 contain unconventional substitution patterns or stereochemistries, we briefly explored the feasibility of removal of the carbocyclic ligand. In earlier studies,7,9 an oxidative decomplexation process was outlined utilizing NBS or CAN. Unfortunately, oxidation of 4-substituted dienone complexes such as 18-20 failed to generate the desired 4-substituted phenols. However, with more saturated carbocycles, CAN and DDQ proved to be effective oxidants. For example, when complex 11 and 1 equiv of CAN were dissolved in acetonitrile, compound 23 was liberated in 70% yield (observed by proton NMR). The diol 23 is an advanced synthetic intermediate (prepared in its enantioenriched form from quinic acid in seven steps; 26% yield) and has been used in the preparation of the polyoxygenated-cyclohexane metabolite epoformin.39 Where the use of CAN resulted in oxidation of the substituted cyclohexanone or where separation of the inorganic salts was difficult, a procedure using DDQ was developed. Using this reagent, several organic products (24-26) could be isolated in moderate yield (54-59%; Scheme 10). Given the ease with which phenol could be oxidized when held in its dienone isomer by tungsten, we questioned whether the 5-hydroxycyclohexenone ligands of complexes such as 8-12 (Scheme 5) would eliminate water at elevated temperatures, thereby constituting the formal oxidation of phenol to resorcinol. While catechol and p-dihydroquinone are readily available from the direct oxidation of phenol, the oxidation of the phenol meta carbon is most unusual.40 Proof of concept came with the elimination of methanol from complex 10 at 100 °C (DMSO) and subsequent decomplexation to give resorcinol in 30% yield (confirmed match with authentic sample).

Conclusions Coordination of phenols to the π base {TpW(NO)(PMe3)} induces their tautomerization to 2H-phenols. In this form, the uncoordinated meta carbon becomes nucleophilic and readily reacts with a host of different electrophiles including oxygen,

General Methods. All NMR spectra were obtained on either a 300 or 500 MHz (Varian INOVA or Bruker Avance) spectrometer. All chemical shifts are reported in ppm versus tetramethylsilane using residual shifts of the deuterated solvent as the internal standard. All coupling constants (J) are reported in hertz (Hz). All 31P NMR data are reported versus an external standard in acetone (triphenylphosphate, δ -16.58 ppm). Infrared spectra were obtained on a MIDAC Prospect Series spectrometer as a glaze on a horizontal attenuated total reflectance (HATR) cell from Pike Technologies. Electrochemical measurements were taken under a nitrogen atmosphere using a BAS Epsilon EC-2000 potentiostat. Cyclic voltammetry data were obtained in a three-electrode cell from þ1.7 to -1.7 V, with a glassy carbon working electrode, a platinum wire auxiliary electrode, and a platinum wire reference electrode. All data were obtained using a 100 mV/s scan rate with tetrabutylammonium hexafluorophosphate (TBAH) as the electrolyte in N,N-dimethylacetamide (DMA) unless otherwise noted. All potentials were reported versus the normal hydrogen electrode (NHE) using cobaltocenium hexafluorophosphate (E1/2 = -0.78 V) as an internal standard. For reversible waves the peak to peak separation was less than 100 mV. All HRMS data were obtained on a Bruker BioTOF-Q spectrometer using a 1:3 water-acetonitrile solution with sodium trifluoroacetate as an internal standard. For metal complexes, these data are reported using the five most intense peaks from the isotopic envelope for either Mþ (for monocationic complexes) or for [M þ H]þ or [M þ Na]þ (for neutral complexes). The data are listed as m/z with the intensity relative to the most abundant peak of the isotopic envelope given in parentheses for both the calculated and observed peaks. The difference between calculated and observed peaks is reported in ppm. For organic species, the calculated and observed peaks for [M þ H]þ or [M þ Na]þ are reported, with the difference between them reported in ppm. All LRMS data were acquired on a Shimadzu G-17A/QP5050 GC-MS instrument operating either in GC-MS or in direct inlet/MS mode. Mass spectra are reported as Mþ for neutral or monocationic samples. In all cases, observed isotopic envelopes were consistent with the molecular composition reported. The data are listed as m/z with the intensity relative to the most abundant peak of the isotopic envelope given in parentheses for both the calculated and observed peaks. All reactions were carried out at ambient or room temperature and in a fume hood using standard glassware unless otherwise noted. Column chromatography was performed using silica gel (60 A, 32-63 μM) from Sorbent Technologies. 3-Chloroperoxybenzoic acid (mCPBA) was 70% tech. grade from Alfa-Aesar and was used as received. All other solvents (37) Pelter, A.; Elgendy, S. M. A. J. Chem. Soc., Perkin Trans. 1993, 1891. (38) Soper, J. D.; Kaminsky, W.; Mayer, J. M. J. Am. Chem. Soc. 2001, 123, 5594. (39) Barros, T. M.; Maycock, C. D.; Ventura, R. M. Tetrahedron 1999, 3233. (40) Costine, A.; O0 Sullivan, T.; Hodnett, B. K. Catal. Today 2005, 99, 199.

Article and chemicals were used as received from Sigma-Aldrich, Acros Chemicals, or Fisher Scientific. All solvents were ACS grade and were not dried or purified prior to use unless otherwise noted. Phenol complex 1 can be prepared by direct reduction from the previously reported complex TpW(NO)(PMe3)Br.2 Complexes 5-8 have been previously reported.2,7 TpW(NO)(PMe3)(5,6-η2-2H-m-cresol) (2) (mixture of coordination diastereomers). In a glovebox under a dinitrogen atmosphere, sodium dispersion (7.89 g, 102 mmol, 30-35% in wax) was added to a 2 L round-bottom flask charged with a stir bar dissolved in 100 mL of hexane, and the mixture was stirred for a period of 20 min. The hexane was decanted, and the sodium dispersion was rinsed with addition of 100 mL of hexane, stirred for 20 min, and decanted. A 500 mL amount of benzene was added to the round-bottom flask with TpW(NO)(PMe3)Br (12.056 g, 20.684 mmol). After 24 h the reaction was filtered through 1 in. of Celite in a 350 mL medium-porosity fritted disk into a 2 L filter flask, charged with a stirbar and containing m-cresol (44.746 g, 413.778 mmol). The Celite was washed with 200 mL of benzene. After 24 h the reaction mixture was chromatographed on silica (2 in. in a 350 mL medium-porosity fritted disk) by first eluting with toluene (300 mL), then diethyl ether (800 mL), then ethyl acetate (800 mL). A separate brown band came off of the column with each change in eluent. The ethyl acetate fraction was stripped to dryness, dissolved in 30 mL of methylene chloride, and added to 500 mL of stirring hexane. A dark yellow precipitate was collected (4.662 g, 7.630 mmol, 37% yield over two steps). TpW(NO)(PMe3)(5,6-η2-2H-m-cresol) (2) (single diastereomer). To an Erlenmeyer flask were added in a glovebox 6 mL of methanol, TpW(NO)(PMe3) (5,6-η2-2H-m-cresol) (2; 3.197 g, 5.232 mmol), DBU (0.214 g, 1.405 mmol), and a stir bar. The flask was sealed with a glass stopper. After stirring for 3 days the reaction was filtered, washed with 4 mL of methanol, and dried in vacuo. A light yellow precipitate was collected (2; 2.368 g, 3.875 mmol, 74% yield). 1H NMR (300 MHz, CDCl3): δ 1.22 (d, 9H, J = 8.6, PMe3), 2.05 (s, 3H, Me), 2.18 (d, 1H, J = 8.6, H6), 2.99 (d, 1H, J = 22.2, H2a), 3.36 (m, 1H, H5), 3.50 (d, 1H, J = 22.2, H2b), 6.06 (br s, 1H, H4), 6.14 (t, 1H, J = 2.0, Tp), 6.20 (t, 1H, J = 2.0, Tp), 6.32 (t, 1H, J = 2.0, Tp), 7.34 (d, 1H, J = 2.0, Tp), 7.52 (d, 1H, J = 2.0, Tp), 7.68 (d, 1H, J = 2.0, Tp), 7.72 (d, 1H, J = 2.0, Tp), 7.85 (d, 1H, J = 2.0, Tp), 8.08 (d, 1H, J = 2.0, Tp). 13C NMR (CDCl3): δ 13.9 (d, J = 29, PMe3), 21.4 (s, C7), 43.8 (s, C2), 57.9 (s, C6), 63.3 (d, J = 11, C5), 105.9 (s, Tp), 106.3 (s, Tp), 107.1 (s, Tp), 123.3 (d, J = 3, C4), 125.4 (s, C3) 135.8 (s, Tp), 136.8 (s, Tp), 140.3 (s, Tp), 142.8 (s, Tp), 144.2 (s, Tp) 209.4 (s, C1). 31P NMR (CDCl3): δ -8.2 (JP-W = 291). Cyclic voltammetry: Ep,a = þ0.71 V. IR: νNO = 1566 cm-1, νCO = 1615 cm-1. HRMS [M þ Na]þ obsd (%), calcd (%), diff. in ppm: 632.14494 (75), 632.14406 (86.1), 1.4; 633.14951 (78.1), 633.14664 (79.5), 4.5; 634.14922 (100), 634.14642 (100), 4.4; 635.15274 (46.3), 635.15076 (40.9), 3.1; 636.15218 (87.4), 636.14968 (84.7), 3.9. [TpW(NO)(PMe3)(η2-5,6-(cyclohexadien-1-onium))]OTf (O-1H) and [TpW(NO)(PMe3)(η3-4,5,6-(cyclohexadien-1-onium))]OTf (C-1H). A solution of triflic acid (0.008 g, 0.053 mmol) in 0.25 mL of CD3CN was added to a solution of 1 (0.030 g, 0.050 mmol) in 0.5 mL of CD3CN, generating O-1H and C-1H in a 2:1 ratio. 1H NMR (500 MHz, CD3CN): O-1H, δ 1.25 (d, 9H, J = 9.5, PMe3), 3.20 (br d, 1H, J = 6.9, H6), 3.35 (m, 1H, H2a) 3.67 (d, 1H, J = 26.5, H2b) 4.18 (m, 1H, H5) 4.91 (ddd, 1H, J = 3.0, 4.3, 9.4, H3), 6.34 (t, 1H, J = 2.0, Tp), 6.42 (buried under Tp, 1H, H4) 6.47 (t, 1H, J = 2.0, Tp) 6.53 (t, 1H, J = 2.0, Tp), 7.47 (d, 1H, J = 2.0, Tp), 7.97 (d, 2H, J = 2.0, Tp), 7.98 (d, 1H, J = 2.0, Tp), 8.05 (d, 1H, J = 2.0, Tp), 8.16 (d, 1H, J = 2.0, Tp). 13C NMR (CD3CN): δ12.7 (d, J = 32.0, PMe3), 32.6 (s, C2), 63.9 (s, C6), 68.6 (m, C5), 107.6 (s, Tp), 108.0 (s, Tp), 108.7 (s, Tp), 113.2 (d, J = 13), 128.0 (q, J = 39.3, TfO), 138.8 (s, Tp), 139.0 (s, 2 Tp), 142.3 (s, Tp), 143.1 (s Tp), 146.0 (s, Tp), 197.8 (s, C1). 1H NMR (500 MHz, CD3CN): C-1H, δ 1.18 (d, 9H, J = 9.9, PMe3), 2.15 (m, 1H), 2.35 (m, 1H), 2.73 (br s, 1H), 3.06


4799

(m, 1H), 4.40 (d, 1H, J = 6.8), 5.96 (dd, 1H, J = 6.8, 7.3), 6.35 (buried, 1H), 6.50 (buried, 1H, Tp), 6.54 (buried, 1H, Tp), 6.58 (t, 1H, J = 2.0, Tp), 7.94 (d, 1H, J = 2.0, Tp), 8.08 (d, 1H, J = 2.0, Tp), 8.19 (d, 1H, J = 2.0, Tp), 8.19 (d, 1H, J = 2.0, Tp), 8.37 (d, 1H, J = 2.0, Tp). 13C NMR (CD3CN): δ 12.7 (d, J = 32.0 PMe3), 63.7 (s), 107.1 (s), 107.8 (s), 108.0 (s), 108.2 (s), 108.3 (s), 108.5 (s), 109.0 (s), 145.0 (m), 146.1 (m), 199.2 (s, C1). [TpW(NO)(PMe3)(η2-2,3-(4-(trimethylphosphonium)cyclohex-2-en-1-one))]OTf (3). A heterogeneous mixture of 1 (0.046 g, 0.077 mmol) in 1 mL of THF was added to Me3P 3 HOTf (0.028 g, 0.123 mmol), followed by 1 mL of CH2Cl2. After 5 min of stirring, the reaction mixture was added to 50 mL of pentane and the resulting precipitate collected by filtration. The collected solid was dried in vacuo. A light brown solid was collected (3; 0.053 g, 0.064 mmol, 72% mass recovery). 1H NMR (300 MHz, d6-acetone): δ 1.31 (d, 9H, J = 8.9, PMe3 on metal), 2.23 (d, 9H, J = 13.8, free HPMe3OTf), 2.25-2.45 (m, 3H), 2.55-2.90 (m, 2H), 3.04 (q, 1H, J = 9.6, H3), 3.82 (dd, 1H, J = 5.9, 11.1, H4), 5.66 (br s, 1H, free HPMe3OTf) 6.21 (t, 1H, J = 2.0, Tp), 6.38 (t, 1H, J = 2.0, Tp), 6.52 (t, 1H, J = 2.0, Tp), 7.82 (d, 1H, J = 2.0, Tp), 7.90 (d, 1H, J = 2.0, Tp), 7.95 (d, 1H, J = 2.0, Tp), 8.05 (d, 1H, J = 2.0, Tp), 8.07 (d, 1H, J = 2.0, Tp), 8.34 (d, 1H, J = 2.0, Tp). 13C NMR (d6acetone): δ 4.9 (d, J = 50), 13.1 (d, J = 30, PMe3 on metal), 20.8 (s), 33.1 (s), 35.6 (d, J = 37), 57.0 (dd, J = 7, 13, C3), 59.6 (s, C2), 106.3 (s, Tp), 107.4 (s, Tp), 108.2 (s, Tp), 137.2 (s, Tp), 138.0 (s, Tp), 138.8 (s, Tp), 143.0 (s, Tp), 143.7 (s, Tp), 144.8 (s, Tp), 204.5 (s, C1). [TpW(NO)(PMe3)(η2-2,3-(4-(phenylsulfanyl)cyclohex-2-en-1onium))]OTf (4). Thiophenol (0.030 g, 0.272 mmol) and 1 (0.051 g, 0.085 mmol) were dissolved in 0.25 mL of CH2Cl2 and added to diphenylammonium triflate (0.031 g, 0.097 mmol). After 15 min the reaction was precipitated in 50 mL of hexanes and filtered. The solid was dried in vacuo. A yellow powder, 4, was collected (0.063 g, 0.073 mmol, 86% yield). 1H NMR (300 MHz, CDCl3): δ 1.14 (d, 9H, J = 9.0, PMe3), 1.94 (m, 1H), 2.39 (m, 1H), 2.77 (dd, J = 6.9, 20.1), 2.97 (m, 1H), 3.10 (d, J = 8.1), 3.54 (m, 1H), 4.17 (br s, 1H, H4), 6.24 (t, 1H, J = 2.0, Tp), 6.40 (m, 2H, Tp), 7.2-7.5 (m, 10H (contains unreacted thiophenol)), 7.52 (d, 1H, J = 2.0, Tp), 7.58 (d, 1H, J = 2.0, Tp), 7.67 (d, 1H, J = 2.0, Tp), 7.82 (d, 1H, J = 2.0, Tp), 7.87 (d, 1H, J = 2.0, Tp), 8.09 (d, 1H, J = 2.0, Tp). 13C NMR (CDCl3): δ13.3 (d, J = 31, PMe3), 23.8 (s), 27.4 (s), 49.2 (s), 60.8 (s), 72.0 (d, J = 15, C3), 107.1 (s), 107.5 (s), 108.0 (s), 121.1 (s), 126.3 (s), 128.7 (s), 129.5 (s), 130.0 (s), 134.8 (s), 137.5 (s), 138.0 (s), 138.3 (s), 140.5 (s), 143.6 (s), 144.2 (s), 205.9 (s, C1). IR: νNO = 1567 cm-1, νCO = 1609 cm-1. Cyclic voltammetry: Ep,a = þ1.11 V. HRMS: [M þ H]þ obsd (%), calcd (%), diff in ppm: 706.16694 (100), 706.16556 (80), 2.0; 707.16784 (96.9), 707.16805 (78.6), 0.3; 708.16558 (86.6), 708.16776 (100), 3.1; 709.17125 (55.3), 709.17139 (46.9), 0.2; 710.17372 (68.7), 710.17084 (84.5), 4.1. TpW(NO)(PMe3)(2,3-η2-(5-hydroxy-5-methy-4-(phenylthio)cyclohexen-1-one)) (9). To a solution of 15 (0.300 g, 0.478 mmol) in 3 mL of CHCl3 was added a separate solution of thiophenol (0.059 g, 0.535 mmol) in 2 mL of CHCl3. The combined solution was yellow and homogeneous. After 1 h the solvent was removed in vacuo. The residue was dissolved in 5 mL of CHCl3 and added to 75 mL of petroleum ether, which resulted in a white precipitate. The precipitate was filtered, then washed three times with 5 mL of petroleum ether and dried in vacuo (0.281 g, 0.381 mmol, 80% yield). 1H NMR (300 MHz, CDCl3): δ 1.15 (d, 9H, J = 8.7, PMe3), 1.36 (s, 3H, Me), 2.08 (d, 1H, J = 9.3, H2), 2.56 (d, 1H, J = 15.2, H6a), 2.74 (s, 1H, OH), 3.17 (d, 1H, J = 15.2, H6b), 3.20 (m, buried under H6b, 1H, H3), 4.96 (br s, 1H, H4), 6.16 (t, 1H, J = 2.0, Tp), 6.22 (t, 1H, J = 2.0, Tp), 6.37 (t, 1H, J = 2.0, Tp), 7.19 (d, 1H, J = 2.0, Tp), 7.20 (m, buried under Tp, 1H, Ar), 7.33 (t, 2H, J = 7.3, Ar), 7.49 (d, 2H, J = 7.3, Ar), 7.54 (d, 1H, J = 2.0, Tp), 7.56 (d, 1H, J = 2.0, Tp) 7.70 (d, 1H, J = 2.0, Tp), 7.78 (d, 1H, J = 2.0, Tp), 8.12 (d, 1H, J = 2.0, Tp).

4800


C NMR (CDCl3): δ 14.3 (d, J = 28.9, PMe3), 29.5 (s, Me), 49.2 (s, C6), 56.8 (s, C4), 61.0 (s, C2), 61.2 (d, J = 12.7, C3), 78.6 (s, C5), 105.9 (s, Tp), 106.3 (s, Tp), 107.6 (s, Tp), 125.7 (s, Tp), 128.0 (s, Ar) 129.1 (s, Ar), 135.9 (s, Tp), 136.6 (s, Tp), 136.8 (s, Tp), 137.6 (s, Ar), 140.1 (s, Tp), 143.8 (s, Tp), 206.8 (s, C1). 31P NMR (CDCl3): δ -10.0 (JP-W = 279). Cyclic voltammetry: Ep,a = þ0.81 V. IR: νNO = 1558 cm-1, νCO = 1620 cm-1. HRMS [M þ H]þ obsd (%), calcd (%), diff. in ppm: 736.17906 (82.5), 736.17614 (79.3), 4.0; 737.17971 (101.5), 737.17863 (78.7), 1.5; 738.18187 (100), 738.17836 (100), 4.8; 739.17754 (54.1), 739.18196 (47.7), 6.0; 740.17963 (87.3), 740.18143 (84.3), 2.4. TpW(NO)(PMe3)(2,3-η2-(5-hydroxy-5-methy-4-(hydroxy)cyclohexen-1-one)) (11). K2CO3 (2.600 g, 18.811 mmol) dissolved in 10 mL of H2O was added to a solution of 2 (2.000 g, 3.273 mmol) in 10 mL of dimethoxymethane, 10 mL of CH3CN, 10 mL of CH2Cl2, and 10 mL of acetone in a one-neck 200 mL round-bottom flask charged with a stirbar. The heterogeneous yellow solution was cooled to ∼0 °C in an ice bath and stirred vigorously. A homogeneous solution of oxone (13.428 g, 21.841 mmol) in 70 mL of H2O was added over a 2 h period to the reaction solution using a vented pressure equilibrating addition funnel. Upon completion of oxone solution addition, the reaction solution was allowed to warm to room temperature; then 30 mL of CH2Cl2 and 20 mL of H2O were added to the reaction solution. The layers were separated and the H2O layer was extracted three times with 10 mL of CH2Cl2. The organic layer was backextracted with 10 mL of H2O, then dried over MgSO4 and filtered through a Celite plug. The solvent was removed in vacuo, and the residue was dissolved in 30 mL of CH2Cl2 and added to 100 mL of hexane, resulting in a white precipitate. The precipitate was filtered, then washed three times with 10 mL of hexane and dried in vacuo (1.43 g, 2.217 mmol, 67% yield). 1H NMR (300 MHz, CDCl3): δ 1.26 (d, 9H, J = 8.7, PMe3), 1.35 (s, 3H, Me), 2.02 (d, 1H, J = 9.4, H2), 2.52 (dd, 1H, J = 1.8, 15.7, H6a), 2.92 (ddd, 1H, J = 1.8, 9.4, 13.0, H3), 3.06 (d, 1H, J = 15.7 H6b), 4.68 (br s, 1H, H4), 6.15 (t, 1H, J = 2.0, Tp), 6.21 (t, 1H, J = 2.0, Tp), 6.37 (t, 1H, J = 2.0, Tp), 7.33 (d, 1H, J = 2.0, Tp), 7.56 (d, 1H, J = 2.0, Tp), 7.61 (d, 1H, J = 2.0, Tp) 7.70 (d, 1H, J = 2.0, Tp), 7.77 (d, 1H, J = 2.0, Tp), 8.14 (d, 1H, J = 2.0, Tp). 13C NMR (CDCl3): δ 13.8 (d, J = 29, PMe3), 26.2 (s, Me), 49.2 (s, C6), 58.6 (s, C2), 65.5 (d, J = 12.3, C3), 76.4 (s, C4), 78.2 (s, C5), 106.0 (s, Tp), 106.5 (s, Tp), 107.2 (s, Tp), 136.0 (s, Tp, 136.8 (s, Tp) 136.9 (s, Tp), 140.2 (s, Tp), 143.6 (s, Tp), 144.0 (s, Tp), 207.5 (s, C1). 31P NMR (CDCl3): δ -10.3 (JP-W = 280). Cyclic voltammetry: Ep,a = þ0.85 V. IR: νNO = 1558 cm-1, νCO = 1612 cm-1. HRMS [M þ H]þ obsd (%), calcd (%), diff. in ppm: 644.1702 (87.1), 644.1682 (85.7), 3.1; 645.1699 (80.4), 645.1708 (79.3), 1.4; 646.1703 (100), 646.1705 (100), 0.3; 647.1769 (43.3), 647.1749 (41.2), 3.1; 648.1735 (86.9), 648.1738 (84.7), 0.5. TpW(NO)(PMe3)(2,3-η2-4-(3-chlorobenzoate)-5-hydroxy-5methylcyclohexen-1-one) (12). To a solution of 2 (0.0510 g, 0.083 mmol) in CH2Cl2 at ∼0 °C was added mCPBA (70% tech. grade w/water, 0.0232 g, 0.134 mmol) dissolved in 1 mL of CH2Cl2 and stirred for 15 min. The resulting reddish homogeneous solution was added to 40 mL of hexanes. The light yellow precipitate 12 (0.048 g, 0.061 mmol, 74% yield) was collected by filtration and dried in vacuo. 1H NMR (300 MHz, CDCl3): δ 1.06 (d, 9H, J = 8.6, PMe3), 1.22 (s, 3H, Me) 2.12 (d, 1H, J = 9.9, H2), 2.50 (dd, 1H, J = 1.8,15.5, H6a), 3.04 (ddd, 1H, J = 2.2, 9.9, 12.4, H3), 3.13 (d, 1H, J = 15.5, H6b), 6.14 (t, 1H, J = 2.0, Tp), 6.20 (t, 1H, J = 2.0, Tp), 6.36 (t, 1H, J = 2.0, Tp), 6.51 (b, 1H, H4), 7.28 (d, 1H, J = 2.0, Tp), 7.43 (t, 1H, J = 7.8, Ar), 7.55 (d, 1H, J = 2.0, Tp), 7.57 (d, 1H, J = 1.0, Ar), 7.59 (d, 1H, J = 2.0, Tp), 7.68 (d, 1H, J = 2.0, Tp), 7.76 (d, 1H, J = 2.0, Tp), 8.08 (d, 1H, J = 7.7, Ar), 8.14 (d, 1H, J = 2.0, Tp), 8.18 (t, 1H, J = 1.8, Ar). 13C NMR (75 MHz, CDCl3): δ 13.7 (d, J = 29.2, PMe3), 27.1 (s, Me), 48.6 (s, C6), 58.7 (s, C2), 59.1 (d, J = 12.3, C3), 79.5 (s, C5), 80.1 (s, C4), 106.2 (s, Tp), 106.6 (s, Tp), 107.4 (s, Tp), 128.2 (s, Ar), 130.0 (s, Ar), 130.2 (s, Ar), 131.9 (s, Ar), 133.7 (s, Ar), 135.1 (s, Ar), 136.2 (s, Tp), 13

Zottig et al. 136.9 (s, Tp), 137.1 (s, Tp), 140.1 (s, Tp), 143.8 (s, Tp), 143.9 (s, Tp), 165.5 (s, ester carbonyl carbon), 207.3 (s, C1). 31P NMR (CDCl3): δ -10.1 (JP-W = 277). Cyclic voltammetry: Ep,a = þ0.93 V. IR: νNO = 1561, νCO = 1708, νCO = 1611. HRMS [M þ H]þ obsd (%), calcd (%), diff. in ppm: 782.15194 (44.1), 782.15493 (64.9), 3.8; 783.15788 (73.8), 783.15731 (68.3), 0.7; 784.15388 (100), 784.15630 (100), 3.1; 785.15750 (35.9), 785.15894 (57.1), 1.8; 786.15592 (66.1), 786.15892 (91.2), 3.8. TpW(NO)(PMe3)(4,5-η2-bicyclo[4.1.0]hept-4-en-3-one) (13). In a glovebox under a dinitrogen atmosphere, a solution of trifluoroacetic acid (0.037 g, 0.324 mmol) in 3 mL of CH2Cl2 in a one-neck round-bottom flask with a stir bar diethyl zinc (0.05 g, 0.404 mmol) in 5 mL of CH2Cl2 was added dropwise over 5 min followed by an additional 10 mL of CH2Cl2. The clear solution was stirred for 5 min. Then a solution of diiodomethane (0.099 g, 0.369 mmol) in 5 mL of CH2Cl2 was added slowly, and the resulting solution was stirred for 5 min. A sample of 1 (0.049 g, 0.082 mmol) dissolved in 5 mL of CH2Cl2 was added slowly and stirred for 1 h, resulting in a homogeneous yellow solution. The reaction was quenched with 3 mL of saturated NH4Cl(aq), and the reaction vessel was then removed from the glovebox. The CH2Cl2 layer was removed, and the H2O layer was extracted three times with 1 mL portions of CH2Cl2. The original CH2Cl2 layer and extract fractions were combined, dried over MgSO4, and filtered through a Celite plug. The solvent was removed in vacuo, and to the residue was added 1.5 mL of CH2Cl2; the resulting solution was added to 50 mL of hexanes. The white precipitate was collected by filtration and dried in vacuo (13; 0.0224 g, 0.036 mmol, 45% yield). 1H NMR (300 MHz, CDCl3): δ 0.27 (dd, 1H, J = 4.5, 9.6, H7a), 0.85 (m, 1H, H7b), 1.24 (d, 9H, J = 8.5, PMe3), 1.38 (m, 1H, H1), 1.52 (m, 1H, H6), 1.98 (d, 1H, J = 9.5, H4), 2.66 (d, 1H, J = 17.4, H2a), 3.05 (dd, 1H, J = 5.8, 17.4, H2b), 3.64 (dd, 1H, J = 9.5, 12.8, H5), 6.14 (t, 1H, J = 2.0, Tp), 6.21 (t, 1H, J = 2.0, Tp), 6.37 (t, 1H, J = 2.0, Tp), 7.33 (d, 1H, J = 2.0, Tp), 7.53 (d, 1H, J = 2.0, Tp), 7.59 (d, 1H, J = 2.0, Tp), 7.68 (d, 1H, J = 2.0, Tp), 7.76 (d, 1H, J = 2.0, Tp), 8.17 (d, 1H, J = 2.0, Tp). 13C NMR (75 MHz, CDCl3): 13.4 (d, J = 29, PMe3), 16.4 (s, C6), 16.7 (s, C7), 36.5 (s, C2), 60.9 (s, C4), 67.6 (d, J = 12.5, C5), 106.1 (s, Tp), 106.4 (s, Tp), 107.1 (s, Tp), 135.9 (s, Tp), 136.6 (s, Tp), 140.2 (s, Tp), 143.2 (s, Tp), 143.7 (s, Tp), 209.9 (s, C3). 31P NMR (CDCl3): δ -8.29 (JP-W = 285). Cyclic voltammetry: Ep,a = þ0.81 V. IR: νNO = 1566, νCO = 1604. HRMS [M þ H]þ obsd (%), calcd (%), diff. in ppm: 610.16148 (102.5), 610.16212 (86.1), 1.0; 611.16411 (83.3), 611.1647 (79.5), 1.0; 612.16511 (100), 612.16447 (100), 1.0; 613.16863 (44.8), 613.16882 (40.9), 0.3; 614.16866 (87.6), 614.16773 (84.7), 1.5. TpW(NO)(PMe3)(4,5-η2-1-methyl-bicyclo[4.1.0]hept-4-en-3one) (14). Using a similar reaction procedure to that for product 13, 2 (0.051 g, 0.083 mmol) was used in place of 1, resulting in the collection of a light yellow precipitate of 14 (0.0326 g, 0.052 mmol, 62% yield). 1H NMR (300 MHz, CDCl3): 0.46 (t, 1H, J = 4.2, H7a), 0.68 (dd, 1H, J = 4.2, 7.5, H7b), 1.21 (s, 3H, Me), 1.25 (d, 9H, J = 8.4, PMe3), 1.32 (m, 1H, H6), 1.91 (d, 1H, J = 9.5, H4), 2.57 (d, 1H, J = 17.0, H2a), 2.87 (d, 1H, J = 17.0, H2b), 3.62 (dd, 1H, J = 19.5, 13.1, H5), 6.14 (t, 1H, J = 2.0, Tp), 6.20 (t, 1H, J = 2.0, Tp), 6.37 (t, 1H, J = 2.0, Tp), 7.34 (d, 1H, J = 2.0, Tp), 7.53 (d, 1H, J = 2.0, Tp), 7.62 (d, 1H, J = 2.0, Tp), 7.68 (d, 1H, J = 2.0, Tp), 7.76 (d, 1H, J = 2.0, Tp), 8.16 (d, 1H, J = 2.0, Tp). 13C NMR (75 MHz, CDCl3): δ 13.3 (d, J = 28.6, PMe3), 19.0 (s), 25.1 (s, Me), 26.1 (s, C7), 26.3 (s, C6), 42.4 (s, C2), 59.1 (s, C4), 68.1 (d, J = 11.4, C5), 106.1 (s, Tp), 106.4 (s, Tp), 107.1 (s, Tp), 135.9 (s, Tp), 136.6 (s, 2C, Tp), 140.2 (s, Tp), 143.2 (s, Tp), 143.7 (s, Tp). 31P NMR (CDCl3): δ -8.39 (JP-W = 286). Cyclic voltammetry: Ep,a = þ0.83 V. IR: νNO = 1566, νCO = 1608. HRMS [M þ H]þ obsd (%), calcd (%), diff. in ppm: 624.17592 (89), 624.17778 (85.5), 3.0; 625.18139 (67.5), 625.18036 (79.7), 1.6; 626.18150 (100), 626.18016 (100), 2.1; 627.18311 (36.6), 627.18444 (41.7), 2.1; 628.18364 (73.6), 628.18341 (84.4), 0.4.

Article TpW(NO)(PMe3)(4,5-η2-1-methyl-7-oxabicyclo[4.1.0]hept-4en-3-one) (15). A sample of K2CO3 (10.185 g, 73.692 mmol) dissolved in 50 mL of H2O was added to a solution of 2 (3.000 g, 4.909 mmol) in a mixture of 30 mL of dimethoxymethane, 24 mL of CH3CN, and 15 mL of acetone in a one-neck 500 mL roundbottom flask charged with a stirbar. The heterogeneous yellow solution was cooled to ∼0 °C in an ice bath and stirred vigorously. A homogeneous solution of oxone (15.09 g, 24.544 mmol) in 100 mL of H2O was added to the reaction solution dropwise over 2 h using a vented pressure equilibrating addition funnel. Upon completion of oxone solution addition, the reaction solution was allowed to warm to room temperature. Then 45 mL of CH2Cl2 and 30 mL of H2O were added to the reaction solution. The layers were separated and the H2O layer was extracted three times with 10 mL of CH2Cl2. The organic layer was back-extracted with 10 mL of H2O, then dried over MgSO4 and filtered through a Celite plug. The solvent was removed by in vacuo, and the residue was dissolved in 45 mL of CH2Cl2 and added to 200 mL of hexane, resulting in a white precipitate. The precipitate was filtered, then washed three times with 10 mL of hexane and dried in vacuo (2.800 g, 4.465 mmol, 91% yield). 1H NMR (300 MHz, CDCl3): δ 1.24 (d, 9H, J = 8.5, PMe3), 1.47 (s, 3H, Me), 2.08 (d, 1H, J = 8.9, H4), 2.79 (d, 1H, J = 18.3, H2a), 2.93 (d, 1H, J = 18.3, H2b), 3.39 (s, 1H, H6), 3.45 (m buried under H6, 1H, H5), 6.14 (t, 1H, J = 2.0, Tp), 6.24 (t, 1H, J = 2.0, Tp), 6.40 (t, 1H, J = 2.0, Tp), 7.36 (d, 1H, J = 2.0, Tp), 7.55 (d, 1H, J = 2.0, Tp), 7.59 (d, 1H, J = 2.0, Tp), 7.71 (d, 1H, J = 2.0, Tp), 7.79 (d, 1H, J = 2.0, Tp), 8.16 (d, 1H, J = 2.0, Tp). 13C NMR (75 MHz, CDCl3): δ 13.7 (d, J = 29.2, PMe3), 23.3 (s, Me), 42.4 (s, C2), 59.4 (s, C4), 60.9 (s, C1), 61.3 (d, J = 12.0, C5), 65.0 (s, C6), 106.1 (s, Tp), 106.6 (s, Tp), 107.4 (s, Tp), 136.1 (s, Tp), 136.9 (s, 2C, Tp), 140.4 (s, Tp), 143.0 (s, Tp), 143.7 (s, Tp), 207.0 (s, C3). 31P NMR (CDCl3): δ -10.62 (JP-W = 271). Cyclic voltammetry: Ep,a = þ1.09 V. IR: νNO = 1566, νCO = 1612. HRMS [M þ H]þ obsd (%), calcd (%), diff. in ppm: 626.1562 (103.2), 626.15703 (108.1), 1.3; 627.15860 (100), 627.15961 (100), 1.6; 628.15950 (121.6), 628.15939 (125.9), 0.2; 629.16295 (50.4), 629.16373 (51.7), 1.2; 630.16299 (116.8), 630.16265 (106.7), 0.5. TpW(NO)(PMe3)(2,3-η2-(5-hydroxy-5-methy-4-(indolin-1-yl)cyclohexen-1-one)) (16). To a solution of 15 (0.2 g, 0.318 mmol) in 1 mL of CH2Cl2 was added indoline (0.198 g, 1.661 mmol) with an additional 0.5 mL of CH2Cl2. The combined solution was yellow and homogeneous. After 10 min, a white precipitate began to form in solution. After an additional 1 day the precipitate was filtered, then washed three times with 5 mL of hexane and dried in vacuo. An off-white solid was collected (0.205 g, 0.274 mmol, 86% yield). 1H NMR (300 MHz, d6-DMSO): δ 0.90 (d, 9H, J = 9.0, PMe3), 1.02 (s, 3H, Me), 1.67 (d, 1H, J = 9.4, H2), 2.07 (d, 1H, J = 14.6, H6a), 2.83 (d, 1H, J = 14.6 H6b), 2.93 (m, 1H, beta methylene of indoline), 3.35 (m buried, 1H, H3), 4.14 (m, 1H, alpha methylene of indoline), 4.42 (s, 1H, OH), 5.06 (br s, 1H, H4), 6.22 (t, 1H, J = 2.0, Tp), 6.38 (t, 1H, J = 2.0, Tp), 6.46 (t, 1H, J = 2.0, Tp), 6.33 (t, 2H, J = 7.6, Ar), 6.89 (t, 1H, J = 7.6, Ar), 6.95 (d, 1H, J = 6.9, Ar), 7.36 (d, 1H, J = 2.0, Tp), 7.69 (d, 1H, J = 2.0, Tp), 7.86 (d, 1H, J = 2.0, Tp) 8.07 (d, 1H, J = 2.0, Tp), 8.09 (d, 1H, J = 2.0, Tp), 8.12 (d, 1H, J = 2.0, Tp). 13C NMR (d6-DMSO): δ 13.2 (d, J = 29.2, PMe3), 28.3 (s, Me and beta methylene of indoline), 47.6 (s, alpha methylene of indoline), 51.9 (s, C6), 58.4 (d, J = 12.2, C3), 60.5 (s,C4), 60.9 (s, C2), 81.8 (s, C5), 105.5 (s, Ar) 105.8 (s, Tp), 107.2 (s, Tp), 107.8 (s), Tp, 115.0 (s, Ar), 124.8 (s, Ar) 127.2 (s, Ar), 128.4 (s, Tp), 136.8 (s, Tp), 137.6 (s, Tp), 143.4 (s, Tp), 144.1 (s, Tp), 152.7 (s, Tp), 207.3 (s, C1). 31P NMR (CDCl3): δ -7.81 (JP-W = 283). Cyclic voltammetry: Ep,a = þ0.83 V. IR: νNO = 1554, νCO = 1608. LRMS: [Mþ]: obsd (mass, % relative intensity) 744.3 (83), 745.3 (81), 746.3 (100), 747.3 (48), 748.3 (82); calcd for C27H36BN8O3PWþ 744.2 (81), 745.2 (81), 746.2 (100), 747.2 (46), 748.2 (82). TpW(NO)(PMe3)(2,3-η2-(5-hydroxy-5-methy-4-(phenylamino)cyclohexen-1-one)) (17). To a solution of 15 (0.101 g, 0.161 mmol) in 1 mL of CHCl3 was added a separate solution of aniline (0.083 g,


4801

0.891 mmol) in ∼0.25 mL of CHCl3. The combined solution was yellow and homogeneous. After 1 min 0.159 mL of 0.001 M anilinium triflate solution in CH2Cl2 was added, and a white precipitate formed in solution. After 5 h, 6 mL of petroleum ether was added to the heterogeneous solution; then the precipitate was filtered, washed three times with 5 mL of petroleum ether, and dried in vacuo. A white solid was collected (0.112 g, 0.156 mmol, 97% yield). 1H NMR (300 MHz, d6-DMSO): δ 0.96 (d, 9H, J = 8.9, PMe3), 1.02 (s, 3H, Me), 1.58 (d, 1H, J = 9.6, H2), 2.08 (d, 1H, J = 14.3, H6a), 2.875 (d, 1H, J = 14.3 H6b), 3.02 (ddd, 1H, J = 2.4, 9.6, 12.7, H3), 4.45 (s, 1H, OH) 4.81 (d, 1H, J = 8.5, H4), 5.54 (d, 1H, J = 10.1, NH) 6.21 (t, 1H, J = 2.0, Tp), 6.40 (t, 1H, J = 2.0, Tp), 6.47 (t, 1H, J = 2.0, Tp), 6.43 (s, 1H, Ar), 6.54 (d, 2H, J = 8.1, Ar), 7.05 (t, 2H, J = 8.1, Ar), 7.4 (d, 1H, J = 2.0, Tp), 7.5 (d, 1H, J = 2.0, Tp), 7.86 (d, 1H, J = 2.0, Tp) 8.08 (d, 1H, J = 2.0, Tp), 8.10 (d, 1H, J = 2.0, Tp), 8.13 (d, 1H, J = 2.0, Tp). 13C NMR (d6-DMSO): δ 13.5 (d, J = 28.9, PMe3), 28.8 (s, Me), 50.2 (s, C6), 58.8 (s, C4), 60.3 (s, C2), 63.4 (d, J = 12.9, C3), 79.3 (CHCl3), 79.4 (s, C5), 106.4 (s, Tp), 107.3 (s, Tp), 108.3 (s, Tp), 112.45 (s, Ar), 115.3 (s, Tp), 129.3 (s, Ar) 136.7 (s, Tp), 137.6 (s, Tp), 137.8 (s, Tp), 140.9 (s, Tp), 143.1 (s, Tp), 143.4 (s, Tp), 149.7 (s, Ar), 207.1 (s, C1). 31 P NMR (d6-DMSO): δ -8.40 (JP-W = 283). Cyclic voltammetry: Ep,a = þ0.76 V. IR: νNO = 1558 cm-1, νCO = 1608 cm-1. HRMS [M þ H]þ obsd (%), calcd (%), diff. in ppm: 719.2156 (86.0), 719.2156 (82.4), 0.0; 720.2207 (82.9), 720.2181 (80.8), 3.6; 721.2209 (100), 721.218 (100), 4.0; 722.2161 (47.1), 722.222 (45.6), 8.2; 723.2233 (80.3), 723.2213 (83), 2.8. TpW(NO)(PMe3)(5,6-η2-(3-methy-4-(morpholino)-2,5-cyclohexadien-1-one)) (18). To a solution of 15 (0.504 g, 0.803 mmol) in 2.5 mL of CH2Cl2 was added a separate solution of morpholine (0.219 g, 2.513 mmol) in 1 mL of CH2Cl2. The combined solution was yellow and homogeneous. After 1 day, 5 mL of 1 M K2CO3(aq) was added to the reaction solution and the two layers were separated. The CH2Cl2 layer was extracted three times with 1 mL of 1 M K2CO3(aq), then dried over MgSO4. The organic layer with filtered through a Celite plug; then the solvent was removed in vacuo. The residue was dissolved in 1 mL of CH2Cl2 and added to 50 mL of hexane, which resulted in a yellow precipitate. The precipitate was filtered, then washed three times with 5 mL of hexane and dried in vacuo (0.452 g, 0.649 mmol, 81% yield). 1H NMR (300 MHz, CDCl3): δ 1.15 (d, 9H, J = 8.3, PMe3), 2.07 (s, 4H, Me and H6), 2.88 (m, 4H, methylene morpholine), 3.07 (dd, 1H, J = 9.4, 12.0, H5), 3.73 (m, 4H, methylene morpholine), 3.86 (s, 1H, H4), 6.04 (s, 1H, H2), 6.16 (t, 1H, J = 2.0, Tp), 6.29 (t, 1H, J = 2.0, Tp), 6.34 (t, 1H, J = 2.0, Tp), 7.4 (d, 1H, J = 2.0, Tp), 7.55 (d, 1H, J = 2.0, Tp), 7.70 (d, 1H, J = 2.0, Tp) 7.76 (d, 1H, J = 2.0, Tp), 7.86 (d, 1H, J = 2.0, Tp), 8.06 (d, 1H, J = 2.0, Tp). 13C NMR (CDCl3): δ 12.7 (d, J = 28.3, PMe3), 23.1 (s, Me), 49.4 (s, morpholine methylene), 59.0-59.2 (s and t overlapping, C5 and C6), 68.0 (s, morpholine methylene), 68.5 (d, J = 3.3, C4), 105.8 (s, Tp), 106.2 (s, Tp), 106.9 (s, Tp), 127.3 (s, C2), 135.7 (s, Tp) 136.5 (s, Tp), 136.6 (s, Tp), 139.9 (s, Tp), 143.2 (s, Tp), 143.4 (s, Tp), 148.0 (s, C3), 198.3 (s, C1). 31P NMR (CDCl3): δ -9.99 (JP-W = 280). Cyclic voltammetry: Ep,a = þ0.79 V. IR: νNO = 1570 cm-1, νCO = 1651 cm-1. HRMS [M þ H]þ obsd (%), calcd (%), diff. in ppm: 695.2098 (92.2), 695.2155 (83.5), 8.2; 696.2259 (95.5), 696.2181 (80.4), 11.2; 697.2205 (100), 697.218 (100), 3.6; 698.2213 (47.1), 698.222 (44.2), 1.0; 699.2228 (92.2), 699.2212 (83.5), 2.3. TpW(NO)(PMe3)(5,6-η2-(3-methy-4-(benzylamino)-2,5-cyclohexadien-1-one)) (19). To a solution of 15 (0.300 g, 0.478 mmol) in 2 mL of CHCl3 was added a separate solution of benzylamine (0.261 g, 2.435 mmol) in 1 mL of CHCl3. The combined solution was yellow and homogeneous. After 8 days, 2 mL of 0.5 M NaHCO3(aq) was added to the reaction solution, and the two layers were separated. The CHCl3 layer was extracted three times with 1 mL of 0.5 M NaHCO3(aq), then dried over MgSO4. The organic layer was filtered through a Celite plug; then the solvent was removed in vacuo. The residue was dissolved in 1 mL of

4802


CH2Cl2 and added to 50 mL of hexanes, which resulted in a yellow precipitate. The precipitate was filtered, then washed three times with 5 mL of hexane and dried in vacuo. A small impurity of 11 was present in the product (0.271 g, 0.378 mmol, 79% yield). 1H NMR (300 MHz, CDCl3): δ 1.16 (d, 9H, J = 8.4, PMe3), 1.96 (d, 1H, J = 9.1, H6), 2.08 (s, 3H, Me), 3.06 (dd, 1H, J = 9.1, 12.8, H5), 3.78 (d, 1H, J = 13.3, benzylamine methylene), 4.06 (d, 1H, J = 13.3, benzylamine methylene), 4.21 (s, 1H, H4), 5.30 (DCM), 6.13 (s, 1H, H2), 6.17 (t, 2H, J = 2.0, Tp), 6.33 (t, 1H, J = 2.0, Tp), 7.14 (d, 1H, J = 2.0, Tp), 7.32 (br t, 1H, J = 7.1, Ar), 7.44 (br d, 3H, J = 7.1, Ar), 7.55 (d, 1H, J = 2.0, Tp), 7.66 (d, 1H, J = 2.0, Tp) 7.75 (d, 1H, J = 2.0, Tp), 7.87 (d, 1H, J = 2.0, Tp), 8.05 (d, 1H, J = 2.0, Tp). 13C NMR (CDCl3): δ 13.0 (d, J = 29, PMe3), 21.9 (s, Me), 47.0 (s, benzylamine methylene), 58.5 (s, C6), 61.1 (s, C4), 62.9 (d, J = 12.2, C5), 106.0 (s, Tp), 106.3 (s, Tp), 107.4 (s, Tp), 126.8 (s, C2), 127.1 (s, Ar) 128.4 (s, Ar), 135.8 (s, Tp), 136.6 (s, Tp), 136.7 (s, Tp) 140.0 (s, Tp), 142.1 (s, Ar), 143.7 (s, Tp), 144.5 (s, Tp) 150.2 (s, C3), 198.5 (s, C1). 31P NMR (CDCl3): δ -8.34 (JP-W = 281). Cyclic voltammetry: Ep,a = þ0.76 V. IR: νNO = 1566 cm-1, νCO = 1651 cm-1. HRMS [M - 1]þ obsd (%), calcd (%), diff. in ppm: 713.20556 (69.7), 713.20441 (82.1), 1.6; 714.20816 (75.8), 714.20694 (81.1), 1.7; 715.20879 (100), 715.20688 (100), 2.7; 716.21293 (54.2), 716.21082 (46.1), 2.9; 717.21246 (71.7), 717.2101 (82.8), 3.3. TpW(NO)(PMe3)(5,6-η2-(3-methy-4-(hydroxy)-2,5-cyclohexadien-1-one)) (20). In a glovebox under a dinitrogen atmosphere a solution of 15 (0.075 g, 0.119 mmol) in 0.5 mL of CH2Cl2 was added to KHMDS (0.037 g, 0.185 mmol) in 0.5 mL of CH2Cl2. The combined solution was yellow and heterogeneous. After 4 h, ∼1/8 mL of MeOH was added, and the reaction mixture was stirred for an additional 45 min. The reaction was removed from the glovebox and quenched with 3 mL of saturated NH4Cl(aq), and the two layers were separated. The CH2Cl2 layer was extracted three times with 1 mL of H2O, then dried over MgSO4. The organic layer was filtered through a Celite plug, and the solvent was removed in vacuo. The residue was dissolved in 1 mL of CH2Cl2 and added to 50 mL of hexane, which resulted in a yellow precipitate. The precipitate was filtered, then washed three times with 5 mL of hexane and dried in vacuo (0.053 g, 0.084 mmol, 71% yield). 1H NMR (300 MHz, CDCl3): δ 1.16 (d, 9H, J = 8.4, PMe3), 2.01 (d, 1H, J = 8.7, H6), 2.08 (s, 3H, Me), 3.27 (dd, 1H, J = 8.7, 12.3, H5), 4.54 (s, 1H, H4), 5.93 (s, 1H, H2), 6.16 (t, 1H, J = 2.0, Tp), 6.22 (t, 1H, J = 2.0, Tp), 6.34 (t, 1H, J = 2.0, Tp), 7.43 (d, 1H, J = 2.0, Tp), 7.57 (d, 1H, J = 2.0, Tp), 7.70 (d, 1H, J = 2.0, Tp) 7.76 (d, 1H, J = 2.0, Tp), 7.81 (d, 1H, J = 2.0, Tp), 8.05 (d, 1H, J = 2.0, Tp). 13C NMR (CDCl3): δ 12.7 (d, J = 28.7, PMe3), 21.6 (s, Me), 56.3 (s, C6), 64.9 (d, J = 11.8, C5), 73.3 (s, C4), 106.2 (s, Tp), 106.6 (s, Tp), 107.3 (s, Tp), 126.1 (s, C2) 136.0 (s, Tp), 136.9 (s, Tp), 140.1 (s, Tp), 143.4 (s, Tp), 143.6 (s, Tp), 151.2 (s, Tp). 31P NMR (CDCl3): δ -9.58 (JP-W = 276). Cyclic voltammetry: Ep,a = þ0.84 V. IR: νNO = 1566 cm-1, νCO = 1655 cm-1. TpW(NO)(PMe3)(4,5-η2-7a-methyl-3-tosyl-3,3a,7,7a-tetrahydrobenzo[d]oxazole-2,6-dione) (21). In a glovebox under a dinitrogen atmosphere, a solution of p-tolunensulfonyl isocyanate (0.077 g, 0.390 mmol) in 0.5 mL of CH2Cl2 was added to a solution of 15 (0.2 g, 0.318 mmol) in 1 mL of CH2Cl2. The combined solution was yellow and homogeneous. After 4 h the reaction mixture was removed from the glovebox and solvent was removed in vacuo. The residue was dissolved in ∼1.5 mL of CHCl3 and added to 50 mL of petroleum ether, which resulted in a white precipitate. The precipitate was filtered, then washed three times with 5 mL of petroleum ether and dried in vacuo (0.226 g, 0.274 mmol, 86% yield). 1H NMR (300 MHz, CDCl3): δ 1.30 (d, 9H, J = 8.7, PMe3), 1.36 (s, 3H, Me), 2.16 (d, 1H, J = 9.7, H5), 2.45 (s, 3H, Ar-Me) 2.65 (d, 1H, J = 16.6, H7), 3.25 (d, 1H, J = 16.6, H7), 3.48 (dd, 1H, J = 9.7, 11.5, H4), 4.98 (s, 1H, H3a), 6.12 (t, 1H, J = 2.0, Tp), 6.27 (t, 1H, J = 2.0, Tp), 6.39 (t, 1H, J = 2.0, Tp), 7.28 (d, 1H, J = 2.0,

Zottig et al. Tp), 7.35-7.37 (peaks overlap, 3H, Tp and Ar), 7.55 (d, 1H, J = 2.0, Tp) 7.73 (d, 1H, J = 2.0, Tp), 7.79 (d, 1H, J = 2.0, Tp), 7.96 (d, 2H, J = 7.4, Ar), 8.13 (d, 1H, J = 2.0, Tp). 13C NMR (CDCl3): δ 14.0 (d, J = 29.6, PMe3), 21.9 (s, tosyl Me), 26.1 (s, Me), 43.4 (s, C7), 60.4 (s, C5), 61.9 (d, J = 11.9, C4), 66.5 (s, C3a), 87.7 (s, C7a), 106.3 (s, Tp), 106.9 (s, Tp), 107.7 (s, Tp), 128.8 (s, Ar), 129.9 (s, Ar), 135.0 (s. Ar), 136.5 (s, Tp), 137.3 (s, Tp), 140.9 (s, Tp), 143.2 (s, Tp), 144.2 (s, Tp), 145.9 (s, Ar), 151.5 (s, C2), 202.2 (s, C6). 31P NMR (CDCl3): δ -9.99 (JP-W = 277). Cyclic voltammetry: Ep,a = þ1.06 V. IR: νNO = 1566 cm-1, νCO = 1631 cm-1, νCO(carbamate)= 1770 cm-1. LRMS [Mþ]: obsd (mass, % relative intensity) 822.3 (84), 823.3 (82), 824.3 (100), 825.3 (59), 826.3 (82); calcd for C22H29BN7O6PWþ 822.2 (77), 823.2 (78), 824.2 (100), 825.2 (49), 826.2 (84). TpW(NO)(PMe3)(4,5-η2-(methyl 2,6-dioxo-2,3,3a,6,7,7a-hexahydrobenzofuran-3-carboxylate) (22). To a solution of dimethyl malonate (0.088 g, 0.666 mmol) in 0.5 mL of THF was added a separate solution of NaH (0.007 g, 0.291 mmol) in 0.5 mL of THF. After 5 min LiOTf (0.052 g, 0.333 mmol) was added. Separately a solution of 1 (0.05 g, 0.083 mmol) in 0.5 mL of CH2Cl2 and a solution of mCPBA (0.025 g, 0.144 mmol) in 0.5 mL of CH2Cl2 were combined. After 5 min the dimethyl malonate reaction mixture was combined with the reaction solution containing 1 and stirred for 15 min. The resulting solution was dark yellow to slightly brown and homogeneous. The reaction solution was quenched with 2 mL of 0.5 M NaHCO3(aq), and the two layers were separated. The CH2Cl2 layer was extracted three times with 1 mL of 0.5 M NaHCO3(aq), then dried over MgSO4. The organic layer with filtered through a Celite plug; then the solvent was removed in vacuo. The residue was dissolved in ∼0.25 mL of CH2Cl2 and added to 50 mL of hexanes, which resulted in a beige precipitate. The precipitate was filtered, then washed three times with 5 mL of hexane and dried in vacuo (0.03 g, 0.042 mmol, 50% yield with slight impurity). 1H NMR (300 MHz, CDCl3): δ 1.25 (d, 9H, J = 8.5, PMe3), 2.21 (d, 1H, J = 9.5, H5), 2.54 (dd, 1H, J = 4.8, 19.1 H7) 2.94 (ddd, 1H, J = 1.5, 9.5, 11.2, H4), 3.22 (d, 1H, J = 8.7, 19.1, H7), 3.75 (d, 1H, J = 10.4, H3), 3.92 (s, 3H, OMe), 3.96 (buried under OMe, 1H, H3a) 5.29 (m, 1H, H7a) 6.19 (t, 1H, J = 2.0, Tp), 6.29 (t, 1H, J = 2.0, Tp), 6.42 (t, 1H, J = 2.0, Tp), 7.37 (d, 1H, J = 2.0, Tp), 7.60 (d, 1H, J = 2.0, Tp), 7.66 (d, 1H, J = 2.0, Tp) 7.77 (d, 1H, J = 2.0, Tp), 7.81 (d, 1H, J = 2.0, Tp), 8.18 (d, 1H, J = 2.0, Tp). 13C NMR (CDCl3): δ 12.9 (d, J = 29.5, PMe3), 39.9 (s, C7), 44.4 (s, C3a), 53.0 (s, OMe), 57.1 (s, C5), 58.7 (s, C3), 60.0 (d, J = 13.2, C4), 77.4 (s, C7a), 106.0 (s, Tp), 106.4 (s, Tp), 107.2 (s, Tp), 136.1 (s, Tp), 136.9 (s, Tp), 137.1 (s, Tp), 140.0 (s, Tp), 142.9 (s, Tp), 143.5 (s, Tp), 168.5 (s, methyl ester carbonyl), 171.6 (s, C2), 203.9 (s, C6). Cyclic voltammetry: Ep,a = þ0.88 V. IR: νCO (lactone) =1776 cm-1; νCO (ester) =1734 cm-1; νCO (ketone) = 1621 cm-1; νNO = 1565 cm-1. HRMS [M þ H]þ obsd (%), calcd (%), diff. in ppm: 712.15691 (79.5), 712.15747 (83.8), 0.8; 713.15897 (80.2), 713.16004 (79.8), 1.5; 714.15914 (100), 714.15989 (100), 1.1; 715.16347 (43.6), 715.16406 (43.6), 0.8; 716.16257 (68.5), 716.16313 (84.1), 0.8. (4R,5S)-4,5-Dihydroxy-5-methyl-2-cyclhexen-1-one (23). Complex 11 (0.0506 g, 0.078 mmol) was added to ceric ammonium nitrate, CAN (0.043 g, 0.078 mmol), followed by 0.5 mL of acetonitrile. The reaction solution was dark orange and heterogeneous. After stirring 10 min the reaction solution was added to 50 mL of Et2O, resulting in an orange precipitate. The precipitate was filtered and discarded; then the filtrate solvent was removed in vacuo. The residue was dissolved in 1.5 mL of CHCl3 and loaded onto a glass supported silica gel preparatory TLC plate (500 μm 20 cm 20 cm) and eluted with 100% EtOAc. The silica containing a UV absorbent band with an Rf = 0.36 was removed from the plate and was slowly washed with 50 mL of EtOAc over a 15 mL fine-porosity fritted funnel. The EtOAc was removed in vacuo, yielding a clear liquid residue in 71% NMR yield. Characterization of 23 has been previously published.39 5-Hydroxy-5-methyl-4-(phenylamino)cyclohex-2-enone (24). Acetone was added to a vial containing 17 (0.109 g, 0.151 mmol)

Article and DDQ (0.073 g, 0.320 mmol) to make a heterogeneous brown solution that became homogeneous after about 2 min. After 13 min the solvent was removed in vacuo to give a black residue. The residue was triturated with 3 4 mL of Et2O, and then the residue was allowed to stir with 15 mL of Et2O for ∼15 h. The precipitate from each trituration was removed via filtration through Celite. The solvent was removed in vacuo and loaded onto a 500 μm 20 cm 20 cm SiO2 preparatory TLC plate and eluted with 1:1 EtOAc-hexanes. The band between Rf 0.37 and 0.46 was scraped from the plate and stirred in EtOAc (15 mL) for ∼30 min. The solution was filtered over a 60 mL course-porosity fritted glass funnel containing 2 cm of Celite on 2 cm of sand, covered with 1 cm of sand, and washed with 200 mL of EtOAc, and the solvent was removed to give a yellow residue (0.018 g, 0.083 mmol, 55% yield). 1H NMR (500 MHz, CDCl3): δ 1.48 (s, 3H, Me), 2.57 (s, 1H, OH), 2.69 (d, J = 16.3, 1H, H60 ), 2.73 (d, J = 16.3, 1H, H6), 4.23 (m, 2H, H4/NH), 6.13 (d, J = 10.1, 1H, H2), 6.73 (d, J = 8.5, 2H, H8), 6.8 (m, 2H, H3/H10), 7.26 (m, 2H, H9). 13C NMR (CDCl3): δ 27.2 (Me), 51.4 (C6), 57.4 (C4), 74.7 (C5), 113.9 (C8), 118.7 (C10), 129.4 (C2), 129.8 (C9), 146.8 (C7), 148.5 (C3), 197.9 (C1). IR: ν(OH) = 3394 cm-1, ν(CO enone) = 1665 cm-1. HRMS [M þ Na]þ obsd (%), calcd (%), diff. in ppm: 240.1005 (100), 240.0995 (100), 4.3. 5-Hydroxy-5-methyl-4-(phenylthio)cyclohex-2-enone (25). A solution of DDQ (0.048 g, 0.212 mmol) in acetone-d6 (1.01 g) was added to a vial containing 9 (0.075 g, 0.101 mmol) to make a red homogeneous solution after about 1 min. After 25 min, the reaction solution was evaporated in vacuo. The residue was stirred in Et2O (15 mL) for ∼15 h. The brown precipitate was collected on a 30 mL medium-porosity fritted funnel, washed with 2 10 mL of Et2O, and discarded. The filtrate solvent was removed in vacuo. The residue was triturated with 2 4 mL of CHCl3, and the precipitate was removed via filtration through Celite. The filtrate solvent was removed in vacuo, and the residue was loaded onto a 500 μm 20 cm 20 cm SiO2 preparatory TLC plate and eluted with 1:1 EtOAc-hexanes. The band between Rf 0.38 and 0.53 was scraped from the plate, and the SiO2 was sonicated in 15 mL of EtOAc for 10 min, filtered on a 60 mL course-porosity fritted glass funnel containing 2 cm of Celite on 2 cm of sand, covered with 1 cm of sand, and washed with 200 mL of EtOAc. The solvent was removed in vacuo to leave a pale yellow residue (0.014 g, 0.060 mmol, 59% yield). 1H NMR (500 MHz, CDCl3): δ 1.45 (d, J = 0.9, 3H, Me), 2.54 (ddd, J = 16.0, 0.9, 0.9, 1H, H60 ), 2.71 (d, J = 16.0, 1H, H6), 2.84 (s, 1H, OH), 3.91 (ddd, J = 4.9, 1.5, 0.9, 1H, H4), 5.98 (dd, J = 9.9, 1.5, 1H, H2), 6.97 (dd, J = 9.9,


4803

4.9, 1H, H3), 7.28-7.36 (m, 3H, Ph), 7.53 (m, 2H, Ph). 13C NMR (CDCl3): δ 27.2 (Me), 50.6 (C6), 58.4 (C4), 72.5 (C5), 128.0 (C2), 128.3 (Ph), 129.6 (Ph), 132.4 (Ph), 134.0 (C7), 146.3 (C3), 197.6 (C1). IR: ν(OH) = 3443 cm-1, ν(Enone-CO) = 1671 cm-1. HRMS [M þ Na]þ obsd (%), calcd (%), diff. in ppm: 257.0613 (100), 257.0607 (100), 2.4. 6-Hydroxy-6-methyl-4-oxocyclohex-2-enyl benzoate (26). 15 (0.100 g, 0.159 mmol) was dissolved in MeCN (∼1 mL) and acetone (∼1 mL) to make a pale yellow heterogeneous solution. The solution became homogeneous upon the addition of benzoic acid (0.021 g, 0.175 mmol). After several minutes a white precipitate formed. Twenty-four hours later H2O was added (∼2 mL). Then 5.5 h later CHCl3 (∼10 mL) and H2O (∼6 mL) were added to the solution. The CHCl3 solution was extracted with 3 3 mL of K2CO3 (1 M in H2O). The organic layer was dried with MgSO4, which was filtered through a 15 mL mediumporosity fritted funnel. The yellow residue was dissolved in CHCl3 (∼1.5 mL) and added to Et2O (∼15 mL) to precipitate a yellow solid. The precipitate was collected on a 15 mL medium-porosity fritted funnel and dried in vacuo (0.076 g, 0.103 mmol, 59% yield). A solution of DDQ (0.032 g, 0.014 mmol) in acetone-d6 (1.00 g) was added to a vial containing a portion of the isolated complex (0.048 g, 0.064 mmol). Isolation of a pale yellow residue (0.0086 g, 0.0349 mmol, 54% yield) was accomplished using an identical procedure to that of 25. 1H NMR (500 MHz, CDCl3): δ 1.4 (s, 3H, Me), 2.16 (s, 1H, OH), 2.62 (d, J = 16.4, 1H, H50 ), 2.82 (dd, J = 16.4, 1.1, 1H, H5), 5.84 (dd, J = 2.7, 2.1, 1H, H1), 6.19 (ddd, J = 10.3, 2.1, 1.1, 1H, H3), 6.76 (dd, J = 10.3, 2.7, 1H, H2), 7.50 (m, 2H, H10), 7.63 (m, 1H, H11), 8.09 (m, 2H, H9). 13C NMR (CDCl3): δ 26.8 (Me), 49.6 (C5), 74.0 (C6), 74.3 (C1), 128.9 (C10), 129.2 (C8), 130.0 (C9), 131.1 (C3), 134 (C11), 144.4 (C2), 166 (C7), 196.4 (C4). IR: ν(OH) = 3476 cm-1, ν(CO) = 1718 cm-1, ν(Enone-CO) = 1685 cm-1. HRMS [M þ Na]þ obsd (%), calcd (%), diff. in ppm: 269.0783 (100), 269.0784 (100), 0.4.

Acknowledgment. This work was supported by the NSF (CHE-0111558 (UVA), 9974875 (UVA), 0116492 (UR), and 0320669 (UR)). Supporting Information Available: Full synthetic details for the preparation of compounds, selected spectra of these compounds, and crystallographic information for 2, 3, 7, 10, 11, 14, and 22. This material is available free of charge via the Internet at http://pubs.acs.org.

Epoxidation, Cyclopropanation, and Electrophilic Addition Reactions

Recommend Documents