PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Adv Synth Catal. Author manuscript; available in PMC 2010 May 6.
Published in final edited form as:
Adv Synth Catal. 2008 July 7; 350(10): 1569–1576.
doi:  10.1002/adsc.200800242
PMCID: PMC2865154
NIHMSID: NIHMS195855

Direct Copper-Free Domino Conjugate Addition-Cycloallylation using Organozinc Reagents

Abstract

The Direct Approach: Enones possessing appendant allylic carbonates react directly with diorganozinc reagents in the presence of zinc diiodide [ZnI2] to provide 5- and 6-membered ring products of tandem or domino conjugate addition-cycloallylation in good to excellent yield. In a related copper-free transformation, allylic carbonates are found to engage in direct allylic substitution with diorganozinc reagents.

Keywords: allylic substitution, catalysis, C–C bond formation, domino reactions, organozinc reagents

Introduction

The development of “tandem,” “cascade” or “domino” C–C bond forming processes remains at the forefront of research, as such transformations promote large increases in molecular complexity.[1,2] As part of a broad program in catalytic reaction development, we have examined conjugate addition-electrophilic trapping[3] as a modular means of devising catalytic processes wherein sequential construction of two C–C bonds is accompanied by ring formation. Through variation of the nucleophilic initiator and terminal electrophile, a diverse family of conjugate addition-cyclization reactions has been devised.[47] These include highly diastereoselective Co-catalyzed conjugate reduction-aldol and Michael cyclizations mediated by silane,[4] Rh-catalyzed conjugate reduction-aldol cyclizations mediated by hydrogen,[5] diastereo- and enantioselective Rh-catalyzed conjugate addition-aldol cyclizations employing arylboronic acids,[6] as well as Cu-catalyzed conjugate addition of diorganozinc reagents with subsequent aldol, Blaise–Thorpe–Ziegler, Dieckmann and Michael cyclizations.[ 7] Beyond the transformations developed in our lab, several elegant examples of tandem or “domino” processes predicated on metal-catalyzed conjugate addition-electrophilic trapping have been reported by others.[8,1216]

Recently, the development of catalytic methods for the direct[9] and indirect[10] asymmetric allylation of ketones has received considerable attention. In connection with our interest in catalytic conjugate addition-electrophilic trapping,[36] the direct allylation of ketone enolates that arise upon enone conjugate addition was examined. It is known that zinc enolates produced in the course of copper-catalyzed conjugate addition[ 11] may be trapped by aldehydes,[12] tethered halides and tosylates,[13] oxocarbenium ions (by way of acetal decomposition),[14] and allylic carboxylates.[12a,15,16] All of these transformations involve capture of stoichiometrically preformed zinc enolates and, in the latter case, allylation is achieved by exposing the preformed zinc enolate to an allylic acetate in the presence of a palladium catalyst. However, related conjugate addition-cyclizations onto tethered enones, ketones, esters and nitriles establish that enolate preformation is not a precondition for such anionic cascades.[6] Indeed, here we disclose that conjugate addition-intramolecular allylation requires neither a copper nor palladium catalyst.[17] Both primary and secondary organozinc reagents react directly with mono-enone mono-allylic carbonates to afford 5- and 6-membered ring products of domino conjugate addition-allylation [Eq. (1)]. Additionally, we find that allylic carbonates engage in direct substitution with diorganozinc reagents under copper-free conditions [Eq. (2)].[18]

equation image
(1)

equation image
(2)

Results and Discussion

Our studies began with an examination of mono-enone mono-allylic carbonate 1a. Exposure of 1a to Et2Zn (300 mol%) in the presence of Cu(OTf)2 (2.5 mol%) and (EtO)3P (5 mol%) at −78 °C in dichloromethane solvent (0.1 M) results in conjugate addition without cyclization onto the tethered allylic carbonate. However, when the reaction was allowed to warm to ambient temperature, a 71% isolated yield (5.2:1 dr) of the conjugate addition-cycloallylation product 1b was obtained (Table 1, entry 1). At this point, control experiments were performed and a significant background reaction was revealed: cycloallylation product 1b is formed in 14% isolated yield (3.4:1 dr) when the reaction is conducted at ambient temperature in the absence of the copper catalyst (Table 1, entry 2). In the interest of optimizing this copper-free process, the effect of various additives was examined. Eventually it was found that reactions conducted in the presence of ZnI2 proceed with greater efficiency.[19] Indeed, the yield of 1b is increased from 14% to 54% when the reaction is conducted using one equivalent of ZnI2 (Table 1, entry 4). Other sources of iodide ion, such as Bu4NI, suppress the reaction (Table 1, entry 6). In contrast, the addition of zinc(II) ion, for example Zn(OTf)2, appears to be generally beneficial, and ZnI2 is the best promoter among those screened (Table 1, entry 7). A slight increase in temperature to 35 °C was also found to facilitate conjugate addition-cycloallylation. The isolated yield of 1b is 58% and 72% for reactions conducted in the absence and presence of ZnI2, respectively, at 35°C (Table 1, entries 8 and 9). The latter reaction conditions represent our standard protocol for conjugate addition-cycloallylation (Table 1, entry 9).

Table 1
Conjugate addition-cycloallylation of 1a using Et2Zn.[a]

To explore the scope of this process, mono-enone mono-allylic carbonates 1a7a were exposed to the diorganozinc reagent (300 mol%) in the presence of ZnI2 (100 mol%) at 35 °C in DCM (0.1 M). For each substrate, reactions with Et2Zn and i-Pr2Zn were examined. As demonstrated by the cyclizations of substrates 1a and 2a, both 5- and 6-membered ring formation is possible (Table 2, entries 1 and 2). Heteroaromatic enones 3a and 4a, which incorporate 2-furyl and 3-indolyl residues, participate in the cyclization (Table 2, entries 3 and 4), as do aliphatic enones 5a and 6a (Table 2, entries 5 and 6). Interestingly, the α,β-unsaturated ester 7a does not cyclize upon exposure to Et2Zn. Rather, the product of allylic substitution 7b, in which the enone moiety remains intact, was obtained in 35% yield. However, use of i-Pr2Zn, which is more reactive with respect to conjugate addition, provides the cyclized product 7c in good yield (Table 2, entry 7). Diastereoselectivities range from 1.3–5.2:1. The relative stereochemistry of the five-and six-membered ring products 1b,c7b,c was determined as follows. Hydrogenation of the five-membered ring product 1b generates a mixture of two diastereomers. The non-symmetric diastereomer 1d appears as the major isomer and the symmetric diastereomer 1e appears as the minor isomer. The stereochemical assignment of the remaining five-membered ring products is made in analogy to the stereochemical assignment of 1b. The stereochemical assignment of the six-membered ring products is based upon evaluation of the coupling constants in the 1H NMR. For example, in the 1H NMR spectrum of compound 2b, proton Ha appears as a triplet at δ = 3.05 ppm with a coupling constant Ja,b = Ja,c = 10.8 Hz. These data suggest a trans-diaxial relationship between the methine hydrogens Ha, Hb, and Hc (Scheme 1, top). A plausible model enabling prediction of relative stereochemistry involves addition of the Z-enolate to the tethered allylic carbonate, which resides in an extended conformation (Scheme 1, bottom).

Scheme 1
Top: Stereochemical assignment of compounds 1b and 2b. Bottom: Proposed stereochemical model.
Table 2
Conjugate addition-cycloallylation 1a7a employing Et2Zn and i-Pr2Zn.[a]

The divergent outcome observed in the reaction of enoate 7a with Et2Zn versus i-Pr2Zn merited further investigation in view of the fact that direct substitution reactions of allylic acetates or allylic carbonates with diorganozinc reagents or zinc enolates, to our knowledge, has not been described.[18] Surprisingly, direct substitution of methyl carbonate 8a occurs spontaneously upon exposure to Et2Zn (300 mol%) in the presence of ZnI2 (100 mol%) to deliver the products of allylic substitution 8b and 8c in 48% yield as a 1.7:1 mixture of regioisomers, respectively. The yield of 8b and 8c is increased to 72% if ZnI2 is omitted from the reaction. In order to evaluate the nature of the reactive intermediate, the regioisomeric carbonate iso-8a was exposed to Et2Zn under identical conditions in the absence of ZnI2. The products of allylic substitution 8b and 8c were produced in 61% yield as a 1.7:1 mixture of regioisomers. Similarly, 9a and iso-9a were exposed to Et2Zn under identical conditions to produce allylic substitution products 9b and 9c. In each case, a 1:1.6 ratio was observed. These data suggest intervention of a common reactive intermediate, such as a zinc-π-allyl, or possibly an equimolar distribution of σ-allyl haptomers which rapidly equilibrate through the intermediacy the π-allyl haptomer. As demonstrated by the reaction of allylic carbonate 10a, this method is preparatively useful in the case of systems possessing identical allylic termini. Corresponding reactions of allylic acetates gave diminished yields of substitution product (Scheme 2).[20]

Scheme 2
Direct substitution of allylic carbonates 8a, iso-8a, 9a, iso-9a, and 10a by diethylzinc.

Conclusions

In summary, through the use of enone-electrophile templates, one may systematically evaluate the reactivity of various transition metal enolates, thereby discovering new patterns of reactivity and, ultimately, new C–C coupling processes. In the present study, we find that diorganozinc reagents engage enones in direct conjugate addition reactions.[17] More surprisingly, the resulting zinc enolates engage appendant allylic carbonates in SN2’ type substitution reactions in the absence of a copper or palladium catalyst.[12a,15,16] Finally, in a related copper-free transformation, allylic carbonates are found to participate in direct allylic substitution reactions with the diorganozinc reagent, Et2Zn.[18] The new patterns of reactivity uncovered by this study set the stage for the development of corresponding stereoselective variants of the transformations reported herein.[17d]

Experimental Section

See Supporting Information for spectroscopic data.

Carbonic Acid Methyl 8-Oxo-8[1-(toluene-4-sulfonyl)-1H-indol-3-yl]-octa-2,6-dienyl Ester (4a)

To a solution of carbonic acid 8-(1H-indol-3-yl)-8-oxo-octa-2,6-dienyl methyl ester[16b] (240 mg, 0.76 mmol, 100 mol%) at 0 °C in dichloromethane (4.0 mL) were added tosyl chloride (220 mg, 1.15 mmol, 150 mol%), triethylamine (0.16 mL, 1.15 mmol, 150 mol%) and a catalytic amount of DMAP (9 mg, 0.07 mmol, 10 mol%). The reaction mixture was stirred at ambient temperature for 2 h and quenched with aqueous ammonium chloride solution and extracted with dichloromethane (2 × 20 mL). The organic layer was washed with brine solution (20 mL), dried (Na2SO4), filtered and the resulting liquor was concentrated under vacuum. Purification of the oily residue by flash column chromatography (SiO2: 20% ethyl acetate:hexanes, Rf = 0.25) provides the title compound as an yellow solid, mixture of E:Z (8:1) isomers; yield: 330 mg (0.70 mmol, 92%).

General Procedure for Tandem Conjugate Addition–Cycloallylation Reaction with Diorganozinc Reagents; Preparation of (2-Ethyl-5-vinylcyclopentyl)phenylmethanone (1b)

To a suspension of the substrate 1a[21] (50 mg, 0.18 mmol, 100 mol%) and zinc iodide (58 mg, 0.18 mmol, 100 mol%) in dichloromethane at 0 °C in a 15-mL sealed tube under argon atmosphere was added a 1.0 M diethylzinc solution in hexanes (0.54 mL, 0.54 mmol, 300 mol%) over a period of 5 min. Once the addition was complete, the reaction vessel was flushed with argon, sealed tightly and the reaction mixture was stirred at 35 °C for 10.5 h. The reaction mixture was cooled to room temperature, quenched with four drops of water and stirred for 30–40 min. The reaction mixture was filtered through a pad of celite and the resulting liquor was concentrated under vacuum. Purification of the oily residue by flash column chromatography (SiO2: 3% diethyl ether:hexanes, Rf = 0.30) provides the title compound as a colorless oil, 5.2:1 mixture of diastereomers; yield: 30 mg (0.13 mmol, 72%).

(2-Isopropyl-5-vinylcyclopentyl)phenylmethanone (1c)

In accordance with the general procedure, substrate 1a (50 mg, 0.18 mmol, 100 mol%) was exposed to diisopropyl-zinc (0.54 mL, 0.54 mmol, 300 mol%) and zinc iodide (58 mg, 0.18 mmol, 100 mol%). Purification by flash column chromatography (SiO2: 2% diethyl ether:hexanes, Rf = 0.3) provides the title compound as a colorless oil, 3.8:1 mixture of diastereomers; yield: (43 mg, 0.18 mmol, 97%).

(2-Ethyl-6-vinyl-cyclohexyl)phenylmethanone (2b)

In accordance with the general procedure, substrate 2a (100 mg, 0.36 mmol, 100 mol%) was exposed to diethylzinc (1.04 mL, 1.10 mmol, 300 mol%) and zinc iodide (110 mg, 0.36 mmol, 100 mol%). Purification by flash column chromatography (SiO2: 2% diethyl ether:hexanes, Rf = 0.24) provides the title compound as a colorless oil, 2.5:1 mixture of diastereomers; yield: 50 mg (0.21 mmol, 60%).

(2-Isopropyl-6-vinylcyclohexyl)phenylmethanone (2c)

In accordance with the general procedure, substrate 2a (50 mg, 0.17 mmol, 100 mol%) was exposed to diisopropyl-zinc (0.52 mL, 0.52 mmol, 300 mol%) and zinc iodide (55 mg, 0.17 mmol, 100 mol%). Purification by flash column chromatography (SiO2: 2% diethyl ether:hexanes, Rf = 0.26) provides the title compound as a colorless oil, 1.4:1 mixture of diastereomers; yield: 33 mg (0.13 mmol; 78%).

(2-Ethyl-5-vinylcyclopentyl)furan-2-ylmethanone (3b)

In accordance with the general procedure, substrate 3a (66 mg, 0.27 mmol, 100 mol%) was exposed to diethylzinc (0.80 mL, 0.80 mmol, 300 mol%) and zinc iodide (85 mg, 0.27 mmol, 100 mol%). Purification by flash column chromatography (SiO2: 5% ethyl acetate:hexanes, Rf = 0.30) provides the title compound as an yellow oil, 3.1:1 mixture of diastereomers; yield: 41 mg (0.19 mmol, 71%).

(2-Isopropyl-5-vinylcyclopentyl)furan-2-ylmethanone (3c)

In accordance with the general procedure, substrate 3a (76 mg, 0.31 mmol, 100 mol%) was exposed to diisopropyl-zinc (0.92 mL, 0.92 mmol, 300 mol%) and zinc iodide (98 mg, 0.31 mmol, 100 mol%). Purification by flash column chromatography (SiO2: 5% ethyl acetate:hexanes, Rf = 0.30) provides the title compound as a yellow oil, 2.6:1 mixture of diastereomers; yield: 59 mg (0.29 mmol, 80%).

(2-Ethyl-5-vinylcyclopentyl)-[1-(toluene-4-sulfonyl)-1-H-indol-3-yl]methanone (4b)

In accordance with the general procedure, substrate 4a (50 mg, 0.11 mmol, 100 mol%) was exposed to diethylzinc (0.32 mL, 0.32 mmol, 300 mol%) and zinc iodide (34 mg, 0.11 mmol, 100 mol%). Purification by flash column chromatography (SiO2: 5% ethyl acetate:hexanes, Rf = 0.23) provides the title compound as an yellow oil, 2.6:1 mixture of diastereomers; yield: 23 mg (0.05 mmol, 51%).

(2-Isopropyl-5-vinylcyclopentyl)-[1-(toluene-4-sulfonyl)-1-H-indol-3-yl]methanone (4c)

In accordance with the general procedure, substrate 4a (67 mg, 0.14 mmol, 100 mol%) was exposed to diisopropyl-zinc (0.43 mL, 0.43 mmol, 300 mol%) and zinc iodide (46 mg, 0.14 mmol, 100 mol%). Purification by flash column chromatography (SiO2: 5% ethyl acetate:hexanes, Rf = 0.26) provides the title compound as a yellow oil, 2.9:1 mixture of diastereomers; yield: 32 mg (0.07 mmol, 54%).

(2-Ethyl-5-vinylcyclopentyl)ethanone (5b)

In accordance with the general procedure, substrate 5a (80 mg, 0.38 mmol, 100 mol%) was exposed to diethylzinc (1.1 mL, 1.13 mmol, 300 mol%) and zinc iodide (120 mg, 0.38 mmol, 100 mol%). Purification by flash column chromatography (SiO2: 5% diethyl ether:hexanes, Rf = 0.30) provides the title compound as a colorless oil, 4:1 mixture of diastereomers; yield: 41 mg (0.24 mmol, 66%).

(2-Isopropyl-5-vinylcyclopentyl)ethanone (5c)

In accordance with the general procedure, substrate 5a (52 mg, 0.24 mmol, 100 mol%) was exposed to diisopropyl-zinc (0.73 mL, 0.73 mmol, 300 mol%) and zinc iodide (78 mg, 0.24 mmol, 100 mol%). Purification by flash column chromatography (SiO2: 3% diethyl ether:hexanes, Rf = 0.30) provides the title compound as an yellow oil, 4.0:1 mixture of diastereomers; yield: 34 mg (0.18 mmol, 75%).

Cyclopropyl-(2-ethyl-5-vinylcyclopentyl)methanone (6b)

In accordance with the general procedure, substrate 6a (100 mg, 0.42 mmol, 100 mol%) was exposed to diisopropyl-zinc (1.26 mL, 1.26 mmol, 300 mol%) and zinc iodide (134 mg, 0.42 mmol, 100 mol%). Purification by flash column chromatography (SiO2: 5% diethyl ether: pentane, Rf = 0.25) provides the title compound as a colorless oil, 1.3:1 mixture of diastereomers; yield: 52 mg (0.27 mmol, 61%).

Cyclopropyl-(2-isopropyl-5-vinylcyclopentyl)methanone (6c)

In accordance with the general procedure, substrate 6a (50 mg, 0.21 mmol, 100 mol%) was exposed to diisopropyl-zinc (0.63 mL, 0.63 mmol, 300 mol%) and zinc iodide (67 mg, 0.21 mmol, 100 mol%). Purification by flash column chromatography (SiO2: 5% diethyl ether: pentane, Rf = 0.30) provides the title compound as a colorless oil, 1.5:1 mixture of diastereomers; yield: 40 mg (0.19 mmol, 87%).

Deca-2,6-dienoic Acid Ethyl Ester (7b)

In accordance with the general procedure, substrate 7a (48 mg, 0.19 mmol, 100 mol%) was exposed to diethylzinc (0.52 mL, 0.19 mmol, 300 mol%) and zinc iodide (62 mg, 0.19 mmol, 100 mol%). Purification by flash column chromatography (SiO2: 5% diethyl ether:pentane, Rf = 0.28) provides the title compound as a pale yellow oil; yield: 22 mg (0.11 mmol, 35%).

2-Isopropyl-5-vinylcyclopentanecarboxylic Acid Ethyl Ester (7c)

In accordance with the general procedure, substrate 7a (100 mg, 0.41 mmol, 100 mol%) was exposed to diisopropyl-zinc (1.27 mL, 1.27 mmol, 300 mol%) and zinc iodide (130 mg, 0.41 mmol, 100 mol%). Purification by flash column chromatography (SiO2: 5% ethylacetate:hexanes, Rf = 0.24) provides the title compound as a colorless oil, 2.6:1 mixture of diastereomers; yield: 71 mg (0.33 mmol, 77%).

(2,5-Diethylcyclopentyl)phenylmethanone (1d)

To a solution of compound 1b (40 mg, 0.17 mmol, 100 mol%) in ethanol (2.0 mL) in a 10-mL round-bottomed flask, was added a catalytic amount of palladium catalyst on charcoal (18 mg, 0.017 mmol, 10 mol%) and stirred under hydrogen atmosphere at ambient temperature for 48 h. The reaction mixture was filtered through a celite pad with the aid of ethyl acetate (20 mL). The organic layer was concentrated under vacuum. Purification by flash column chromatography (SiO2: 2% ethyl acetate:hexanes, Rf = 0.30) provides the title compound as a colorless oil, 5:1 mixture of diastereomers; yield: 37 mg (0.16 mmol, 92%).

General Procedure for the Allylic Substitution of Allylic Carbonates with Diorganozinc Reagents

In a 15-mL sealable test tube charged with carbonate 8a (100 mg, 0.52 mmol, 100 mol%) was added dichloromethane (5.2 mL). The vessel was purged with argon gas and kept under a blanket of argon gas. The reaction mixture was cooled to 0 °C and a 1.0 M diethylzinc solution in hexanes (1.56 mL, 1.56 mmol, 300 mol%) was added over a period of 5 min. Once the addition was complete, the vessel was immediately sealed and the reaction mixture was warmed to 35 °C. The reaction mixture was allowed to stir for 16 h, at which point 5 drops of water were added to the reaction mixture. The reaction mixture was filtered through a pad of silica gel with the aid of dichloromethane and the solution was concentrated under vacuum. Purification of the residue by flash column chromatography (SiO2: neat hexanes) provides 8b and 8c, 1.7:1 mixture of regioisomers; yield: 54 mg (0.36 mmol, 72%).

3-Phenyl-1-pentene (8b) and (E)-1-Phenyl-1-pentene (8c)

In accordance with the general procedure, substrate iso-8a (100 mg, 0.52 mmol, 100 mol%) was exposed to diethylzinc (1.56 mL, 1.56 mmol, 300 mol%). Purification by flash column chromatography (SiO2: neat hexanes, Rf = 0.50) provides 8b and 8c as a colorless oil, 1.7:1 mixture of regioisomers; yield: 47 mg (0.31 mmol, 61%). The NMR data obtained for 8b are identical to those previously reported.[21] The NMR data obtained for 8c are identical to those previously reported.[22]

(E)-4-Phenyl-2-hexene (9b) and (E)-1-Phenyl-3-methyl-1-pentene (9c)

In accordance with the general procedure, substrate 9a (100 mg, 0.48 mmol, 100 mol%) was exposed to diethylzinc (1.45 mL, 1.45 mmol, 300 mol%). Purification by flash column chromatography (SiO2: neat hexanes, Rf = 0.60) provides 9b and 9c as a colorless oil, 1:1.6 mixture of regioisomers; yield: 36 mg (0.22 mmol, 46%).

In accordance with the general procedure, substrate iso-9a (100 mg, 0.48 mmol, 100 mol%) was exposed to diethylzinc (1.45 mL, 1.45 mmol, 300 mol%). Purification by flash column chromatography (SiO2: neat hexanes, Rf = 0.60) provides 9b and 9c as a colorless oil, 1:1.6 mixture of two regioisomers; yield: 41 mg (0.25 mmol, 52%). The NMR data for 9b are identical to those previously reported.[23] The NMR data obtained for 9c are identical to those previously reported.[24]

(E)-1,3-Diphenyl-1-pentene (10b)

In accordance with the general procedure, substrate 10a (100 mg, 0.37 mmol, 100 mol%) was exposed to diethylzinc (1.19 mL, 1.19 mmol, 300 mol%). Purification by flash column chromatography (SiO2: neat hexanes, Rf = 0.60) provides 10b as a colorless oil; yield: 70 mg (0.31 mmol, 84%). The NMR data obtained for 10b are identical to those previously reported.[25]

Supplementary Material

Supplementary Data

Acknowledgements

Acknowledgements is made to the Robert A. Welch Foundation (F-1466), the Dreyfus Foundation, the Eli Lilly Faculty Grantee program, the Research Corporation Cottrell Scholar Award (CS0927) and the Alfred P. Sloan Foundation for partial support of this research.

Footnotes

Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.

References

1. For selected reviews on “tandem,” “cascade” or “domino” transformations, see: a) Tietze LF, Beifuss U. Angew. Chem. 1993;105:137–170. Angew. Chem. Int. Ed. Engl. 1993;32:131–163. b) Tietze LF. Chem. Rev. 1996;96:115–136. [PubMed] c) Mayer SF, Kroutil W, Faber K. Chem. Soc. Rev. 2001;30:332. d) Nicolaou KC, Montagnon T, Snyder SA. Chem. Commun. 2003:551–564. [PubMed] e) Pellissier H. Tetrahedron. 2006;62:2143–2173. f) Chapman CJ, Frost CG. Synthesis. 2007:1–21. g) Walji AM, MacMillan DWC. Synlett. 2007:1477–1489. h) Miura T, Murakami M. Chem. Commun. 2007:217–224. [PubMed]
2. For selected reviews on stoichiometric conjugate addition-electrophilic trapping, see: a) Suzuki M, Noyori R. Organocopper Reagents. 1994:185–216. b) Taylor RJK. Synthesis. 1985:364–392. c) Chapdelaine MJ, Hulce M. Org. React. 1990;38:225–653. d) Ihara M, Fukumoto K. Angew. Chem. 1993;105:1059–1071. Angew. Chem. Int. Ed. Engl. 1993;32:1010–1022.
3. For selected reviews on metal catalyzed conjugate addition-electrophilic trapping, see: a) Balme G, Bouyssi D, Monteiro N. Top. Organomet. Chem. 2006;19:115–148. b) Guo H-C, Ma J-A. Angew. Chem. 2006;118:362–375. Angew. Chem. Int. Ed. 2006;45:354–366. [PubMed] c) Christoffers J, Koripelly G, Rosiak A, Rössle M. Synthesis. 2007:1279–1300.
4. For Co-catalyzed 1,4-reduction-aldol and Michael cyclization, see: a) Baik T-G, Luiz A-L, Wang L-C, Krische MJ. J. Am. Chem. Soc. 2001;123:5112–5113. [PubMed] b) Wang L-C, Jang H-Y, Roh Y, Schultz AJ, Wang X, Lynch V, Krische MJ. J. Am. Chem. Soc. 2002;124:9448–9453. [PubMed]
5. For Rh-catalyzed 1,4-reduction-aldol cyclization, see: a) Jang H-Y, Huddleston RR, Krische MJ. J. Am. Chem. Soc. 2002;124:15156–15157. [PubMed] b) Huddleston RR, Krische MJ. Org. Lett. 2003;5:1143–1146. [PubMed] c) Huddleston RR, Cauble DF, Krische MJ. J. Org. Chem. 2003;68:11–14. [PubMed] d) Koech P, Krische MJ. Org. Lett. 2004;6:691–694. [PubMed]
6. For diastereo- and enantioselective Rh-catalyzed 1,4-addition-aldol cyclization, see: a) Cauble DF, Gipson JG, Krische MJ. J. Am. Chem. Soc. 2003;125:1110–1111. [PubMed] b) Bocknack BM, Wang L-C, Krische MJ. Proc. Natl. Acad. Sci. USA. 2004;101:5421–5424. [PubMed]
7. For Cu-catalyzed and mediated conjugate addition-aldol, Blaise-Thorpe–Ziegler, Dieckmann and Michael cyclizations, see: a) Agapiou K, Cauble DF, Krische MJ. J. Am. Chem. Soc. 2004;126:4528–4529. [PubMed] b) Yang J, Cauble DC, Berro AJ, Bauld NL, Krische MJ. J. Org. Chem. 2004;69:7979–7984. [PubMed]
8. For additional examples of tandem or “domino” C–C bond forming processes based on metal catalyzed conjugate addition-electrophilic trapping, see: a) Yamada K, Arai T, Sasai H, Shibasaki M. J. Org. Chem. 1998;63:3666. b) Yoshida K, Ogasawara M, Hayashi T. J. Am. Chem. Soc. 2002;124:10984–10985. [PubMed] c) Subburaj K, Montgomery J. J. Am. Chem. Soc. 2003;125:11210–11211. [PubMed] d) Li K, Alexakis A. Tetrahedron Lett. 2005;46:8019–8022. e) Nicolaou KC, Tang W, Dagneau P, Faraoni R. Angew. Chem. 2005;117:3942–3947. Angew. Chem. Int. Ed. 2005;44:3874–3879. [PubMed] f) Howell GP, Fletcher SP, Geurts K, ter Horst B, Feringa BL. J. Am. Chem. Soc. 2006;128:14977–14985. [PubMed] g) Shintani R, Yamagami T, Hayashi T. Org. Lett. 2006;8:4799–4801. [PubMed] h) Miura T, Harumashi T, Murakami M. Org. Lett. 2007;9:741–743. [PubMed] i) Le Nôtre J, van Mele D, Frost CG. Adv. Synth. Catal. 2007;349:432–440. j) Oisaki K, Zhao D, Kanai M, Shibasaki M. J. Am. Chem. Soc. 2007;129:7439–7443. [PubMed]
9. For direct asymmetric allylation of ketone enolates, see: a) Trost BM, Tang W. J. Am. Chem. Soc. 2003;125:8744–8745. [PubMed] b) Trost BM, Pissot-Soldermann C, Chen I, Schroeder GM. J. Am. Chem. Soc. 2004;126:4480–4881. [PubMed] c) Zheng W-H, Zheng B-H, Zhang Y, Hou X-L. J. Am. Chem. Soc. 2007;129:7718–7719. [PubMed]
10. For indirect asymmetric allylation of ketones, see: a) Kazmaier U. Curr. Org. Chem. 2003;7:317–328. b) Behenna DC, Stoltz BM. J. Am. Chem. Soc. 2004;126:15044–15045. [PubMed] c) Trost BM, Xu J. J. Am. Chem. Soc. 2005;127:2846–2847. [PubMed] d) Trost BM, Xu J. J. Am. Chem. Soc. 2005;127:17180–17181. [PubMed]
11. For selected reviews on enantioselective Cu-catalyzed conjugate addition, see: a) Alexakis A, Benhaim C. Eur. J. Org. Chem. 2002:3221–3236. b) Feringa BL, Naasz R, Imbos R, Arnold LA. In: Modern Organo-copper Chemistry. Krause N, editor. Dortmund: Wiley-VCH; 2002. pp. 224–258. c) Feringa B. Acc. Chem. Res. 2000;33:346–353. [PubMed]
12. For aldehydes as terminal electrophiles in Cu-catalyzed conjugate addition-electrophilic trapping, see: a) Kitamura M, Miki T, Nakano K, Noyori R. Tetrahedron Lett. 1996;37:5141–5144. b) Feringa BL, Pineschi M, Arnold LA, Imbos R, de Vries AHM. Angew. Chem. 1997;109:2733–2736. Angew. Chem. Int. Ed. Engl. 1997;36:2620–2623. c) Keller E, Maurer J, Naasz R, Schader T, Meetsma A, Feringa BL. Tetrahedron: Asymmetry. 1998;9:2409–2413. d) Arnold LA, Naasz R, Minnaard AJ, Feringa BL. J. Org. Chem. 2002;67:7244–7254. [PubMed]
13. For halides and tosylates as terminal electrophiles in Cu-catalyzed conjugate addition-electrophilic trapping, see: a) Degrado SJ, Mizutani H, Hoveyda AH. J. Am. Chem. Soc. 2001;123:755–756. [PubMed] b) Mizutani H, Degrado SJ, Hoveyda AH. J. Am. Chem. Soc. 2002;124:779–781. [PubMed]
14. For acetals as terminal electrophiles in Cu-catalyzed conjugate addition-electrophilic trapping, see: Alexakis A, Trevitt GP, Bernardinelli G. J. Am. Chem. Soc. 2001;123:4358–4359. [PubMed]
15. For allylic carboxylates as terminal electrophiles in Cu-catalyzed conjugate addition-electrophilic trapping, see: Naasz R, Arnold LA, Pineschi M, Keller E, Feringa BL. J. Am. Chem. Soc. 1999;121:1104–1105. see also ref.[12a]
16. For related catalytic 1,4-addition-allylations, see: a) Muraoka T, Matsuda I, Itoh K. J. Am. Chem. Soc. 2000;122:9552–9553. b) Jellerichs BG, Kong J-R, Krische MJ. J. Am. Chem. Soc. 2003;125:7758–7759. [PubMed]
17. The uncatalyzed conjugate addition of diorganozinc reagents to enones is highly uncommon: a) Hanson MV, Rieke RD. J. Am. Chem. Soc. 1995;117:10775–10776. b) Reddy Ch. K, Devasagayaraj A, Knochel P. Tetrahedron Lett. 1996;37:4495–4498. c) Jones P, Reddy Ch. K, Knochel P. Tetrahedron. 1998;54:1471–1490. d) Bräse S, Höfener S. Angew. Chem. 2005;117:8091–8093. Angew. Chem. Int. Ed. 2005;44:7879–7881. [PubMed]
18. Diorganozincs react directly with allylic chlorides, bromides and phosphonates in the presence of strongly Lewis basic ligands, such as DMF, HMPA, and TMEDA: Arai M, Kawasuji T, Nakamura E. Chem. Lett. 1993:357–360.
19. This is likely due to generation of the alkylzinc halide: Boersma J, Noltes JG. Tetrahedron Lett. 1966:1521–1525. and references cited therein.
20. In allylic substitutions catalyzed by palladium, competition experiments reveal that carbonates ionize more readily than acetates: a) Tsuji J, Shimizu I, Minami I, Ohashi Y. Tetrahedron Lett. 1982;23:4809–4812. b) Genet JP, Ferroud D. Tetrahedron Lett. 1984;25:3579–3582. c) Tsuji J, Shimizu I, Minami I, Ohashi Y, Sugiura T, Takahashi K. J. Org. Chem. 1985;50:1523–1529. d) Ferroud D, Genet JP, Kiolle R. Tetrahedron Lett. 1986;27:23–26. e) Oppolzer W, Gaudin J-M. Helv. Chim. Acta. 1987;70:1477–1481. f) Montforts F-P, Gesing-Zibulak I, Grammenos W, Schneider S, Laumen K. Helv. Chim. Acta. 1989;72:1852–1859. g) Genet JP, Thorimbert S, Mallart S, Kardos N. Synthesis. 1993:321–324.
21. Tanaka J, Nojima M, Kusabayashi S. J. Chem. Soc. Perkin Trans. 2. 1987:673–678.
22. Farhat S, Zouev I, Marek I. Tetrahedron. 2004;60:1329–1337.
23. Giacomelli G, Bertero L, Lardicci L, Menicagli R. J. Org. Chem. 1981;46:3707–3711.
24. Zhou J, Fu GC. J. Am. Chem. Soc. 2004;126:1340–1341. [PubMed]
25. Uozumi Y, Danjo H, Hayashi T. J. Org. Chem. 1999;64:3384–3388. [PubMed]