Direct copper-free domino conjugate addition-cycloallylation using organozinc reagents

Article abstract of DOI:10.1002/adsc.200800242

The Direct Approach: Enones possessing appendant allylic carbonates react directly with diorganozinc reagents in the presence of zinc diiodide [ZnI ₂] 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.

Full text of DOI:10.1002/adsc.200800242

FULL PAPERS
DOI: 10.1002/adsc.200800242
Direct Copper-Free Domino Conjugate Addition-Cycloallylation
using Organozinc Reagents
Venukrishnan Komanduri,a Fernando Pedraza,a and Michael J. Krischea,*
a
University of Texas at Austin, Department of Chemistry and Biochemistry, 1 University Station – A5300, Austin, TX
78712-1167, USA
Fax : (+1)-512-471-8696; e-mail: mkrische@mail.utexas.edu
Received: February 20, 2008; Revised: April 22, 2008; Published online: June 13, 2008
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: The Direct Approach: Enones possessing free transformation, allylic carbonates are found to
appendant allylic carbonates react directly with dio- engage in direct allylic substitution with diorganozinc
rganozinc reagents in the presence of zinc diiodide reagents.
[ZnI2] to provide 5- and 6-membered ring products
of tandem or domino conjugate addition-cycloallyla- Keywords: allylic substitution; catalysis; C C bond
tion in good to excellent yield. In a related copper- formation; domino reactions; organozinc reagents
À
Introduction
nection with our interest in catalytic conjugate addi-
tion-electrophilic trapping,[3–6] the direct allylation of
The development of “tandem,” “cascade” or ketone enolates that arise upon enone conjugate addi-
À
“domino” C C bond forming processes remains at tion was examined. It is known that zinc enolates pro-
the forefront of research, as such transformations pro- duced in the course of copper-catalyzed conjugate ad-
mote large increases in molecular complexity.[1,2] As dition[11] may be trapped by aldehydes,[12] tethered
part of a broad program in catalytic reaction develop- halides and tosylates,[13] oxocarbenium ions (by way
ment, we have examined conjugate addition-electro- of acetal decomposition),[14] and allylic carboxy-
philic trapping[3] as a modular means of devising cata-
A
lytic processes wherein sequential construction of two ture of stoichiometrically preformed zinc enolates
À
C C bonds is accompanied by ring formation. and, in the latter case, allylation is achieved by expos-
Through variation of the nucleophilic initiator and ing the preformed zinc enolate to an allylic acetate in
terminal electrophile, a diverse family of conjugate the presence of a palladium catalyst. However, relat-
addition-cyclization reactions has been devised.[4–7] ed conjugate addition-cyclizations onto tethered
These include highly diastereoselective Co-catalyzed enones, ketones, esters and nitriles establish that eno-
conjugate reduction-aldol and Michael cyclizations late preformation is not a precondition for such
mediated by silane,[4] Rh-catalyzed conjugate reduc- anionic cascades.[6] Indeed, here we disclose that con-
tion-aldol cyclizations mediated by hydrogen,[5] dia- jugate addition-intramolecular allylation requires nei-
stereo- and enantioselective Rh-catalyzed conjugate ther a copper nor palladium catalyst.[17] Both primary
addition-aldol cyclizations employing arylboronic and secondary organozinc reagents react directly with
acids,[6] as well as Cu-catalyzed conjugate addition of mono-enone mono-allylic carbonates to afford 5- and
diorganozinc reagents with subsequent aldol, Blaise– 6-membered ring products of domino conjugate addi-
Thorpe–Ziegler, Dieckmann and Michael cycliza- tion-allylation [Eq. (1)]. Additionally, we find that al-
tions.[7] Beyond the transformations developed in our lylic carbonates engage in direct substitution with
lab, several elegant examples of tandem or “domino”
C
Recently, the development of catalytic methods for
the direct[9] and indirect[10] asymmetric allylation of
ketones has received considerable attention. In con-
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er 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 re-
action (Table 1, entry 6). In contrast, the addition of
zinc(II) ion, for example Zn(OTf)2, appears to be
G
generally beneficial, and ZnI2 is the best promoter
among those screened (Table 1, entry 7). Aslight in-
crease in temperature to 358C was also found to facil-
itate conjugate addition-cycloallylation. The isolated
yield of 1b is 58% and 72% for reactions conducted
in the absence and presence of ZnI2, respectively, at
358C (Table 1, entries 8 and 9). The latter reaction
conditions represent our standard protocol for conju-
gate addition-cycloallylation (Table 1, entry 9).
Results and Discussion
To explore the scope of this process, mono-enone
Our studies began with an examination of mono- mono-allylic carbonates 1a–7a were exposed to the di-
enone mono-allylic carbonate 1a. Exposure of 1a to organozinc reagent (300 mol%) in the presence of
Et2Zn (300 mol%) in the presence of Cu(OTf)2 (2.5 ZnI2 (100 mol%) at 358C in DCM (0.1M). For each
U
mol%) and (EtO)3P (5 mol%) at À788C in dichloro- substrate, reactions with Et2Zn and i-Pr2Zn were ex-
methane solvent (0.1M) results in conjugate addition amined. As demonstrated by the cyclizations of sub-
without cyclization onto the tethered allylic carbon- strates 1a and 2a, both 5- and 6-membered ring for-
ate. However, when the reaction was allowed to mation is possible (Table 2, entries 1 and 2). Heteroar-
warm to ambient temperature, a 71% isolated yield omatic enones 3a and 4a, which incorporate 2-furyl
(5.2:1 dr) of the conjugate addition-cycloallylation and 3-indolyl residues, participate in the cyclization
product 1b was obtained (Table 1, entry 1). At this (Table 2, entries 3 and 4), as do aliphatic enones 5a
point, control experiments were performed and a sig- and 6a (Table 2, entries 5 and 6). Interestingly, the
nificant background reaction was revealed: cycloally- a,b-unsaturated ester 7a does not cyclize upon expo-
lation product 1b is formed in 14% isolated yield sure to Et2Zn. Rather, the product of allylic substitu-
(3.4:1 dr) when the reaction is conducted at ambient tion 7b, in which the enone moiety remains intact,
temperature in the absence of the copper catalyst was obtained in 35% yield. However, use of i-Pr2Zn,
(Table 1, entry 2). In the interest of optimizing this which is more reactive with respect to conjugate addi-
copper-free process, the effect of various additives tion, provides the cyclized product 7c in good yield
was examined. Eventually it was found that reactions (Table 2, entry 7). Diastereoselectivities range from
conducted in the presence of ZnI2 proceed with great- 1.3–5.2:1. The relative stereochemistry of the five-
and six-membered ring products 1b,c–7b,c was deter-
mined as follows. Hydrogenation of the five-mem-
Table 1. Conjugate addition-cycloallylation of 1a using
bered ring product 1b generates a mixture of two dia-
stereomers. The non-symmetric diastereomer 1d ap-
pears as the major isomer and the symmetric diaste-
reomer 1e appears as the minor isomer. The stereo-
chemical assignment of the remaining five-membered
ring products is made in analogy to the stereochemi-
cal assignment of 1b. The stereochemical assignment
of the six-membered ring products is based upon eval-
Et2Zn.[a]
1
uation of the coupling constants in the H NMR. For
1
example, in the H NMR spectrum of compound 2b,
proton Ha appears as a triplet at d=3.05 ppm with a
coupling constant Ja,b =Ja,c =10.8 Hz. These data sug-
gest a trans-diaxial relationship between the methine
hydrogens Ha, Hb, and Hc (Scheme 1, top). Aplausi-
ble model enabling prediction of relative stereochem-
istry involves addition of the Z-enolate to the teth-
ered allylic carbonate, which resides in an extended
conformation (Scheme 1, bottom).
[a]
The divergent outcome observed in the reaction of
enoate 7a with Et2Zn versus i-Pr2Zn merited further
See experimental section for detailed experimental pro-
cedures.
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Table 2. Conjugate addition-cycloallylation 1a–7a employing
Et2Zn and i-Pr2Zn.[a]
investigation in view of the fact that direct substitu-
tion 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 prod-
ucts 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 condi-
tions 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 sug-
gest intervention of a common reactive intermediate,
such as a zinc-p-allyl, or possibly an equimolar distri-
bution of s-allyl haptomers which rapidly equilibrate
through the intermediacy the p-allyl haptomer. As
demonstrated by the reaction of allylic carbonate 10a,
this method is preparatively useful in the case of sys-
tems possessing identical allylic termini. Correspond-
ing reactions of allylic acetates gave diminished yields
of substitution product (Scheme 2).[20]
Conclusions
In summary, through the use of enone-electrophile
templates, one may systematically evaluate the reac-
tivity of various transition metal enolates, thereby dis-
covering new patterns of reactivity and, ultimately,
À
new C C coupling processes. In the present study, we
find that diorganozinc reagents engage enones in
direct conjugate addition reactions.[17] More surpris-
ingly, the resulting zinc enolates engage appendant al-
lylic 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 corre-
sponding stereoselective variants of the transforma-
tions reported herein.[17d]
[a]
See experimental section for detailed experimental pro-
cedures.
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Scheme 1. Top : Stereochemical assignment of compounds 1b and 2b. Bottom: Proposed stereochemical model.
Scheme 2. Direct substitution of allylic carbonates 8a, iso-8a, 9a, iso-9a, and 10a by diethylzinc.
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FULL PAPERS
matography (SiO2: 2% diethyl ether:hexanes, Rf =0.24) pro-
vides the title compound as a colorless oil, 2.5:1 mixture of
diastereomers; yield: 50 mg (0.21 mmol, 60%).
ExperimentalSection
See Supporting Information for spectroscopic data.
(2-Isopropyl-6-vinylcyclohexyl)phenylmethanone (2c)
Carbonic Acid Methyl8-Oxo-8[1-(toul ene-4-
sulfonyl)-1H-indol-3-yl]-octa-2,6-dienyl Ester (4a)
A
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%).
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 08C in dichloromethane (4.0 mL) were added tosyl chlo-
ride (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 chromatog-
raphy (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%).
(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 chro-
matography (SiO2: 5% ethyl acetate:hexanes, Rf =0.30) pro-
vides the title compound as an yellow oil, 3.1:1 mixture of
diastereomers; yield: 41 mg (0.19 mmol, 71%).
GeneralProcedure for Tandem Conjugate Addition–
Cycloallylation Reaction with Diorganozinc
(2-Isopropyl-5-vinylcyclopentyl)furan-2-ylmethanone
(3c)
Rea
cyclopentyl)
ACHTREUNG
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%).
ACHTREUNG
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 08C in a 15-mL sealed tube under
argon atmosphere was added a 1.0M 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 mix-
ture was stirred at 358C 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 res-
idue 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-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 chro-
matography (SiO2: 5% ethyl acetate:hexanes, Rf =0.23) pro-
vides the title compound as an yellow oil, 2.6:1 mixture of
diastereomers; yield: 23 mg (0.05 mmol, 51%).
(2-Isopropyl-5-vinylcyclopentyl)phenylmethanone
(1c)
(2-Isopropyl-5-vinylcyclopentyl)-[1-(toluene-4-
sulfonyl)-1-H-indol-3-yl]methanone (4c)
A
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%).
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-6-vinyl-cyclohexyl)phenylmethanone (2b)
(2-Ethyl-5-vinylcyclopentyl)ethanone (5b)
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 chro-
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 chro-
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matography (SiO2: 5% diethyl ether:hexanes, Rf =0.30) pro-
vides the title compound as a colorless oil, 4:1 mixture of
diastereomers; yield: 41 mg (0.24 mmol, 66%).
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 concen-
trated under vacuum. Purification by flash column chroma-
tography (SiO2: 2% ethyl acetate:hexanes, Rf =0.30) pro-
vides the title compound as a colorless oil, 5:1 mixture of
diastereomers; yield: 37 mg (0.16 mmol, 92%).
(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%).
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 08C and a 1.0M 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 im-
mediately sealed and the reaction mixture was warmed to
358C. 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) pro-
vides 8b and 8c, 1.7:1 mixture of regioisomers; yield: 54 mg
(0.36 mmol, 72%).
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%).
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) pro-
vides 8b and 8c as a colorless oil, 1.7:1 mixture of regioisom-
ers; yield: 47 mg (0.31 mmol, 61%). The NMR data ob-
tained for 8b are identical to those previously reported.[21]
The NMR data obtained for 8c are identical to those previ-
ously reported.[22]
Deca-2,6-dienoic Acid EthylEster (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 chro-
matography (SiO2: 5% diethyl ether:pentane, Rf =0.28) pro-
vides the title compound as a pale yellow oil; yield: 22 mg
(0.11 mmol, 35%).
(E)-4-Phenyl-2-hexene (9b) and (E)-1-Phenyl-3-
methyl-1-pentene (9c)
2-Isopropyl-5-vinylcyclopentanecarboxylic Acid Ethyl
Ester (7c)
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) pro-
vides 9b and 9c as a colorless oil, 1:1.6 mixture of regioisom-
ers; 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) pro-
vides 9b and 9c as a colorless oil, 1:1.6 mixture of two re-
gioisomers; 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]
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
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Direct Copper-Free Domino Conjugate Addition-Cycloallylation
FULL PAPERS
[6] For diastereo- and enantioselective Rh-catalyzed 1,4-
addition-aldol cyclization, see: a) D. F. Cauble, J. G.
Gipson, M. J. Krische, J. Am. Chem. Soc. 2003, 125,
1110–1111; b) B. M. Bocknack, L.-C. Wang, M. J. Kri-
sche, Proc. Natl. Acad. Sci. USA 2004, 101, 5421–5424.
[7] For Cu-catalyzed and mediated conjugate addition-
aldol, Blaise-Thorpe–Ziegler, Dieckmann and Michael
cyclizations, see: a) K. Agapiou, D. F. Cauble, M. J. Kri-
sche, J. Am. Chem. Soc. 2004, 126, 4528–4529; b) J.
Yang, D. C. Cauble, A. J. Berro, N. L. Bauld, M. J. Kri-
sche, J. Org. Chem. 2004, 69, 7979–7984.
(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) pro-
vides 10b as a colorless oil; yield: 70 mg (0.31 mmol, 84%).
The NMR data obtained for 10b are identical to those previ-
ously reported.[25]
À
[8] For additional examples of tandem or “domino” C C
Acknowledgements
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Acknowledgements is made to the Robert A. Welch Founda-
tion (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 par-
tial support of this research.
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