Alkynylcyanation of alkynes and dienes catalyzed by nickel

DOI: 10.1016/j.tet.2009.03.079

Source and publish data:

Tetrahedron p. 5037 - 5050 (2009)

Update date:2022-08-03

Topics:

Authors:

Hirata, Yasuhiro

Tanaka, Masaaki

Yada, Akira

Nakao, Yoshiaki

Hiyama, Tamejiro

Read Full Text PDF DownLoad Join now for total 90,000,000 free articles

Article abstract of DOI:10.1016/j.tet.2009.03.079

Alkynyl cyanides are found to add across alkynes and 1,2-dienes in the presence of a catalyst prepared in situ from Ni(cod)₂, xantphos, and BPh₃. A range of functionalized conjugated cis-enynes are obtained with high regioselectivity. The addition reaction across norbornadiene proceeds in the absence of BPh₃ to give exo-cis adduct exclusively. A stoichiometric reaction of an alkynyl cyanide, Ni(cod)₂, xantphos, and BPh₃ gives trans-(xantphos)Ni(CNBPh₃)(C{triple bond, long}CSiMe₂t-Bu), which is suggested to be a plausible reaction intermediate of the alkynylcyanation reaction.

Full text of DOI:10.1016/j.tet.2009.03.079

Tetrahedron 65 (2009) 5037–5050

Contents lists available at ScienceDirect

Tetrahedron

journal homepage: w ww.elsevier.com/locate/tet

Alkynylcyanation of alkynes and dienes catalyzed by nickel

Yasuhiro Hirata, Masaaki Tanaka, Akira Yada, Yoshiaki Nakao , Tamejiro Hiyama

Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan

a r t i c l e i n f o

a b s t r a c t

Article history:

Alkynyl cyanides are found to add across alkynes and 1,2-dienes in the presence of a catalyst prepared in

situ from Ni(cod)₂, xantphos, and BPh₃. A range of functionalized conjugated cis-enynes are obtained

with high regioselectivity. The addition reaction across norbornadiene proceeds in the absence of BPh₃to

give exo-cis adduct exclusively. A stoichiometric reaction of an alkynyl cyanide, Ni(cod)₂, xantphos, and

BPh₃gives trans-(xantphos)Ni(CNBPh₃)(C^CSiMe₂t-Bu), which is suggested to be a plausible reaction

intermediate of the alkynylcyanation reaction.

Received 2 February 2009

Received in revised form 25 March 2009

Accepted 26 March 2009

Available online 1 April 2009

Keywords:

Nickel

Lewis acid

Carbocyanation

C–C bond activation

Alkyne

Diene

1. Introduction

enynes.⁹Also demonstrated is that alkynyl cyanides add across

norbornadiene stereoselectively. A mechanism for the alkynylcya-

Transition metal-catalyzed direct insertion of unsaturated

bonds into C–C -bonds has gained much attention as a method for

nation reaction is discussed based on both stoichiometric and

catalytic reactions using structurally characterized trans-(xant-

phos)Ni(CNBPh₃)(C^CSiMe₂t-Bu), which is obtained by the oxi-

dative addition of an alkynyl cyanide to nickel/xantphos in the

presence of BPh₃.

efﬁcient construction of carbon frameworks with high regio- and

stereoselectivity as well as atom efﬁciency. Whereas ring expansion

reactions of strained three-¹and four-membered²compounds have

served as this new synthetic strategy, we and others have dem-

onstrated that nickel or palladium-catalyzed addition of nitriles

across unsaturated bonds provides a new entry to this class of

transformation, namely carbocyanation reactions,³that proceed

through oxidative addition of C–CN bonds to nickel(0) or palla-

dium(0).^4–6Scope of nitriles for the carbocyanation covers aryl,

allyl, alkenyl, and alkyl cyanides by virtue of Lewis acid cocataly-

sis,^3j,4qthat has been developed originally by DuPont in the adi-

ponitrile process.⁶Alkynyl cyanides, readily available from terminal

alkynes and cyano phenolate,⁷have also been demonstrated to

undergo the oxidative addition to platinum(0) through the activa-

tion of C(sp)–CN bonds.⁸We therefore have anticipated that the

carbocyanation reaction using alkynyl cyanides would be achieved

by transition metal catalysts to allow direct installation of alkynyl

and cyano groups in a single operation. Herein we report nickel/

BPh₃-catalyzed regio- and stereoselective alkynylcyanation of al-

kynes and 1,2-dienes to afford highly functionalized conjugated

2. Results and discussion

2.1. Nickel/BPh₃-catalyzed alkynylcyanation of alkynes

We ﬁrst examined the reaction of 3-tert-butyldimethylsilyl-

propynenitrile (1a) with 4-octyne (2a) in the presence of a catalytic

amount of Ni(cod)₂with various ligands and Lewis acid (LA) cata-

lysts (Table 1). All the phosphorous ligands examined including

monodentate or bidentate gave at most only a detectable amount of

expected alkynylcyanation product 3aa, whereas use of xantphos

was signiﬁcantly effective to obtain 3aa in a moderate yield (entry

14). The cis-addition was unambiguously conﬁrmed by NOE ex-

periments of ¹H NMR after reduction of the cyano group to for-

myl.¹⁰We then examined the effect of Lewis acid cocatalysts and

found that triarylboranes such as BPh₃and B(C₆F₅)₃were highly

effective (entries 15 and 16), while aluminum-based Lewis acid

catalysts, which are effective for arylcyanation reaction,^3jgave

lower yields of 3aa (entries 17 and 18). A high catalyst turnover was

attained even in the presence of 1 mol % of the nickel catalyst and

3 mol % of BPh₃to give 3aa in 95% yield after isolation by ﬂash

column chromatography on silica gel (entry 19). Use of BPh₃in less

* Corresponding authors. Tel.: þ81 75 383 2443; fax: þ81 75 383 2445.

E-mail addresses: yoshiakinakao@npc05.mbox.media.kyoto-u.ac.jp (Y. Nakao),

thiyama@z06.mbox.media.kyoto-u.ac.jp (T. Hiyama).

doi:10.1016/j.tet.2009.03.079

5038

Y. Hirata et al. / Tetrahedron 65 (2009) 5037–5050

Table 1

Table 2

Alkynylcyanation of 4-octyne (2a) using alkynyl cyanide 1a^a

Nickel/BPh₃-catalyzed alkynylcyanation of 4-octyne (2a)^a

Ni(cod)₂(5 mol %)

Ligand

Ni(cod)₂(n mol %)

xantphos (n mol %)

BPh₃(3n mol %)

t-BuMe₂Si

toluene

toluene, 80 °C, 21 h

(2.0 mmol)

1 (1.0 mmol)

Entry Alkynyl cyanide

Et₃Si

3aa

Yield^b(%)

Ph₂P

PPh₂

Temp Time

Product

Ph₂P

PPh₂

Ph₂P

PPh₂

(^ꢀC)

(h)

Et₃Si

dppb (n = 1)

dpppent (n = 2)

dpphex (n = 3)

dppf

dpephos

xantphos

1^c

t-BuMe₂Si

2^c

3ba

Entry

Ligand (mol %)

Lewis acid

(mol %)

Solvent

Yield^b(%)

t-BuMe₂Si

PMe₃(10)

PCy₃(10)

Pt-Bu₃(10)

PMe₂Ph (10)

PMePh₂(10)

PPh₃(10)

P(4-MeO–C₆H₄)₃(10)

P(4-CF₃–C₆H₄)₃(10)

dppb (5)

dpppent (5)

dpphex (5)

None

BPh₃(15)

B(C₆F₅)₃(15)

AlMe₃(15)

AlMe₂Cl (15)

BPh₃(3)

BPh₃(2)

BPh₃(1)

BPh₃(3)

Toluene

DMF

100

3ca

10 100

3da

19^c

20^c

21^c

22^c

23^c

MeO

dppf (5)

MeO

dpephos (5)

Xantphos (5)

Xantphos (1)

10 100

3ea

100 (95)^d

Dioxane

10 100

3fa

All the reactions were carried out using 1a (0.20 mmol), 2a (0.20 mmol),

Ni(cod)₂(5.0 mol %), a ligand, and a Lewis acid catalyst in toluene (0.3 mL).

Estimated by GC using tetradecane as an internal standard.

Ni(cod)₂(1.00 mol %) was used.

Isolated yield obtained with a 1 mmol scale.

3ga

than 3 mol % resulted in low yield of 3aa (entries 20 and 21). Polar

solvents like 1,4-dioxane and DMF were less effective (entries 22

and 23). Attempted reactions set up outside a dry box using

nickel(0) catalysts prepared in situ from air-stable NiCl₂$DME/Zn or

Ni(acac)₂/AlMe₃with xantphos did not give 3aa, presumably be-

cause the residue of the reducing agents inhibits this particular

carbocyanation reaction.

Hex

10 100

3ha

With the optimized conditions in hand, we next studied scope of

alkynyl cyanides with 2a as an alkyne substrate (Table 2). Tri-

ethylsilyl variant 1b also added across 2a in an excellent yield

(entry 1). Using diynyl cyanide 1c as a nitrile substrate, conjugated

endiyne 3ca was successfully obtained in 72% yield (entry 2). Re-

actions of aryl-, alkenyl-, and alkylethynyl cyanides with 2 mol

equiv of 2a also gave the corresponding conjugated enynes in

modest to good yields in the presence of 10 mol % of the nickel

catalyst and 30 mol % of BPh₃at higher reaction temperatures

(entries 3–10).¹¹It is noteworthy that a C(sp)–CN bond is prefer-

entially activated over C–Cl and C(sp³)–CN bonds, which may also

oxidatively add to nickel(0) (entries 5, 8, and 9). A conjugated

dienyne structure was obtained with 3-cyclohexenylpropynenitrile

(1g) (entry 6).

10 100

3ia

3ja

OSiMe₂t-Bu

10 100

3ka

All the reactions were carried out using an alkynyl cyanide (1.00 mmol), 2a

(2.0 mmol), Ni(cod)₂(1.00–10.0 mol %), xantphos (1.00–10.0 mol %), and BPh₃(3.0–

30 mol %) in toluene (1.50 mL).

Scope of alkynes was next investigated with 1a (Table 3). All the

reactions proceeded through exclusive cis-addition of the alkynyl

cyanide as conﬁrmed by NOE experiments of ¹H NMR, ¹H–¹H

Isolated yield.

Compound 2a (1.00 mmol) was used.

Y. Hirata et al. / Tetrahedron 65 (2009) 5037–5050

5039

Table 3

Table 4

Nickel/BPh₃-catalyzed alkynylcyanation of alkynes using 1a^a

Nickel/BPh₃-catalyzed alkynylcyanation of aryl-substituted alkynes using 1a^a

Ni(cod)₂(1 mol %)

xantphos (1 mol %)

BPh₃(3 mol %)

xantphos (1 mol %)

TBS

(1.0 mmol)

BPh₃(3 mol %)

R²

R¹CN

R¹

2 (1.0 mmol)

R²

R¹R²

(Z)-3

R¹R²

R¹

R²

toluene, 40 °C

toluene

(1.0 mmol)

R¹R²

2 (1.0 mmol)

(E)-3

TBS = SiMe₂t-Bu

R¹, R²= 4-MeO−C₆H₄(2j)

H, Ph (2k)

H, 4-MeO−C₆H₄(2l)

H, 4-NC−C₆H₄(2m)

Entry

Temp Time

(^ꢀC) (h)

Products

Yield^b(%)

(3/3⁰) ^c

TBS

Entry 2 Time (h)

Products

Yield^b(%)

[(Z)-3/(E)-3/3⁰]^c

CN NC

94 (60:40)

Me Ph Me Ph

OMe

TBS

3ab, 3⁰ab

TBS

1^d

2j 48

100 (11:89)

TBS

CN NC

82 (22:78)

84 (13:87)

47 (5:>95)

MeO

TBS

OMe

MeO

3ac, 3⁰ac

TBS

OEt

TBS

OEt

2k 36

97 (77:11:12)

93 (75:25)

EtO

OEt Me

EtO

3ad, 3⁰ad

TBS

OMe

Hex

TBS

2l 48

4^d

100

OEt

EtO

3⁰hd

OMe

TBS

Hex

CN NC

2m 17

96 (98:2)

96 (83:13)

79 (82:18)^e

Hex

3ae, 3⁰ae

TBS

All the reactions were carried out using 1a (1.00 mmol), an alkyne (1.00 mmol),

Ni(cod)₂(1.00 mol %), xantphos (1.00 mol %), and BPh₃(3.0 mol %) in toluene

(1.50 mL).

CN NC

3af, 3⁰af

Isolated yield.

Estimated by ¹H NMR analysis of an isolated product.

TBS

The reaction was carried out using Ni(cod)₂(3.0 mol %), xantphos (3.0 mol %),

and BPh₃(9.0 mol %) in toluene (1.50 mL) at 80 ^ꢀC.

CN NC

99 (88:12)

93 (87:13)

3ag, 3⁰ag

biased substituents such as 4-methyl-2-pentyne (2c) and 2-butyn-

1-al diethyl acetal (2d) showed regioselectivities opposite to aryl-

cyanation of alkynes,^3c,g,jgiving adducts with a bulkier substituent

at the alkynyl substituted carbon (entries 2 and 3). The addition of

1h across 2d showed higher regioselectivity, and 3⁰hd was isolated

as a sole product albeit in a modest yield (entry 4). Terminal alkynes

also participated in the reaction with 1a to give conjugated enynes

having a substituent at the cyano-substituted carbon with fair to

excellent regioselectivities (entries 5–9). Functional groups like

chloro, alkanenitrile, and ester were tolerated (entries 6–8).

The addition reaction across aryl-substituted alkynes gave

trans-adducts in varying amounts (Table 4). Diaryl acetylene 2j

gave trans-adduct (E)-3aj as a major product, the stereochemistry

of which was determined by X-ray crystallographic analysis

(Fig. 1).¹²Electron-neutral and -poor arylacetylenes 2k and 2m

showed moderate to good regioselectivities similar to those ob-

served with other terminal alkynes and gave only a small amount of

trans-adducts and regioisomers (entries 2 and 4), whereas elec-

tron-rich one 2l reacted regioselectively but gave trans-adducts in

a larger amount (entry 3). In all cases, ratios of these isomers were

constant throughout the reaction revealed by GC analyses.

TBS

CO₂Me

MeO₂C

8^f

MeO₂C

TBS

3ah, 3⁰ah

TBS

CN NC

86 (95:5)

3ai, 3⁰ai

All the reactions were carried out using 1a (1.00 mmol), an alkyne (1.00 mmol),

Ni(cod)₂(1.00 mol %), xantphos (1.00 mol %), and BPh₃(3.0 mol %) in toluene

(1.50 mL).

Isolated yield.

Estimated by ¹H NMR analysis of an isolated product.

The reaction was carried out using Ni(cod)₂(10.0 mmol %), xantphos

(10.0 mol %), and BPh₃(30 mol %).

Calculated based on yields of isolated products.

The amount of 2h used was 1.10 mmol.

couplings, and/or HMBC experiments of the corresponding alde-

hydes 24 (vide infra).¹⁰Addition of 1a across 1-phenyl-1-propyne

(2b) gave the corresponding adducts (3ab and 3⁰ab) in good yields

but with poor regioselectivitiy (entry 1). Alkynes having sterically

To gain a mechanistic insight, we examined a stoichiometric re-

action. Upon mixing stoichiometric amounts of 1a, Ni(cod)₂, xant-

phos, and BPh₃in benzene, the initially heterogeneous reaction

5040

Y. Hirata et al. / Tetrahedron 65 (2009) 5037–5050

completely consumed after 6 h to give a complex, which showed

signals for ³¹P NMR at 23.7 ppm (d, J¼22.3 Hz) and 23.2 ppm (d,

J¼22.3 Hz), and alkynylcyanation products 3ae and 3⁰ae were also

observed in ¹H NMR in 79% and 14% yields as estimated by GC,

respectively (Eq. 1). The new nickel complex observed was assigned

to be cis-(xantphos)Ni(1-octyne) (5) based on the same set of peaks

observed in the reaction of Ni(cod)₂, xantphos, and 2e (5.0 equiv).

These data indicate that coordination and migratory insertion fol-

lowed by reductive elimination are very rapid with terminal al-

kynes as has also been anticipated by the difference of the reaction

temperature (80 ^ꢀC vs 40 ^ꢀC, Table 3).

Hex

2e (5.0 equiv)

3ae + 3'ae

93%, 85:15 (GC)

C₆D₆, rt, 6 h

(1)

³¹P NMR:

δ 23.7 (d, J = 22.3 Hz)

δ 23.2 (d, J = 22.3 Hz)

Thus, the catalytic cycle for the alkynylcyanation reaction should

be initiated by oxidative addition of a C(sp)–CN bond to nickel(0) by

the aid of BPh₃^4q,6to give 4 (Scheme 2). Coordination of an alkyne to

the nickel center of 4 followed by migration of the alkynyl group in 6

or 7 to the alkyne gives cis-alkenylnickel intermediate 8 or 9, which

then reductively eliminates cis-alkynylcyanation product 3 or 3⁰,

respectively. With internal alkynes, the coordination of alkynes

seems to be rate-determining to favor alkyne-coordinated nickel 6

to avoid steric repulsion between C^N–B and bulkier R³to give 3⁰as

a major product through 8. Improved regioselectivity observed with

1h over 1a in the reactionwith 2d (entry 3 vs entry 4, Table 3) may be

understood rationally by this scenario. On the other hand, migration

of the alkynyl group to the less-hindered alkyne carbon through 7

may be favored with terminal alkynes to give 9 and then ﬁnally 3 as

a major product, because coordination of terminal alkynes to the

nickel center is likely to be feasible. The excellent regioselectivity

Figure 1. ORTEP drawing of (E)-3aj.

mixture immediately turned to a homogeneous solution at room

temperature. After evaporation of benzene in vacuo followed by

washing the resulting precipitates with hexane, trans-(xant-

phos)Ni(CNBPh₃)(C^CSiMe₂t-Bu) (4) was obtained as a brown

powder in 84% yield (Scheme 1). Dark red single crystals suitable for

X-ray crystallographic analysis were obtained by recrystallization

from hexane and dichloromethane. The X-ray structure of 4 shown

in Figure 2 clearly indicates the trans geometry with a cyano ligand

coordinating to BPh₃.¹²Treatment of 4 with 2a (5.0 equiv) and BPh₃

(2.0 equiv) in toluene at 80 ^ꢀC for 14 h gave alkynylcyanation prod-

uct 3aa in 81% yield as estimated by GC. Reaction below 50 ^ꢀC

showed no appreciable change in both 4 and 2a: thus, the co-

ordination of 2a to the nickel center appears to be a plausible rate-

determining step. Moreover, the reaction of 1a (1.00 mmol) with 2a

(1.00 mmol) in the presence of a catalytic amount of 4 (1 mol %) and

BPh₃(2 mol %) in toluene at 80 ^ꢀC for 21 h also gave 3aa in 94% yield,

clearly indicating that 4 should be a plausible reaction intermediate

for the present alkynylcyanation reaction.

attained with 2i (entry 9 of Table 3) may indicate the presence of

allylnickel-like stabilization in 9. Such stabilization provided by an

additional -system connecting directly to an alkyne may also be

important in the reactions of aryl-substituted alkynes, especially

those having electron-donating aryl groups, to direct regioselective

migratory insertion. Alternatively, an electron-withdrawing group

could also affect the regioselection by making the LUMO of the al-

kyne-terminus low enough to allow the nucleophilic alkynyl group

to migrate selectively at this position. The trend of regioselectivities

observed with arylacetylenes (entries 2–4 of Table 4) would be de-

rived from the sum of those effects. Formation of trans-adducts

could be ascribed to partial isomerization of cis-alkenylnickel in-

termediates 10 through resonance forms 11 or 12 (Scheme 3).¹³

Electron-donating aryl groups may facilitate this isomerization by

stabilizing the transient nickel–carbene species having formal pos-

itive charge on nickel, thus favoring trans-adducts. Alternatively,

isomerization of the double bond of alkenylnickel intermediates

catalyzed by phosphorus in an intramolecular manner cannot be

ruled out.¹⁴

On the other hand, the reaction of 4 with 1-octyne (2e,

5.0 equiv) in C₆D₆proceeded at room temperature, and 4 was

TBS

BPh₃

Ni(cod)₂

Ph₂P

PPh₂

benzene, rt

xantphos

BPh₃

4, 84%

2a (5 equiv)

BPh₃(2 equiv)

2.2. Nickel/BPh₃-catalyzed alkynylcyanation of 1,2-dienes

81% (GC)

toluene, 80 °C, 14 h

In the presence of the same catalyst, 1,2-dienes also underwent

the alkynylcyanation. The reaction took place at an internal double

bond of 1,2-dienes, and an alkynyl group was introduced to the

cumulative carbon to give conjugated enynes 15 having

a substituted cyanomethyl substituent (entries 1–4 of Table 5). On

the other hand, silylallene 14e showed opposite regioselectivity,

giving (Z)-alkenylsilane 15⁰e exclusively (entry 5). The reactions of

propadiene and phenylallene gave no desired product due to rapid

TBS

4 (1 mol %)

1a (1.0 mmol)

BPh₃(2 mol %)

toluene, 80 °C, 21 h

94%

2a (1.0 mmol)

3aa

Scheme 1. Synthesis and reactions of trans-(xantphos)Ni(CNBPh₃)(C^CSiMe₂t-Bu) (4).

Y. Hirata et al. / Tetrahedron 65 (2009) 5037–5050

5041

Figure 2. ORTEP drawings of 4.

R¹

Ni(0)

R¹

R²

R³

R²

R³

R¹

= xantphos

B = BPh3

R³

R²

R³

R²

R¹

R²

R³

R²

R³

Scheme 2. Plausible mechanism for the nickel/BPh₃-catalyzed alkynylcyanation of alkynes.

5042

Y. Hirata et al. / Tetrahedron 65 (2009) 5037–5050

terminal double bond in 1,2-dienes coordinates to the nickel

center to give 16, and migratory insertion of the 1,2-diene takes

R¹

place into the alkynyl–Ni bond to give a

p-allylnickel species 18,

which may be thermodynamically more stable than 19.^5gRe-

ductive elimination of the allyl and cyano groups would give

conjugated enynes 15. Regioisomers 15⁰may be formed through

the coordination of 14 in an opposite direction to give 20, fol-

cis-adduct

lowed by similar steps through

p-allylnickel intermediates.

R = H or Ar

However, 20 should be sterically unfavored. A bulky silyl group for

R may inhibit C–C bond-forming reductive elimination from 18.

Instead, reductive elimination from 19 could be operative to afford

15⁰with particular 1,2-diene 14e.

trans-adduct

R¹

2.3. Nickel-catalyzed alkynylcyanation of norbornadiene

We next turned our attention to the addition reaction of

alkynyl cyanides across alkene substrate. Attempted reactions of

alkynyl cyanide 1a with simple alkenes including 1-octene, sty-

rene, and 1,3-dodecadiene in the presence of a diverse range of

nickel, a ligand, and a Lewis acid catalyst disappointedly gave no

alkynylcyanation products in any detectable amounts. On the

other hand, the reaction of 1a with norbornadiene (21) took

place in the presence of Ni(cod)₂(2 mol %) and xantphos

(2 mol %) in toluene at 80 ^ꢀC for 17 h to afford exo-cis-alky-

nylcyanation product 22 in 89% yield (Scheme 5). The structure

of 22 was assigned based on NOE experiments of ¹H NMR of

aldehyde 23, which was obtained by reduction of 22. Lewis acid

cocatalysts were not effective for the alkynylcyanation of 21 to

result in lower yields of 22. Highly functionalized norbornene

derivatives like 22 may ﬁnd further applications as precursors for

functionalized cyclopentanes^3eor monomers for functionalized

cyclic oleﬁn polymers through ring-opening metathesis

polymerization.¹⁵

Scheme 3. Plausible mechanism for the formation of trans-alkynylcyanation products

(3aj–3am).

oligomerization of the allenes. The reactions of 1,1- and 1,3-di-

substituted allenes such as 3-methyl-1,2-butadiene and 5,6-

dodecadiene did not proceed, and these 1,2-dienes were recovered

intact due presumably to steric hindrance to prevent the dienes

coordinating to the nickel center of 4.

The catalytic cycle for the alkynylcyanation of 1,2-dienes

shown in Scheme 4 should also be initiated by formation of 4. The

Table 5

Nickel/BPh₃-catalyzed alkynylcyanation of 1,2-dienes using 1a^a

Ni(cod)₂(2 mol %)

xantphos (2 mol %)

TBS

BPh₃(6 mol %)

toluene, 50 °C

(0.8 mmol)

14 (0.8 mmol)

15'

2.4. Transformations of alkynylcyanation products

Entry

Time

(h)

Products

Yield^b

(15/15⁰)^c

Reduction of the cyano group in alkynylcyanation product 3da

to formyl was successfully performed with DIBAL-H with complete

retention of stereochemistry (Scheme 6).¹⁰The resulting formyl

group in 24da was further transformed to afford highly substituted

allylic alcohol 25 upon treatment with a Grignard reagent. Alde-

hydes 24 and allylic alcohols 25 have been demonstrated to serve as

versatile synthetic intermediates for a variety of highly substituted

cyclic compounds.¹⁶

Desilylation of 1,2-diene-alkynylcyanation product 15b followed

by stannylative cross-cycloaddition reaction of the resulting 26

with ethyl (Z)-2-undecene-4-ynoate (27) in the presence of a pal-

ladium/iminophosphine 28 catalyst gave highly substituted phe-

nylstannane 29 (Scheme 7).¹⁷

TBS

Hex

73 (93:7)^d

Hex

15a, 15⁰a

14a

TBS

15b, 15⁰b

82 (91:9)

14b

TBS

OTBS

TBS

OTBS

14c

75 (92:8)^e

OTBS

15c, 15⁰c

3. Conclusion

TBS

In conclusion, we have demonstrated alkynylcyanation re-

actions of alkynes and 1,2-dienes catalyzed by nickel/xantphos/

BPh₃. The transformations proceed with high stereo-, regio-, and

chemoselectivities to afford a wide variety of highly functionalized

conjugated enynes in an atom-economic manner. These enyne

products are shown to serve as potent versatile synthetic pre-

cursors for various cyclic and linear compounds. We have also

achieved stereoselective alkynylcyanation of norbornadiene to af-

ford a highly functionalized norbornene. The catalytic cycles of the

alkynylcyanation reactions initiated by oxidative addition of

alkynyl cyanides to nickel(0)/xantphos have been investigated in

detail by isolation, structural characterization, and stoichiometric

and catalytic reactions of trans-(xantphos)Ni(CNBPh₃)(C^CSiMe₂t-

Bu) (4).

74 (>95:5)^d

15d, 15⁰d

14d

TBS

SiMe₂Bu

15⁰e

SiMe₂Bu

55 (5:>95)

14e

All the reactions were carried out using 1a (0.80 mmol), a 1,2-diene (0.80 mmol),

Ni(cod)₂(2.0 mol %), xantphos (2.0 mol %), and BPh₃(6.0 mol %) in toluene (ca.1 mL).

Isolated yield.

Calculated based on yields of isolated products.

Estimated by ¹H NMR analysis of an isolated product.

E/Z of 15⁰c was 11:89.

Y. Hirata et al. / Tetrahedron 65 (2009) 5037–5050

5043

15'

Ni(0)

R¹

= xantphos

B = BPh

Si = SiMe₂t-Bu

•

Scheme 4. Plausible mechanism for the nickel/BPh₃-catalyzed alkynylcyanation of 1,2-dienes.

4. Experimental

4.1. General

DIBAL-H (2.5 equiv)

3da

toluene, −78 °C, 2h

then SiO₂

24da, 90%

All manipulations of oxygen- and moisture-sensitive materials

were conducted with a standard Schlenk technique or in a dry box

under an argon atmosphere. Flash column chromatography was

p-Me−C₆H₄MgBr

(3.0 equiv)

performed using Kanto Chemical silica gel (spherical, 40–50 mm).

Et₂O, 0 °C, 2h

Analytical thin layer chromatography (TLC) was performed on

Merck Kieselgel 60 F₂₅₄(0.25 mm) plates. Visualization was ac-

complished with UV light (254 nm) and/or an aqueous alkaline

KMnO₄solution followed by heating. Proton and carbon nuclear

magnetic resonance spectra (¹H NMR and ¹³C NMR) were recor-

ded on a Varian Mercury 400 (¹H NMR, 400 MHz; ¹³C NMR,

101 MHz) or a Varian Gemini 300 (³¹P NMR, 121 MHz) spectro-

meter with solvent resonance as an internal standard (¹H NMR,

CHCl₃at 7.26 ppm, C₆D₅H at 7.15 ppm; ¹³C NMR, CDCl₃at

77.0 ppm, C₆D₆at 128.6 ppm) or resonance of phosphoric acid as

an external standard (³¹P NMR at 0 ppm). Melting points were

determined using a YANAKO MP-500D. Elemental analyses were

performed by Elemental Analysis Center of Kyoto University.

25, 83%

ref. 17d

Scheme 6. Possible transformations of alkynylcyanation products.

TBAF (2.0 equiv)

AcOH (2.7 equiv)

15b

THF, rt, 1 h

Ni(cod)₂(2 mol %)

TBS

Xantphos (2 mol %)

26, 77%

EtO₂C

Hex

toluene, 80 °C, 17 h

22, 89%

[CpPd(π-allyl)] (1.67 mol %)

28 (3.3mol%)

(Bu₃Sn)₂O (0.33 equiv)

Bu₃Sn

nOe

EtO₂C

TBS

THF, 50 °C, 24 h

DIBAL-H (2.5 equiv)

toluene, -78 °C, 1 h

then SiO₂

Hex

29, 53% (based on Sn)

nOe

PPh₂

23, 82%

Scheme 7. Transformations of the 1,2-diene-alkynylcyanation product 15b.

Scheme 5. Nickel-catalyzed alkynylcyanation of norbornadiene (21).

5044

Y. Hirata et al. / Tetrahedron 65 (2009) 5037–5050

High-resolution mass spectra were obtained with a JEOL JMS-700

(EI) or JEOL JMS-HX110A (FABþ) spectrometer. X-ray crystal data

were collected with a Bruker SMART APEX diffractometer. Pre-

parative recycling gel permeation chromatography (GPC) and

preparative recycling silica gel chromatography were performed

with a JAI LC-908 chromatograph equipped with JAIGEL-1H and

-2H (chloroform as an eluent) and JAIGEL-SIL or Nacalai Tesque

5SL-II (hexane–ethyl acetate as an eluent). GC analysis was per-

formed on a Shimadzu GC 2014 equipped with an ENV-1 column

(Kanto Chemical, 30 mꢁ0.25 mm, pressure¼31.7 kPa, detec-

tor¼FID, 290 ^ꢀC) with a helium gas as a carrier. Unless otherwise

noted, commercially available reagents were used without puri-

ﬁcation. Toluene was distilled from sodium/benzophenone ketyl

or purchased from Kanto Chemical and degassed by purging

vigorously with argon for 20 min and further puriﬁed by passing

through activated alumina under positive argon pressure as de-

scribed by Grubbs et al.¹⁸Anhydrous benzene was purchased from

Nacalai Tesque and degassed by bubbling an argon gas vigorously

for 20 min before use. Benzene-d₆was distilled from sodium/

benzophenone ketyl. Alkynyl cyanides⁷and 1,2-dienes¹⁹were

prepared according to the respective literature procedure.

4.2.5. 4-tert-Butyldimethylsiloxypent-2-ynenitrile (1k)

A colorless oil, R_f0.43 (hexane–ethyl acetate¼20:1). ¹H NMR

(400 MHz, CDCl₃)

4.58 (q, J¼6.6 Hz, 1H), 1.48 (d, J¼6.6 Hz, 3H),

0.91 (s, 9H), 0.14 (s, 3H), 0.13 (s, 3H); ¹³C NMR (101 MHz, CDCl₃)

104.7, 86.8, 58.9, 57.7, 25.7, 24.3, 18.2, ꢂ4.7, ꢂ4.9; IR (neat) 2957,

2932, 2888, 2861, 2311, 2280, 1748, 1472, 1464, 1445, 1391, 1371,

1362, 1339, 1308, 1260, 1153, 1109, 1028, 1005, 984, 939, 839, 829,

812, 781, 739, 667 cm^ꢂ1. Anal. Calcd for C₁₁H₁₉NOSi: C, 63.11; H,

9.15. Found: C, 63.32; H, 9.11.

4.3. Alkynylcyanation of alkynes. A general procedure

In a dry box, an alkynyl cyanide (1.00 mmol), an alkyne (1.00–

2.0 mmol), and tetradecane (internal standard, 99 mg, 0.50 mmol)

were added sequentially to a solution of Ni(cod)₂(2.8–28 mg, 10.0–

100

mmol), BPh₃(7.3–73 mg, 30–300

mmol), and xantphos (5.8–

58 mg, 10.0–100

mmol) in toluene (1.5 mL) placed in a vial, which

was taken outside the dry box and heated at the temperature for

the time speciﬁed in Tables 1–4. The resulting reaction mixture was

ﬁltered through a silica gel pad. The ﬁltrate was concentrated in

vacuo, and the residue was puriﬁed by ﬂash column chromatog-

raphy on silica gel to give the corresponding alkynylcyanation

products in yields listed in Tables 1–4. Mixtures of regioisomers

were further separated by preparative recycling silica gel chroma-

tography to give isomerically pure products.

4.2. Synthesis of alkynyl cyanides. A general procedure

To a solution of a terminal alkyne (40 mmol) in diethyl ether

(10 mL) was added a 1.6 M solution of n-BuLi (28 mL, 44 mmol) in

hexane at ꢂ78 ^ꢀC. The resulting reaction mixture was stirred at

ꢂ78 ^ꢀC for 1 h, and then cyano phenolate (5.2 g, 44 mmol) was

added. The reaction mixture was warmed up to room temperature

and further stirred for 1 h before quenching with water. The

aqueous layer was extracted with diethyl ether for three times. The

combined organic layers were washed with water and brine, dried

over anhydrous magnesium sulfate, and concentrated in vacuo. The

residue was puriﬁed by ﬂash column chromatography on silica gel

to give the corresponding alkynyl cyanides.

4.3.1. (Z)-3-tert-Butyldimethylsilylethynyl-2-propylhex-2-

enenitrile (3aa)

A brownish oil, R_f0.63 (hexane–ethyl acetate¼5:1). ¹H NMR

(400 MHz, CDCl₃)

2.31 (q, J¼7.2 Hz, 4H), 1.66–1.54 (m, 4H), 0.96 (s,

9H), 0.97 (t, J¼7.4 Hz, 3H), 0.95 (t, J¼7.3 Hz, 3H), 0.18 (s, 6H); ¹³C

NMR (101 MHz, CDCl₃)

d 138.9, 119.8, 118.7, 103.2, 102.0, 34.1, 31.9,

26.2, 21.7, 21.4, 16.8, 13.8, 13.7, ꢂ4.6; IR (neat) 2961, 2932, 2858,

2210, 2143, 1464, 1252, 1159, 839, 826, 812, 777, 735, 679 cm^ꢂ1

Anal. Calcd for C₁₇H₂₉NSi: C, 74.11; H, 10.61. Found: C, 74.22; H,

10.60. The stereochemistry was assigned based on ¹H NMR NOE

experiments of 24aa.¹⁰

4.2.1. 3-tert-Butyldimethylsilylpropynenitrile (1a)

A colorless oil, R_f0.28 (hexane–ethyl acetate¼20:1). ¹H NMR

(400 MHz, CDCl₃)

CDCl₃)

2862, 2259, 2104, 1472, 1366, 1256, 1047, 966, 843, 824, 810, 783,

685, 581, 511, 459 cm^ꢂ1; HRMS (EI) calcd for C₉H₁₅NSi: M^þ,

165.0974. Found: m/z 165.0975.

0.97 (s, 9H), 0.21 (s, 6H); ¹³C NMR (101 MHz,

4.3.2. (Z)-3-Triethylsilylethynyl-2-propylhex-2-enenitrile (3ba)

A pale yellow oil, R_f0.22 (hexane–ethyl acetate¼50:1). ¹H NMR

104.9, 94.3, 76.6, 25.8, 16.6, ꢂ5.5; IR (neat) 2955, 2934,

(400 MHz, CDCl₃)

2.24 (q, J¼7.1 Hz, 4H), 1.61 (sept, J¼7.3 Hz, 4H),

1.04 (t, J¼7.9 Hz, 9H), 0.96 (q, J¼7.0 Hz, 6H), 0.67 (q, J¼7.9 Hz, 6H);

¹³C NMR (101 MHz, CDCl₃)

139.1, 119.7, 118.7, 103.8, 101.2, 34.1,

31.9, 21.7, 21.4, 13.8, 13.7, 7.6, 4.4; IR (neat) 2961, 2876, 2212, 2143,

1458, 1416, 1381, 1236, 1157, 1005, 727 cm^ꢂ1. Anal. Calcd for

C₁₇H₂₉NSi: C, 74.11; H, 10.61. Found: C, 74.13; H, 10.61.

4.2.2. 3-(Triethylsilyl)propynenitrile (1b)

A colorless oil, R_f0.28 (hexane). ¹H NMR (400 MHz, CDCl₃)

d 1.03

(t, J¼8.0 Hz, 9H), 0.71 (q, J¼7.9 Hz, 6H); ¹³C NMR (101 MHz, CDCl₃)

104.8, 93.8, 76.9, 7.3, 3.7; IR (neat) 2961, 2914, 2880, 2259, 2102,

4.3.3. (Z)-7-tert-Butyldimethylsilyl-2,3-dipropylhept-2-en-4,6-

diynenitrile (3ca)

1460, 1416, 1236, 1045, 1007, 964, 731 cm^ꢂ1; HRMS (EI) calcd for

C₉H₁₅NSi: M^þ, 165.0974. Found: m/z 165.0979.

A yellow oil, R_f0.35 (hexane–ethyl acetate¼20:1). ¹H NMR

(400 MHz, CDCl₃)

2.27 (q, J¼8.1 Hz, 4H), 1.65–1.54 (m, 4H), 0.97 (s,

4.2.3. 5-tert-Butyldimethylsilylpenta-2,4-diynenitrile (1c)

9H), 0.99–0.93 (m, 6H), 0.17 (s, 6H); ¹³C NMR (101 MHz, CDCl₃)

137.8, 122.3, 118.4, 93.5, 87.6, 81.6, 73.8, 34.2, 32.2, 26.2, 21.6, 21.5,

A yellow oil, R_f0.38 (hexane). ¹H NMR (400 MHz, CDCl₃)

0.96

(s, 9H), 0.19 (s, 6H); ¹³C NMR (101 MHz, CDCl₃)

105.2, 93.0, 85.8,

16.9, 13.8, 13.6, ꢂ4.7; IR (neat) 2959, 2932, 2858, 2214, 2095, 1464,

1252, 1007, 920, 841, 827, 810, 777, 735, 681 cm^ꢂ1. Anal. Calcd for

C₁₉H₂₉NSi: C, 76.19; H, 9.76. Found: C, 76.35; H, 9.85.

67.4, 49.2, 25.9, 16.8, ꢂ5.3; IR (neat) 2955, 2932, 2860, 2239, 2179,

2079, 1472, 1254, 1209, 843, 824, 812, 781 cm^ꢂ1; HRMS (EI) calcd

for C₁₁H₁₅NSi: M^þ, 189.0974. Found: m/z 189.0980.

4.3.4. (Z)-3-Phenylethynyl-2-propylhex-2-enenitrile (3da)

4.2.4. 2-Heptynedinitrile (1j)

A pale yellow oil, R_f0.48 (hexane–ethyl acetate¼5:1). ¹H NMR

A pale yellow oil, R_f0.20 (hexane–ethyl acetate¼2:1). ¹H NMR

(400 MHz, CDCl₃) d 7.57–7.48 (m, 2H), 7.39–7.29 (m, 3H), 2.32 (q,

(400 MHz, CDCl₃)

2.59 (t, J¼7.0 Hz, 2H), 2.52 (t, J¼7.0 Hz, 2H), 1.99

J¼7.7 Hz, 4H), 1.74–1.58 (m, 4H), 0.99 (t, J¼7.4 Hz, 6H); ¹³C NMR

(quint, J¼7.0 Hz, 2H); ¹³C NMR (101 MHz, CDCl₃)

117.9, 104.7, 84.0,

(101 MHz, CDCl₃) d 139.3, 132.0, 129.1, 128.4, 122.2, 119.1, 119.0, 97.2,

56.9, 23.2, 18.0, 16.4; IR (neat) 2957, 2874, 2315, 2263, 1762, 1686,

1599, 1454, 1425, 1350, 1329, 1312, 1296, 1215, 1074, 1042,

773 cm^ꢂ1; HRMS (FAB^þ) calcd for C₇H₆N₂: M^þ,118.0531. Found: m/z

118.0535.

88.0, 34.0, 31.8, 21.6, 21.4, 13.7, 13.5; IR (neat) 2963, 2932, 2874,

2208,1491, 756, 691 cm^ꢂ1. Anal. Calcd for C₁₇H₁₉N: C, 86.03; H, 8.07.

Found: C, 85.73; H, 8.16. The stereochemistry was assigned based

on ¹H NMR NOE experiments of 24da.¹⁰

Y. Hirata et al. / Tetrahedron 65 (2009) 5037–5050

5045

4.3.5. (Z)-3-(4-Methoxyphenyl)ethynyl-2-propylhex-2-

enenitrile (3ea)

(t, J¼7.5 Hz, 3H), 0.92 (s, 9H), 0.15 (s, 3H), 0.14 (s, 3H); ¹³C NMR

(101 MHz, CDCl₃)

d 138.8, 118.8, 99.7, 81.6, 59.4, 34.2, 31.8, 25.9,

A pale yellow oil, R_f0.13 (hexane–ethyl acetate¼20:1). ¹H NMR

25.8, 25.3, 21.7, 21.4,18.4,13.8,13.6, ꢂ4.5, ꢂ4.8; IR (neat) 2961, 2932,

2874, 2859, 2211, 1591, 1464, 1341, 1252, 1119, 1101, 1057, 988, 949,

835, 812, 779 cm^ꢂ1; HRMS (EI) calcd for C₁₅H₂₄NOSi: [Mꢂ(t-Bu)]^þ,

262.1627. Found: m/z 262.1617.

(400 MHz, CDCl₃)

7.46 (d, J¼9.0 Hz, 2H), 6.85 (d, J¼9.0 Hz, 2H),

3.81 (s, 3H), 2.30 (q, J¼7.5 Hz, 4H), 1.74–1.56 (m, 4H), 0.98 (t,

J¼7.3 Hz, 6H); ¹³C NMR (101 MHz, CDCl₃)

d 160.0, 139.4, 133.3, 119.1,

117.7, 114.0, 113.8, 97.4, 87.0, 55.2, 34.0, 31.7, 21.7, 21.5, 13.7, 13.5; IR

(neat) 2963, 2872, 2185, 1607, 1508, 1458, 1290, 1252, 1173, 1032,

833 cm^ꢂ1. Anal. Calcd for C₁₈H₂₁NO: C, 80.86; H, 7.92. Found: C,

80.98; H, 8.01.

4.3.12. (Z)-5-tert-Butyldimethylsilyl-3-methyl-2-phenylpent-2-en-

4-ynenitrile (3ab)

A colorless oil, R_f0.30 (hexane–ethyl acetate¼20:1). ¹H NMR

(400 MHz, CDCl₃) d 7.45–7.32 (m, 5H), 2.09 (s, 3H), 1.03 (s, 9H), 0.23

4.3.6. (Z)-3-(4-Chlorophenyl)ethynyl-2-propylhex-2-

enenitrile (3fa)

(s, 6H); ¹³C NMR (101 MHz, CDCl₃)

d 135.1, 132.6, 128.9, 128.8, 128.6,

119.6, 118.3, 104.4, 104.2, 26.2, 20.9, 16.8, ꢂ4.7; IR (neat) 2955, 2930,

A pale yellow oil, R_f0.23 (hexane–ethyl acetate¼20:1). ¹H NMR

2885, 2858, 2214, 2127, 1580, 1493, 1472, 1445, 1373, 1364, 1252,

(400 MHz, CDCl₃)

7.45 (d, J¼8.4 Hz, 2H), 7.31 (d, J¼8.4 Hz, 2H),

1227, 1005, 926, 839, 826, 812, 777, 766, 700, 677, 625, 588 cm^ꢂ1

2.36–2.28 (m, 4H),1.72–1.57 (m, 4H),1.00 (t, J¼7.4 Hz, 6H); ¹³C NMR

Anal. Calcd for C₁₈H₂₃NSi: C, 76.81; H, 8.24. Found (as a mixture

with 3⁰ab): C, 76.97; H, 8.40. The stereochemistry was assigned

based on ¹H NMR NOE experiments, and the regiochemistry was

determined based on HMBC experiments of 24ab.¹⁰

(101 MHz, CDCl₃) d 138.9, 135.1, 133.0, 128.6, 120.1, 119.4, 118.9, 95.8,

88.8, 34.0, 31.9, 21.8, 21.6, 13.8, 13.6; IR (neat) 2963, 2932, 2212,

1489, 1458, 1398, 1381, 1090, 1015, 829 cm^ꢂ1. Anal. Calcd for

C₁₇H₁₈NCl:C, 75.13; H, 6.68. Found: C, 75.39; H, 6.83.

4.3.13. (Z)-5-tert-Butyldimethylsilyl-2-methyl-3-phenylpent-2-en-

4-ynenitrile (3⁰ab)

4.3.7. (Z)-5-(1-Cyclohexenyl)-2,3-dipropylpent-2-en-4-

ynenitrile (3ga)

A colorless solid, mp 65.2–65.6 ^ꢀC, R_f0.25 (hexane–ethyl

A pale yellow oil, R_f0.13 (hexane–ethyl acetate¼30:1). ¹H NMR

acetate¼20:1). ¹H NMR (400 MHz, CDCl₃)

7.45–7.34 (m, 5H), 2.07

(400 MHz, CDCl₃)

6.30–6.25 (m, 1H), 2.30–2.11 (m, 8H), 1.72–1.52

(s, 3H), 1.00 (s, 9H), 0.19 (s, 6H); ¹³C NMR (101 MHz, CDCl₃)

d 137.5,

(m, 8H), 1.00–0.92 (m, 6H); ¹³C NMR (101 MHz, CDCl₃)

139.6,

134.9, 129.1, 128.5, 128.3, 119.5, 115.0, 103.2, 103.0, 26.2, 18.3, 16.8,

ꢂ4.7; IR (KBr) 2951, 2926, 2883, 2856, 2212, 2143, 1566, 1491, 1470,

1448, 1439, 1389, 1362, 1296, 1275, 1250, 1103, 1072, 1007, 826, 812,

773, 721, 702, 677, 538, 455 cm^ꢂ1. The stereochemistry was

assigned based on ¹H NMR NOE experiments.

137.4, 120.2, 119.2, 117.6, 99.3, 85.7, 34.2, 31.7, 28.9, 25.9, 22.2, 21.8,

21.51, 21.45, 13.8, 13.6; IR (neat) 2963, 2932, 2872, 2210, 2187, 1576,

1456, 1435, 1348, 918, 843, 799, 737 cm^ꢂ1; HRMS (EI) calcd for

C₁₇H₂₃N: M^þ, 241.1830. Found: m/z 241.1833.

4.3.8. (Z)-2,3-Dipropylundec-2-en-4-ynenitrile (3ha)

4.3.14. (Z)-5-tert-Butyldimethylsilyl-2-isopropyl-3-methylpent-2-

en-4-ynenitrile (3ac)

A brown oil, R_f0.15 (hexane–ethyl acetate¼30:1). ¹H NMR

(400 MHz, CDCl₃)

2.41 (t, J¼7.0 Hz, 2H), 2.27–2.18 (m, 4H), 1.65–

A colorless oil, R_f0.23 (hexane–ethyl acetate¼20:1). ¹H NMR

1.24 (m, 12H), 0.95 (q, J¼7.7 Hz, 6H), 0.90 (t, J¼6.9 Hz, 3H); ¹³C NMR

(400 MHz, CDCl₃)

2.78 (sept, J¼6.8 Hz, 1H), 1.99 (s, 3H), 1.14 (d,

(101 MHz, CDCl₃)

140.0, 119.3, 117.4, 99.3, 79.4, 34.5, 31.7, 31.4,

J¼6.8 Hz, 6H), 0.99 (s, 9H), 0.18 (s, 6H); ¹³C NMR (101 MHz, CDCl₃)

28.6, 28.5, 22.6, 21.7, 21.5, 19.7, 14.2, 13.8, 13.6; IR (neat) 2961, 2932,

2872, 2206, 1589, 1458, 1379, 1329, 1111 cm^ꢂ1. Anal. Calcd for

C₁₇H₂₇N: C, 83.20; H, 11.09. Found: C, 83.45; H, 11.00. The stereo-

chemistry was assigned based on ¹H NMR NOE experiments of

24ha.¹⁰

132.0, 126.7, 116.9, 104.4, 100.7, 28.7, 26.2, 21.1, 19.1, 16.8, ꢂ4.6; IR

(neat) 2957, 2930, 2858, 2212, 2143, 1464, 1364, 1277, 1252, 1026,

926, 876, 839, 824, 810, 777, 689 cm^ꢂ1. Anal. Calcd for C₁₅H₂₅NSi: C,

72.81; H, 10.18. Found (as a mixture with 3⁰ac): C, 73.02; H, 10.30.

The stereochemistry was assigned based on ¹H NMR NOE

experiments.

4.3.9. (Z)-8-Chloro-2,3-dipropyloct-2-en-4-ynenitrile (3ia)

A brown oil, R_f0.22 (hexane–ethyl acetate¼20:1). ¹H NMR

4.3.15. (Z)-5-tert-Butyldimethylsilyl-3-isopropyl-2-methylpent-2-

en-4-ynenitrile (3⁰ac)

(400 MHz, CDCl₃)

3.73 (t, J¼6.2 Hz, 2H), 2.63 (t, J¼6.7 Hz, 2H),

2.28–2.18 (m, 4H), 2.05 (quint, J¼6.5 Hz, 2H), 1.65–1.53 (m, 4H),

A colorless oil, R_f0.23 (hexane–ethyl acetate¼20:1). ¹H NMR

0.96 (q, J¼5.0 Hz, 6H); ¹³C NMR (101 MHz, CDCl₃)

139.5, 119.1,

(400 MHz, CDCl₃)

2.77 (sept, J¼6.7 Hz, 1H), 1.97 (s, 3H), 1.10 (d,

118.2, 96.6, 80.3, 43.5, 34.2, 31.5, 31.1, 21.6, 21.4, 17.0, 13.7, 13.5; IR

J¼6.8 Hz, 6H), 0.99 (s, 9H), 0.18 (s, 6H); ¹³C NMR (101 MHz, CDCl₃)

(neat) 2963, 2874, 2206,1589,1458,1290,1231,1113, 854, 656 cm^ꢂ1

145.5, 119.4, 112.4, 103.6, 100.7, 29.8, 26.2, 20.9, 16.7, 16.1, ꢂ4.6; IR

Anal. Calcd for C₁₄H₂₀ClN: C, 70.72; H, 8.48. Found: C, 70.97; H, 8.41.

(neat) 2930, 2858, 2216, 2145, 1466, 1364, 1252, 1153, 1043, 1007,

914, 826, 777, 731, 675 cm^ꢂ1. The stereochemistry was assigned

based on ¹H NMR NOE experiments, and the regiochemistry was

determined by HMBC experiments of 24⁰ac.¹⁰

4.3.10. (Z)-8-Cyano-2,3-dipropyloct-2-en-4-ynenitrile (3ja)

A pale yellow oil, R_f0.30 (hexane–ethyl acetate¼5:1). ¹H NMR

(400 MHz, CDCl₃)

2.62 (t, J¼6.6 Hz, 2H), 2.61 (t, J¼7.0 Hz, 2H), 2.25

(t, J¼7.6 Hz, 2H), 2.21 (t, J¼7.6 Hz, 2H), 1.95 (quint, J¼6.9 Hz, 2H),

4.3.16. (Z)-5-tert-Butyldimethylsilyl-2-diethoxymethyl-3-

methylpent-2-en-4-ynenitrile (3ad)

1.65–1.51 (m, 4H), 0.96 (q, J¼7.6 Hz, 6H); ¹³C NMR (101 MHz, CDCl₃)

139.4, 119.2, 119.0, 118.9, 95.4, 81.2, 34.2, 31.6, 24.4, 21.7, 21.5, 18.7,

A pale yellow oil, R_f0.13 (hexane–ethyl acetate¼20:1). ¹H NMR

16.2, 13.8, 13.6; IR (neat) 2965, 2934, 2874, 2247, 2207, 1589, 1462,

(400 MHz, CDCl₃) d 5.19 (s, 1H), 3.71–3.54 (m, 4H), 2.09 (s, 3H), 1.25

1456, 1431, 1381, 1346, 1316, 1173, 1113, 1090, 889, 791, 741 cm^ꢂ1

(t, J¼7.0 Hz, 6H), 0.99 (s, 9H), 0.19 (s, 6H); ¹³C NMR (101 MHz,

Anal. Calcd for C₁₅H₂₀N₂: C, 78.90; H, 8.83. Found: C, 79.19; H, 8.95.

CDCl₃) d 138.3, 119.3, 116.3, 104.6, 103.5, 96.3, 61.7, 26.2, 19.9, 16.7,

15.1, ꢂ4.7; IR (neat) 2980, 2955, 2930, 2885, 2856, 2218, 2147, 1591,

1539, 1472, 1462, 1445, 1391, 1364, 1335, 1286, 1252, 1173, 1105,

1061, 1007, 934, 841, 826, 812, 777, 683, 665 cm^ꢂ1. Anal. Calcd for

C₁₇H₂₉NO₂Si: C, 66.40; H, 9.51. Found (as a mixture with 3⁰ad): C,

66.67; H, 9.35. The stereochemistry was assigned based on NOE

experiments of ¹H NMR.

4.3.11. (Z)-6-tert-Butyldimethylsiloxy-2,3-dipropylhept-2-en-4-

ynenitrile (3ka)

A pale yellow oil, R_f0.20 (hexane–ethyl acetate¼20:1). ¹H NMR

(400 MHz, CDCl₃)

4.73 (q, J¼6.5 Hz, 1H), 2.24 (q, J¼7.6 Hz, 4H),

1.67–1.53 (m, 4H), 1.49 (d, J¼6.6 Hz, 3H), 0.96 (t, J¼7.4 Hz, 3H), 0.94

5046

Y. Hirata et al. / Tetrahedron 65 (2009) 5037–5050

4.3.17. (Z)-5-tert-Butyldimethylsilyl-2-methyl-3-

diethoxymethylpent-2-en-4-ynenitrile (3⁰ad)

6H); ¹³C NMR (101 MHz, CDCl₃)

d 144.6, 116.1, 107.1, 104.5, 100.5,

43.4, 34.2, 30.3, 26.1, 16.7, ꢂ4.8; IR (neat) 2955, 2930, 2858, 2220,

1587, 1472, 1445, 1364, 1252, 885, 866, 841, 824, 808, 779,

681 cm^ꢂ1; HRMS (EI) calcd for C₁₄H₂₂ClNSi: M^þ, 267.1210. Found:

m/z 267.1209.

A pale yellow oil, R_f0.10 (hexane–ethyl acetate¼20:1). ¹H NMR

(400 MHz, CDCl₃) d 5.08 (s,1H), 3.72–3.63 (m, 2H), 3.60–3.51 (m, 2H),

2.09 (s, 3H), 1.24 (t, J¼7.0 Hz, 6H), 0.98 (s, 9H), 0.17 (s, 6H); ¹³C NMR

(101 MHz, CDCl₃)d136.9,118.8,118.5,105.1,100.7, 98.0, 62.1, 26.1,16.9,

16.8, 15.2, ꢂ4.7; IR (neat) 2976, 2955, 2930, 2885, 2858, 2218, 2145,

1578, 1541, 1472, 1462, 1445, 1391, 1373, 1364, 1337, 1286, 1252, 1167,

1113, 1063, 1007, 920, 841, 826, 812, 777 cm^ꢂ1. The stereochemistry

was assigned based on ¹H NMR NOE experiments, and the regio-

chemistry was determined by HMBC experiments of 24⁰ad.¹⁰

4.3.23. (Z)-8-tert-Butyldimethylsilyl-5-cyanopent-5-en-6-

ynenitrile (3ag)

A pale brown oil, R_f0.15 (hexane–ethyl acetate¼5:1). ¹H NMR

(400 MHz, CDCl₃)

6.14 (s, 1H), 2.47 (t, J¼7.5 Hz, 2H), 2.41 (t,

J¼7.0 Hz, 2H), 1.93 (quint, J¼7.2, 2H), 0.96 (s, 9H), 0.16 (s, 6H); ¹³C

NMR (101 MHz, CDCl₃)

d 125.3, 122.7, 118.3, 116.2, 105.7, 99.5, 32.6,

4.3.18. (Z)-3-Diethoxymethyl-2-methylundec-2-en-

4-ynenitrile (3⁰hd)

26.0, 23.4, 16.6, 16.2, ꢂ4.9; IR (neat) 2955, 2930, 2858, 2247, 2218,

1595, 1462, 1364, 1252, 1094, 841, 826, 812, 777, 681 cm^ꢂ1. Anal.

Calcd for C₁₅H₂₂N₂Si: C, 69.71; H, 8.58. Found: C, 69.84; H, 8.68. The

stereochemistry was assigned based on NOE experiments of

¹H NMR.

An orange oil, R_f0.33 (hexane–ethyl acetate¼5:1). ¹H NMR

(400 MHz, CDCl₃)

d 5.06 (s, 1H), 3.73–3.62 (m, 2H), 3.60–3.50 (m,

2H), 2.44 (t, J¼7.0 Hz, 2H), 2.07 (s, 3H), 1.60 (quint, J¼7.3 Hz, 2H),

1.52–1.16 (m, 6H), 1.24 (t, J¼7.0 Hz, 6H), 0.89 (t, J¼6.8 Hz, 3H); ¹³C

NMR (101 MHz, CDCl₃)

137.5, 119.2, 116.1, 102.2, 98.1, 77.1, 62.3,

4.3.24. (Z)-3-tert-Butyldimethylsilylethynylhept-2-enedinitrile (3⁰ag)

A pale brown oil, R_f0.10 (hexane–ethyl acetate¼5:1). ¹H NMR

31.4, 28.6, 28.3, 22.6, 20.2, 16.6, 15.2, 14.2; IR (neat) 2976, 2957,

2932, 2870, 2861, 2209, 1686, 1454, 1373,1333, 1123, 1063, 764, 725,

696 cm^ꢂ1. Anal. Calcd for C₁₇H₂₇NO₂: C, 73.61; H, 9.81. Found: C,

73.73; H, 9.51. The stereochemistry was assigned based on ¹H NMR

NOE experiments, and the regiochemistry was determined by

HMBC experiments of 24⁰hd.¹⁰

(400 MHz, CDCl₃)

5.54 (t, J¼1.3 Hz, 1H), 2.47 (td, J¼5.3, 1.3 Hz, 2H),

2.41 (t, J¼7.0 Hz, 2H), 1.97 (quint, J¼7.2, 2H), 0.99 (s, 9H), 0.20 (s,

6H); ¹³C NMR (101 MHz, CDCl₃)

143.6, 118.4, 115.8, 107.9, 105.1,

100.0, 35.5, 26.1, 23.5, 16.7, 16.4, ꢂ4.8; IR (neat) 3055, 2953, 2930,

2858, 2247, 2220, 2147, 1589, 1464, 1364, 1252, 1157, 1007, 874, 841,

824, 808, 779, 681, 478 cm^ꢂ1; HRMS (FAB^þ) calcd for C₁₅H₂₃N₂Si:

[MþH]^þ, 259.1631. Found: m/z 259.1635.

4.3.19. (Z)-5-tert-Butyldimethylsilyl-2-hexylpent-2-en-

4-ynenitrile (3ae)

A colorless oil, R_f0.20 (hexane–ethyl acetate¼30:1). ¹H NMR

4.3.25. Methyl (Z)-8-tert-butyldimethylsilyl-5-cyano-oct-5-en-7-

ynoate (3ah)

(400 MHz, CDCl₃)

6.03 (s, 1H), 2.29 (t, J¼7.6 Hz, 2H), 1.62–1.50 (m,

2H),1.39–1.23 (m, 6H), 0.99 (s, 9H), 0.90 (t, J¼6.6 Hz, 3H), 0.18 (s, 6H);

A colorless oil, R_f0.13 (hexane–ethyl acetate¼10:1). ¹H NMR

¹³C NMR (101 MHz, CDCl₃)

126.0, 123.3, 117.1, 103.9, 100.1, 34.5,

(400 MHz, CDCl₃)

6.03 (t, J¼1.4 Hz, 1H), 3.64 (s, 3H), 2.32 (t,

31.5, 28.5, 27.9, 26.1, 22.6,16.7,14.1, ꢂ4.7; IR (neat) 2930, 2858, 2218,

1464, 1252, 1111, 1074, 841, 826, 812, 777 cm^ꢂ1; HRMS (EI) calcd for

C₁₇H₂₉NSi: M^þ, 275.2069. Found: m/z 275.2061. The stereochemis-

try was assigned based on ¹H NMR NOE experiments, and the

regiochemistry was determined by ¹H NMR spectra of 24ae.¹⁰

J¼7.2 Hz, 4H), 1.87 (quint, J¼7.4, 2H), 0.94 (s, 9H), 0.13 (s, 6H); ¹³C

NMR (101 MHz, CDCl₃)

d 172.5, 124.5, 124.1, 116.6, 104.5, 99.8, 51.6,

33.3, 32.4, 26.0, 23.0, 16.5, ꢂ4.9; IR (neat) 2953, 2930, 2858, 2218,

1740, 1437, 1364, 1252, 1202, 1173, 1094, 1007, 841, 826, 812, 777,

683 cm^ꢂ1. Anal. Calcd for C₁₆H₂₅NO₂Si: C, 65.93; H, 8.65. Found (as

a mixture with 3⁰ah): C, 66.18; H, 8.66. The stereochemistry was

assigned based on NOE experiments of ¹H NMR.

4.3.20. (Z)-5-tert-Butyldimethylsilyl-3-hexylpent-2-en-

4-ynenitrile (3⁰ae)

A colorless oil, R_f0.13 (hexane–ethyl acetate¼30:1). ¹H NMR

4.3.26. Methyl (Z)-7-tert-butyldimethylsilyl-5-

cyanomethylenehept-6-ynoate (3⁰ah)

(400 MHz, CDCl₃)

5.43 (s, 1H), 2.28 (t, J¼7.5 Hz, 2H), 1.60–1.50 (m,

2H),1.39–1.20 (m, 6H),1.00 (s, 9H), 0.90 (t, J¼6.4 Hz, 3H), 0.20 (s, 6H);

A colorless oil, R_f0.10 (hexane–ethyl acetate¼10:1). ¹H NMR

¹³C NMR (101 MHz, CDCl₃)

146.9, 116.5, 106.2, 103.2, 101.2, 37.4,

(400 MHz, CDCl₃) d 5.46 (s, 1H), 3.69 (s, 3H), 2.40–2.31 (m, 4H), 1.92

31.5, 28.5, 27.7, 26.1, 22.6,16.7,14.2, ꢂ4.7; IR (neat) 2930, 2858, 2220,

1585, 1466, 1364, 1252, 880, 839, 824, 808, 777 cm^ꢂ1; HRMS (EI)

calcd for C₁₇H₂₉NSi: M^þ, 275.2069. Found: m/z 275.2069. The ste-

reochemistry was assigned based on NOE experiments of ¹H NMR.

(quint, J¼7.5 Hz, 2H), 0.99 (s, 9H), 0.19 (s, 6H); ¹³C NMR (101 MHz,

CDCl₃)

d 172.9, 145.4, 116.2, 106.9, 104.1, 100.7, 51.7, 36.3, 32.7, 26.1,

23.0, 16.7, ꢂ4.8; IR (neat) 2953, 2930, 2858, 2220, 1740, 1587, 1462,

1437,1364, 1252,1175,1150,1007, 872, 841, 824, 808, 779, 681 cm^ꢂ1

4.3.21. (Z)-5-tert-Butyldimethylsilyl-2-(3-chloroprop-1-yl)pent-2-

en-4-ynenitrile (3af)

4.3.27. (Z)-5-tert-Butyldimethylsilyl-2-(cyclohexen-1-yl)pent-2-

en-4-ynenitrile (3ai)

A pale yellow oil, R_f0.20 (hexane–ethyl acetate¼20:1). ¹H NMR

colorless solid, mp 71.3–72.7 ^ꢀC, R_f0.35 (hexane–ethyl

(400 MHz, CDCl₃)

(td, J¼7.2, 1.0 Hz, 2H), 2.03 (quint, J¼6.7 Hz, 2H), 0.97 (s, 9H), 0.17 (s,

6.12 (t, J¼1.3 Hz, 1H), 3.56 (t, J¼6.1 Hz, 2H), 2.49

acetate¼20:1). ¹H NMR (400 MHz, CDCl₃)

6.46 (td, J¼4.4, 0.6 Hz,

1H), 6.03 (d, J¼0.7 Hz,1H), 2.30–2.21 (m, 2H), 2.14–2.05 (m, 2H),1.76–

6H); ¹³C NMR (101 MHz, CDCl₃)

124.8, 123.6, 116.6, 105.0, 99.7,

1.56 (m, 4H), 0.99 (s, 9H), 0.18 (s, 6H); ¹³C NMR (101 MHz, CDCl₃)

43.2, 31.2, 30.2, 26.1, 16.6, ꢂ4.8; IR (neat) 2955, 2930, 2858, 2218,

1593, 1472, 1462, 1445, 1364, 1252, 1092, 1007, 841, 826, 777, 694,

681 cm^ꢂ1; HRMS (EI) calcd for C₁₄H₂₂ClNSi: M^þ, 267.1210. Found:

m/z 267.1213. The stereochemistry was assigned based on NOE

experiments of ¹H NMR.

d 134.1, 131.4, 127.2, 116.3,115.4,106.2,101.5, 26.1, 24.5, 22.1, 21.7, 16.7,

ꢂ4.7; IR (KBr) 3032, 2930, 2856, 2226, 2129, 1620, 1470, 1462, 1448,

1433, 1362, 1254, 1096, 1080, 824, 681 cm^ꢂ1. Anal. Calcd for

C₁₇H₂₅NSi: C, 75.21; H, 9.28. Found: C, 75.06; H, 9.20. The stereo-

chemistry was assigned based on ¹H NMR NOE experiments. The

regiochemistry wasassigned based on ¹H NMRexperiments of24ai.¹⁰

4.3.22. (Z)-3-tert-Butyldimethylsilylethynyl-6-chloropent-2-

enenitrile (3⁰af)

4.3.28. (Z)-5-tert-Butyldimethylsilyl-3-(cyclohexen-1-yl)pent-2-

en-4-ynenitrile (3⁰ai)

A pale yellow oil, R_f0.15 (hexane–ethyl acetate¼20:1). ¹H NMR

(400 MHz, CDCl₃)

5.52 (t, J¼1.4 Hz, 1H), 3.56 (t, J¼6.2 Hz, 2H), 2.48

A pale yellow oil, R_f0.38 (hexane–ethyl acetate¼20:1). ¹H NMR

(td, J¼7.2, 1.2 Hz, 2H), 2.06 (quint, J¼7.0 Hz, 2H), 0.99 (s, 9H), 0.19 (s,

(400 MHz, CDCl₃) d 6.54–6.48 (m, 1H), 6.11 (s, 1H), 2.62–2.52 (m,

Y. Hirata et al. / Tetrahedron 65 (2009) 5037–5050

5047

2H), 2.29–2.19 (m, 2H), 1.73–1.55 (m, 4H), 0.95 (s, 9H), 0.15 (s, 6H);

¹³C NMR (101 MHz, CDCl₃)

134.6, 132.3, 126.0, 118.6, 117.9, 109.7,

7.41 (m, 3H), 6.00 (s, 1H), 1.05 (s, 9H), 0.27 (s, 6H); ¹³C NMR

(101 MHz, CDCl₃) 142.6,134.1,130.8,128.7,126.6,117.1,107.8,101.2,

101.6, 27.3, 26.1, 26.0, 22.3, 21.4, 16.9, ꢂ4.8; IR (neat) 2930, 2858,

2224, 1616, 1556, 1470, 1462, 1433, 1250, 1194, 1092, 1072, 839, 824,

810, 777, 685, 633 cm^ꢂ1; HRMS (EI) calcd for C₁₇H₂₅NSi: M^þ,

271.1756. Found: m/z 271.1764.

100.1, 26.2, 16.8, ꢂ4.7; IR (KBr) 3055, 2949, 2926, 2883, 2855, 2214,

2152, 1618, 1582, 1556, 1493, 1470, 1450, 1408, 1389, 1360, 1344,

1333, 1313, 1252, 1184, 1067, 1026, 1005, 970, 947, 835, 804, 768,

692, 679, 664, 642, 592, 517, 444, 413 cm^ꢂ1. The stereochemistry

was assigned based on ¹H NMR NOE experiments.

4.3.29. (Z)-5-tert-Butyldimethylsilyl-2,3-di(4-methoxyphenyl)-

pent-2-en-4-ynenitrile [(Z)-3aj]

4.3.34. (Z)-5-tert-Butyldimethylsilyl-2-(4-methoxyphenyl)pent-2-

A yellow oil, R_f0.33 (hexane–ethyl acetate¼5:1). ¹H NMR

en-4-ynenitrile [(Z)-3al]

(400 MHz, CDCl₃)

7.24 (d, J¼8.6 Hz, 2H), 7.17 (d, J¼8.4 Hz, 2H), 6.76

yellow solid, mp 55.7–56.3 ^ꢀC, R_f0.12 (hexane–ethyl

(d, J¼8.6 Hz, 2H), 6.75 (d, J¼8.4 Hz, 2H), 3.80 (s, 6H), 1.03 (s, 9H),

acetate¼30:1). ¹H NMR (400 MHz, CDCl₃)

7.51 (d, J¼9.0 Hz, 2H),

0.23 (s, 6H); ¹³C NMR (101 MHz, CDCl₃)

160.1, 159.7, 134.7, 131.0,

6.92 (d, J¼9.0 Hz, 2H), 6.51 (s, 1H), 3.84 (s, 3H), 1.02 (s, 9H), 0.22 (s,

130.7, 127.4, 125.3, 119.3, 117.2, 114.0, 113.6, 104.5, 55.3, 31.7, 26.3,

16.9, ꢂ4.6; IR (neat) 2953, 2930, 2899, 2857, 2209, 2141, 1605, 1574,

1512, 1505, 1470, 1462, 1443, 1416, 1362, 1323, 1298, 1287, 1254,

1177, 1128, 1105, 1032, 1013, 984, 939, 878, 833, 812, 799, 777, 694,

683, 654, 633, 602, 571 cm^ꢂ1. Anal. Calcd for C₂₅H₂₉NO₂Si: C, 74.40;

H, 7.24. Found: C, 74.22; H, 7.24.

6H); ¹³C NMR (101 MHz, CDCl₃)

d 161.0, 127.0, 124.6, 124.4, 118.2,

116.2, 114.4, 107.0, 101.4, 55.5, 26.2, 16.8, ꢂ4.7; IR (KBr) 3059, 3032,

3007, 2926, 2855, 2224, 2133, 1879, 1744, 1609, 1576, 1512, 1464,

1443, 1421, 1410, 1391, 1362, 1333, 1319, 1285, 1254, 1186, 1119, 1101,

1034, 1011, 974, 937, 876, 824, 810, 773, 754, 681, 637, 625, 588,

519 cm^ꢂ1. Anal. Calcd for C₁₈H₂₃NOSi: C, 72.68; H, 7.79. Found [as

a mixture with (E)-3al]: C, 72.62; H, 7.79. The stereochemistry was

determined by ¹H NMR NOE experiments, and the regiochemistry

was assigned based on ¹H NMR experiments of (Z)-24al.¹⁰

4.3.30. (E)-5-tert-Butyldimethylsilyl-2,3-di(4-methoxyphenyl)-

pent-2-en-4-ynenitrile [(E)-3aj]

A colorless crystal, mp 96.2–96.4 ^ꢀC, R_f0.40 (hexane–ethyl

acetate¼5:1). ¹H NMR (400 MHz, CDCl₃)

7.88 (d, J¼9.0 Hz, 2H),

4.3.35. (E)-5-tert-Butyldimethylsilyl-2-(4-methoxyphenyl)pent-2-

en-4-ynenitrile [(E)-3al]

7.73 (d, J¼9.0 Hz, 2H), 6.96 (d, J¼9.0 Hz, 2H), 6.92 (d, J¼9.1 Hz, 2H),

3.87 (s, 3H), 3.86 (s, 3H), 0.92 (s, 9H), 0.14 (s, 6H); ¹³C NMR

A pale yellow oil, R_f0.13 (hexane–ethyl acetate¼30:1). ¹H NMR

(101 MHz, CDCl₃)

160.6, 160.1, 134.3, 130.23, 130.17, 129.4, 126.5,

(400 MHz, CDCl₃)

8.02 (d, J¼8.8 Hz, 2H), 6.91 (d, J¼9.0 Hz, 2H),

119.3, 116.4, 113.7, 113.5, 108.8, 103.9, 55.44, 55.40, 26.2, 16.9, ꢂ4.8;

IR (KBr) 2951, 2930, 2857, 2205, 1605, 1578, 1541, 1512, 1466, 1441,

1418, 1360, 1323, 1306, 1277, 1256, 1179, 1113, 1078, 1047, 1022, 937,

837, 777, 768, 704, 681, 586, 540, 527 cm^ꢂ1. Anal. Calcd for

C₂₅H₂₉NO₂Si: C, 74.40; H, 7.24. Found: C, 74.56; H, 7.27. The ste-

reochemistry was assigned based on X-ray crystallography. Color-

less single crystals were obtained by recrystallization from

methanol suitable for X-ray crystallographic analysis.

6.32 (s, 1H), 3.86 (s, 3H), 0.98 (s, 9H), 0.19 (s, 6H); ¹³C NMR

(101 MHz, CDCl₃) 160.8, 129.5, 124.5, 122.9, 119.0, 118.3, 113.7,

110.6, 101.5, 55.5, 26.2, 16.9, ꢂ4.8; IR (neat) 2953, 2930, 2897, 2856,

2218, 1605, 1580, 1555, 1514, 1464, 1443, 1420, 1364, 1304, 1259,

1205, 1182, 1078, 1049, 1028, 1007, 939, 835, 831, 810, 777, 685, 631,

519 cm^ꢂ1; The stereo- and regiochemistry was assigned based on

¹H NMR NOE experiments of (E)-24al.¹⁰

4.3.36. (Z)-5-tert-Butyldimethylsilyl-2-(4-cyanophenyl)pent-2-en-

4-ynenitrile [(Z)-3am]

4.3.31. (Z)-5-tert-Butyldimethylsilyl-2-phenylpent-2-en-4-

ynenitrile [(Z)-3ak]

A colorless solid, mp 113.7–114.2 ^ꢀC, R_f0.20 (hexane–ethyl

colorless solid, mp 75.1–75.9 ^ꢀC, R_f0.22 (hexane–ethyl

acetate¼10:1). ¹H NMR (400 MHz, CDCl₃)

7.71 (d, J¼8.8 Hz, 2H),

acetate¼20:1). ¹H NMR (400 MHz, CDCl₃)

7.60–7.54 (m, 2H), 7.46–

7.67 (d, J¼8.8 Hz, 2H), 6.76 (s, 1H), 1.01 (s, 9H), 0.22 (s, 6H); ¹³C NMR

7.38 (m, 3H), 6.64 (s, 1H), 1.04 (s, 9H), 0.24 (s, 6H); ¹³C NMR

(101 MHz, CDCl₃) d 136.1, 132.7, 126.0, 124.0, 123.0, 117.8, 115.2,

(101 MHz, CDCl₃)

132.0, 130.1, 129.0, 125.5, 124.8, 120.8, 116.0,

113.6, 111.9, 100.5, 26.1, 16.8, ꢂ4.8; IR (KBr) 3098, 3065, 3026, 2953,

2926, 2885, 2856, 2230, 2135, 1935, 1605, 1572, 1558, 1506, 1470,

1462, 1441, 1416, 1391, 1362, 1333, 1319, 1252, 1186, 1097, 1005, 976,

937, 889, 841, 812, 779, 683, 602, 550, 479, 453, 426 cm^ꢂ1. Anal.

Calcd for C₁₈H₂₀N₂Si: C, 73.92; H, 6.89. Found: C, 73.73; H, 6.89. The

stereochemistry was assigned based on ¹H NMR NOE experiments,

and the regiochemistry was assigned based on ¹H NMR experi-

ments of (Z)-24am.¹⁰

108.3, 101.1, 26.2, 16.8, ꢂ4.7; IR (KBr) 3065, 3051, 3038, 3013, 2947,

2928, 2885, 2856, 2222, 2139, 1936, 1871, 1740, 1582, 1497, 1472,

1464, 1448, 1410, 1391, 1364, 1327, 1257, 1248, 1101, 1005, 978, 939,

908, 872, 829, 810, 772, 754, 679, 596, 502, 476, 434, 422 cm^ꢂ1

Anal. Calcd for C₁₇H₂₁NSi: C, 76.35; H, 7.91. Found [as a mixture with

(E)-3ak and 3⁰ak]: C, 76.45; H, 7.87. The stereochemistry was

assigned based on ¹H NMR NOE experiments. The regiochemistry

was determined by ¹H NMR experiments of (Z)-24ak.¹⁰

4.3.37. (E)-5-tert-Butyldimethylsilyl-2-(4-cyanophenyl)pent-2-en-

4-ynenitrile [(E)-3am]

4.3.32. (E)-5-tert-Butyldimethylsilyl-2-phenylpent-2-en-4-

ynenitrile [(E)-3ak]

A colorless oil, R_f0.25 (hexane–ethyl acetate¼10:1). ¹H NMR

A pale yellow oil, R_f0.30 (hexane–ethyl acetate¼30:1). ¹H NMR

(400 MHz, CDCl₃)

8.13 (d, J¼8.6 Hz, 2H), 7.71 (d, J¼8.4 Hz, 2H), 6.61

(400 MHz, CDCl₃)

8.05–7.98 (m, 2H), 7.44–7.39 (m, 3H), 6.46 (s,

(s, 1H), 0.97 (s, 9H), 0.20 (s, 6H); ¹³C NMR (101 MHz, CDCl₃)

d 135.8,

1H), 0.97 (s, 9H), 0.19 (s, 6H); ¹³C NMR (101 MHz, CDCl₃)

131.7,

132.1, 128.4, 124.1, 121.6, 117.9, 117.8, 114.7, 113.6, 100.3, 26.1, 16.9,

ꢂ4.9; IR (neat) 3021, 2953, 2930, 2886, 2859, 2232,1609,1578,1547,

1508, 1470, 1464, 1408, 1364, 1252, 1207, 1078, 1007, 912, 843, 824,

812, 779, 735, 685, 631, 540 cm^ꢂ1; HRMS (EI) calcd for C₁₈H₂₀N₂Si:

M^þ, 293.1474. Found: m/z 293.1463. The stereo- and regiochemistry

was assigned based on ¹H NMR NOE experiments of (E)-24am.¹⁰

130.2, 128.3, 127.9, 123.5, 121.1, 118.8, 111.5, 101.0, 26.1, 16.9, ꢂ4.8; IR

(neat) 2953, 2928, 2897, 2856, 2218, 1583, 1560, 1541, 1497, 1470,

1445, 1412, 1364, 1252, 1202, 1086, 1070, 1007, 839, 824, 812, 770,

689, 667 cm^ꢂ1; The stereo- and regiochemistry was assigned based

on ¹H NMR NOE experiments of (E)-24ak.¹⁰

4.3.33. (Z)-5-tert-Butyldimethylsilyl-3-phenylpent-2-en-4-

4.4. Sythesis of trans-(xantphos)Ni(CNBPh₃)(C^CSiMe₂t-Bu) (4)

ynenitrile (3⁰ak)

colorless solid, mp 58.7–59.2 ^ꢀC, R_f0.15 (hexane–ethyl

To a benzene solution (3.5 mL) of Ni(cod)₂(138 mg, 0.50 mmol)

and xantphos (145 mg, 0.50 mmol) placed in a vial were added 1a

acetate¼30:1). ¹H NMR (400 MHz, CDCl₃)

7.70–7.64 (m, 2H), 7.49–

5048

Y. Hirata et al. / Tetrahedron 65 (2009) 5037–5050

(83 mg, 0.50 mmol) and BPh₃(121 mg, 0.50 mmol) in a dry box at

room temperature. The vial was shaken vigorously to give a ho-

mogeneous solution within 10 min. The resulting dark red solution

was concentrated in vacuo, and the resulting precipitates were

washed with hexane to give the title compound (439 mg, 84%) as

J¼7.3, 1.5 Hz, 1H), 3.19 (d, J¼1.5 Hz, 2H), 2.78–2.71 (m, 2H), 2.70–

2.61 (m, 2H), 0.97 (s, 9H), 0.16 (s, 6H); ¹³C NMR (101 MHz, CDCl₃)

140.84, 140.80, 128.3, 128.2, 125.9, 116.4, 113.1, 100.8, 99.7, 34.8,

32.5, 26.2, 25.0, 16.7, ꢂ4.5; IR (neat) 2953, 2930, 2856, 2253, 2149,

1497, 1458, 1364, 1252, 1007, 839, 777, 700 cm^ꢂ1. Anal. Calcd for

C₂₀H₂₇NSi: C, 77.61; H, 8.79. Found: C, 77.83; H, 8.86. The stereo-

chemistry was assigned based on ¹H NMR NOE experiments.

a brown powder. ¹H NMR (400 MHz, C₆D₆)

d 8.10–7.96 (br m, 4H),

7.55 (q, J¼6.2 Hz, 4H), 7.30–6.94 (m, 25H), 6.86 (t, J¼7.5 Hz, 2H),

6.76 (t, J¼7.6 Hz, 2H), 6.70 (t, J¼7.7 Hz, 4H), 1.49 (s, 3H), 1.26 (s,

3H), 0.36 (s, 9H), ꢂ0.46 (s, 6H); ¹³C NMR (101 MHz, C₆D₆)

155.9 (t,

4.5.5. 5-tert-Butyldimethylsilyl-2-(2-tert-butyldimethylsiloxyethy-

1-yl)-3-methylenepent-4-ynenitrile (15c)

J_C–P¼5.9 Hz), 155.3 (br, s), 136.3 (t, J_C–P¼6.1 Hz), 136.1, 135.1, 133.8 (t,

J_C–P¼23.0 Hz), 133.6 (t, J_C–P¼5.8 Hz), 131.9, 131.5, 131.3, 129.9 (t, J_C–P

A pale yellow oil, R_f0.20 (hexane–ethyl acetate¼20:1). ¹H NMR

5.0 Hz), 129.2 (t, J_C–P¼5.4 Hz), 128.5, 128.2, 127.4, 125.1, 125.0, 124.8

(t, J_C–P¼26.8 Hz), 122.8 (t, J_C–P¼44.1 Hz), 37.1, 33.9, 27.1, 24.5, 17.1,

(400 MHz, CDCl₃)

5.64 (t, J¼0.82 Hz, 1H), 5.61 (s, 1H), 3.82–3.71

(m, 2H), 3.59 (dd, J¼9.0, 5.9 Hz, 1H), 2.18–2.08 (m, 1H), 2.00–1.90

ꢂ3.1; ³¹P NMR (121 MHz, C₆D₆)

15.7 (s); IR (KBr) 3414, 3061, 2953,

(m, 1H), 0.96 (s, 9H), 0.91 (s, 9H), 0.151 (s, 3H), 0.148 (s, 3H), 0.08 (s,

2924, 2851, 2180, 2035, 1586, 1481, 1435, 1404, 1242, 1213, 1096,

826, 745, 702, 617, 530, 519, 471 cm^ꢂ1. Dark red single crystals

suitable for X-ray crystallographic assay were obtained by re-

crystallization from hexane and dichloromethane.

3H), 0.07 (s, 3H); ¹³C NMR (101 MHz, CDCl₃)

d 126.0, 124.5, 118.9,

101.8, 96.1, 59.2, 35.1, 34.9, 26.2, 25.9, 18.3, 16.7, ꢂ4.6, ꢂ5.26, ꢂ5.30;

IR (neat) 2955, 2930, 2858, 2154, 1610, 1472, 1389, 1362, 1254, 1109,

1007, 939, 914, 837, 812, 777, 681 cm^ꢂ1; HRMS (EI) calcd for

C₁₉H₃₄ONSi₂: [MꢂMe]^þ, 348.2179. Found: m/z 348.2191.

4.5. Alkynylcyanation of 1,2-dienes. A general procedure

4.5.6. 3-(tert-Butyldimethylsilylethynyl)-6-(tert-

In a dry box, a 1.00 M solution of 1a (132 mg, 0.80 mmol) and

a 1,2-diene (0.80 mmol) in toluene (0.80 mL) and a solution of BPh₃

butyldimethylsiloxy)hex-3-enenitrile (15⁰c, E/Z¼11:89)

A pale yellow oil, R_f0.08 (hexane–ethyl acetate¼20:1). ¹H NMR

(11.6 mg, 48

a solution of Ni(cod)₂(4.4 mg, 16

16 mol) in toluene (0.40 mL) placed in a vial. The vial was taken

mmol) in toluene (0.40 mL) were added successively to

(400 MHz, CDCl₃)

6.13 (tt, J¼7.3, 1.5 Hz, 0.89H), 5.75 (tt, J¼4.8,

mmol) and xantphos (9.3 mg,

2.4 Hz, 0.11H), 3.69 (t, J¼6.6 Hz, 1.78H), 3.68 (t, J¼6.6 Hz, 0.22H),

3.21 (d, J¼1.5 Hz, 1.78H), 3.05 (d, J¼2.2 Hz, 0.22H), 2.55 (dt, J¼7.3,

6.6 Hz, 1.78H), 2.37 (dt, J¼7.3, 6.2 Hz, 0.22H), 1.04 (s, 0.99H), 0.99 (s,

0.99H), 0.97 (s, 8.01H), 0.90 (s, 8.01H), 0.39 (s, 0.66H), 0.36 (s,

0.66H), 0.15 (s, 5.34H), 0.07 (s, 5.34H); ¹³C NMR (for Z-isomer,

outside the dry box and heated at 50 ^ꢀC for the time speciﬁed in

Table 5. The resulting mixture was ﬁltered through a silica gel pad,

concentrated in vacuo, and puriﬁed by ﬂash column chromatog-

raphy on silica gel to give the corresponding alkynylcyanation

products in yields listed in Table 5.

101 MHz, CDCl₃)

26.0, 25.2, 18.4, 16.7, ꢂ4.5, ꢂ5.1; IR (neat) 2955, 2930, 2858, 2149,

1472, 1416, 1389, 1362, 1256, 1103, 939, 837, 810, 777, 685 cm^ꢂ1

d 138.7, 116.4, 113.7, 100.9, 99.6, 61.7, 34.5, 26.2,

4.5.1. 2-(4-tert-Butyldimethylsilyl-1-buten-3-yl)octanenitrile (15a)

A pale yellow oil, R_f0.23 (hexane–ethyl acetate¼20:1). ¹H NMR

Anal. Calcd for C₂₀H₃₇NOSi₂: C, 66.05; H, 10.25. Found: C, 66.15; H,

10.26.

(400 MHz, CDCl₃)

5.65(s,1H), 5.61 (s,1H), 3.31(t, J¼7.0 Hz, 1H), 1.94–

1.78 (m, 2H), 1.56–1.22 (m, 8H), 0.96 (s, 9H), 0.90 (t, J¼6.9 Hz, 3H),

4.5.7. 5-tert-Butyldimethylsilyl-2-cyclohexyl-3-methylpent-4-

ynenitrile (15d)

0.153 (s, 3H), 0.150 (s, 3H); ¹³C NMR (101 MHz, CDCl₃)

126.2, 124.2,

119.0,102.0, 96.0, 38.3, 31.9, 31.5, 28.7, 26.5, 26.2, 22.6,16.8,14.2, ꢂ4.6;

IR (neat) 2955, 2930, 2858, 2247, 2152, 1612, 1466, 1364, 1252, 1007,

914, 839, 826, 810, 777, 737, 681 cm^ꢂ1. Anal. Calcd for C₁₈H₃₁NSi: C,

74.67; H, 10.79. Found (as a mixture with 15⁰a): C, 74.96; H, 10.76.

A yellow oil, R_f0.25 (hexane–ethyl acetate¼20:1). ¹H NMR

(400 MHz, CDCl₃)

5.64 (t, J¼0.6 Hz, 1H), 5.63 (dd, J¼1.2, 0.6 Hz,

1H), 3.18 (d, J¼5.0 Hz, 1H), 2.00–1.62 (m, 6H), 1.36–1.04 (m, 5H),

0.96 (s, 9H), 0.153 (s, 3H), 0.149 (s, 3H); ¹³C NMR (101 MHz, CDCl₃)

125.2, 125.0, 118.1, 102.3, 95.9, 45.1, 38.9, 31.4, 28.9, 26.19, 26.15,

4.5.2. (Z)-3-(tert-Butyldimethylsilylethynyl)dec-3-enenitrile (15⁰a)

A pale yellow oil, R_f0.10 (hexane–ethyl acetate¼20:1). ¹H NMR

25.9, 16.8, ꢂ4.6; IR (neat) 2930, 2856, 2249, 2149, 1470, 1450, 1362,

1252, 1007, 939, 839, 777, 683 cm^ꢂ1; HRMS (FAB^þ) calcd for

C₁₈H₃₀NSi: [MþH]^þ, 288.2148. Found: m/z 288.2158.

(400 MHz, CDCl₃)

6.08 (tt, J¼7.5, 1.4 Hz, 1H), 3.20 (d, J¼1.1 Hz, 2H),

2.32 (q, J¼7.4 Hz, 2H),1.48–1.24 (m, 8H), 0.97 (s, 9H), 0.90 (t, J¼6.8 Hz,

3H), 0.10 (s, 6H); ¹³C NMR (101 MHz, CDCl₃)

142.3,116.6,112.2,101.1,

99.1, 31.7, 30.8, 29.0, 28.6, 26.2, 25.0, 22.7, 16.7, 14.2, ꢂ4.5; IR (neat)

2955, 2930, 2856, 2147, 1464, 1252, 1007, 839, 810, 777, 683 cm^ꢂ1

4.5.8. (Z)-5-tert-Butyldimethylsilyl-3-butyldimethylsilyl-

methylenepent-4-ynentirile (15⁰e)

A colorless oil, R_f0.25 (hexane–ethyl acetate¼20:1). ¹H NMR

(400 MHz, CDCl₃)

6.24 (t, J¼1.6 Hz, 1H), 3.30 (d, J¼1.6 Hz, 2H),

4.5.3. 5-tert-Butyldimethylsilyl-3-methylene-2-(2-phenylethyl)-

pent-4-ynenitrile (15b)

1.40–1.24 (m, 4H), 0.96 (s, 9H), 0.90 (t, J¼7.0 Hz, 3H), 0.75–0.40 (m,

2H), 0.19 (s, 6H), 0.15 (s, 6H); ¹³C NMR (101 MHz, CDCl₃)

141.3,

A colorless oil, R_f0.57 (hexane–ethyl acetate¼5:1). ¹H NMR

126.2, 116.3, 103.8, 98.5, 29.0, 26.6, 26.2, 26.1, 16.8, 15.0, 14.0, ꢂ2.9,

ꢂ4.7; IR (neat) 2955, 2930, 2858, 2143, 1578, 1472, 1464, 1414, 1250,

1111, 839, 826, 810, 777, 677 cm^ꢂ1. Anal. Calcd for C₁₈H₃₃NSi₂: C,

67.64; H, 10.41. Found: C, 67.44; H, 10.63. The stereochemistry was

assigned based on ¹H NMR NOE experiments.

(400 MHz, CDCl₃)

d 7.34–7.28 (m, 2H), 7.26–7.18 (m, 3H), 5.66 (d,

J¼0.73 Hz, 1H), 5.64 (s, 1H), 3.32–3.25 (m, 1H), 2.90–2.72 (m, 2H),

2.30–2.10 (m, 2H), 0.96 (s, 9H), 0.160 (s, 3H), 0.155 (s, 3H); ¹³C NMR

(101 MHz, CDCl₃)

d 139.6, 128.5, 128.3, 126.3, 125.8, 124.6, 118.7,

101.8, 96.3, 37.5, 33.6, 32.6, 26.2, 16.7, ꢂ4.6; IR (neat) 3028, 2953,

2930, 2856, 2149, 1605, 1497, 1472, 1456, 1362, 1250, 914, 839, 826,

777, 748, 700 cm^ꢂ1. Anal. Calcd for C₂₀H₂₇NSi: C, 77.61; H, 8.79.

Found: C, 77.79; H, 8.56.

4.6. Alkynylcyanation of norbornadiene (21)

Alkynyl cyanide 1a (165 mg, 1.00 mmol), 21 (92 mg, 1.00 mmol),

and C₁₄H₂₉(internal standard, 99 mg, 0.50 mmol) were added se-

4.5.4. (Z)-3-(tert-Butyldimethylsilylethynyl)-6-phenylhex-3-

enenitrile (15⁰b)

quentially to a solution of Ni(cod)₂(5.5 mg, 20 mmol) and xantphos

(11.6 mg, 20 mmol) in toluene (1.00 mL) in a dry box. The vial was

taken outside the dry box and heated at 80 ^ꢀC for 17 h. The resulting

mixture was ﬁltered through a silica gel pad, concentrated in vacuo,

A colorless oil, R_f0.50 (hexane–ethyl acetate¼5:1). ¹H NMR

(400 MHz, CDCl₃)

d 7.34–7.26 (m, 2H), 7.23–7.16 (m, 3H), 6.10 (tt,

Y. Hirata et al. / Tetrahedron 65 (2009) 5037–5050

5049

and puriﬁed by ﬂash column chromatography on silica gel to give

(5R ,6S )-6-(tert-butyldimethylsilylethynyl)-5-cyanobicyclo[2.2.1]-

washed with a saturated NH₄Cl aqueous solution and brine, dried

over anhydrous magnesium sulfate, and concentrated in vacuo. The

residue was puriﬁed by ﬂash chromatography on silica gel (hexane–

ethyl acetate¼10:1 as an eluent) to give (Z)-3-phenylethynyl-2-

propyl-1-p-tolylpent-2-en-1-ol^16d(25,110 mg, 83%) as a yellow oil, R_f

hept-2-ene (22, 0.23 g, 89%) as an colorless solid, R_f0.20 (hexane–

ethyl acetate¼20:1), mp 58.9–59.3 ^ꢀC. ¹H NMR (400 MHz, CDCl₃)

6.19 (dd, J¼5.6, 3.0 Hz, 1H), 6.11 (dd, J¼5.7, 3.1 Hz, 1H), 3.28 (s, 1H),

3.10 (s, 1H), 2.60 (dd, J¼8.6, 2.1 Hz, 1H), 2.56 (dd, J¼8.5, 1.8 Hz, 1H),

1.95 (d, J¼9.5 Hz, 1H), 1.65 (dt, J¼9.5, 1.9 Hz, 1H), 0.97 (s, 9H), 0.15 (s,

0.13 (hexane–ethyl acetate¼20:1). ¹H NMR (400 MHz, CDCl₃)

d 7.47–

7.41 (m, 2H), 7.41 (d, J¼8.1 Hz, 2H), 7.36–7.27 (m, 3H), 7.16 (d,

J¼8.1 Hz, 2H), 6.29 (s, 1H), 2.36 (s, 3H), 2.27 (t, J¼7.6 Hz, 2H), 2.20–

1.97 (m, 3H),1.72 (sext, J¼7.5 Hz, 2H),1.48–1.32 (m,1H),1.20–1.05 (m,

1H), 1.00 (t, J¼7.4 Hz, 3H), 0.86 (t, J¼7.2 Hz, 3H); ¹³C NMR (101 MHz,

3H), 0.14 (s, 3H); ¹³C NMR (101 MHz, CDCl₃)

d 137.8, 135.6, 120.2,

105.5, 87.7, 50.0, 48.1, 46.0, 35.5, 35.2, 26.2,16.7, ꢂ4.4; IR (KBr) 2994,

2953, 2928, 2884, 2857, 2234, 2174, 1472, 1460, 1410, 1387, 1360,

1331, 1317, 1250, 1072, 1007, 939, 922, 912, 901, 837, 827, 775, 745,

714, 679, 631, 583, 529, 476 cm^ꢂ1. Anal. Calcd for C₁₆H₂₃NSi: C,

74.65; H, 9.00. Found: C, 74.74; H, 8.93. The stereochemistry was

assigned based on ¹H NMR NOE experiments of 23.

CDCl₃)

d 149.3, 139.6, 136.5, 131.3, 128.8, 128.3, 127.9, 125.3, 123.6,

120.8, 93.4, 89.3, 75.2, 34.0, 29.8, 23.8, 21.8, 21.1, 14.8, 13.9; IR (neat)

2959, 2930, 2870, 1504, 1495, 1454, 1111, 1034, 818, 754, 691 cm^ꢂ1

4.10. Desilylation of 15b

4.7. Reduction of 22 with DIBAL-H

To a solution of 15b (0.43 g, 1.40 mmol) in THF (28 mL) were

added AcOH (0.23 g, 3.8 mmol) and a 1.0 M solution of TBAF

(2.8 mL, 2.8 mmol) in THF successively at 0 ^ꢀC. The resulting re-

action mixture was warmed to room temperature and further

stirred for 1 h before quenching with water. The aqueous layer was

extracted three times with diethyl ether. The combined organic

layers were washed with water and brine, dried over anhydrous

magnesium sulfate, and concentrated in vacuo. The residue was

puriﬁed by ﬂash chromatography on silica gel (hexane–ethyl

acetate¼40:1 as an eluent) to give 3-methylene-2-(2-phenylethyl)-

pent-4-ynenitrile (26, 0.21 g, 77%) as a pale yellow oil, R_f0.44

To a solution of 22 (26 mg, 0.100 mmol) in toluene (1.00 mL) was

added a 1.5 M solution of DIBAL-H (170 mL, 0.25 mmol) in toluene at

ꢂ78 ^ꢀC, and the resulting mixture was stirred at the same tem-

perature for 1 h. The reaction was quenched with MeOH at ꢂ78 ^ꢀC,

and the resulting mixture was warmed to room temperature. The

mixture was diluted with CH₂Cl₂and ﬁltered through a glass ﬁlter.

The ﬁltrate was concentrated in vacuo. The residue was puriﬁed by

ﬂash chromatography on silica gel (hexane–ethyl acetate¼50:1 as

an eluent) to give (5R

,6S )-6-(tert-butyldimethylsilylethynyl)-5-

formylbicyclo[2.2.1]hept-2-ene (23, 21 mg, 82%) as a colorless oil, R_f

0.28 (hexane–ethyl acetate¼20:1). ¹H NMR (400 MHz, CDCl₃)

9.88

(hexane–ethyl acetate¼5:1). ¹H NMR (400 MHz, CDCl₃)

d 7.35–7.28

(d, J¼2.9 Hz, 1H), 6.17 (m, 2H), 3.17 (s, 1H), 3.06 (s, 1H), 2.67 (dd,

J¼9.1, 1.8 Hz, 1H), 2.27 (dt, J¼9.3, 2.3 Hz, 1H), 1.81 (d, J¼9.1 Hz, 1H),

1.54 (dt, J¼9.1, 1.8 Hz, 1H), 0.91 (s, 9H), 0.08 (s, 6H); ¹³C NMR

(m, 2H), 7.27–7.19 (m, 3H), 5.72 (d, J¼0.73 Hz, 1H), 5.71 (s, 1H), 3.31

(t, J¼7.1 Hz, 1H), 3.06 (s, 1H), 2.90–2.73 (m, 2H), 2.28–2.13 (m, 2H);

¹³C NMR (101 MHz, CDCl₃)

d 139.5, 128.5, 128.3, 126.4, 125.9, 125.0,

(101 MHz, CDCl₃)

203.7, 137.1, 136.9, 106.5, 87.0, 52.6, 50.2, 45.3,

118.6, 80.2, 80.1, 37.4, 33.3, 32.6; IR (neat) 3285, 3028, 2930, 2864,

2243, 1616, 1603, 1497, 1454, 1030, 922, 750, 700 cm^ꢂ1; HRMS (EI)

calcd for C₁₄H₁₃N: M^þ, 195.1048. Found: m/z 195.1046.

43.7, 33.5, 26.1, 16.6, ꢂ4.4; IR (neat) 2953, 2928, 2884, 2857, 2729,

2172, 1724, 1472, 1462, 1391, 1362, 1329, 1250, 1076, 1007, 907, 839,

826, 812, 775, 733, 710, 681, 617 cm^ꢂ1; HRMS (EI) calcd for

C₁₂H₁₅OSi: [Mꢂt-Bu]^þ, 203.0892. Found: m/z 203.0885.

4.11. Stannylative cross-cyclodimerization of 26 with ethyl

(Z)-2-undecen-4-ynoate (27)

4.8. Reduction of 3da with DIBAL-H

To a solution of Cp(

were added N-(2-diphenylphosphinobenzylidene)cyclohexylamine

(28) (3.7 mg, 10.0 mol), (Bu₃Sn)₂O (60 mg, 0.100 mmol), 26 (59 mg,

p-allyl)Pd (1.06 mg, 5.0 mmol) inTHF (0.60 mL)

To a solution of 3da (48 mg, 0.20 mmol) in toluene (2.0 mL) was

added a 1.5 M solution of DIBAL-H (0.33 mL, 0.5 mmol) in toluene at

ꢂ78 ^ꢀC, and the resulting mixture was stirred at the same tem-

perature for 2 h before quenching with MeOH at ꢂ78 ^ꢀC. The

mixture was warmed to room temperature, diluted with CH₂Cl₂,

and ﬁltered through a glass ﬁlter. The ﬁltrate was concentrated in

vacuo to give a residue, which was puriﬁed by ﬂash chromatogra-

phy on silica gel (hexane–ethyl acetate 50:1) to give (Z)-3-phe-

nylethynyl-2-propylhex-2-en-4-ynal (24da, 44 mg, 90%) as

a yellow oil, R_f0.53 (hexane–ethyl acetate¼5:1). ¹H NMR (400 MHz,

0.30 mmol), and ethyl (Z)-2-undecen-4-ynoate (27) (63 mg,

0.30 mmol) sequentially. The resulting mixture was stirred at 50 ^ꢀC

for 24 h, ﬁltered through a Florisil pad, and concentrated in vacuo.

The residue was puriﬁed by ﬂash chromatography on silica gel

(hexane–ethyl acetate¼30:1 with 0.2% Et₃Nas an eluent) followed by

preparative GPC gave ethyl (Z)-3-[2-hexyl-4-(1-cyano-3-phenyl-

prop-1-yl)-5-(tributylstannyl)phenyl]-2-propenoate (29, 74 mg,

53%) as a pale yellow oil, R_f0.30 (hexane–ethyl acetate¼20:1). ¹H

CDCl₃)

10.4 (s, 1H), 7.55–7.44 (m, 2H), 7.40–7.32 (m, 3H), 2.48 (t,

NMR (400 MHz, CDCl₃)

7.37–7.20 (m, 7H), 7.15 (d, J¼11.7 Hz, 1H),

J¼7.7 Hz, 2H), 2.33 (t, J¼7.8 Hz, 2H), 1.76 (sext, J¼7.5 Hz, 2H), 1.39

6.03 (d, J¼12.1 Hz,1H), 4.04 (q, J¼7.1 Hz, 2H), 3.53 (dd, J¼11.0, 4.9 Hz,

1H), 3.08–2.96 (m, 1H), 2.92–2.80 (m, 1H), 2.59 (t, J¼7.9 Hz, 2H),

2.32–2.18 (m, 1H), 2.10–1.96 (m, 1H), 1.62–1.24 (m, 20H), 1.09 (t,

(sext, J¼7.6 Hz, 2H), 1.03 (t, J¼7.4 Hz, 3H), 0.94 (t, J¼7.4 Hz, 3H); ¹³C

NMR (101 MHz, CDCl₃)

d 193.8, 145.5, 142.9, 131.6, 129.1, 128.5,

122.4, 99.7, 86.3, 35.9, 27.0, 22.4, 21.5, 14.2, 13.9; IR (neat) 2963,

2932, 2872, 2195, 1672, 1599, 1578, 1489, 1458, 1443, 1256, 1225,

1138, 756, 691 cm^ꢂ1; HRMS (EI) calcd for C₁₇H₂₀O: M^þ, 240.1514.

Found: m/z 240.1517.

J¼7.1 Hz, 3H), 0.98–0.86 (m,18H); ¹³C NMR (101 MHz, CDCl₃)

d 165.6,

143.0,142.3,141.5,139.6,137.6,137.3,134.1,128.6,128.4,127.2,126.4,

121.6, 120.9, 60.0, 39.5, 38.4, 33.9, 33.8, 31.7, 30.6, 29.3, 29.1, 27.4,

22.7, 14.2, 14.1, 13.7, 10.5; IR (neat): 2957, 2928, 2870, 2855, 2239,

1726,1634,1589,1464,1456,1416,1377,1173,1032, 908 cm^ꢂ1; HRMS

(EI) calcd for C₃₅H₅₀NO₂Sn: [MꢂBu]^þ, 636.2864. Found: m/z

636.2859.

4.9. Reaction of 24da with a p-tolyl Grignard reagent

A solution of p-tolylmagnesium bromide in diethyl ether (ca.

1.20 mmol) was added to a solution of 24da (96 mg, 0.40 mmol) in

diethyl ether (2.0 mL) at 0 ^ꢀC, andthe resulting mixturewas stirred at

0 ^ꢀC for 2 h before quenching with a saturated NH₄Cl aqueous solu-

tion. The organic layer was separated, and the aqueous layer was

extracted with diethyl ether. The combined organic layers were

Acknowledgements

The authors are grateful to Professor Masaki Shimizu for

X-ray crystallographic analysis of (E)-3aj and 4. This work has

been supported ﬁnancially by

a Grant-in-Aid for Creative

5050

Y. Hirata et al. / Tetrahedron 65 (2009) 5037–5050

2007, 1993–2002; (u) Acosta-Ramı´rez, A.; Flores-Gaspar, A.; Mun˜oz-Herna´ndez,

Scientiﬁc Research and for Priority Areas ‘Molecular Theory for

Real Systems’ from MEXT. Y.H. and A.Y. acknowledge the JSPS for

a predoctoral fellowship. Y.N. acknowledges Japan Chemical In-

novation Institute, Showa Shell Sekiyu Foundation for Promotion

of Environmental Research, and The Sumitomo Foundation for

supports.

M.; Arevalo, A.; Jones, W. D.; Garcıa, J. J. Organometallics 2007, 26, 1712–1720;

(v) Nishihara, Y.; Miyasaka, M.; Inoue, Y.; Yamaguchi, T.; Kojima, M.; Takagi, K.

Organometallics 2007, 26, 4054–4060.

5. Catalytic reactions involving oxidative addition of C–CN bonds: (a) Blum, J.;

Oppenheimer, E.; Bergmann, E. D. J. Am. Chem. Soc. 1967, 89, 2338–2341; (b)

Murahashi, S.; Naota, T.; Nakajima, N. J. Org. Chem. 1986, 51, 898–901; (c) Miller,

J. A. Tetrahedron Lett. 2001, 42, 6991–6993; (d) Miller, J. A.; Dankwardt, J. W.

Tetrahedron Lett. 2003, 44, 1907–1910; (e) Miller, J. A.; Dankwardt, J. W.; Penney,

J. M. Synthesis 2003, 1643–1648; (f) Penney, J. M.; Miller, J. A. Tetrahedron Lett.

2004, 45, 4989–4992; (g) Chaumonnot, A.; Lamy, F.; Sabo-Etienne, S.; Donna-

dieu, B.; Chaudret, B.; Barthelat, J. C.; Galland, J. C. Organometallics 2004, 23,

3363–3365; (h) van der Vlugt, J. I.; Hewat, A. C.; Neto, S.; Sablong, R,; Mills, A.

M.; Lutz, M.; Spek, A. L.; Mu¨ ller, C.; Vogt, D. Adv. Synth. Catal. 2004, 346, 993–

1003; (i) Wilting, J.; Mu¨ ller, C.; Hewat, A. C.; Ellis, D. D.; Tooke, D. M.; Spek, A. L.;

Supplementary data

Supplementary data associated with this article can be found in

the online version, at doi:10.1016/j.tet.2009.03.079.

Vogt, D. Organometallics 2005, 24, 13–15; (j) Acosta-Ramırez, A.; Munoz-Her-

na´ndez, M.; Jones, W. D.; Garcı´a, J. J. Organometallics 2007, 26, 5766–5769; (k)

Swartz, B. D.; Reinartz, N. M.; Brennessel, W. W.; Garcı´a, J. J.; Jones, W. D. J. Am.

Chem. Soc. 2008, 130, 8548–8554.

References and notes

1. (a) Noyori, R.; Odagi, T.; Takaya, H. J. Am. Chem. Soc. 1970, 92, 5780–5781; (b)

Noyori, R.; Kumagai, Y.; Umeda, I.; Takaya, H. J. Am. Chem. Soc. 1972, 94, 4018–

4020; (c) Baba, A.; Ohshiro, Y.; Agawa, T. J. Organomet. Chem. 1976, 110, 121–127;

(d) Kondo, T.; Kaneko, Y.; Taguchi, Y.; Nakamura, A.; Okada, T.; Shiotsuki, M.;

Ura, Y.; Wada, K.; Mitsudo, T.-a. J. Am. Chem. Soc. 2002, 124, 6824–6825; For

reviews, see: (e) Nakamura, I.; Yamamoto, Y. Adv. Synth. Catal. 2002, 344, 111–

129; (f) Rubin, M.; Rubina, M.; Gevorgyan, V. Chem. Rev. 2007, 107, 3117–3179.

2. (a) Huffman, M. A.; Liebeskind, L. S. J. Am. Chem. Soc. 1991, 113, 2771–2772; (b)

Murakami, M.; Itahashi, T.; Ito, Y. J. Am. Chem. Soc. 2002, 124, 13976–13977; (c)

Mu¨ ller, C.; Lachicotte, R. J.; Jones, W. D. Organometallics 2002, 21, 1975–1981; (d)

Matsuda, T.; Fujimoto, A.; Ishibashi, M.; Murakami, M. Chem. Lett. 2004, 33, 876–

877; (e) Kondo, T.; Taguchi, Y.; Kaneko, Y.; Niimi, M.; Mitsudo, T.-a. Angew. Chem.,

Int. Ed. 2004, 43, 5369–5372; (f) Murakami, M.; Ashida, S.; Matsuda, T. J. Am. Chem.

Soc. 2005, 127, 6932–6933; (g) Murakami, M.; Ashida, S.; Matsuda, T. J. Am. Chem.

Soc. 2006, 128, 2166–2167; (h) Murakami, M.; Ashida, S.; Matsuda, T. Tetrahedron

2006, 62, 7540–7546; (i) Murakami, M.; Ashida, S. Chem. Commun. 2006, 4599–

4601; (j) Ashida, S.; Murakami, M. Bull. Chem. Soc. Jpn. 2008, 81, 885–893.

3. (a) Nozaki, K.; Sato, N.; Takaya, H. J. Org. Chem. 1994, 59, 2679–2681; (b) Nozaki,

K.; Sato, N.; Takaya, H. Bull. Chem. Soc. Jpn. 1996, 69, 1629–1637; (c) Nakao, Y.;

Oda, S.; Hiyama, T. J. Am. Chem. Soc. 2004, 126, 13904–13905; (d) Nishihara, Y.;

Inoue, Y.; Itazaki, M.; Takagi, K. Org. Lett. 2005, 7, 2639–2641; (e) Nakao, Y.;

Yada, A.; Satoh, J.; Ebata, S.; Oda, S.; Hiyama, T. Chem. Lett. 2006, 790–791; (f)

Kobayashi, Y.; Kamisaki, H.; Yanada, R.; Takemoto, Y. Org. Lett. 2006, 8, 2711–

2713; (g) Nakao, Y.; Oda, S.; Yada, A.; Hiyama, T. Tetrahedron 2006, 62, 7567–

7576; (h) Nishihara, Y.; Inoue, Y.; Izawa, S.; Miyasaka, M.; Tanemura, K.;

Nakajima, K.; Takagi, K. Tetrahedron 2006, 62, 9872–9882; (i) Nakao, Y.; Yukawa,

T.; Hirata, Y.; Oda, S.; Satoh, J.; Hiyama, T. J. Am. Chem. Soc. 2006, 128, 7116–7117;

(j) Nakao, Y.; Yada, A.; Ebata, S.; Hiyama, T. J. Am. Chem. Soc. 2007, 129, 2428–

2429; (k) Kobayashi, Y.; Kamisaki, H.; Takeda, H.; Yasui, Y.; Yanada, R.; Take-

moto, Y. Tetrahedron 2007, 63, 2978–2989; (l) Yasui, Y.; Kamisaki, H.; Takemoto,

Y. Org. Lett. 2008, 10, 3303–3306; (m) Watson, M. P.; Jacobsen, E. N. J. Am. Chem.

Soc. 2008, 130, 12594–12595; (n) Nakao, Y.; Ebata, S.; Yada, A.; Hiyama, T.;

Ikawa, M.; Ogoshi, S. J. Am. Chem. Soc. 2008, 130, 12875–12876.

6. (a) Tolman, C. A.; Seidel, W. C.; Druliner, J. D.; Domaille, P. J. Organometallics

1984, 3, 33–38; (b) McKinney, R. J. Organometallics 1985, 4, 1142–1143; (c)

McKinney, R. J.; Nugent, W. A. Organometallics 1989, 8, 2871–2875.

7. (a) Murray, R. E.; Zweifel, G. Synthesis 1980, 150–151; (b) Kende, A. S.; Smith,

C. A. J. Org. Chem. 1988, 53, 2655–2657.

8. Baddley, W. H.; Panattoni, C.; Bandoli, G.; Clemente, D. A.; Belluco, U. J. Am.

Chem. Soc. 1971, 93, 5590–5591.

9. For preliminary communication, see: Nakao, Y.; Hirata, Y.; Tanaka, M.; Hiyama,

T. Angew. Chem., Int. Ed. 2008, 47, 385–387.

10. See Supplementary data for details.

11. The reaction of 1d (1.00 mmol) with 2a (2.0 mmol) in the absence of BPh₃gave

a mixture of substituted benzenes as major products in 66% yield through

cyclotrimerization of 1d. The yield of 3da was only 11%.

Ni(cod)₂(10 mol%)

xantphos (10 mol%)

(1.0 mmol)

3da

Ph, CN

PhMe, 100 °C, 3 h

11%

(2.0 mmol)

66%

For an example of nickel-catalyzed cyclotrimerization of alkynes, see: (a) Mori,

N.; Ikeda, S. i.; Odashima, K. Chem. Commun. 2001, 181–182; For a review on the

nickel-catalyzed cyclotrimerization of alkynes, see: (b) Saito, S. In Modern

Organonickel Chemistry; Tamaru, Y., Ed.; Wiley-VCH: Weinheim, 2005; pp 175–

182.

12. Crystallographic data (excluding structure factors) for structures of (E)-3aj and

4 have been deposited with the Cambridge Crystallographic Data Center as

supplementary publication numbers CCDC 718299 and CCDC 717696. Copies of

the data can be obtained, free of charge, on application to CCDC, 12 Union Road,

Cambridge CB2 1EZ, UK (fax: þ44 1223 336033 or e-mail: deposit@ccdc.

cam.ac.uk).

13. Ojima, I.; Clos, N.; Donovan, R. J.; Ingallina, P. Organometallics 1990, 9, 3127–

3133.

4. (a) Burmeister, J. L.; Edwards, L. M. J. Chem. Soc. A 1971, 1663–1666; (b) Gerlach,

D. H.; Kane, A. R.; Parshall, G. W.; Jesson, J. P.; Muetterities, E. L. J. Am. Chem. Soc.

1971, 93, 3543–3544; (c) Parshall, G. W. J. Am. Chem. Soc. 1974, 96, 2360–2366;

(d) Clarke, D. A.; Hunt, M. M.; Kemmitt, D. W. J. Organomet. Chem. 1979, 175,

303–313; (e) Morvillo, A.; Turco, A. J. Organomet. Chem. 1981, 208, 103–113; (f)

Ozawa, F.; Iri, K.; Yamamoto, A. Chem. Lett. 1982, 1707–1710; (g) Favero, G.;

Morvillo, A.; Turco, A. J. Organomet. Chem. 1983, 241, 251–257; (h) Bianchini, C.;

Masi, D.; Meli, A.; Sabat, M. Organometallics 1986, 5, 1670–1675; (i) Adam, R.;

Villiers, C.; Ephritikhine, M.; Lance, M.; Nierlich, M.; Vigner, J. J. Organomet.

Chem. 1993, 445, 99–106; (j) Abla, M.; Yamamoto, T. J. Organomet. Chem. 1997,

532, 267–270; (k) Churchill, D.; Shin, J. H.; Hascall, T.; Hahn, J. M.; Vridgewater,

B. M.; Parkin, G. Organometallics 1999, 18, 2403–2406; (l) Marlin, D. S.; Olm-

stead, M. M.; Mascharak, P. K. Angew. Chem., Int. Ed. 2001, 40, 4752–4754; (m)

Garcı´a, J. J.; Brunkan, N. M.; Brestensky, D. M.; Jones, W. D. J. Am. Chem. Soc.

2002, 124, 9547–9555; (n) Yamamoto, T.; Yamaguchi, I.; Abla, M. J. Organomet.

Chem. 2003, 671, 179–182; (o) Liu, Q. X.; Xu, F. B.; Li, Q. S.; Song, H. B.; Zhang, Z.

Z. Organometallics 2004, 23, 610–614; (p) Garcı´a, J. J.; Are´valo, A.; Brunkan, N.

M.; Jones, W. D. Organometallics 2004, 23, 3997–4002; (q) Brunkan, N. M.;

Brestensky, D. M.; Jones, W. D. J. Am. Chem. Soc. 2004, 126, 3627–3641; (r) Lu, T.;

Zhuang, X.; Li, Y.; Chen, S. J. Am. Chem. Soc. 2004, 126, 4760–4761; (s) Ates¸in, T.

A.; Li, T.; Lachaize, S.; Brennessel, W. W.; Garcı´a, J. J.; Jones, W. D. J. Am. Chem.

Soc. 2007, 129, 7562–7569; (t) Schaub, T.; Do¨ring, C.; Radius, U. Dalton Trans.

14. Huggins, J. M.; Bergman, R. G. J. Am. Chem. Soc. 1981, 103, 3002–3011.

15. (a) Nishihara, Y.; Inoue, Y.; Nakayama, Y.; Shiono, T.; Takagi, K. Macromolecules

2006, 39, 7458–7460; (b) Nishihara, Y.; Inoue, Y.; Saito, A. T.; Nakayama, Y.;

Shiono, T.; Takagi, K. Polym. J. 2007, 39, 318–329; (c) Nishihara, Y.; Izawa, S.;

Inoue, Y.; Nakayama, Y.; Shiono, T.; Takagi, K. J. Polym. Sci., Part A: Polym. Chem.

2008, 46, 3314–3325.

16. For accounts, see: (a) Rubin, M.; Sromek, A. W.; Gevorgyan, V. Synlett 2003,

2265–2291; (b) Miki, K.; Uemura, S.; Ohe, K. Chem. Lett. 2005, 34, 1068–

1073; (c) Asao, N. Synlett 2006, 1645–1656; For selected recent examples,

see: (d) Liu, Y.; Song, F.; Song, Z.; Liu, M.; Yan, B. Org. Lett. 2005, 7, 5409–

5412; (e) Rubina, M.; Conley, M.; Gevorgyan, V. J. Am. Chem. Soc. 2006, 128,

5818–5827; (f) Lian, J. J.; Lin, C. C.; Chang, H. K.; Chen, P. C.; Liu, R. S. J. Am.

Chem. Soc. 2006, 126, 9661–9667; (g) Du, X.; Chen, H.; Liu, Y. Chem.dEur. J.

2008, 14, 9495–9498.

17. Nakao, Y.; Hirata, Y.; Ishihara, S.; Oda, S.; Yukawa, T.; Shirakawa, E.; Hiyama, T.

J. Am. Chem. Soc. 2004, 126, 15650–15651.

18. Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.; Timmers, F. J.

Organometallics 1996, 15, 1518–1520.

19. (a) Brandsma, L. Synthesis of Acetylenes, Allenes and Cumulenes: Methods and

Techniques; Elsevier: New York, NY, 2004; (b) Trost, B. M.; Pinkerton, A. B.;

Seidel, M. J. Am. Chem. Soc. 2001, 123, 12466–12476.

Products guided by the article

Product name:(E)-5-tert-butyldimethylsilyl-2-(4-methoxyphenyl)pent-2-en-4-ynal

Cas No:1174272-37-7

R&D Labs maybe for 1174272-37-7

Compro Shijiazhuang Fine Chemical Co., Ltd

Contact:0086-311-89689838

Address:Economic and Technological Development Zone of Shijiazhuang,Hebei
Zhejiang Homart Chemical & Technology Co., Ltd.(expird)

Contact:13587107601

Address:Cuijiatianpu,Quzhou, Zhejiang, China (Mainland)
Jiangsu Fengshan Group Co., Ltd.

Contact:86-25-86558671

Address:1903,Central International Mansion 105-6 North Zhongshan Road, Nanjing, China
Shandong Yuanli Science and Technology Co., Ltd.

Contact:86-0536-6777557

Address:Zhuliu Industiral Park,Changle County
TAIZHOU XINGCHENG CHEMPHARM CO.,LTD.

Contact:0086-0576-88551200,88886292 ,88880039

Address:B Area. 10 Floor.Yaodadasha. 289#.Shifu Road.Taizhou.Zhejiang.China

Relevant to this article

Efficient one-pot synthesis of α,β-unsaturated carbyne complexes fac-[RuX₃{≡CC(H)=CR₂}(dppf)] (X = Cl, Br; R = aryl, alkyl; dppf = 1,1′-bis(diphenylphosphino)ferrocene)

Doi:10.1021/om050204u
(2005)
Efficient synthesis of polysubstituted pyridine under solvent-free conditions without using any catalysts

Doi:10.1080/00397910801991184
(2008)
Doi:10.1021/ja01629a042
(1955)
Doi:10.1039/jr9320002358
(1932)
Doi:10.1039/JR9262902432
()
Bis(phosphinimino)methanides as ligands in divalent lanthanide and alkaline earth chemistry - Synthesis, structure, and catalysis

Doi:10.1016/j.jorganchem.2005.03.023
(2005)

Article Doi

Alkynylcyanation of alkynes and dienes catalyzed by nickel

DOI: 10.1016/j.tet.2009.03.079

Source and publish data:

Authors:

Article abstract of DOI:10.1016/j.tet.2009.03.079

Full text of DOI:10.1016/j.tet.2009.03.079

Products guided by the article

R&D Labs maybe for 1174272-37-7

Relevant to this article

Hot Product