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Title Palladium-Catalyzed Nucleophilic Allylation of Carbonyl Compounds withAllyl Alcohols
Author(s) Shimizu, Masamichi
Citation (2005-03-18)
Issue Date 2005-03-18
URL http://hdl.handle.net/10069/9825
Right
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Chapter3
Pd・CatalyzedNucleop1皿icAllylationofIminesPromotedby
Et3B and Et2Zhl
One・potSynthesisofHomoalylAmines
Ab8tract; Inthe presence ofa catalyst Pd(0)complex,Et3B and Et2Zn promote
nucleoph丑icε皿ylation of allyl alcohols with hnines prepared丘om the various
combinations of aldehyde and amines to provide homoanyl amines in good to
moderateyieldsthroughafゑc且eone・potprocedure,hcaseofthe allylationus士ng
methyl substituted a且yl alcohols(e,g.,crotyl alcoholorα・methyl anyl alooho1),the
reaction shows unique stereoselectivity giving aη出somers selectively
106
Introduction
Nucleophi五c anylation of hnines have been wi(1ely utnized fbr the syntheses,
since the corresponding homoa皿yl amines are an important synthetic tmit and a
Ilumber of reagents have been(1eveloped fb〔r this pu竿pose.1,2 h con七rast tD
carbonyl compound likeεユdehyde,howeve蔦 the results have o丘en been
unsatisfactoly refbr to the low electoph皿city of血nhユe.Furthermore,the use of
monαs“bs廿tuted飢y㎞etalcQmpo㎜dsraisestheadditionalproblemofregio・舗
al1(l stereoselectivityl6’g In or(1er to address this issues,vεudous anyhnetal
reagentswere employed.1α13
1nChapber1,wehavedem・ns廿a囲thatEtβ14・rEt2zn15pr・m・bes
mcle・P地canylati・n幅th飢y1飢c・h・1s血thepresence・facat飢画6㎜・㎜t・f
pa皿adium(0)via umpolung ofπ・a皿ylpa皿adium(eq,1and2).Based on the
investiga廿on of Chapter1,we attempte&that加11adium・catalyzed a皿ylation of
血ines幅th飢yl alcoholsinthe presence o畑ethylborane and釦mdthat七he
sim丑ar allylation pr㏄eeds nicely to fl皿nish homoa皿yl amhles through a facile
one・pot proced』u■e.
PhCHO
・。
十 ( OH
Pd cat.
Et3B
+,
Ph〉㌔ OH
r†,
Pd cat.
Et2Zn
OH
〈/kPh
-
OH
rt. Ph
(1)
(2)
Herein we would like to report that the same Pd.一Etβcataly廿c system is
su㏄essfb皿y・extended to the nucleoph丑icε皿ylatio11.of aldi1血1es of aromatic
107
aldehydes and even aldnlaines of aliphatic aldehydes bearing enolizable protons
RCHO THF / reflux
R'NH2 azeotrope
NR' ~ R
~~~OH NHR' ~r (3 ) Pd cat./ Et3B R
1 08
Result8and D蛤cu88ion
The reac廿on was conducted as fb丑ows: .加・就α fbrmation of a
benzaldehyde・μanisid士neimine丘om benzaldehyde la(1,0mmol)andpanisidine
2a(2.O mmo1)(30mln at refしux in dry THF l mL),dist皿ation of an azeotropic
m鱗皿e・fTHF・H20tw・times,㎝dexp・s肥e・f㎞eresiduet・am麟皿e・f
Pd(OAc)2(0,1mmoD,P(エrBu)3(0,2mmo1),a丑ylalcohols(1,2mmo1),Et3B(3.6mlin
lMhexane soltion)andTHF(1ml〉at500Cfbr24hunder N2.
をMethoxyN(1・phelly1・3・butenyDan丑圭ne 4a was μoduced in 59%,gas
chromat6garphic yield together withハ沼ally1・7ani8idine25%(rul11,Table1).14
1n order tD丘n.d out best reac廿on condition,we examined theεdlylation mder
vaduousreactioncondition,Byreducingtheamomtofpanisidine2a2.0㎜01
to1.05mmol,the fbrmation ofNa皿yl・par直sidine was suppressed andyieldof4a
was血pr。vedrem飢kably(r㎜勿,職e外eld・f4adeαeasedb・31%,29%,副
0%,when PPh3,P(πHex)3,dppp and dppf were used,respectivelyl in place of
P(刀・Bu)3(run3・6).
τaわ’eブ.Effect of Reaction Condition on the Pd-Et3B Promoted Nucleophilic AIlylation of
Benzaldehyde一ρ一Anisidine Imine with Allyl Alcohola
GCyield(%)
run Pd Phosphine solv Et3B eq. temp/time4a 3a
1c・d
2
Pd(OAc)2
(10mol%)
Pd(OAc)2
(10mol%)
PBu3 THF 3,6
(20mol%)
PBu3 THF 3.6
(20mol%)
50/24
50124
57
75(72)b
8
9
109
3
4
5
6
7
8
9
10
11
12
13
14
Pd(OAc)2
(10 mol'/.)
Pd(OAc)2 (1 O mol'/,)
Pd(OAc)2 (1 O mol'/,)
Pd(OAc)2 (10 mol'/.)
Pd(OAc)2 (10 mol"/,)
Pd(OAc)2 (1 O mol'/.)
Pd(OAc)2 (10 mol'/.)
Pd(OAc)2
(10 mol'/.)
Pd(OAc)2
(5 mol'l.)
Pd(OAc)2
(1 mol'l.)
Pd (acac)2
(10 molo/o)
Pd Cl z
(1 O mol'/・)
PPh3 THF 3.6 (20 mol'/・)
PCy3 THF 3,6 (20 mol"I.)
dppp THF 3,6 (20 mol'/・)
dppf THF 3,6 (20 mol"/.)
PBu3 THF 3,6 (20 mololo)
PBu3 THF 2 4 (20 mol"/・)
PBu3 tolene 3 6 (20 mololo)
PBu3 none 3 6 (20 mololo)
PBu3 THF 3.6 (10 moPl.)
PBu3 THF 3.6 (2 mol'l.)
PBu3 THF 3.6 (20 mol'l*)
PBu3 THF 3.6 (2C mololo)
50/24
50/24
50/24
50/24
rtl:2d
50/24
50/24
50/24
5 0/2 4
50/24
5 0/2 4
50/24
31
29
56
52
no reaction 99
no reaction 89
28
56
53
15
61
44
70
56
13
19
33
5
33
3
no reaction 71
15 Pd (PPhd 4
(1 O mol"/,) none THF 3.6 5 0/2 4 8 44
1 6 Pd (dba) CHC13 none 2(1 O mol'/.) THF 3.6 50/24 no reaction 82
a Reaction Conditions: aldehyde (1.0 mmol), amine (1.05 mmol) in THF1.0mL at reflux 0.5h, then remove
water from azeotrope. Pd(OAc)2 (0.1 mmol), P(n-Bu)3 (0.2 mmol), allyl alcohol (1 .2 mmol), Et2Zn 3.6ml
(1 M n-hexane) and THF 1.0ml were added at under N2・ b Isolated yield was shown in parenthesis. c p
Anisidine (2.0 mmol) was used. d N-allyl-p-anisidine was produced in 250/0 yield.
As is apparent from run 7-10, the allylation should be carried out at 500C in
110
THF㎝d3,6e俳。ftnethylb・r㎝eisreq血edもr血h・e,』e亘eld・f4awas
decreased when the catalyst was used in less than10mo1%,howeve蔦the
ε皿ylation pr㏄eededto give the homoa皿ylic amine in44%yield even though the
amomtofcatalystwaslmo1%(rm12),AlthoughPd(acac)2wasdemons廿ated
coequal catalytic ab丑ityl PdC12,Pd(PP1翻4,and Pd2(dba)3・CHCl3did not work fbr
thi副yla廿・nascat飢yst(r㎝13・16)・
τab,e2,Pd-Catalyzed,Et3B-Prom6ted Nucleophilic AIlylation of Various Benzaldehyde一
lmines with A”yl alcohola
P鷲la龍悪[‘NR
3
、響1ぬ,IHR(2)
500C/24h 4
run RNH22 isolated yield of4(%)
1
2
3
4
5
H2Nゆ。Me
2a
OMe
H2Nウ 2b
H2Nゆ\
2c
H2Nゆ2d
H2NゆCI
2e
、hNゆ。、,
4a
OMe
4b
、,Nゆ\ 4c
4き,N\〔》
ンhN窺C、・
72
83
96
93
76
111
6
7
8
ACl H2N
2f
H2N O
29
H2N02S'CL¥
2h
H ~Ar~' N ~' Ph
Ph 4f
H ~~/~~ NCl
Ph 49
HO N, ,, Ph O,,s~~l~¥1 ~
4h
37
27
55
aReaction Conditions: aldehyde+(1 .O mmol), amine (1 .05 mmol), THF I .O mL, reflux 0.5h, then
Pd(OAc)2 (0.Immol), P(n-Bu)3 (0.4 mmol), allyl alcohol (i .2 mmol)and Et3B (3.6 mmol, i M
n-hexane) in THF 1.0 ml at under N2,
Table 2 shows the results for the various combinations of aldehydes and amines.
These results indicate that the yields of homoallyl amine 4 sharply depend on the
kinds of arDines, and aromatic amines (run I - 5) are the reagents of choice. The
best yield was recorded with ptoluidule, however, hereafter we utilized panisidine
because of its synthetic utility; F anisidine could be readily removed to give rise to
a priinary homoallyl amine. Although the yields of homoallyl arDjne were
moderate to law, irnines formed from aliphatic amines or sulfone alldde 2h and
benzaldehyde also provided products (run 6-8).
Ph Ph Ph Pd oat. / Et3B )¥ reflux in THF
N C02Me azeotrope oL-phenyl allylalcohol ph
500c / 20h
2.0 mmol 2.0 mmol yield 430/0, d,r. [2:1]
Scheme 1. The allylation of imine from amino acid ester and benzaldehyde with allyl alcohol. Reaction condition: Pd(OAc)2 (0.1 mmol), P(n-Bu)3 (0.2 mmol), allyl alcdhol (i .2 mmol), Et3B 3.6 ml (1 M n-
hexane) and THF I .O ml were added at under N2・ ' '
112
Furthermore,am虹10acid ester2i was also able to use fbr this a且ylation to
producehomoallylamine4sinmoderateyield(Scheme1),
Next,we examined theε皿yla廿on ofpanisidine・㎞ine fbrmed fヒom aroma廿c
飢4ehydes(Table3).』ereac廿・n蛉c・mpatitible幅thelec廿・∬d・na廿・ng仕皿
2・6)㎝delec旋・n・輌th血a血gsubstiugnts(r㎜7)・He㊥r・一訓・ma廿c飢dehydes
and cimamaldehyde also behave s血皿arly and provide homoa皿yl amines in
reasonableyields(rm8・10),
τaわ,e3,Pd-Catalyzed,Et3B-Promoted Nucleophilic A”ylation ofρ一Anisidine-1mines with
A”ylalcohola
THF - Pdcat. RCHO1 + 「eflux aIlylalcoh。1晒R (3)
ρ.Anlsidine2a azeot「。pe Et3B NH一ρ一Anis 4
run RCHO1 temp(oC)/time(h) isolated yield of4(%)
1
2
3
4
α 一
CHOla
= 一
CHOlb
MeOOCH。
1C
く1〕〔》\cH。
1d
50124
50124
50124
50/22
ノ 1
\ \
NH一ρ一Anis4a
〆 1
\ \
NH一ρ一Anis 4」
OMe 〆 i
、 、
NH一ρ一Anis
4k
ノ’ O I〉
、 、 O
NH一ρ一Anis
41
72
76
76
77
113
5
6
7
8
9
OH
CHO
le
HOゆCH。
1f
αゆCH。
19
だ〉CH・
1h
○、CH。
1i
50/24
50/24
50/24
50/24
50/20
グ 1
\ \ OH
NH一ρ一Anis
4m
〉Yく)rOH
NH一ρ一Anis
4n
Cl グ 1
、 、
NH一ρ一Anis
40
O、、 、
NH一ρ一Anis4P
クN I
、 \
NH一ρ一Anis4q
76
68
84
73
79
10 Ph\ノ\CHO
1」
50!20 \ 、 Ph
NH一ρ一Anis4r
79
aReaction qonditions:aldehyde(1,0mmol),amine(1.05mmol)in THF1.O mL at refluxO.5h,
then removewaterfrom azeotrope,Pd(OAc)2(0.1mmol),P(η一Bu)3(0.2mmol),A”yllcalcohol
(12mmol),Et3B3.6mL(1Mη一hexane)and THF1.O mL were added at under N2.
ItmaybeworthnotingthateveninthepresenceofallacidicOHgroup(run5・6)
an(1basic am血o group(rul19),it is not necessary t天)use any exセa amount ofEt3B,
i.e.,the opt血血6d amoullt of Et3B fbr ord血a笈y aldehyd.es is su岱cient8nough fbr
the anylation ofsuch substrates.
,On the other hand,ε江dhエ吐ne bea血ghetero atom at the碗h6position did Ilot
114
provi.de homoallyl amine at all (Scheme ~9) , The results could be explained by
taking into consideration the decrease of Lewis acidity of borane was caused by the
chelation of borane to nitrogen or oxygen at the ortho position.
C(H H2N reflux in THF Pd cat / Et B no reaction
CHO OMe azeotrope allyl alcohol
'¥cHO H2N o¥ reflux in THF Pd cat. / Et3B complex mixture
OM azeotrope allyi alcohol
scheme 2. NUcteophinc Anylation ot p-Anisidine-Imines I k and I I with Avyl Acohol.
ReactiOn conditio: aldehyde (1 .o mmoD, ami'ne (1 .os mmoD in THF I .o mL at re~ux 0.5h, then remove
waterfrom azeotrope, pd(oAc)2 (0.1 mmoD, p(n-Bu)3 (0.2 mmoD, avyl atcohol (1.2 mmol), Et3B 3.6ml
(1 M n-hexane) and THF I .o mL Were added at under N2'
In Table 4 are surnmarized the allylation of panisidihe'imines prepared from
aliphatic aldehydes. For primary aldehydes (run I -~9), ordinary secondary
aldehyd~s recorded acceptable yields Gun 3・5) . Imines of oc.P unsaturated
aldehydes lr and Is also react with allyl al.cohol smoothly to provide an expected
homoallyl amines 4x and 4y respectively (run 6- 7), however, the yield of 4x was
lower than others of secondary aldehydes and 4y. This result clearly suggests
that the yields go down as acidities of orprotons increase. Tbis is supported that
the reactions of cinnamaldehyde (run 10, Table 3) which does not possess
enolizable protons or the reaction of myrtenal (run 5) that may be attributed to
steric protection of allylic protons by bridged carbons from an approach of a base
were proceeded nicely, while for aldehyde lk and II bearing more enolizable
protons was failed (Scheme 3) .
115
Table 4. Pd-Catalyzed, EtsB-Promoted Nucleophilic Allylation of Aliphatic Aldehyde-
Imines .with Allyl alcohole
RCHO I THF reflux
+ p-Anisidine 2a azeotrope
Pd cat,
allyl alcohol
E t3 B
R
NH-p-Anis
4
ru n RCHO temp(oc)/time(h) isolated yield of 4 (・/・)
1 f CHO Ph
Im
50 1 18 ~. Ph
N H - p-An is
4s
31
2
3
n-C5H 1 1 C HO
In
'¥CHO
10
rtll8
50 / 24
~Ar~~, n-C5H11
N H- p-Anis
4t
N H- p-Anis
4u
44
62
4 tCHO lp
50 / 19 ~~
NH-p-Anis
4v
73
5
6
7
tCHO lq
-CHO lr
~ CHO
Is
50 / 24
50 / 24
50 / 24
~.
~~.
~~'
N H- p-An is
4w
N H- p-A n i s
4,x
NH-p-Anis
4y
72
41
71
8
gb (HCHO)~
It
50 / 24
50 / 24
~~l~~ N H-p-An is
4z
28
52
a Reaction Conditions: aldehyde (1 .O mmol), amine (1 .05 mmol) in THF I .O mL at refiux 0.5h,
then remove waterfrom azeotrope. Pd(OAc)2 (0.1 mmol), P(n-Bu)3 (0.2 mmo,1), AIlylic alcohol
(i .2 mmol), Et3B 3.6 mL (1 M n-hexane) and THF I .O mL were added at under N2・ b o-Anisidine
was used in place of p-Anisidine.
116
On the other han~ in case of paraformaldehyde It, the yield of homoallyl amine
4z was albeit in law because of ethylation product of It provided was generated as
by'product (run 8) . The reason for the difference is most likely responsible for low
solubility of paraformaldehyde in THF.
/l¥ + H2N.¥ reflux in THF Pd cat, / Et3B complex mixture
Ph C H O OMe azeotrope allyl alcohol
Ph H2N.¥ reflux in THF Pd cat / Et B complex mixture /l¥ +
Ph CHO OMe azeotrope allyl alcohol
Scheme 3. Nucleophilic Allylation of Aldehyde-Imines lu and lvl with Allyl Alcohol.
Reaction condition: aldehyde (1.0 mmol), amine (1 .05 mmol) in THF 1.0 mL at reflux 0.5h, then
remove water from azeotrope. Pd(OAc)2 (0.1 mmol), P(n-Bu)3 (0.2 mmol), allyl alcohol
(1.2 mmol), Et3B (3.6ml, IM n-hexane) and THF 1.0 mL were added at under N2-
Previously, we have been found that the electrophilic alLylation with allyl alcohol
at the C3 position of indole proceed successfulLy to afford the corresponding irnine
3aa in excellent yield. 16 The reaction of the obtained imine 3aa with allyl alcohol
also gives rise to the nucleophilic allylation. In Scheme 4 is illustrated,
3,3-diallyl-3H・indole 3aa furnished _9, 3,3-triallylindoline 4aa in 550/0 isolated yield
under similar conditions.
V~
~~
l j d~N 3aa
0.5 mmol
+ ~¥1~P OH Pd cat, / Et3B
500c / 24h
V~
I~ ~~N H
4aa yield 55"/.
Scheme 4 The allylation of imine from indol with allylaicohol. . Reaction condition: Pd(OAc)2(0.05 mmol), P(n-Bu)3 (O.i mmol), allyl alcohol (0.6 mmol), imine
(0.5 mmol), Et3B I .8 mL (1 M n-hexane) and THF 0.5 ml were added at under N2-
117
'lb compare the chemoselectivity in this reaction, we next examined the
allylation in the presence of benzaldehyde and its imine drivative 3a under the
same reaction condition shown in Table -9 (Scheme 3) . The reactivity of
benzaldehyde was ca. 8 times higher than that of its imine. This result agrees
with the allylation of other allyl metalloids 17 and indicates that the generation of
allylborane species via umpolung of lrallylpalladium. ActualLy, Yamamoto et al
have been reported that the chemoselectivity of allylation via bis-1c'allylpalladium
is opposite that of allyl metalloids. 18* It should be also noted that the success of
the present allylation is not due to increased reactivity of allylboranes toward
imines, 18b Rather, the success may owe its origine to rDinirnization of side
reactions that aldehydes suffer from, especially to reduced capability of irnines
undergoing enolization.
PhCHO Ia rl~~~~~l (1 .O mmol) (1 .O mmol) + ~ N- p-Anis
p-Anisidine 2a Ph 3a allyl alcohol Pd cat./ Et3B
(1 .05 mmol)
~~l~~. N H- p-Anls OH +
yield 8010 yield 69010
Scheme 5. Competition Reaction of Benzaldehyde-Imine and Benzaldehyde.
Reaction condition; aldehyde (1.0 mmol), amine (1.05 mmol) in THF 1.0 mL at reflux 0.5h, then remove
water from azeotrope. Pd(OAc)2 (0.Immol), P(n-Bu)3 (0.2 mmol), allyl alcohol (1 ,2 mmol), aldehyde (1 .O
mmol), Et3B 3.6ml (iM n-hexane) and THF 1.0 mL were added at under N2-
In Scheme 6 is outlined our workurg hypothesis for the present palladium
catalyzed allylation reaction, which invokes an allyl-ethy]. exchange between
7rallylpalladiurn and Et3B as a key step. The allylborane thus formed would
readily react with ilnines to give homoallylic amines, and ethyl-palladiullL
118
complexes mi客ht mdergoβ・hydro ehnina廿on thereby regenerat±ng a Pd(0)
species.皿豆s scheme is acoord with the dτop in yield.whenρanisidine was used
in excess(rm l,Table1),Anπ・証yl副a出um intermidiate shows出chotomy
wor1血g either as an electrophile to react withρanisidine or as an nucleoph丑e by
the change hltx)ε皿y1(diethy1)borane via umpolung.19・20
( OH
Et3B↓
( /O\
H BEt3
CH2=CH2
H20
Pd(0)
〈?d
1O\H BEt3
EtPdOH
PhCHO la
十
ρ一Anisidlne 2a
( BEt2
↓一
早Et2
Nr\伊AnisPh 3a
N \ρ一Anis
4a Ph
Scカe」me6.A plausible catalytic cycle for allylation of imine via umpolung ofπ一paIladium with Et3B
In Table3,the results fbr the a且ylation ofbenzaldehyde・メ7anisidine血血e with
allyli.calcoholspossessingoneortwosubstituents are summε血zed.Asisobserved,
mono・subsitituteda且ylicalcoholsreactregioselectivelyatthemostsubstituted
a皿ylicterm血iandprovidehomoallyl amhle4ab and4ac血goodyield(r㎜2’6);
however,the stereoselectivitywas quite unexpectedandturned outtDbe sublectto
the㎞d o:fsubstituents and the substitution patt£rns. Genera且y,α・substituted
a皿yl alcohols showedhigher stereoselectivity,giving a刀が4pref¢entiε皿y over
卿4(rm2vs,rm3andr㎜5vs.rm6).
119
Table 5. Pd-Catalyzed, Et3B-Promoted Nucleophilic Allylation of Imine with Allyl alcohols a
PhCHO Ia
p-Anisidine 2a
reflux in THF allylic alcohol
azeotrope Pd cat, / Et3B
Homoallyl amine
4
(5)
ru n allylic alcohol temp(oc)/time(h) isolated yield of 4 ('/,)
[anti:s yn]
1
2
3
4
5
6
~¥/~ OH
¥~~~ OH
110H
Ph_~~~ OH
l¥roH Ph
50 / 24
50 / 24
50 / 24
50 / 24
rt 1 18
50 1 18
~Ar~~ N H- p-Anls
Ph
4a
JY NH-p-Anis
Ph 4a b
4a b
Ph ~/ NH-~Anis
Ph
4ac
4a c
72
82 [5: I J
89 [8: I J
40 [1:1]
68 [1:1]
64 [2:1]
7
8
'OH
vYoH
50 1 8
50 1 48
nph N H-PAnls
4ad
IVLr N H~~Anis
Ph 4a e
71
15b
9
10
¥rvOH
/XO H ~
50 / 42
50 / 42
~r NH~p~Anis
Ph
4af
4af
o
o
a Reaction Conditions:aldehyde(1 .O mmol), amine(1.05 mmol) in THF I .O mL at re~ux 0.5h, then
remove water from azeotrope. Pd(OAc)2 (0.1 mmol), P(n-Bu)3 (0.2mmol), Allylic alcohol (1 .2
mmol), Et3B 3.6 mL (1M n-hexane) and THF I .O mL were added at under N2・ b Isomer ratio is
not determined.
120
Furthermore,in contrastto manypreoedents22236indicating thatphenyl group
generε皿y displays better stereoselectivity than methyl group does,in the present
case,methylgroupshowedhigherseleαivitythaロphenylgroup(rm3vs,run6),
Under the reaction condition,a皿ylboranes are expected to react with an imine as
soon as it is fbrmed,23hence the results observed in皿n2,3and6(Table5)
suggestthat(2)・a丑ylboranes are fbrmed selectively via transmeta丑a廿on between
EtぎB andρallylpa皿adium species(卿Tor aoが・isom磯whichmightequnibrateto
each other)and react with士mine through a transition state n(L=Et,Scheme
5),2425 qb o皿best輩nowledge,this is the ftrst example demollstrating
a刀がselectivity fbr the allylation of曲es,start血1g with 飴刀θ℃roty1・type(an(1
㏄methyla皿y})substratesl all p卑cedents starting with翻aηβ℃rotyl substrates
supPose a transtion statB hke I to,rationa五ze the並卿・selec廿ve a丑ylations.2627・ε6
These transition states I and H share a common struct皿alfbat皿e,,Pladngboth
substituents of舳コθ認dimine at quasi・diεじdal position of cyclic six・membered
chair・1ike confbrmation,because the latter experienoes severe gauche repulsion
between、ρ油syl and the五gands on metal(in this case,two Et group on B).28A
transionstate皿thatischaracterizedby面θ加neisanothercandidate,which
seemstρbemos七stablebecauseofno1,3・diaxialrepulsiqns,
L し L l Ph I Ph l
肉へ RJ)属β\L B R∠ 、・\L ノ\N Ph I ムAnis ρ一Anis R ρ一Anis
↓ 1 \∬ / 皿 SγηiSOmer aηガiSOmer
Scわe」me5.Most Probable Transition State for A”ylation of lmine with Mong-Sロ、bstituted A”yl AcohoL
‡ ‡ ‡
121
At the moment, it is premature to assign which of the transition states II or 111
is responsible; the former supposing (~ ・allylboranes and the latter a less stable
cl~~ldimine as intermediates. In case of di'substituted alcohols, we are not
successful for allylation with ce.Y- or Y,Y-djmethylallyl alcohol yet.
The structure of anti-4ab was verified by the comparison of the IH NMR spectral
data with those of an authentic sample after conversion to an arDines 6 (Scheme 6) .
Futhermore, the structure of antj4ab was determined unequivocally by X-ray
crystallographic analysis of the tosylamide derivative 7 (Scheme 7, Figure 1).29
CAN
: Ph MeCN / H20 : ph rt. /2 h
4ab I .O mmoL 6 yield 45010 [anti:syn = 8:1 J [anti:syn = 8:1]
Scheme 6. The synthesis of 2-methyl-1-phenylbut-3-en-1-amine 6.
Reaction condition: (NH4)2Ce(N03)6 (5.0 mmol), amine (1 .O mmol) and MeCN (22 mL) /
H20(16 mL) were added at under atmosphere.
: Ph TsCl / Pyridine : ph N H- p-Ani s Ts' N-p-Anis rt. / 24 h
4ab I .O mmoL 7 yield 940/0 recrystalized in ether / hexane
Scheme 7. The synthesis of Tosylamide 7.
Reaction condition: TsCl (3.0 mmol) were added into a solution 4ab in pyridine (4.0 mL) at
under N2-
¥
Although, Palladium'triethylborane promote the allylation for the vatious
irnines, the reaction for the irDines prepared from aliphatic amines .(run 7 and 8,
Table 9-) or primary aldehydes (run 9- and 3, Table 2) was unsatisfied. Indeed, the
122
㌧-
紀
転
」
.秘
Fig1.The X-ray structure of7
123
.夢k
硲
“謬
Fig1.The X-ray structure of7 ,
123
yield ofthe oo皿espondinghomoa皿yl am血es was law With thaちwe examined
the nu(江eophnic allyla虹on of in血es us血g diethンL盆nc血plaoe of tdethン1bo肥ane
and飾mdthat七hereadiongivesexoelentresu1柏伽the漉pha怠csu馳加ates,
The resultB of the.a皿yla怠on uε血1g Et2Zn“between benzaldehyde la and
・cydohe琢1am血e2g are summar吻e(i血Table6.
殆わ1e6.Pd-Catalyzed,EtnM-Promoted NucleophilicA”ylation of lmine with A”yl alcohola
THF ・Pdcat HPhC捜01a、藷陶響1、N\()(6).
ひC6Hl1NH22g 49
田n EtnM .equiv. solv. temp(oC)/time(h)yield(%)
1
2
3
4
5
Et3B
Et2Zn
Et2Zn
Et2Zn
Et2Zn
3.6eq.
3.6eq.
3.6eq.
3、Oeq.
3.6eq.
THF
THF
toluene
THF
THF
50/24
50/4
5014
50μ
財24
22
96
85
58
35
aReaction Conditions:aldehyde(1.O mmol),amine(1.05mmol),THF(1.O mL),re利ux O.5h,then
Pd(OAc)2(0.1mmol),P(η一Bu)3(0.2mmol),A”ylic alcohol(1.2mmol)and Et2Zn or Et3B(1Mη一
hexane)in solv.(tOmL)at under N2.
The a皿yla廿on of cyclohexyla皿血e・benzald血血e,卑 the preε総noe of Et函n・
provided七he homoa皿ylic amine4g in96%・isolated.yield(nm.2).Non・polar
801vent like t61uene al80was ava丑able in thi8reac樋on(㎜3).The inαease in
yieldofhomoa皿yl amine4gmaybe七h6resultofenhance ofthenudeophihci域of
譜yl metal by using Et函n in place of EtぎB.The reducing the amo㎜t ofthe
124
Et2Zn or the reaction at room temperature causes a decrease in yleld of 4g (run 4
and 5) .
Table 7. Pd-Catalyzed, Et2Zn-Promoted Nucleophilic Allylation of Imine with Allyl alcohola
PhCHO Ia reflux allyl alcohol ~A/~. + 5 phN¥ (7) NHR ~~ ~Ar I
+
4 Ph RNH2 2 azeotrope Et2Zn
ru n RNH2 solvent temp(oc)/time(h) isolated yield('/.) total yield('/,)
1
2
3
4
5
NH THF ImL
29
crNH2 50 / 4 THF I mL
2f
toluene I mL
/WNH2 THF ImL 50 / 4 2 i
THF 5mL
4g 96 5g o 96
4f 45 5f 37 82
4f 90 5f traoe . 90
4ag 57 5ag 31 88
4ag 75 5ag trace 75
a Reaction conditions: aldehyde (1 .o mmoD, amine (1 .05 mmoD in THFI .o mL at reflux 0.5h, then
remove water from azeotrope. pd(oAc)2 (0.1 mmol). P(n-Bu)3 (0.2mmol), aMyi alcohol (1 .2 mmol),
Et2zn 3.6ml (1 M n-hexane) and THF I .o mL were added at under N2'
The allylation of other aliphatic amines also proceeded smoothly (Table 7) ,
However, benzylamine 'benzaldimine 2f or n ~lexylamine -benzaklinline 2j gave
diallylation product 5 in addition to expected product 4 under similar condition of
run I ~un 9- and 4) . Tbis is most likely due tc an electrophili'c allylation between
product 4 and the 7rallylpalladium intermidiate followed by generation of
125
homoallyl amine 4 (Scheme 8). It may be explained that the more Lewis acidic
Zn enhances the nucleophilicity by the coordination of Zn to nitrogen. On the
other hand, in case of cyclohexylamine, diallyl product was not observed at all. It
is surmised that this difference is attribute to the steric barrier of cyclohexyl group
on nitrogen.
' The over allylation of homoallyl amine 4 can be suppressed to adjust the amount
or kind of solvent. As is shown in run 3 and 5, the adj ustmen.t of reaction
condition led to excellent result to furnish only expected products 4.
ML 4441~~~:p~~) l
N¥ I
ML, L-Pd-X
(L=Et, X=0H)
Scheme 8. Electrophilic allyiation of homoallyl amine 4 to p-ally]palladium intermidiate.
The allylation of imine formed from aliphatic aldehydes and Fanisidnle also
proceed smoothly but the reaction also gave the homoahylic amine and the diallyl
product respectively (Table 8) . In thi.s cases, the adjustment of solvent or
concentration is not effective. This result may be caused due to higher
nucleophilicity of nitrogen on aromatic amines in contrast to aliphatic amine,'
In conclusion, we have demon.strated that a Pd-Et3B or Et2Zn catalytic system is
capable of promoting allylation of aromatic and aliphatic aldimines using allylic
alcohols as allylating agents. The advantage using allylic alcohols30 rather than
other allylating agents, e,g., allylic metals (Zn 31 In,26.27 Pd3-2) and metalloids (B,23
Si 33 Sn 24,34 Ge35), may be apparent from their ready availabiLi:ty an~ stability as
well as non-toxic side products (H20 an d organoboric acids) .
126
Table 8. Pd-Catalyzed, Et2Zn-Promoted Nucleophilic Allylation of Imine with Allyl alcohola
RCHO 1
p-Anisidine 2a
THF ref I ux
Pd cat.
allyl alcohol
azeotrope Et2Zn 500c / 4h
R
N H- p-Anis
4
PIAnis
~ '
run RCHO solvent isorated yield(o/.) total yield("/o)
1
2
OICHO
lp
lp
THF I mL
toluene ImL
4V 41 5V 35
4v 36 5v 30
76
66
3 lp THF 5mL 4v 54 5v 1 3 67
4 n-C5H 1 1 CHO THF i mL 4t 58 5t 27 85
In
5 In toluen6 1 mL 4t 38 5t 37 75
6 In THF 5mL 4t, 52 5t 21 73
7
8b
CHO
la
la
THF ImL
THF ImL
4a 1 5 5a 50
4a 34 5a 58
65
92
gC la THF ImL 4a 14 5a 85 99
a Reaction Conditions: aldehyde (i .O mmol), amine (1 .05 mmol) in THFI .O mL at refiux 0.6h, then
remove water from azeotrope. Pd(OAc)2 (O.i mmol), P(n-Bu)3 (0.2 mmol), Allylic alcohol (1 .2
mmol) Et2Zn (3.6 ml, I M n-hexane) and THF I .O mL were added at under N2・ b Allylic alcohol (2.2
mmol) was used and the reaction mixture was stired for 24 h at 500c. ・ Allylic alcohol (2.2 mmol)
and Et2Zn (4.8 ml) were used and the reaction mixture was stired for 24 h at 500c.
127
E琴pe血nenta18ection
Miαoanalyses were perfbrmed by the Center of王nstrumental Analysis of
Nagasaki University AnεJysis agree with the calculated values within±0.4%.
HighTesolution mass spectra were measured with JEOL JMS・DX303,In丘ared
spectra were measure with a JASCO A・100血丘ared spectrophotometeL IH’NMR
or13C・NMR were meas皿ed on▽adan Ge11血300and EOL JNM・AL400
instr㎜.entwithtetramethyls丑aneasanintemalstandard,Chemicals蹟values
were given in ppm downfield fヒom the intemal s㌻andard.Melting point were
determined with Yanaco micro melting Point apParatus-and were not corrected.
Boihng points are mean to re蝕to the oven temperatures in short・path
(bulbtκ)・bulb)disti皿ation by a Klugeh℃hr apparatus,
Solvent8 and Rεagents;・Tb廿ahydro血ran was dned and dist皿ed,丘om
benzophenone andl sodium hnniediat£1y prior to use un(1er1オtrogen atomosphere.
Tbluene was di就皿ed over calcium hydrid.e,Pd(OAc)2(P皿ity97、0%,Nakaral
tesque),πBu3P(pu亘ty90.0+%,%kyo Kasei Kogyo Co,,Lt(L),EtざB(1.OM hexane
solution,1㎝TO CHEM工KAI、Co.,工NC.)an(l Et2Zn (1.OM hexane solutiol1,
KANTO CHEMIKAL Co.,n灯C,)were p皿chased and used.without五皿ther
purt且cation The fbllowingεαdehyd.es,amine,and.allyl alcohols were purchased
and dis七皿e(1pnor to use by a Kugeh℃hr apparatus:allyl alcoho1,(πotyl alcohol,
but・3・en・2・01, cinnamyl alcoho1,,a・vinylbenzy1 εacoho1, preny1 ε江coho1,
peIlt・3・en・2・01, benzal(1ehyde (1a),メ7tDlylaldehy(1e (1b),メ7anisal(lehy(ie (1c),
piperona1 (1d), mhydroxybenzaldehyde (1e), μhydroxybenzaldehyde (1f),
P℃hlorobenzal(1ehyde (19), fur丘皿a1 (1h), 刀2pyri(㎞ecεぼboxal(1ehy(le (li),
c脚am田dehyde(1j),σhy⑳。xybenz飢dehyde(m,・P翼i血ec諭x飢dehyde(P,
128
出hydrochmamaldehyde (1m), hexana1 (:hD, isobutyraldehyde (10),
cyClohexanecarboxa1(1ehy(le (1p),cyclohex・3・en㏄arboxaldehyde (1q),cyclohex・
1・enecarbox田dehyde (1r), (・)・myrtenal (1s), paraibrm瓠dehyde (1t),
α・phenylpropion aldehy(ie (1u), diphenyacetaldehyde (1v),メ7anisi(㎞e (2a),
σ・anisi(㎞e(2b〉,ptolui(hle(2c),an丑血e(2d),ンワ℃hloroan丑hle(2e),benzylan丘ne(2i),
cyclohexylε皿圭ne(29),P{Dluenesuhbnamide(21D,(S>methy12・amino・2・Phenyl
acetate(2i),.η・hexylamine(2」).3,3・dially1・3H・indole(3aa)were prepared丘om
indo1(see blow).
Preparation of3,3・di2皿y1・3H血dole (3aa).Tb a solution of t£trakis七dopheny1
・phosph圭nepanadium(578mg,0,5mmo1)andindol(1.17gl10mmol)in dry THF
(50mL)was,ad.ded allylεユcohol(697mg,12.O mmo1)and面ethylborane(24.O
mmolIMinhexanesolution)atroomtemperature,Themixturewasstl㎞ed㎜.der
nitrogen at room temperature fbr2h,A丘er complete reaction,the血xture was
d丑uted with AcOEt and washed sat Nε〔HCO3aq.εmd b血ne.The extract was
evapora㌻ed and p皿迅ed by means of column chromatOgraphy over曲ca ge1
(hexane:ethylacetate・=4:1)to give珈in95%yield.IR(neat)3076(s),2978(m),「
2924(m),1738(m),1640(m),1480(vs),1456(vs),1349(m),995(s),914(m),745
(vs)cm’1;1HNMR(300MHz,CDC19
General Pr㏄edure ibr the Prepar註Uoln of Homoa皿yl Amine by the Reac樋on of
pAnisidine・Ber副dehydeh血eand翻欝C1℃仁y1A㎞ho1(㎜2,丁巨ble5):A
solutionofbenzaldehyde(1.ommoD andρε皿isid血e(1.05mmoDindryTHF(1m1)
was refluxed fbr30加n mder N2εmd then the solvent was removed by
磁皿ati・n(a鴉・廿・picrem・v田・fwate葛bp63。C)・THF(1、切wasadded㎝d
dist皿ed oEmder atmosphehc press皿e ofN2.Over the h血1e residue were
129
su㏄essively added Pd(OAc)2(0.1mmo1),BuざP(0.2mmol),crotyl alcohols(1.2
mmo1),THF(1mD,andEt3B(3.6mmo1,1Mhlhexalle),Thehomogeneous
血ure was stirred and.heated.fbr24h at500C under N2.The mixt1皿e was
dilutBd with EtOAc and washed with sat.NaHCO3εmd brine,and then the
organicphasewas d血ed(MgSO4)alldconcentrated圭nvacuoto give anye皿owoi1,
which was pu血丘ed by column chfomatography over s丑ica gel(EtOAc/hexane,
1/100tD1/20v/v)tD・give4ab in82%yield(R卉0.83,EtOAc加exane二1/2),皿1e
fbllowing homoanyl an立nes were charactenzed by compahson with liter帥皿e:
4methoxy・N(1・(4・methoxypheny1)but・3・eny1)an出ne(4k),甲ハ弄(1・(4・chloropheny1)
・3・buteny1>4・methoxyani㎞e(40),374Methoxy・2V:(1・(3・pyridiny1)but・3・enyDan曲ユ
e(侮),胎
4・Methoxy・ハF(1てpheny1・3・buteny])an皿ne(佃):IR(neat)3400(w),3025,(w),1640
,(w),1512(s),1452(w),1必0(w),12如(s),1178(m),1038(m),995(w),920(w),820
(m),756(m),702(m)cm‘1;享H NMR(400MEz,CDC19:δ2,50(dt,♂=14.3,8ユ,1
H),2。59(ddd,」=14.3,6.4,5,3,1H),3,68(s,3H),4,30(dd,♂=8.1,5.3,1H),5,12
(d,♂=10.3,1H),5,16(d,♂=・17.0,1H),5.74(dddd,♂=17,0,10.3,8,1,6,3,1H),
6,47(d,」=8,8,2H),6,67(d,♂=8.8,2H)7.20・7.37(m,5H);13CNMR(100MHz,
CDC19:δ43.2,55.8,一58,3,114.8,115.0,118.2,126,5シ127,0,128.6,1347,1413,
143,6,152.3;HRMS calcd、fbr C]7HlgNO253.1466,fbund加/z(relative intensity):
253.1461(M+,10),212(100).
2Me七hoxy・ハ汚(1・phenylbut・3・enyDaniline(4b):IR(neat)3423(w),3100(w),1640
(w),1603(s),1512(s),1491(w),1454(s),1225(s),1176(m),1030(m),995(w),918
(m),737(s),702(m)c血1;1H㎜R(400MHz・CDC珍:δ2・56(dd裸,♂〒145,7・7,6・6・
1H),2,60(ddd.,♂=14.5,7,7,5,5,l H),3,87(s,3H),4,37(dd,♂=7、7,5,5,1H),5,12
130
(d,♂ニ10,3,1H),5.16(己♂=16,9,1H),5.78(dddd,♂=1a9,10.3,7,7,6,6,1H),
6.30(d,♂=7.7,1H),6.59(t,♂=7.7,1H),6,67(t,♂=7.7,1H),6.75(d,♂ま7,7,1H),
7,19・7,37(m,5H);13C NMR(100MHz,CDClゆ:δ55.7,57,4,57,5,109.5,111.3,
116.5,118.0,121.2,126,4,126.9,128.6,134.7,137,3,143.7,146.9;HRMS calcdfb■
C17HlgNO253.1466,痴md漉(rela廿veintensity):253.1468(10),212(100)
4・Methy1・ハ再(1・pheny1・3・butenyDa皿ine(4φ:IR(neat)3410(w),3025(w),1640(w),
1618(m),1520(s),1489(m),1452(m),1301(m),1263(m),1182(w),993(w),920
(m),808(m),754(m),700(s)cnTll・HN皿(400MHz,CDC19:δ2.16(s,3H),2.50
(ddd,♂=143,6,6,7.7,1H),2.60(d.dd,♂ニ14,3,5.1,7.7,1H),434(dd,♂=7.7,5、1,
1H),5.12(d,♂=10.3,1H),5.16(d,♂=17,4,1H),5.75(dd.dd,♂=17,4,6.6,7.7,
10.3,1H),6.42(d,♂=8.2,2H),6.88(d,♂=8.2,2H),7.19・7.36(m,5H);13CNMR
(100MHz,CDC19:δ30,9,43,2,57,7,113.8,118,2,126,4,127.0,128.6,130.0,1347,
143,6,144.9;HRMScalcd鉤rC17HlgN237.1517,飾tmd漉(relativeinte・・sity):
237,1497(9),196(106)
ハF(1・P五enylbut・3・eny1)a皿肚ne(4d):IR(neat)3412(w),3020(w),1640(w),1602(s),
1504(s),1452(m),1317(m),1267(m),1180(w),993(w),920(m),750(s),692(s)
cm“1;1HNMR(400MHz,CDC斐):δ2,50(dt,♂=14.3,7.7,1H),2.61(4dd,♂=143,
5,1,6,4,1H),438(dd,」=7.7,5.3,IH),5.14(d,♂=10.4,1H),5,17(d,♂=17.0,1
H),5,76(dddd,♂=17.0,6.4,7,7,10.4}1H),6.49(d,♂=8,8,2H),6,63(t,♂=7.3,1
H),7,07(dd,♂ニ8,8,7.3,2H)7.20・7.37(血,5H);13C NMR(100MHz,CDC1ρ:δ
43.2,57,2,113.5,117.4,1182,126,3,127,0,128.6,129ユ,134.6,143.5,147・4;
HRMScalcd伽C16H17N223.1361,飾md漉(relativeintensity):223.1386(10),
183(100)
131
4・Chloro・ハ不(1,henylbut・3・eny】)an丑量ne(4e):IR(neat)3416(w),3025(w)シ1640(w),
1599(m),1499(s),1452(w),1315(m)。1263(w),1177(m),1092(m),993(w),921
(m),815(m),758(m),700(m)cm』1;1H NMR(400MHz,CDCl9:δ2,50(ddd,♂ニ
14.1,7,0,7.7,l H),2,61(ddd,♂=14ユ,5,5,7.7,1H),433(dd,♂=7,7,5.5,1H),5,14
(d,♂=9,9,1H),5.17(d,♂=16,9,1H),5,74(dd.dd,♂=16,9,9,9,7.0,7,7,1H),6,41
(d,♂=8,8,2H),7.00(d,」=8.8,2H)7,21・7.32(m,5H);13C NMR(100MHz,
CDC1ρ:δ43,1,57.5,114.9,118,5,122,3,126.3,127。2,128.7,1290,1344,142,8,
145.6;HRMS calcd伽C16H16Cm257.0971,fbmd魏(relative intensity):
257,0970(9〉,216(100)
ハFBen多y1・1Theny1・3・butenylamine(始:IR(neat)3300(br),3062(w),3026(w),
2928(vs),2853(s),1639(w),1602(w),1493(m),1450(m),1124(m),1028(w),993
(w),914(m),758(m),700(s)cm’1;1HNMR(400MHz,CDC13):δ2.39(ddd,♂ニ13.9,
7.7,6.2,1H),2,43(ddd,」士13.9,7,7,6,2,1H),3,53(d,♂=13,4)1H),3.67(氏♂=
13.4,1H),3.69(dd,」ヒ7.7,62,1H),5.03(d.,♂:=10.4,1H),5.06(d,♂=16.9,1耳),
5.70(dddd,♂=16,9,1α4,7.7,6.2,1H),7.21・7,37(m,10H);13C NMR(100MHz,
CDC1♂:δ43.1,5L5,61.7,117.5,126.8,127.1,127.3,128.1,1284135.5,140.7,
143,9;HRMS calcd fbr C17H]gN g37,1517,ibund1ユ物(relative intensity):237,1517
(0,3),196(100)
N(1・Pheny1・3・buteny1)¢ydohexanamine(勉:IR(neat)3300(w),3063(m),3063
(m),1637(w),1602(w),1493(m),1454(m),1437(w),1117(w),1070(w),1028(w),
995(w),916(m),760(m),700(s)cm’1;1HNMR(400MHz,CDC1ρ:δ0.92・1,15(m,
5H),2.25(ddd,♂=13,9,7,5,6,3,1H),2,37(ddd,♂=13,9,7.9,6.0,1H),2,37(qutnt,
♂=7・9,1H),3・84(dα♂=7・5,60,1H),5・03(d・♂=10・2,1H),5・q7(母,♂=17・2・1
H),5,69(dd(ld,♂=17,2,10,2,7,9,6,3,1H),7,20・7.41(m,10H);13C NMR(100
132
’
MHz,CDC19:δ26.2,33.0,34,7,43,4}53.5,59、0,117。1,126.6,127.0,128ユ,135.6,
144.6;HRMS cε凸cd fbr C16H2ぎN229,183,fbmd皿吻(rela廿ve intensity):229.1818
(5),225(5),189(19),188(100)
1・pheny1・Nto6ylbut・3・en・1・amine(4h);m(KB1):3271(s),3063(m),2909(m),
1643(w),1597(m),1497(m),1450(m),1319(s),1165(s),1095(m),1057(m),988
(m),918(m),810(m),764(m),702(s),671(s);1H・NMR(400MH属CDαゆ:δ2.38
(s,3H),2,43(ddd,み14.3,7.3,6,6,1H),2.50(ddd,」』143,7.1,6,6,2H),438(q,
み6.6,1H),4.81(d,誇6.6,1H),5,06(d,み10.9,1H),5,07(d,み16.1,1H),5.51(dddd,
赤16,1,10.9,7.3,7.1,1H),7.06・7,19(m,5H),7,17(d,赤8.1,2H),7,55(d,赤8.1,
2H);13C-NMR(100MHろCDC1ゆ:δ21,4,41.8,57.1,119.1,126,4,127.0,1272,
128.2,129.2,132.9,137.4,140.2,142.9;]旺R醐,calc(1丘)r C17H1姻02S301.1136,
丘)un(1nVz(relative血bensity):301,1210(0.3),260(100)
4・Methoxy・ハF(1アtolylbut・3・eny1)a血e(4j):IR(neaオ):3398(w),2930(m),1831
(m)1637(w),1618(w),1514(s),1463(m),1440(m),1296(m),1240(s),1178(m),
1039(m),9g5(w),918(m),817(s),775(m),756(m),721(w);1H・NMR(400MHz,
CDC1ξ):δ2.32(s,3H),2,45(dt,み14,4,7.8,1H),2.57(dt,」ま14.4,5,1,1H),3.68(s,
3H),427(dd,み7.8,5,1,1H),5.12(d,赤10』2,1H〉,5.17(d,み16.9,1H),5.74(ddt,
赤16.9,10,2,7.8,1H),6.45(d,み8.9,2H),6.67(d,赤8.9,2H)7.12(d,赤7.9,2H),
7.24(d,み7,9,2H);13CNMR(100MHろCDC恥:(121.0,30.8,433,与5.6,57.6,114.4,
117,7,125.9,128.9,134.6プ136.1,140.4,141.4,151.6;HRMS calcd fbr C18H21NO
267,1623,ft)und nVz(relative血t£nsity):267.1602(55),226(100)
万(・価㎜1司[・・31面・x・卍6・ゆbuむ3・enゆ’4齢me血・靭曲e(砂:卑(neat)3402(w),
2900(m),2831(m),2777(w),1846(w),1686(w),1β38(w),1608(w),1514(s),1485
133
(s),1440(s),1406(w),1373(w),1240(s),1180(m),1097(m),993(w),929(m),818
(s),754(w)cm瞥1:1HNMR(400MHz,CDC13):δ2.44(dd,♂=142,8.0,1H〉,2.54(dd,
♂=142,5.9,1H),3,69(s,3H),4,20(dd,♂=8.0,5,9,1H),5,12(dd,♂=10ユ,1,6,1
H),5.16(dd,♂=17.1,1.6,1H),5.74(dddd,♂=17,1,10,1,8.0,5.9,1H),5.91(d,♂=
1,5,1H),5.92(d,♂=・1,5,1H),6。46(d,♂=8.8,2H),6,68(d,♂=8.8,2H),6.74(d,♂
=7,8,1H),6.81(dd,♂:=7.8,1.7,1H),6.85(d,」=1,7,1H);13C NMR(100MHz,
CDCl白〉:δ43.6,55,8,57.8,100.9,106,7,108.2,114.6,114.7,1182,119.4,134.7,
138.0,141,5,146,3,147.8,151.9;HRMS calcd fbr C1暮HlgNO3297.1365,fbundヱη/z
(relativeintensity):297.1349(M+,100),274(2)
3・(1・(4Me血。卿heny㎞・)but・3・eny恥hen・1(血);m脇⇒:3294(m),3055
(brm),2900(m),2831(m),2607(m),1589(m),1512(s),1380(m),1319(m),1242
(s),1157(w),1042(m),980(w),925(w),864(m),826(m),787(m),741(m),702
(w);1H・NMR(400配皿z,CDC1ゆ:δ1.42(s,1H),2,45(ddd,み14.4,8.1,7,8,1H),
2,58(ddd,赤14.4,6。3,4.9,1H),3,70(s,3H),4.25(dd,み8.1,49,1H)5ユ5(d,∂』10,0,
1H),5.18(d,」』17,1,1H),5.76(dddd,み17.1,10.0,7,8,6.3,1H),6.45(d,」』8.8,2H),
6.69(d,。焉8.8,2H),6.70(d,み7.8,1H),6,85(s,1H),6,93(d,」士7,8,2H),7,19(t,
赤7.8,1H):13C・NMR(100MHz,CDC1ゆ:δ 43.2,55.7,57.8,113.0,113.8,114.6,
114.7,118.1,118,8,129.6,134.5,141,4,145,9,151,9,155.7:HRMScalcd蝕
C17HlgNO2269,1416血mdnVz(relativeintensity):269,1417(46),228(100)
4・(1・(4・Me五ho区ypheny㎞no)・3・butenyヨ)pheno1(4n):IR(neat)3301(br),2907(m),
2833(m),1614(m),1597(w),1514(s),1443(m),1406(m),1238(s),1178(m),1109
(m),1036(m),997(w),920(m),822(s),752(m)cm’1;1HNMR(400MHz,CDC1ゆ:δ
1.21(s,1H),2・42(dt,♂=146,8・0,1H),2・55(ddd,♂=14・6,8・0・52,、1H)・3・69(sβ
H),5.12(d,♂=享0.2,1H),5ユ5(d,み17.1,1H),5、74(dddd,赤17ユ,102,8,0,6.6,
134
1H),6.45(d,」…=8,8,2H),6,72(d,み8.8,2H),6.77(d,♂=8、5,2H),7.21(dン♂=8.5,2
H),:13C NMR(100MHz,CDC1ゆ:δ43,4,55.7,57.4,114.6,114.6,115.3,118.0,
127,4,1347,135,8,141,5,151,8,1542:HRMScalcd蝕C17HlgNO2269ユ416痴md
刀2/z(relative int£nsity):269.1427(13),228(100).
ハ戸(1・(2・FuranyD bute・3・nyl)・4・methoxy;benzenamine(4p):IR(neat)3350(w)β100
(w),2934(w),1640(w),1512(s),1464(w),1441(w),1408(w),1240(m),1180(w),
1038(m),1009(w),922(w),820(m),737(m)c血・;1H剛R(400MHz,CDC恥:δ
2.40(dd,♂=・7.0,6.2,2H),3.72(s,3H),446(t,♂=6,2,1H),5.12(d,♂ニ1α2,1H),
5,16(己♂ニ17,2,1H),5.76(ddt,♂=17.2,10,2,7,0,1H),6,14(d,」=3.2,1H),628
(dd,♂:=3,2,1,9,1H),6.57(d,♂=8,8,2H),6,74(dウ♂=8.8,2H),7.34(d,cノ’=・L9,
1H);13C NMR(100MHz,CDClゆ:δ39.2,52.5,55.7,106.0,109.9,一114.7,115.1,
113,1,133.9,140,9,141,3,152,4,155.8;H剛Sc副cd蝕C15H17NO2243・1259,
飾tmd血勿(rela廿veintensity):243.1217(45),202(100)
4・Metho翼y・ハF((五)・1てpheny1・1,5・hexadien・3・yDaniline(4r):IR(neat)3390(w),3025
(w),1676(m),1626(w),1512(s),1448(w),1240(m),1178(w),1038(m),970(m),
918(m),820(m),748(m),694(m)cm-1;1HNMR(400MHz,CDC19:δ2.44(dt,♂=
141,7.1,1H),2,46(dt,♂=141,7.1,1H),3.72(s,3H),3.97(dt,♂=6,1,7.1,1H),
5.14(d,♂=10.0,1H),5,17(d,」=17,0,1H),5.85(ddt,♂=17,0,10.0,7ユ,1H),6.18
(dd,c7’=16.0,6.1,1H),6.58(d,♂=16.0,1H),6,62(d,♂ニ8.9,2H),6.74(d,♂=8.9,
2H)7,18・7.35(m,5H);13CNMR(100M耳z,CDCl9:δ40.5,55.7,55.8,114,7,1エ5.0,
118,1,126.2,127.2,128,4,129.0,130,2,134,4,136.9,141.4,152.1;HRMScalcdfbr
ClgH21NO279.1623,fbund翻z(relativeintensity):279,1634(M+,11),238(100)
4・Meth曝y・ハ汚(1てpheny1・5・hexen・3・yDa曲e(4s):IR(neat)3393(w),3026(w),
135
2920(m),1640(w),1603(w),1512(s),1441(m),1408(m),1240(s)ン1178(m),1040
(m),997(m),912(m),820(m),7娼(m),7qO(m)cm“1;1HNMR(400MEz,CDC珍:δ
1,46(dt,♂=142,7.1,1H),1.55(dd己♂=142,7,1,6.8,1H),1.78(ddt,♂=14.5,7.6,
6.0,1H),1.81(ddt,」=14,5,7.1,5,5,1H),,2,31(dd,♂=6.0,5,5,2H),2.75(dddd,
み7.6,7.1,6.8,6.o,1H),3.75(8,3H),5、08(d,♂=17・6,1H),5・09(d,」’=10・4,1H),
5.80(dd』t,♂=17.6,10,4,7.1,1H),6,52(d,♂=8.9,.2H),6,76(d,♂=8.9,2H)
7,16・7.35(m,5H)113CNMR(100MHz,CDC1ゆ:δ32,4,36,2,38.6,53、0,55.9,114.5,
114.9,115,0,117.7,125.9,128,4,134.8,141.9,142.1,152.0;HRMS calcd fbr
ClgH23N281.1780,飾und磁(relativetntensity):281.1765(26),240(100)・
4・Methoxy・ハF(non・1・en・4・yDaniline(4t):IR(neat)3396(w),3100(w),2930(s),
2856(m),1638(w),1618(w),1512(s),1466(m),1441(m),1408(w),1240(s),1180
(m),1042(m),997(w)912(m),818(m)cm』1;1HNMR(400MHz,CDC19:δ0.88(t,
♂=6.8,3H)1,26・1,55(m,8H),2.25(ddd,♂=14,1,7,0,5,9,1H),2,29(ddd,♂=
14,1,7,3,与.9,1H),3.31(q血・t,♂=5.9,1H),3・74(s,3H),5・06(α♂=17・6,1H),
5。07(d,♂=11.0,1H),5.81(dddd,♂ニ17.6,11.0,7,3,7.0,1H),6,54(d,♂ニ8.8,2H),
6.76(d,♂=8.8,2H);13CNMR(100MHz,CDC19:δ14.1,22.7,25,7,32.0,34.4,38.6,
53.6,55.9,114,8,115.0,117.4,135.1,142.1,152.0;HRMS calcd fbr C16H塞NO
247.1936,fbmd並(relativeintensity):247,19i6(M+,100),235(1),232(1)
4・Methoxy・ハ弄(2・methy1・5・hexen・3胡)a曲e(4u):IR(neat)3398(w),2957(m),
2909(m),2872(w),2831(w),1639(w),1618(w),1512(s),1464(m),1441(w),1238
(s),1180(w),1041(s),995(w),914(m),817(s),754(m)cm’1:1H NMR(400MHz,
CDC1ゆ:δ0.93(d,♂=6.8,3H),0,96(d,♂=6,8,3H),1.88(dsept,。β5.1,6,8,1H),
2,17(dt,♂=14.1,7.1,1H),2.30(dt,♂=141,7・1,1H)β・15(d㌻,♂〒5ユ,7・1,3H),
3.73(s,3H),5、04(d,」=10.2,1H),5,06(d,♂=17.1,1H),5,81(dd』t,」=17.1,102,
136
7,1,1H),6,14(d,♂=8,8,2H),6,75(d,♂=8.8,2H):13C NMR(100MEz,CDC恥:δ
】.8,4,18,6,30.7,35.6,55,9,59.1,114.5,114.6,114.7,1149,116,9,135.7,1425,
151,5:HRMS calcd 長)r C14H21NO 219.1623,丑)un(1 皿プz (relative 血bensity):
219,1622(M+,27),178(100)
ハF(1・Cydohexy1・3・butenyD・4・ar曲dine(4v):IR(KBr)3354(w),2924(s),2849(m),
1508(s),1448(面,1410(w),1287(m),1231(s),1178(w),1097(w),1031(m),1001
(w),912(w),822(m),750(w),702(w)cm’1;1HNMR(400MHz,CDClゆ:δ0,92・1.84
(m,11H),2,19(dt,」’=14.2,7,1,1H),2,32(ddd,♂=14.2,7,1,59,1耳),3.15(dd,♂=
7,1,5.9,1H),3.74(s,3H),5.04(d,♂=10.4,1H),5.05(d,♂=17.5,1H),5,74(ddt,♂
=17,5,10,4,7,1,1H),6.53(己♂=8,9,2H),6.75(α♂:=8.9,2H);13C NMR(100
MHz,CDC1怠):826.5,29.2,29.6,35.9,・41.3,55,8,58.6,1144,零14.9,116.8,135.6,
142.5,151.5;H脚S弓飢c曲rC17H25NO259・1936⑳㎜d酩(rela廿ve血ben磁ty):
259,1921(M+,32),219(17),218(100),176(17)
ハ再(1・(3・CydohexenyD・3・buteny分・4・metihoxyanihne(4w):IR(neat)3396(w)13020
(m),2912(s),2833(m),2343(w)ン1637(w),1618(w),1510(s),1437(m),1408(w),・
1236(s),1180(w),1042(m),997(w),914(m),818(m),731(w)cm’1;1HNMR(400
MHz,CDC19:δ1.24・2.38(m,7H),3.20・3.29(m,2H),3.73(s,3H),5.05(d,♂’=10.6,
1H),5,06(d,♂=17,3,1,7,1H),5.67(s,2H),5.80(ddt,」=17.3,10,6,7,3ユH),6.54
(d,」=8.8,2H),6.75(d,♂=8,8,2H),13C NMR(100MHz,CDClの:δ25.1,25.7,
28.6,35,8,37,4,55.8,57.9,114,5,1149,118,2,117,2,126,2,12710,135.1,135.2,
134.7,151.6;HRMS cε旺cd fbr C17H2ぎNO257,1780,fbund lzヅz(relative intensity):
257.1776(M+,100),256(5),246(1),245(5),233(1)
ハF(1・Cydohex6nylbut・3・enyD・4・metho区yan皿ne(砥):IR(neat)3400〈w),2927(m),
137
2833(m),1679(w),1639(w),1618(w),1510(s),1439(m),1406(w),1292(m),1236
(s),1178(m),1039(m〉,993(w),918(m),818(m),756(w):1H NMR(400MHz,
CDC13):δ1,44・1,65(m,2H),1,95・2,05(m,2H),2.31(dt,♂=14,3,7,1,1H〉,2,37
(dt,♂=14,3,6,3,1H),3,40・3.62(b鴨1H),3.58(t,♂=6.3,1H),3.73(s,3H),5、08
(dd,♂=10,2,1.7,1H),5,12(d,♂=17,0,1.7,1H),5,67(s,1H),5.77(ddt,♂=17.0,
10,2,7,11H),6,53(dd,♂=6,9,2.22H),6,74(dd,♂:=6,9,2.2,2H),13C NMR(100
MHz,CDCl9:δ22.7,22,8,24.6,25,0,39.2,55,8,59.8,114,5,114.6,114.8,114.9,
117.0,122.9,135.3,137、7,142,0,151.6;HRMS calcd fbr C17H23NO257.1780,
飾md漉(relativeintensity):257.1784(M+,100),256(7),246(1),245(3)
4・Me七hoxy・N・(1・(6,6・dimethylb訟ydo[3.1.1】hept・2・ep・3・y】)but・3・enyl)anihne (4y):
IR(neat)3400(w),2986(s),2912(s),2831(s),1678(w),1639(w),1618(w),1512(s),
1466(m),1440(m〉,1364(w),1240(s),1180(m),1041(s),991(w),916(m),817(s),
758(w)cm’1;1HNMR(300MHz,CDC1ゆ:δone ofisomer O,67(s,3H),0,96(d,♂=
8,5,1H),1,28(s,3H),2,01・2,44(m,7H),3.45・3,65(b鴎1H),3,65(dd,♂=7,3,5.1,l
H),3,72(s,3H),5.09(d,♂=10.2,1H),5,13(d,♂ニ17.3,1H),5,41(s,1H),5,80
(dddd,♂=17.3,10,2,7.3,3.7,1H),6.51(d,♂=8.8,2H),6.72(d,♂=8,8,2H),δ
anotlherisomer O,86(s,3H〉,1ユ8(d,♂・=8.5,l H〉,1.26(s,3H),2.01・2.44(m,7H),
3.45・3,65(b鵯1H),3.59(t,♂=6.1,1H),3.72(s,3H),5.10(d,。同0.2,1H),5,14(d,
」=17.3,1H),5.41(s,1H),5.76(dddd,♂=17.3,10.2,7.3,3.7,1H),6.54(d,」=8.8,
2H),6.71(d,♂=8,8,2H);13CNMR(100MHz,CDC19:δoneofisomer21.426,4,
31.1,31,9,38,1,38.4,4L1,42.8,55,8,58.0,114.5,114.6,114.7,117.4,1179,135.4,
141,9,148.5,151.6;δanother isomer21.6,26,4,31.2,31.7,38ユ,38.5,41.1,432,
55.8,58.1,114,5,114.6,114、7,117.5,117.7,135,3,141.9,147,7,151,7;HRMS calc(1
蝕C2・H27NO297・209鏑m・d・吻(relative加痴nsity):2972096(革+,ユ00),296(5)
138
ハF(But・3・enyD・4・m就ho翼yaniline(4z);IR(血eat):3387(w),2954(m)ン2870(m),2831
(田),1639(w),1620(w),1512(s),1466(m),1381(w),1242(s),1180(w),ll41(w),
1042(s),918(m),818(s),756(w),715(w):1H・NMR(400MHz,CDC1ゆ:δ2.37(q,
」』6.8,2H),3、14(t,み6,8,3H),3.37(s,1H),3.75(s,3H),5.11(α「赤10.2,1H),5,14(d,
み17,1,1H),5,82(ddt,∂E17,1,10,2,6.8,1H),6,58(d,誇9,0,2H),6,78(d,訴9.0,
2H):13C・NMR(100MHz,6DC1ξ):δ11.6,33.7,43.9,114.2,1148,116.8,135.7,
142.4,152.0:HRMScalc曲rCl1H15NO177,1154,飾mdm/z(relativeintensity):、
177.1130(7),136(100)
4・Metho翼y・ハF(2・methy1・1てpheny1・3・buteny1)aniline(4ab):IR(neaO3396(w),3026
(w),2930(m),1638(w),1512(s),1452(m),1406(w)身1240(m),1178(w),1038(m),
1001(w),918(w),817(m〉,762(m),702(m)cm昌1;1H NMR(400MHz,CDC1ゆ:δ
θ1ηがisomerα99(d,♂ニ7,0,3H),理加somer o.95(d,♂=7.0,3H),2.49(dqフ♂=7.o,
7.3,1H),3,67(s,3H),3.98(d,♂=7.3,1H),釦ケisomer5,16(d,♂=10,3,1H),
卿7i$omer4.88(d,♂=10,3,1H),甜2がisomer5.19(d,♂’=173,1耳),霞卿嘘omer
4.91(d,♂=・17,3,1H),aηがisomer5.76(ddd,♂=17,3,10.3,7,0,1H),研加somer
5.62(ddd,♂=17,3,10,3,7.0,1H),6,42(d,♂=9.0,2H)16.62(α♂=9,0,2H)
7.20・7,36(m,5H);13CNMR(100MHz,CDC1ゆ:δ17.4,45.4,55,7,63。2,1144114.6,
116.0,126.8,127.2,128.1,140.6,141.8,142.7,151.7;HRMS calcd ft)r C18H21NO
267.1623,允㎜d・並z(relative血tensity):267ユ649(M+,12),212(1qO)
4・Me血o翼y・2V(1,2・d‡pheny1・3・buteny1)an皿ne(4ac):IR(neat)3392(w),3028(w),
1624(m),1602(w),1512(s),1452(m),1242(m),1180(m),1036(m),968(w),922
(w),820(m),758(m),700(m)cm-1;1HNMR(400MHz,CDC19:δ3.53(dd,」ニ8.1,
9・q・H)・3・67(q3H),44・(d,♂=8ユ,・H),露is・mer5・32(財=凧1H),
θ躍isomer4.93(d,♂=17,1,1H),aηケisomer5.26(d,♂=102,1H),卿」isomer
139
5,05(d,♂=10.2,1H),釦が・isomer6.19(ddd,♂=9,0,10,2,17.1,1H),鋼・isomer
5.96(ddd,♂=9.0,10,2,17,1,1H),6,45(d,♂=9.0,2H),6,66(d,♂=9.0,2H〉
6,93・7,24(m,10H)113C NMR(100MEz,CDC19:δ55.4}58.3,63,0,114,3,114,6,
127,2,127,8,128,1,128.3,128.6,140.6,141.4,141,9,144.8,152,0;HRMS calcd長)r
C23H23NO329,1780,長)u11(1nVz(relative intensity):329,1742.(M+,2),212(100)
4Methoxy・ハF(3・:ne七hy1・1・p五eny1・3・butenyDal曲ne(4ad):IR(neat)3393(w),3026
(w),2909(m),1647(碗),1512(s),1452(m),1406(w),1238(怠),1178(w),1040(m),
899(m),820(m),754(m),700(m)cm-1;’H㎜(400MHz,CDC19:δ1・76(s・3H),
2,39(dd,♂=14.2,10,3,1H),2.50(dd,♂=14,2,44,1H),3,69(s,1H),4.31(dd,
♂=10,3,4、4,1H),4。86(s,1H),4,92(s,1H),6.44(d,♂=9,0,2H),6,67(d,」=9.0,2
H),7.22・7.42(m,5H):13C NMR(100MHz,CDC1ゆ:δ21.7,48,1,55.7,56,5,113.8,
114、6,126.1,126,7,128.5,141.7,142.4」44.4,151.9:HRMS cε江cd fbr C18H21耳0
267.123,fb㎜d加z(relativeintensity):267.1649(M+,11),212(100)
ハF(1・phenylbut・3・enyDhexylamine(4a9;IR(neaオ):3332(w),2924(s),2855(m),
1637(w),1602(w),1458(m),1358(w),1126(w),995(w),918(m),756(m),702(s),
648(w);】H・NMR(400MHz,CDC恥:δ0.86(t,赤6.8,3H),1,21・1,44(m,8H),
2.36(dd,赤7,8,6,3,2H),2,41(t,赤7.3,2H),3,63(t,」…・6.3,1H),5,04(d,み10.2,1H),
5.08(d,∂E16.9,1H),5.71(dd』t,み17,2,10,2,7.8,1H),7.21・7.34(m,5H);13C・NMR
(100MHろCD(勘:δ14.0,22.6,27.0,30.1,31.7,43.0,47.7,62.7,117.2,126.7,
127,0,128,1,135.5,144.1;HRMScalc曲rC16H25N231,1987,蝕md血/z(rela廿ve
intensity):231.195(0,4),190(100)
〃皿訊渦e吻1・1Then画ut・3・en・1・血e(50;R血eat):3071(卑),3024(m)・
2932(m),2808(m),1643(w),1604(w),1497(m),1450(m),1366(w),1258(w〉,
140
1095(m),995(m),918(s),740(m),702(s),656(w),;1H・NMR(400MHろCDOゆ:
δ2,52(ddd,赤14.1,73,6.8,1H),2.76(ddd,赤14,1,7,3,6,8,1H),3.22(d,み142,
1H),3,25(dd,」』14.3,5、1,1H),3.79(d,誇142,1H),3,84(t,み7.3,1H),4,96(d,
み10.2,1H),5,01(αみ17.1,1H),5.11(d,赤10.2,1H),5.16(d,み17,1,1H),5.76
(ddt,み17,1,10.2,6,8,1H),5.84(dddd,赤17.1,10,2,7,3,5,1,1H),7.19・7,35(m,
10H);13C・NMR(100MHろCDC恥:δ36.0,52,4,53,5,63.7,115.8,116.7,126.5,
126.8,127.8,128,0,128.5,128.6,136,4,136.8,139.4,140.3;HRMScalcd伽
C20H23N277,183,飾mdnVz(relativeintensity):277.1$10(1),236(100)
ハFAny1・ハF(1「phenyIbut・3・eny】)hexan・1・amin白(5ag);IR(nea起):3071(w),2932(8),
2855(m),12808(m),1643(w),1450(m),1373(w),1258(m),1096(m),1018(m),910
(m),820(m),748(w),702(m),656(w),;1H・NMR(400MHz,CDC恥:δ0.87(t,
み618,3H),1.22・1.42(m,8H),2.22(ddd,み15.2,7,7,6.0,1H),2.51(ddd,み152,
10,517.7,1H),2.52(ddd,弄142,8.5,6,8,1H),2,65(ddd,み142,6.8,6.3,1H),2.85
(dd,赤14.4,7,1,1H),3,22((1d,」』14.4,5,4,1H),3.76(dd,誘8,5,6.3,1H),4.92(d,
誇10,2,1H),499(d,誘17.1,1H),5.08(d,み10.2,1H),5,14(d,み17,1,1H),5.70
(ddt,赤17,1,10.2,6,8,1H),5.81(dd.dd,」ま17.1,10.2,7.1,5.4,1H),7,25・732(m,
5H);13σNMR(100MHz,CD(勘:δ14.0,22.7,27.0,27.6,31.8,36,4,49,6,53,2,
64.0, 115.7, 116.1, 126.6, 127.7,128,6, 136,5, 137,4, 14Q,4 ;Ii[R鵬 calc(1f受)r
ClgH2gN271.23,fbundm/z(relativeintensity):271.2279(0,9),230(100)
ハFA皿y1・ハF(1・卿ddhexylbut・3・enジ)・4・methoxyan趾ne(5v);IR(nea◎:3071(m),
2924(s),2855(m),1643<w),1512(s),1450(m),1242(s),1080(m),1041(m),995
(w),910(m),810(m),717(w),648(w),;1H・NMR(400MH2,CDC1ゆ:δ0.81・1.82
(m,・・H),琴・28(dd餅・4・6・7・・,5・9,・H),2・43(ddd,甜6,7・0,,5・411H)・3・娼(ddd,
み5.9,5.4,4.1,1H),3,73 (s,3H),3,79(d,み5.4,1H),4.90(d,赤10,2,1H),5,01(d,
141
み17.3,1H),5,09(d,赤10,4,1H),5.19(d,∂E17,3,1H),5.75(ddt,み17.3,10,2,7.0,
1H),5.77(dddd,∂E17.3,10.4,5.4,1H),6.68(d,赤9.3,2H),6.75(d,み9.3,2H〉;
13σNMR(100MHz,CDC1ゆ:δ26.2,26,3126.5,26,6,31,3,35.3,42,0,47.4,55,7,
65,6, 114,3, 115,2, 115,7, 115.8, 136.8, 137.1, 144.6, 150、8;㎜ calc(1 丑)r
C20H2gNO299,2249,fbmdm/z(relativeintensity):299.2233(65),258(100)
ハFAIly1-4・me七hoxy・2》(non・1・en・4・yDaniHne(5t);IR(neat):3071(m),2931(s),
2855(m),1643(w),1512(s),1458(m)11242(s),1180(w),1103(w),1042(m),995
(w),910(m),810(m),717(w),648(w),;1H・NMR(400MHz,CDC1ξ):δ0,85(t,
み6,8,3H),1.21・1,55(m,8H),2,18(dt,凋41,7.1,1宜),2.32(ddd,み141,7.1,5,3,
1H),3.67(quint,み7.1,1H),3、74(s,3H),3,74(dd,み145,5,3,1H〉13,75(dd,み14,5,
7,1,1H),4.97(d,み10.0,1H〉,5.03(d,」』17.1,1H),5.08(d,み10,2,1H),5.19(d,
赤17,3,1H),5.77(dddd,み17,1,10.0,7,1,5,4,1H),5,78(dddd,み17,3,10.2,7.1,5,1,
1H),6,73(d,み9,4,2H),6,78(d,み9.4,2H);13C・NMR(100MHろCD(瀞:δ14.0,
22.6,26.6,31.9,32,7,37,6,47.0,55,6,60,1,114.3,115.6,116.1,136,5,136.9,1439,
151.3;HRMS cε江cd fbr ClgH2gNO287.2249,fblmd m/z(relative intensity):
287.2248(12),246(100)
ハ汚!皿y1・4・metho岬〃(1・phenylbut・3・enyDanibne(5a);IR(血ea◎:3062(w),2931
(m),1831(w),1639(w),1510(s),1450(m),1417(w),1242(s),1180(m),1042(m),
995(m),916(m)814(m),758(w),700(m):1H・NMR(400MHろCDC恥:δ2,73
(dd.d,∂』14,8,7,3,7.1,1H),2,74(d.dd,み14,8,7,3,6.8,1H),3.59(dd,赤16.3,5,4,
lH),3,69(dd,み16,3,5,4,1H),3.77(s,1H),4。74(t,∂E7,3,1H),5,01(d,み10.3,1H),
5.03(αみ10,3,1H),5.08(d,」ま17,2,1H),5.10(d,。β17,3,1H),5.71(ddt,赤17.2,
10・3,5・4,1H),5・80(dddd,赤172,103,7ユ,6・8,1H)・6・79(d,弄9・3,2H),6・82(d,
誇9.2,2H),7,22・7.32(m,5H):13C・NMR(100MHろCDC1ゆ:δ36,6,50,3,55.5,
142
64.2,114,1,115.9,116,5,118,9,126,9,127,8,128,0,136.0,136,3,140.8,143ユ,
152.7 :HI㎜ calcd癒r C2(正123NO 293.178,f斐)un(1nyz (relative 血tβnsity) :
293.1776(83),252(100)
Genera1Proced皿eibrthePrepara廿onof1・Pheny1・3・buten・1・amine6;39A
solutioll ofammonium cenum nitrate(15.O mmo1)i皿water(50mL)was added
slowly to a s廿腔ed solution ofhomoallyl amine4ab(3.O mmo1)in aoetonit飢e(60
mL)at room temperat皿e,A銑er2hours,a solution of sat NaHCO3was added
un磁pH6was reached.Then sodium sulfite was added,un飢the mixt皿eあecame
brown suspension.The reaction皿t溢皿e was ex廿acted,with碑hyl acetate andthe
organicphaseswer6mixed and.dhedoverεuihydrous sodium s曲te.The reaction
mixture was then f丑t6red and the solvents were removed.加圏oπo to yield the
crudle prod』uct1・pheny1・3・buten・1・a血ne6,which were pu面ed.by colu皿n
chromatobraphy tD give the p皿e6in50%yield,The stnct皿e of product was
determined.by the companson of the lH-NMR spectrεa data of an authentic
san1Ple.25
143
恥免rences
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H.;Yamamoto,Y.♂6㎏:α2θ■η,1999,642614, (e)Nakam皿a,H,l
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Yamamoto,Y.;Asao,N,α2θm,励π1993,9β2207,(g)Wang D.・K;Dai,
L,・X.;Hou,X,・L,;Zhang,Y.7わあ訪θ轟oη五θ6孟1996,3Z4187 (h)Negoro,N.;
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11.Pa且adium・medieted nudleoph丑ic allylation of imine with organometε曲lc
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7516
12.Bisallylpε皿adium・mediated nudleoph丑ic a且ylation of imine with
organometa皿ic reagents,see;(a)Nakε皿mra,H.;Iwama,H.;Yamamoto,Y.♂
窃η,α2θ1η,5比.1996,1186641.(b)Wa皿ner,0,A,;Szabo’,・K,」1Jl6㎏
砿θ塑.2003,682934. (c)Sohn,N.;]Kjelgren,」1;Szabo’,K.♂ノh1.(鍛θ妬ロ.5bc
2004,12617026
13.Indium・mediated nucleophilic a且ylation of imine with anylsilane,see;
Onishi,Y.lIto,T.lYasuda,M,lBaba,Aπ舳加伽oη、2002,588227,
14.Kimuヱa,M.;Tomizawa,T.;Ho血llo,Y.;Tanaka,S.;Tamaru,Y.π伽hθ協㎝
Z冶洗,2000,41,3627.
15.Khn皿a,M.;Sh血izu,M,;Shibata,K.;Tazoe,M;Tamaru,Y
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16,Kimura,M.;Futamata,M.;Shibata,K,;Tamaru,Y.Chem.Comm.,2003,234ゼ
・7・(切Nis噸cb,Y;丁欲uwa・A;N鍵uta,Y;甑u・kaK聯孝θ伽19♀3,42
7395.(b)Yamamoto,Y;Asao,N.α~6m・励区,1993,9窃2207・
145
18.Nεよam¶皿a,H.;Iwama,H.;Yamamoto,Y,♂肋.α1θzη.5bc1996,11616641.
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E.;W田te靖WE.;Manyik,RM.π翻ゐθゐoηZカ6孟1970,11,3821.(c)Y帥g,C.
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124110968,
21.Without removing watB靖reactions beoome dirty(many tafhng spots on TLC)
εmdnoallylationμoductsaredetected.
22.For example,in the presence o〔fPd〈PPh3)4(5mo1%)an(l Et2ZI1(240mo1%)血・
THF(3m1)・πhexane(1,2mD at room temperatu■e,α・andγ・methyla皿yl
alcohols(1mmo1)react with benzaldehyde(1.2mmoD to provide mixtures of
aηがaad理zr2・methyl・1・pheny1・3・buten・1・ols in the same ra廿o(2,4:1),皿le
same reactions with α・ and γ・phenyla皿yl alcohols provide 珈が and
銀τ1,2・dipheny}3・but£n・1℃ls :hl the same,but 血 higher ratios of 10:1:
Tanlaru,Y♂Oz・卿o加θ姦Z Oゐθ盟b畝1999,5761215.
23.Itsmo,S,;Watanabe,K,;ItD,K.;El・Shehawy A.A,;Sarhan,A A/4η躍㎎
0ゐθπ~.Zカゑ石ヒZ.1997,361109.
24.(a)Hirabayashi,R,;Ogawa,C.;Sugiuヱa,M.Kobayashi,S,♂血,α~θ塑,5比.
2001,12ヌ9493,(b)Kobayashi,S,;Ogawa,C,;.Konishi,H,;Sugiura,M,♂血コ.
砒θzη.5bc2003,1%6610.
25・H・茄nam,RW;Endes色1de吟A血θ伽血4α}θ皿1987,2手5・,
26.(a)Shibata,1.;Nose,K.;Sakamoto,K,;ぬsuda,M,;Baba,A。π6肱9α~aπ
,146
2004,622158, (b)Yanada,R;Klaieda,み.;丁欲emotx),Y♂(2乙g、(防θ2皿2001,
砥7516.
27,Coop鉱1.R;Ghgg Rl MacLachlan,W S,;皿10mton・Pett,M,Sndharan,V Jl
伽塑・伽α励2・ω塑切㎜・20q2,1372・
28,Khn皿a,M,;Miyachi,A.;Kqlima,K,;Tanε〔ka,S,;Tamaru,Y♂肋、α2am,伽.
2004,126114360.
29.Crys圃・離aphi6data(exdu血gs伽ct耀e鉛伽rs)伽thes廿uct肥e・f7have
been deposited.with the Cambridge Crysta皿ographic Data Cen母e as
ゴ supplementary publication nαCCDC・256123.Copies of the data can玲e
obtε丘ned f士ee of charge on apPlication to CCDC,12Union Road,Car血b血dge
CB21EZ,UK(fax:(+44)1223・336・033;e・ma丑:一),
30.Allylation withε皿y1ε江oohol was reporbed.fbr benzε荘dehyde・imine using an
umpo1皿1gtechnique ofπ・a且ylpa皿adiumwithindium(1)iodide.Anylbromide,
iodide,acetate,and carbonate showed good yields;however chlohde and
alcoholmoderate andpooryields,respectively Seere£26b
31.Boye葛F・D.;Hama,1.%飴lhθゐoη五θ6ム2001,421275,「
32.(a)Nakam皿a,H.;Aoyagi,K.;Sh㎞,Jl・G,¥amamoto,Y♂肋,α~㎝,5わc
2001,12呈372,(b)Femandes,RA;St㎞ac,A.;Yamamoto,Y♂z1加.α2θ盟,
5b(λ2003,1%14133,
33,Yamasaki,S.;Fuj五,K,;Wada,R;Kanai,M.;Shibasaki,M.♂血■α}㎝.伽
2002,1」2嘱6536,
34(a)Gastne葛Tl Ishitani,H,;Akiyama,R;Kobayashi,S.且η望槻0ゐθ皿血孟」昭
2001,401896.(b)Chouda堀B.M.l Chidara,S,;Sekhar,C.VR,鋼θ662002,
1694.(c)Yadav JI S,;ReddX B.V S.;Redd蕩P S.R,;Rao,M.S.%伽ゐθ画㎝
厩2・・躍6245( レ舶P瞬HC・;Bisset鳳S;Grりev“亀N;琵血,D・
循翻ahθ盈切2五θ猛2002,43323.(e)yadaVJS.;ReddylB,VS.;Raj隅AK
147
伽~激θ砿θ2003,883,
35.Akiyama,T;Iwai,よ鋼θ甜1998,273.
36,Kunlar,S.;Kla皿,P,π翻ゐθゐoη加6ゑ2004,45,3413,
37,ぬdaV JI S.;Redd湧B,V S,;Red砲P S.R;Shesha R M%飽hθ伽oη」乙θ猛
2002,43,6245,
38,Vargas,L Y,;Castelli,M.V、;Kouznetsov,V.V.;Urbh13GJ M.;Lopez,S,N.;
Sor血10,M.;庖n血,R D,;Ribas,よC.;Zacc㎞oS.及’oo眉g漉Oi(必θヱη.2003,11,
1531,
39.Fustero,S.;Sole鴎」1G.;Bartolome,A,;Rosello,M.S.α客五θ猛2003,5,2707,
148
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