Preparation of Boc-protected cinnamyl-type alcohols: A comparison of the Suzuki-Miyaura coupling, cross-metathesis, and Horner-Wadsworth-Emmons approaches and their merit in parallel synthesis

Article abstract of DOI:10.1135/cccc20080705

Three synthetic strategies for the construction of tert-butyl (E)-3-arylprop-2-en-1-ol carbonates are described. Complementary approaches employing Suzuki-Miyaura coupling and cross-metathesis reaction gave moderate yields of the title compounds in one-step, both methods are suitable for high-throughput and parallel chemistry. A detailed investigation into the Suzuki-Miyaura coupling reaction is provided along with the studies on the synthesis of pinacolyl 1-(tert-butyloxycarbonyl)propenol-3-ylboronate, the key building block. Conventional synthesis of the title compounds via the Horner-Wadsworth-Emmons reaction as a key step in a three-step-one-purification protocol was optimized and the results are compared with those of the latter reactions.

Full text of DOI:10.1135/cccc20080705

Preparation of Boc-Protected Cinnamyl-Type Alcohols
705
PREPARATION OF Boc-PROTECTED CINNAMYL-TYPE ALCOHOLS:
A COMPARISON OF THE SUZUKI–MIYAURA COUPLING,
CROSS-METATHESIS, AND HORNER–WADSWORTH–EMMONS
APPROACHES AND THEIR MERIT IN PARALLEL SYNTHESIS
1,
2,
Jan ŠTAMBASKÝ, Andrei V. MALKOV * and Pavel KOČOVSKÝ *
Department of Chemistry, WestChem, University of Glasgow, Glasgow G12 8QQ, U.K.;
1
2
e-mail: amalkov@chem.gla.ac.uk, pavelk@chem.gla.ac.uk
Received May 21, 2008
Accepted Jun e 25, 2008
Publish ed on lin e July 31, 2008
Th ree syn th etic strategies for th e con struction of tert-butyl (E)-3-arylprop-2-en -1-ol carbon -
ates are described. Com plem en tary approach es em ployin g Suzuki–Miyaura couplin g an d
cross-m etath esis reaction gave m oderate yields of th e title com poun ds in on e-step, both
m eth ods are suitable for h igh -th rough put an d parallel ch em istry. A detailed in vestigation
in to th e Suzuki–Miyaura couplin g reaction is provided alon g with th e studies on th e syn th e-
sis of pin acolyl 1-(tert-butyloxycarbon yl)propen ol-3-ylboron ate, th e key buildin g block. Con -
ven tion al syn th esis of th e title com poun ds via th e Horn er–Wadsworth –Em m on s reaction as
a key step in a th ree-step-on e-purification protocol was optim ized an d th e results are com -
pared with th ose of th e latter reaction s.
Keyw ord s: C–C bon d form ation ; Palladium ; Ruth en ium ; Suzuki–Miyaura reaction ; Metath e-
sis.
Asym m etric allylic substitution is a versatile m eth od for th e con struction of
a n ew ch iral cen ter, startin g with ach iral allylic substrates, such as 1
(Sch em e 1). Th is tran sform ation is catalyzed by ch iral com plexes of tran si-
tion m etals, such as palladium 1,2, m olybden um 3, tun gsten 3b,4, ruth en ium 5,
rh odium 6, iridium 7, n ickel8, platin um 9, an d copper10, an d typically pro-
ceeds th rough th e π-allyl in term ediate 2. To date, asym m etric allylic substi-
tution h as evolved in to a powerful syn th etic tool for th e en an tioselective
form ation of C–C, C–N, an d C–O bon ds1–10. Am on g th e leavin g groups,
esters (1, R2 = alkyl), carbon ates (1, R2 = OR′) an d, in particular, tert-butyl
carbon ates (1, R2 = t-BuO), h old a dom in an t position . Alth ough th e con ver-
sion of an alcoh ol in to th e correspon din g Boc derivative is well estab-
lish ed11, expedien t syn th esis of even a sm all library of desirable carbon ates
m ay actually becom e con siderably m ore cum bersom e th an expected. With
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732
© 2008 Institute of Organic Chemistry and Biochemistry
doi:10.1135/cccc20080705

706
Štambaský, Malkov, Kočovský:
3-arylallyl alcoh ols, as precursors to 1, th ere is little ch oice in diversity with
a view of m atch in g th e portfolio of th e com m ercially available aryl build-
in g blocks with a suitable m eth odology.
SCHEME 1
Metal-catalyzed asym m etric allylic substitution
Herein , we report on two n ew m eth ods for th e con struction of tert-butyl
(E)-3-arylprop-2-en -1-ol carbon ates (4) from com m ercially available startin g
m aterials th at are suitable for parallel syn th esis tech n iques (Sch em e 2). Also
reported is an optim ization of th e con ven tion al syn th etic approach to th ese
com poun ds, based on th e Horn er–Wadsworth –Em m on s reaction (HWE).
Our approach to th e target carbon ates 4 was based upon th e desire to de-
velop a on e-step syn th etic protocol suitable for parallel syn th esis (Sch em e 2).
SCHEME 2
Retrosyn th etic an alysis of tert-butyl 3-arylprop-2-en -1-yl carbon ates. For Ar, see th e follow-
in g Sch em es
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

Preparation of Boc-Protected Cinnamyl-Type Alcohols
707
Th e m ain in terest was laid upon th e discon n ection a em ployin g th e com -
m ercially available aryl h alides 5 an d th e com m on buildin g block 6. Route
b is based on th e (E)-double bon d con struction via a cross-m etath esis reac-
tion of th e com m ercially available styren es 7 an d th e Boc-protected allyl al-
coh ol 8 as com m on buildin g blocks. Th e last part of our in vestigation was
focused on th e optim ization of th e Boc derivatization of th e cin n am yl-type
alcoh ols 9 (c). Som e of th ese alcoh ols are com m ercially available or easy to
m ake from th e correspon din g cin n am ic acids, oth ers can be syn th esized
usin g th e Horn er–Wadsworth –Em m on s reaction . Optim ization of th e latter
sequen ce, startin g with th e com m ercially available aldeh ydes 11 an d th e
ph osph on ate reagen t 12, in to a th ree-step-on e-purification protocol (c–e) is
also reported.
RESULTS AND DISCUSSION
Boc Derivatization
Th e Boc derivatization of cin n am yl alcoh ol (9a) was in vestigated un der var-
ious con dition s (Sch em e 3)11. Th e procedure em ployin g Boc2O an d NaOH
with a ph ase-tran sfer catalyst failed11a, wh ile reaction s11b with Boc2O in
CH2Cl2, catalyzed by V(O)(OTf)2, gave on ly th e sym m etric carbon ate
SCHEME 3
Form ation of tert-butyl carbon ates an d isolated yields
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

708
Štambaský, Malkov, Kočovský:
(Ph CH=CHCH2O)2CO in h igh yield. On th e oth er h an d, by followin g th e
procedure11c,11d, in wh ich Boc2O is added to a solution of th e correspon d-
in g alkoxide in THF, we were able to isolate th e desired product 4a in about
40% yield alon g with th e sym m etric carbon ate (Ph CH=CHCH2O)2CO.
A m odified protocol, in wh ich th e alcoh olate solution is tran sferred to
an excess of th e solution of Boc2O, afforded 4a in h igh yield an d was th en
em ployed th rough out th is study (Sch em e 3).
Suzuki–Miyaura Coupling
Th e syn th esis of th e buildin g block 15 was based upon th e procedure for
th e preparation of boron ic acid 16 (Sch em e 4)12. In our h an ds, th e estab-
lish ed protocol was successful on ly for propargyl alcoh ol 14, wh ich pro-
duced acid 16 (Table I, en try 1), an d failed in th e case of th e Boc derivative
13 (en tries 2 an d 3). Altern ative h ydroboration con dition s were also in ves-
tigated13: th us, for in stan ce, treatm en t of alkyn e 13 with boran e dibrom ide
proved fruitless (en try 4) an d an attem pted reaction with dicycloh exyl-
SCHEME 4
Hydroboration ; for con dition s, see Table I
TABLE I
Hydroboration of 12 an d 13
En try
Con dition s
Alkyn e
Product Yield, %a
1
2
3
4
5
6
7
Catech olboran e (2 equiv.), n eat, 70 °C, 1 h
Catech olboran e, THF, 70 °C, 12 h
14
13
13
13
13
13
13
16
15
15
15
15
15
6
40
0
Catech olboran e, n eat, 70 °C, 12 h
0
Br2BH·Me2S, DCM, 0 °C to 20 °C, 6 h
0
c-Hex2BH, Me3NO, THF, 0 °C to 20 °C, 1.5 h
Catech olboran e, c-Hex2BH (10%), n eat, 20 °C, 12 h
Pin acolboran e, c-Hex2BH (10%), n eat, 20 °C, 12 h
40
62
95
a
Isolated yields.
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

Preparation of Boc-Protected Cinnamyl-Type Alcohols
709
boran e, followed by addition of trim eth ylam m on ium N-oxide, gave on ly
m oderate yield (en try 5). On th e oth er h an d, em ployin g dicyclo-
h exylboran e as catalyst14, with a stoich iom etric am oun t of catech olboran e,
afforded th e desired product 15 in good yield (en try 6)15. Fin ally, a reaction
of 13 with pin acolboran e, catalyzed by dicycloh exylboran e, produced vin yl
boron ate 6 in an excellen t isolated yield (en try 7). In th e latter protocol,
th e h igh purity of th e h ydroboratin g reagen ts proved to be crucial for at-
tain in g h igh yields.
Th e publish ed procedure16 for th e Suzuki-type couplin g reaction s of th e
h ydroxy acid 16 required th e presen ce of th allium eth oxide in aqueous
m edium . Application of th e latter protocol to th e couplin g of th e Boc-
protected acid 15 with p-iodotoluen e resulted in th e form ation of on ly
traces of th e desired product 4d (Sch em e 5, Table II, en try 1). By con trast,
sim ple stan dard con dition s for th e aqueous Suzuki–Miyaura couplin g reac-
tion s, em ployin g K2CO3 as a base, gave rise to th e form ation of 4d in good
yield (en try 2).
A con siderable drawback to th e latter protocol is th e beh avior of th e acid
15: wh en fresh ly prepared, it is a wh ite solid, wh ich in th e air (m oisture)
m elts to a very viscous oil con tain in g variable am oun t of th e correspon din g
oligom ers; upon prolon ged stan din g, both form s (oil or solid) becom e a
sticky brown -grey solid, con tain in g products of decom position . Th ese fea-
tures, in con jun ction with th e lower yield of th e h ydroboration , drew our
atten tion to boron ate 6, a colorless, ben ch stable17, well-defin ed liquid th at
can be distilled.
In itially, we ch ose alkali carbon ates in aqueous 1,2-dim eth oxyeth an e
(DME) as th e reaction m edium for th e 5d + 6 couplin g. An overn igh t h eat-
in g with alkali carbon ates gave th e desired product 4d in about 10% yield
(Table II, en tries 3 an d 4). High er loadin g of th e iodide 5d an d th e base led
to an im provem en t (en tries 5 an d 6), wh ereas a sign ifican t decrease of th e
yield was observed wh en potassium tert-butoxide was em ployed (en try 7),
alth ough th e use of a toluen e–water two-ph ase system resulted in som e
im provem en t (en try 8). Th e reaction failed wh en a larger am oun t of water
(>80%) was used in th e solven t m ixture, wh en th allium eth oxide was used
as a base, or wh en DMF was ch osen as a solven t. Th e best results were at-
tain ed wh en th e reaction tim e was kept sh ort (en try 9). Oth er publish ed
con dition s did n ot lead to an y furth er im provem en t18. Furth erm ore, th e
recyclable m icroen capsulated palladium 19 gave lower yields alon g with a
relatively h igh am oun t of un iden tified side-products (en tries 10 an d 11),
wh ereas th e use of an advan ced ligan d20, such as S-Ph os (2-dicycloh exyl-
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

710
Štambaský, Malkov, Kočovský:
SCHEME 5
Suzuki–Miyaura couplin g
TABLE II
Optim ization of th e Suzuki–Miyaura couplin ga
5d
equiv
allyl
carbon ate
catalyst
m ole %
base
equiv
yieldb
En try
1
solven t
con dition s
%
2.0
15
(Ph 3P4)Pd
(5)
EtOTl
(2.1)
DME–H2O
(7:3)
20 °C, 1 h
traces
(Ph 3P4)Pd
(5)
K2CO3
(1.8)
DME–H2O
(20:3)
2
3
4
5
6
7
8
9
0.7
1.0
1.0
1.8
3.3
1.9
2.2
5.0
15
6
85 °C, 20 h
100 °C, 15 h
80 °C, 18 h
85 °C, 18 h
100 °C, 20 h
100 °C, 20 h
100 °C, 20 h
80 °C, 2 h
61
8
(Ph 3P4)Pd
(5)
Na2CO3
(5.3)
DME–H2O
(7:5)
(Ph 3P4)Pd
(5)
K2CO3
(2.5)
DME–H2O
(20:3)
6
12
33
40
6
(Ph 3P4)Pd
(5)
K2CO3
(7.8)
DME–H2O
(20:3)
6
(Ph 3P4)Pd
(5)
K2CO3
(5.5)
DME–H2O
(4:1)
6
(Ph 3P4)Pd
(5)
t-BuOK
(4.8)
DME–H2O
(4:1)
6
(Ph 3P4)Pd
(5)
t-BuOK
(5.2)
Toluen e–H2O
(4:1)
6
26
42
(Ph 3P4)Pd
(5)
K2CO3
(4.0)
DME–H2O
(1:1)
6
K2CO3
(3.3)
DME–H2O
(1:1)
10
11
1.4
0.9
6
6
Pd(0) En Cat™
Pd(0) En Cat™
80 °C, 14.5 h
80 °C, 2 h
25
16
K2CO3
(2.7)
DME–H2O
(1:1)
a
Reaction s were perform ed on 1 m m ol scale, usin g 10 m l of th e solven t m ixture, all th e
b
equivalen ts are based on th e boron ate (boron ic acid). Isolated yields.
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

Preparation of Boc-Protected Cinnamyl-Type Alcohols
711
ph osph in o-2′,6′-dim eth oxybiph en yl), resulted in n o reaction or gave on ly
traces of 4d .
Havin g th us iden tified potassium carbon ate as th e optim al base, a
DME–water m ixture (1:1) as th e optim al solven t system , an d (Ph 3P)4Pd as
th e m ost suitable pre-catalyst, we th en in vestigated th e role of th e reaction
tim e in th e ran ge of 1–32 h at 40 °C (Ch art 1). Th e data clearly sh ow an in -
crease in th e yield of 4d with a m axim um reach ed in 8 h an d suggest th at
both th e product 4d an d th e startin g boron ate 6 are un stable un der th e re-
action con dition s an d gradually decom pose.
CHART 1
Suzuki–Miyaura couplin g of 5d with 6: isolated yields versus reaction tim e. Reaction s were per-
form ed on 1 m m ol scale; con dition s: aryl iodide (0.9 equiv.), K2CO3 (3 equiv.), DME–H2O (1:1,
10 m l), 40 °C, (Ph 3P)4Pd, isolated yields.
A deeper in sigh t was obtain ed via m on itorin g th e reaction by 1H NMR
spectroscopy. Th e couplin g was perform ed at a h igh er tem perature (80 °C),
with sam plin g every 20 m in (Ch art 2). Th e spectra plot sh owed an in creas-
in g am oun t of th e product 4d , reach in g th e m axim um in about 2 h . After
th is poin t, both sign als begun to disappear slowly in to th e baselin e n oise.
Hen ce, at th e tem peratures ran gin g from 40 to 80 °C, boron ate 6 is suffi-
cien tly reactive to form a sign ifican t am oun t of th e product 4d , wh ose rate
of form ation is estim ated to be on e order of m agn itude faster th an th e rate
of its decom position . Th ese results also sh ow th at 80 °C for 2 h are optim al
reaction param eters for th is process.
Th e last sets of param eters to be optim ized were th e ratios of th e startin g
iodide an d th e base em ployed (Table III). Th ese experim en ts also dem on -
strated th e n eed for h igh er am oun ts of water (50%), com bin ed with h igh er
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

712
Štambaský, Malkov, Kočovský:
CHART 2
1H NMR spectra plot based on Sch em e 5, reaction was perform ed on 1 m m ol scale; con dition s:
aryl iodide (0.9 equiv.), K2CO3 (2.5 equiv.), DME–H2O (1:1, 10 m l), 80 °C, (Ph 3P)4Pd (5.4 m ol %)
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

Preparation of Boc-Protected Cinnamyl-Type Alcohols
713
dilution . Un der th ese con dition s, th e reaction s were h om ogen eous (com -
pare en tries 2 versus 3). Th e oth er results sh ow th e h igh est yields wh en
eith er excess of boron ate 6 (en try 4) or iodide 5d (en try 6) were used alon g
with an excess of base. A furth er in crease in loadin g of th e base (en tries 6
an d 7) h ad a m ore n egative effect th an th e in crease in th e loadin g of th e
iodide (en tries 5 an d 6).
TABLE III
Th e in fluen ce of th e m olar ratios on th e Suzuki–Miyaura couplin g of 5d with 6a
Iodide
equiv
Base
equiv
Pd(0)
m ole %
Yieldb
%
En try
Solven t
1
2
3
4
5
6
7
1.4
0.8
0.8
0.6
4.7
3.1
4.6
2.9
1.7
2.3
1.7
2.9
3.0
4.6
2 m l, DME–H2O (9:1)
2 m l, DME–H2O (9:1)
10 m l, DME–H2O (1:1)
10 m l, DME–H2O (1:1)
10 m l, DME–H2O (1:1)
10 m l, DME–H2O (1:1)
10 m l, DME–H2O (1:1)
5.2
5.2
4.0
3.1
5.6
6.0
4.8
11c
9c
20
36
33
36
24
a
Reaction s were perform ed on 1 m m ol scale; con dition s: 80 °C, 2 h , (Ph 3P)4Pd, all equiva-
len ts are based on th e boron ate. Isolated yields. Th e yield was determ in ed by 1H NMR
b
c
spectroscopy in th e reaction m ixture after th e work up.
Th e optim ized reaction protocol was em ployed in th e syn th esis of a series
of various carbon ates 4d –4r (Sch em e 6). Th e results fully correspon d to th e
previous observation s as well as to th e com m on reactivity of aryl h alides in
th e Suzuki–Miyaura couplin g reaction . Th e h igh est yields were attain ed
with electron -poor aryl iodides lackin g ortho substituen ts. Aryl brom ides did
n ot reacted un der an y variation of th e reaction con dition s, suggestin g th at
th is effect can be utilized for discrim in atin g between th e reaction sites of
polyh alogen ated substrates. In deed, 4-brom oiodoben zen e (5f) selectively
reacted at th e C–I bon d to produce 4f, leavin g th e brom ide m oiety in tact.
In som e cases, th e excess of aryl iodide was successfully recovered (4e, 4j,
4l, an d 4n ). High er loadin g of both th e iodide 5 an d base furth er im proved
th e yields, even in th e case of ortho-substituted iodides (5e an d 5j).
3-Iodopyridin e (5q) did also react to afford 4q. Despite th e low to m oderate
yields, th e m ain syn th etic utility of th is m eth od lies in th e fast reaction an d
m ild reaction con dition s. An aqueous workup gen erally gave m ixtures con -
tain in g m ain ly th e un reacted startin g iodide (in excess) an d th e desired
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

714
Štambaský, Malkov, Kočovský:
product. With th e subsequen t sim ple ch rom atograph y, th e wh ole reac-
tion -purification procedure did n ot exceed 3 h , wh ich is very con ven ien t
for autom ation . Th ese advan tages were dem on strated in th e reaction of
21
salicylate 5r th at afforded th e h igh ly substituted carbon ate 4r.
SCHEME 6
Suzuki–Miyaura couplin g of aryl an d h eteroaryl h alides 5 with vin yl boron ate 6
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

Preparation of Boc-Protected Cinnamyl-Type Alcohols
715
Cross-Metathesis
Th e cross-m etath esis reaction 22 was in vestigated as an altern ative syn th etic
approach to carbon ates 4 (Sch em e 7). Man y of th e startin g vin yl arom atics
7 are com m ercially available or are readily accessible in on e step by th e
well-developed vin ylation of aryl h alides 5 23, wh ich ren ders th is approach
attractive.
Em ployin g styren e (7a) an d allyl tert-butyl carbon ate (8) as m odel sub-
strates, a brief screen in g of th e reaction con dition s was con ducted to fin d
an optim al protocol. Th e secon d-gen eration Grubbs catalyst gave gen erally
twice as h igh yields as th e Grubbs first-gen eration catalyst, alon g with th e
full con version of allyl carbon ate 8 (Table IV, en tries 1 an d 2). In both cases,
trans-stilben e was isolated as th e m ajor product as a result of self-m etath esis
of 7a. On th e oth er h an d, self-m etath esis of allyl carbon ate 8 was observed
on ly as a very m in or side reaction . Th e h igh er yields of th e desired product
4a were attain ed by in creasin g th e excess of styren e (en tries 6 an d 7), wh ich
SCHEME 7
Syn th esis of carbon ates 4 via cross-couplin g m etath esis
TABLE IV
Screen in g of th e cross-m etath esis reaction a
Catalyst
7a
equiv
Tim e
h
Yieldb
%
En try
m ole %
1
2
3
4
5
6
7
2.0
2.0
Grubbs 1st (5.6)
Grubbs 2n d (2.7)
Grubbs 2n d (0.7)
Grubbs 2n d (0.8)
Grubbs 2n d (0.4)
Grubbs 2n d (2.4)
Grubbs 2n d (2.7)
12
2
17
36
21
23
16
37
43
0.5
2
0.4
2
0.2
2
5.0
2
10.0
2
a
Reaction s were perform ed on 1 m m ol scale; con dition s: DCM (2 m l), 40 °C, all th e equiva-
b
len ts are based on allyl carbon ate. Isolated yields.
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

716
Štambaský, Malkov, Kočovský:
is an acceptable scen ario in th e case of ch eap, com m ercially available vin yl
arom atics.
Various vin yl arom atics were th en subm itted to th e optim ized cross-
m etath esis protocol (Sch em e 8). Th e reaction sh owed reversed electron ic
dem an ds to th e Suzuki–Miyaura couplin g an d did n ot work for electron i-
cally poor substrates, such as n itrostyren e or pen tafluorostyren e, an d for
vin yl pyridin es. On th e oth er h an d, th e reaction proceeded successfully
with ortho-substituted styren es to produce 4e an d 4g.
SCHEME 8
Rh -catalysed cross m etath esis of styren es 7 with allyl carbon ate 8
Horner–Wadsworth–Emmons Reaction
Optim ization of th e con ven tion al syn th etic approach 24 to carbon ates 4 was
also in vestigated (Sch em es 2 an d 9). Com m ercially available aryl aldeh ydes
11 were reacted with ph osph on ate 12 to afford th e correspon din g eth yl
acrylates 10. Th e reaction proved to be clean an d h igh ly stereoselective, n o
1
(Z)-isom ers were detected by H NMR spectroscopy25. Th e acrylates 10 were
th en reduced with DIBAL-H directly after th e aqueous work-up with out fur-
th er purification . Th e resultin g aryl propen ols 9 were obtain ed again in suf-
ficien t purity an d were directly tran sform ed in to th e desired Boc derivatives
4, usin g our optim ized protocol (vide supra), th e crude products were th en
subjected to th e on ly purification (by ch rom atograph y), required in th is
sequen ce.
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

Preparation of Boc-Protected Cinnamyl-Type Alcohols
717
Th is classical syn th etic approach proved to be very robust in a n um ber of
structural pattern s (Sch em e 9). Th e on ly difficulties were en coun tered in
th e reaction sequen ces of aldeh ydes 11v an d 11w . Th e γ-picolin ic aldeh yde
11v reacted well in th e HWE reaction but subsequen t reduction at room
tem perature resulted in th e form ation of in tractable products on ly. Reduc-
tion at low tem perature (–80 °C) gave propen ol 9v in about 40% yield (over
two steps) but addition al purification of th e propen ol 9v was n ecessary.
Carbon ate 4v was obtain ed from th e latter product (48%) by usin g th e stan -
dard procedure. Th e N-m eth ylpyrrole carbon ate 4w was prepared by th e
stan dard reaction sequen ce. Th e problem atic part h ere was th e fin al puri-
fication , due to th e low stability of th e pyrrole m oiety26. Even if th e ch ro-
SCHEME 9
Horn er–Wadsworth –Em m on s approach to carbon ate 4
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

718
Štambaský, Malkov, Kočovský:
m atograph y was carried out on a colum n of n eutral alum in a an d with
trieth ylam in e as co-eluen t, th e blue color of pyrrole-based oligom ers was
observed upon th e station ary ph ase. Furth erm ore, th e fin al pyrrole carbon -
ate 4w proved un stable at room tem perature, as it un derwen t spon tan eous
polym erization . Despite th ese particular problem s, th is optim ized HWE ap-
proach proved to be a very con ven ien t m eth od for a gram scale (all reac-
tion s were carried out on 20 m m ol scale) syn th esis of carbon ates 4 bearin g
various structural pattern s in cludin g th e ortho substituen ts an d
arom atic/h eteroarom atic m oieties with diverse electron ic properties.
CONCLUSIONS
We h ave system atically in vestigated n ew syn th etic approach es to tert-butyl
(E)-3-arylprop-2-en ol carbon ates 4a–4w an d com pared th em with an opti-
m ized con ven tion al approach . All th ese th ree approach es proved to be to
be com plem en tary. Th e Suzuki–Miyaura couplin g reaction is a versatile
m eth od for aryls lackin g an ortho substituen t an d for n on -coordin atin g
h eterocycles, bearin g preferen tially electron -with drawin g fun ction alities.
Th is m eth od em ploys a wide ran ge of com m ercially available aryl iodides
an d its m ain advan tage relates to polyfun ction al substrates, such as m eth yl
acetylsalicylate (5r → 4r). Th e cross-m etath esis is a un iversal m eth od with
preferen ce for electron ically n eutral or electron -don atin g groups, h igh -
ligh ted by th e toleran ce to ortho substituen ts27. Both th ese m eth ods give
m oderate an d reproducible yields with in th e lim itation s spelt out h ere.
Th ese on e-step reaction s are fast an d atom -econ om ic, yieldin g relatively
clean products th at are easy to purify, wh ich m akes th em am en able to th e
use in parallel syn th esis of large sets of derivatives with diverse fun ction al-
ity. Th e HWE-based reaction sequen ce, optim ized to a th ree-step-on e-
purification protocol, represen ts a robust m eth od for th e stan dard prepara-
tion of carbon ates 4 th at can be easily scaled up. Com parin g th e th ree
m eth ods sh ows th at each h as its m erit so th at th ey are com plem en tary an d
n on e is a clear, gen eral win n er. Th us, for in stan ce, th e syn th esis of 4r
would be rath er difficult via th e classical HWE approach in view of th e re-
quired protection -deprotection s step, selective reactivity, etc. On th e oth er
h an d, som e of th e low yields obtain ed in th e Suzuki–Miyaura couplin g
(e.g., 4e) would direct th e strategy eith er toward th e cross-m etath esis or
HWE approach .
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

Preparation of Boc-Protected Cinnamyl-Type Alcohols
719
EXPERIMENTAL
Gen eral Meth ods
Meltin g poin ts were determ in ed on a Kofler block an d are un corrected. Th e NMR spectra
were m easured in ch loroform -d1 (δ 7.26, 1H; δ 77.00, 13C) an d CCl3F (δ 0.00, 19F) as in tern al
stan dards un less oth erwise in dicated. Ch em ical sh ifts are given in ppm (δ-scale), couplin g
con stan ts (J) in Hz. Com plete assign m en t of all NMR sign als was perform ed usin g a com bi-
n ation of H,HCOSY, H,CHSQC an d H,CHMBC experim en ts. Th e IR spectra (ν in cm –1) were
recorded for a th in film between NaCl plates or for CHCl3 solution s. Th e m ass spectra (EI or
CI-isobutan e, un less oth erwise specified) were m easured on a dual sector m ass spectrom eter
usin g direct in let an d th e lowest tem perature en ablin g evaporation . All reaction s were per-
form ed un der an atm osph ere of dry, oxygen -free argon in oven -dried glassware th ree tim es
evacuated an d backfilled with th e argon th ree tim es. Reaction tem perature –83 °C refers to
th e coolin g bath filled with an eth yl acetate–liquid n itrogen m ixture. Solven ts an d solution s
were tran sferred by syrin ge-septum an d can n ula tech n iques. All solven ts for th e reaction s
were of reagen t grade an d were dried an d distilled im m ediately before use as follows:
tetrah ydrofuran (THF) from sodium /ben zoph en on e, dich lorom eth an e from calcium h ydride.
Solven ts for th e palladium - an d ruth en ium -catalyzed reaction s were degassed in vacuo an d
stored over m olecular sieves (4 Å) un der argon atm osph ere. Yields are given for isolated
products sh owin g on e spot on a TLC plate an d n o im purities detectable in th e NMR spec-
trum . Th e iden tity of th e products prepared by differen t m eth ods was ch ecked by com pari-
son of th eir NMR, IR, an d MS data an d by th e TLC beh avior.
Gen eral Procedure A: tert-Butyloxycarbon ylation of Alcoh ols to Produce Carbon ates 4
An alcoh ol (100.0 m m ol, n eat or 5 M solution in THF if solid) was slowly added to a suspen -
sion of sodium h ydride (6.0 g, 150 m m ol, 60% suspen sion in m in eral oil, 3 × wash ed with
dry THF) in THF (100 m l) at room tem perature an d th e m ixture was stirred for 1 h . Th e re-
sultin g solution was slowly added to a solution of tert-butoxy- (tert-butoxycarbon yloxy)-
m eth an on e (Boc an h ydride, 25.0 g, 115.0 m m ol) in THF (400 m l) at room tem perature an d
th e m ixture was stirred at room tem perature overn igh t. Th e reaction was quen ch ed with
brin e (100 m l) an d th e product was extracted in to eth er (500 m l). Th e organ ic layer was
dried (Na2SO4) an d evaporated.
Gen eral Procedure B: Suzuki–Miyaura Couplin g Reaction to Produce Carbon ates 4 (for th e
solid iodide 5)
A flask con tain in g aryl iodide 5 (3.00 m m ol), K2CO3 (415 m g, 3.00 m m ol) an d (Ph 3P)4Pd
(60.0 m g, 0.052 m m ol) was sealed an d th ree tim es evacuated an d backfilled with argon .
Boron ate 6 (n eat, 280 m g, 1.00 m m ol), DME (5 m l) an d water (5 m l) were added an d th e
m ixture was stirred at 80 °C for 2 h . Th e resultin g solution was cooled to room tem perature,
diluted with Et2O (80 m l), wash ed with brin e (3 × 50 m l), dried (Na2SO4) an d evaporated.
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

720
Štambaský, Malkov, Kočovský:
Gen eral Procedure C: Suzuki–Miyaura Couplin g Reaction to Produce Carbon ates 4 (for th e
liquid iodide 5)
A flask con tain in g K2CO3 (415 m g, 3.00 m m ol) an d (Ph 3P)4Pd (60.0 m g, 0.052 m m ol) was
sealed an d th ree tim es evacuated an d backfilled with argon . Aryl h alide 5 (3.00 m m ol),
boron ate 6 (n eat, 285 m g, 1.00 m m ol), DME (5 m l) an d water (5 m l) were added an d th e
m ixture was stirred at 80 °C for 2 h . Th e resultin g solution was cooled to room tem perature,
diluted with Et2O (80 m l), wash ed with brin e (3 × 50 m l), dried (Na2SO4) an d evaporated.
Gen eral Procedure D: Cross-Metath esis Reaction to Carbon ates 4
A flask con tain in g ben zyliden e[1,3-bis(2,4,6-trim eth ylph en yl)-2-im idazolidin yliden e]dich loro-
(tricycloh exylph osph in e)ruth en ium (2n d gen eration Grubbs catalyst, 23.9 m g, 0.028 m m ol)
was sealed an d th ree tim es evacuated an d backfilled with argon . Dich lorom eth an e (2.0 m l),
n eat allyl carbon ate 8 (1.00 m m ol) an d n eat vin yl arom ate 7 (0.40 to 5.00 m m ol) were
added an d th e m ixture was stirred at 40 °C for 2 h . Th e resultin g solution was cooled to
room tem perature an d evaporated.
General Procedure E: Horner–Wadsworth–Em m ons Based Reaction Sequence to Carbonates 4
n-BuLi (11 m l, 22 m m ol, 2 M solution in pen tan e) was slowly added to a solution of
trieth ylph osph on oacetate 12 (4.49 g, 20.0 m m ol) in THF (20 m l) at –83 °C. After 5 m in , al-
deh yde 11 (20.0 m m ol) was slowly added an d th e resultin g m ixture was stirred at –83 °C for
10 m in an d th en at room tem perature for 2 h . Th e reaction was quen ch ed with brin e
(10 m l), th e m ixture was diluted with eth er (100 m l), wash ed with brin e (3 × 50 m l), dried
(Na2SO4), an d evaporated. Th e crude eth yl ester 10 was dissolved in THF (20 m l), cooled to
0 °C an d DIBAL-H (40 m l, 60 m m ol, 1.5 M solution in toluen e) was slowly added at th is
tem perature. Th e resultin g m ixture was stirred at room tem perature for an addition al 2 h
an d th an th e reaction was quen ch ed with a saturated aqueous solution of potassium -sodium
tartrate (50 m l). Th e resultin g solution was stirred at 40 °C an d a solid potassium -sodium
tartrate (approxim ately 15 g) was added in portion s, un til th e solution becam e h om oge-
n eous. Th e resultin g m ixture was diluted with eth er (300 m l), wash ed with a saturated aque-
ous solution of potassium -sodium tartrate (3 × 100 m l), dried (Na2SO4), an d evaporated. Th e
crude allyl alcoh ol 9 was dissolved in THF (20 m l) an d slowly added to a suspen sion of so-
dium h ydride (1.21 g, 30.3 m m ol, 60% suspen sion in m in eral oil, 3 × wash ed with dry THF)
in THF (20 m l) at room tem perature an d th e m ixture was stirred for 1 h . Th e resultin g solu-
tion was slowly added to a solution of Boc an h ydride (4.84 g, 22.2 m m ol) in THF (50 m l) at
room tem perature an d th e m ixture was stirred at room tem perature overn igh t. Th e reaction
was quen ch ed with brin e (10 m l) an d th e m ixture diluted with eth er (250 m l), wash ed with
brin e (3 × 50 m l), dried (Na2SO4), an d evaporated.
tert-Butyl (E)-3-phenylprop-2-en-1-yl carbonate (4a). Fraction distillation of th e crude product
obtain ed by procedure A produced 4a as a colorless oil (34.07 g, 73%): b.p. 114 °C at 270 Pa.
3
4
1H NMR (400.1 MHz, CDCl3): 1.54 (s, 9 H, t-Bu), 4.76 (dd, J1-3H,2-H = 6.5, J1-H,3-H = 1.1, 2 H,
1-H), 6.33 (dt, 3J = 15.9, J2-H,1-H = 6.5, 1 H, 2-H), 6.71 (dt, J3-H,2-H = 15.9, J3-H,1-H = 1.1,
1 H, 3-H), 7.27–7.32 (m , 1 H, H-arom ), 7.33–7.38 (m , 2 H, H-arom ), 7.43 (dd, JH,H = 7.2 an d
1.5, 2 H, H-arom ). 13C NMR (100.6 MHz, CDCl3): 27.65 (C(CH3)3), 67.32 (CH2-1), 82.03
(C(CH3)3), 122.74 (CH-2), 126.51, 127.94 an d 128.46 (CH-arom ), 134.25 (CH-3), 136.03
(C-arom ), 153.21 (CO carbon ate). MS (CI-NH3), m/z (%): 252 (M + NH4+, 2), 151 (1), 134 (3),
3
4
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

Preparation of Boc-Protected Cinnamyl-Type Alcohols
721
117 (2), 88 (3). IR (KBr, CHCl3): 2980 (m ), 1740 (s), 1449 (w), 1369 (m ), 1275 (s), 1254 (s),
1163 (s), 1117 (m ), 1085 (w), 967 (m ). For C14H18O3 calculated: 71.77% C, 7.74% H; foun d:
71.93% C, 7.78% H.
tert-Butyl (E)-3-(2′,3′-dimethoxyphenyl)prop-2-en-1-yl carbonate (4b). Th e crude product ob-
tain ed by procedure A was ch rom atograph ed on a colum n of silica gel (5 × 10 cm ) with
a m ixture of h exan es an d AcOEt (90:10) to afford 4b as a yellow oil (1064 m g, 49% of th e-
ory, 62% based on recovered allylic alcoh ol). Con tin ued elution with a m ixture of h exan es
an d AcOEt (80:20) gave th e startin g allylic alcoh ol 9b (272 m g, 19% recovered). 1H NMR
(400.1 MHz, CDCl3): 1.49 (s, 9 H, t-Bu), 3.79 (s, 3 H, CH3O-2′), 3.84 (s, 3 H, CH3O-3′), 4.73
3
4
3
3
(dd, J1-H,2-H = 6.5, J1-H,3-H = 1.2, 2 H, 1-H), 6.31 (dt, J2-H,3-H = 16.1, J2-H,1-H = 6.5, 1 H,
3
4
3
4
2-H), 6.82 (dd, J4′-H,5′-H = 8.0, J4′-H,6′-H = 1.4, 1 H, 4′-H), 6.98 (dt, J3-H,2-H = 16.1, J3-H,1-H
=
3
3
3
1.2, 1 H, 3-H), 7.00 (t, J5′-H,4′-H = 8.0, J5′-H,6′-H = 8.0, 1 H, 5′-H), 7.07 (dd, J6′-H,5′-H = 8.0,
4J6′-H,4′-H = 1.4, 1 H, 6′-H). 13C NMR (100.6 MHz, CDCl3): 27.71 (C(CH3)3), 55.70 (CH3O-3′),
60.87 (CH3O-2′), 67.75 (CH2-1), 82.05 (C(CH3)3), 111.74 (CH-4′), 118.26 (CH-6′), 123.96
(CH-5′), 124.19 (CH-2), 128.72 (CH-3), 130.29 (C-1′), 146.84 (C-2′), 152.89 (C-3′), 153.27
(CO carbon ate). IR (n eat): 2979 (w), 2835 (w), 1740 (s, CO carbon ate), 1478 (m ), 1369 (m ),
1272 (s), 1255 (s), 1161 (s), 1117 (m ), 1090 (m ), 1070 (m ), 1008 (m ). MS (EI, 150 °C), m/z
(%): 294 (M+, 15), 238 (M+ – (CH3)2C=CH2, 100), 194 (M+ – (CH3)2C=CH2 – CO2, 5), 177
(MH+ – (CH3)2C=CH2 – CO2 – H2O, 85). HRMS (EI): 294.1469 (C16H22O5 (M+) requires
294.1467). For C16H22O5 calculated: 65.29% C, 7.53% H; foun d: 65.14% C, 7.66% H.
tert-Butyl (E)-3-(3′,4′-dimethoxyphenyl)prop-2-en-1-yl carbonate (4c). Th e crude product
obtain ed by procedure A was ch rom atograph ed on a colum n of silica gel (5 × 10 cm ) with
a m ixture of h exan es an d AcOEt (90:10) to furn ish 4c as a yellow oil (638 m g, 33% of th e-
ory, 52% based on recovered allylic alcoh ol). Con tin ued elution with a m ixture of h exan es
an d AcOEt (75:25) gave th e startin g allylic alcoh ol 9c (440 m g, 35% recovered). 1H NMR
(400.1 MHz, CDCl3): 1.49 (s, 9 H, t-Bu), 3.86 (s, 3 H, CH3O), 3.87 (s, 3 H, CH3O), 4.69 (dd,
4
3
3
3J1-H,2-H = 6.6, J1-H,3-H = 1.1, 2 H, 1-H), 6.15 (dt, J2-H,3-H = 15.8, J2-H,1-H = 6.6, 1 H, 2-H),
3
4
3
6.59 (dt, J3-H,2-H = 15.8, J3-H,1-H = 1.1, 1 H, 3-H), 6.80 (d, J5′-H,6′-H = 8.1, 1 H, 5′-H), 6.91
(dd, J6′-H,5′-H = 8.1, J6′-H,2′-H = 1.9, 1 H, 6′-H), 6.93 (d, J2′-H,6′-H = 1.9, 1 H, 2′-H). 13C NMR
(100.6 MHz, CDCl3): 27.71 (C(CH3)3), 55.73 an d 55.81 (CH3O), 67.56 (CH2-1), 82.07
(C(CH3)3), 108.81 (CH-2′), 110.94 (CH-5′), 119.97 (CH-6′), 120.78 (CH-2), 129.16 (C-1′),
134.39 (CH-3), 148.93 an d 149.12 (C-arom ), 153.30 (CO carbon ate). IR (n eat): 2979 (w),
1739 (s, CO carbon ate), 1515 (m ), 1369 (m ), 1269 (s), 1256 (s), 1160 (s), 1027 (m ), 966 (m ),
856 (m ). MS (EI, 150 °C), m/z (%): 295 (MH+, 10), 294 (M+, 50), 238 (M+ – (CH3)2C=CH2,
3
4
4
100), 224 (32), 193 (MH+ – (CH3)2C=CH2 – CO2, 15), 177 (MH+ – (CH3)2C=CH2 – CO2
H2O, 100). HRMS (EI): 294.1466 (C16H22O5 (M+) requires 294.1467). For C16H22O5 calcu-
lated: 65.29% C, 7.53% H; foun d: 65.14% C, 7.67% H.
–
tert-Butyl (E)-3-(4′-methylphenyl)prop-2-en-1-yl carbonate (4d). A flask con tain in g 4-iodotoluen e
(109 m g, 0.50 m m ol), boron ic acid 15 (151 m g, 0.75 m m ol), K2CO3 (187 m g, 1.35 m m ol)
an d (PPh 3)4Pd (57.0 m g, 0.049 m m ol) was sealed, th ree tim es evacuated an d backfilled with
argon . DME (5 m l) an d water (0.7 m l) were th en added an d th e reaction m ixture was stirred
at 85 °C for 20 h . Th e resultin g solution was co-distilled th ree tim es with toluen e an d th e
residue was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with a m ixture of h ex-
an es an d AcOEt (100:0 to 97:3) to afford 4d as a colorless oil (76 m g, 61%). Th e crude prod-
uct obtain ed usin g procedure B was ch rom atograph ed on a colum n of silica gel (3 × 10 cm )
with a m ixture of h exan es an d AcOEt (100:0 to 97:3) to furn ish 4d as a colorless oil (89 m g,
3
36%). 1H NMR (400.1 MHz, CDCl3): 1.51 (s, 9 H, t-Bu), 2.34 (s, 3 H, CH3), 4.71 (dd, J1-H,2-H
=
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

722
Štambaský, Malkov, Kočovský:
4
3
3
6.6, J1-H,3-H = 1.3, 2 H, 1-H), 6.25 (dt, J2-H,3-H = 15.9, J2-H,1-H = 6.6, 1 H, 2-H), 6.64 (dt,
3J3-H,2-H = 15.9, J3-H,1-H = 1.3, 1 H, 3-H), 7.13 (d, J3′-H,2′-H = 8.1, 2 H, 3′-H), 7.29 (d, J2′-H,3′-H
=
4
3
3
8.1, 2 H, 2′-H). 13C NMR (100.6 MHz, CDCl3): 21.22 (CH3), 27.76 (C(CH3)3), 67.63 (CH2-1),
82.16 (C(CH3)3), 121.73 (CH-2), 126.54 (CH-2′), 129.26 (CH-3′), 133.36 (C-1′), 134.48
(CH-3), 137.97 (C-4′), 153.33 (CO carbon ate). IR (n eat): 2979 (m ), 1736 (s, CO carbon ate),
1453 (m ), 1368 (m ), 1273 (s), 1155 (s). MS (CI-NH3, 150 °C), m/z (%): 266 (M + NH4+, 35),
165 ([M + NH4+] – Boc, 30), 148 (M + H+ – Boc, 45), 131 (40), 52 (100). For C15H20O3 calcu-
lated: 72.55% C, 8.12% H; foun d: 72.25% C, 7.98% H.
tert-Butyl (E)-3-(2′,4′-dimethylphenyl)prop-2-en-1-yl carbonate (4e). Th e crude product obtain ed
by procedure C was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with a m ixture
of h exan es an d AcOEt (95:5) to give 4e as a yellowish oil (27 m g, 11%). Th e crude product
obtain ed by procedure D was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with
h exan es to yield th e correspon din g stilben e derivate (123 m g); con tin ued elution with a
m ixture of h exan es an d AcOEt (98.5:1.5) gave 4e as a colorless oil (150 m g, 52%). Th e crude
product obtain ed by procedure E was ch rom atograph ed on a colum n of silica gel (5 × 15 cm )
with a m ixture of h exan es an d AcOEt (98.5:1.5) to produce 4e as a colorless oil (3.60 g,
68%). 1H NMR (400.1 MHz, CDCl3): 1.50 (s, 9 H, t-Bu), 2.30 (s, 3 H, CH3), 2.31 (s, 3 H,
3
4
3
3
CH3), 4.72 (dd, J1-H,2-H = 6.6, J1-H,3-H = 1.2, 2 H, 1-H), 6.14 (dt, J2-H,3-H = 15.7, J2-H,1-H
=
3
4
6.6, 1 H, 2-H), 6.85 (dt, J3-H,2-H = 15.7, J3-H,1-H = 1.2, 1 H, 3-H), 6.97 (s, 1 H, 3′-H), 6.98 (d,
JHH = 7.6, H-arom ), 7.34 (d, JHH = 7.6, H-arom ). 13C NMR (100.6 MHz, CDCl3): 19.63 (CH3),
21.06 (CH3), 27.78 (C(CH3)3), 67.84 (CH2-1), 82.12 (C(CH3)3), 123.19 (CH-2), 125.79 an d
126.83 (CH-arom ), 131.04 (CH-3′), 132.41 (CH-3), 132.44, 135.53 an d 137.74 (C-arom ),
153.35 (CO carbon ate). IR (n eat): 2980 (m ), 2932 (m ), 1742 (s, CO carbon ate), 1613 (w),
1369 (s), 1276 (s), 1254 (s), 1162 (s), 1089 (m ), 858 (m ). MS (CI-NH3, 150 °C), m/z (%): 508
(2), 468 ([2 M + NH4+] – t-BuOH, 5), 386 ([2 M + NH4+] – t-BuOH – CO2, 4), 280 ([M +
NH4+], 3), 179 ([M + NH4+] – Boc, 3), 162 (MH+ – Boc, 5), 145 (MH+ – Boc – OH, 42), 52
(100). For C16H22O3 calculated: 73.25% C, 8.45% H; foun d: 73.18% C, 8.48% H.
tert-Butyl (E)-3-(4′-bromophenyl)prop-2-en-1-yl carbonate (4f). Th e crude product obtain ed by
procedure B was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with a m ixture of
h exan es an d AcOEt (99:1) to afford 4f as wh ite crystals (113 m g, 33%): m .p. 57–58 °C.
3
4
1H NMR (400.1 MHz, CDCl3): 1.50 (s, 9 H, t-Bu), 4.70 (dd, J1-H,2-H = 6.4, J1-H,3-H = 1.3, 2 H,
3
3
3
4
1-H), 6.28 (dt, J2-H,3-H = 15.9, J2-H,1-H = 6.4, 1 H, 2-H), 6.60 (dt, J3-H,2-H = 15.9, J3-H,1-H
=
3
3
1.3, 1 H, 3-H), 7.24 (d, Ja-H,b-H = 8.4, 2 H, Ha-arom ), 7.44 (d, Jb-H,a-H = 8.4, 2 H, Hb-arom ).
13C NMR (100.6 MHz, CDCl3): 27.75 (C(CH3)3), 67.13 (CH2-1), 82.30 (C(CH3)3), 121.88
(C-4′), 123.73 (CH-2), 128.10 (CaH-arom ), 131.68 (CbH-arom ), 132.98 (CH-3), 135.10 (C-1′),
153.24 (CO carbon ate). IR (CHCl3): 2983 (m ), 1740 (s, CO carbon ate), 1487 (m ), 1370 (m ),
1277 (s), 1256 (s), 1216 (s), 1157 (s), 1073 (m ), 845 (m ), 755 (s). MS (CI-NH3, 150 °C), m/z
(%): 642/644/646 ([2 M + NH4+], 10), 524/526/528 ([2 M + NH4+] – t-BuOH – CO2, 65),
330/332 ([M + NH4+], 100), 229/231 ([M + NH4+] – Boc, 35), 212/214 (MH+ – Boc, 15),
195/197 (MH+ – Boc – OH, 4), 52 (43). For C14H17BrO3 calculated: 53.69% C, 5.47% H;
foun d: 53.60% C, 5.47% H.
tert-Butyl (E)-3-(2′-fluorophenyl)prop-2-en-1-yl carbonate (4g). Th e crude product obtain ed
by procedure C was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with a m ixture
of h exan es an d AcOEt (100:00 to 98.5:1.5) to give 4g as a colorless oil (25 m g, 10%). Th e
crude product obtain ed by procedure D was ch rom atograph ed on a colum n of silica gel (3 ×
10 cm ) with h exan es to yield th e correspon din g stilben e derivate (17 m g); con tin ued elution
with a m ixture of h exan es an d AcOEt (98.5:1.5) provided 4g as a colorless oil (70 m g, 29%).
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

Preparation of Boc-Protected Cinnamyl-Type Alcohols
723
3
4
1H NMR (400.1 MHz, CDCl3): 1.51 (s, 9 H, t-Bu), 4.74 (dd, J1-H,2-H = 6.3, J1-H,3-H = 1.4, 2 H,
3
3
3
4
1-H), 6.38 (dt, J2-H,3-H = 16.1, J2-H,1-H = 6.3, 1 H, 2-H), 6.82 (dt, J3-H,2-H = 16.1, J3-H,1-H
=
3
3
4
1.4, 1 H, 3-H), 7.03 (ddd, JHF4 = 10.7, J3′-H,4′-H = 8.2, J3′-H,5′-H = 1.2, 1 H, 3′-H), 7.10 (dt,
3J5′-H,4′-H = 7.6, J5′-H,6′-H = 7.6, J5′-H,3′-H = 1.2, 1 H, 5′-H), 7.22 (ddd, J4′-H,3′-H = 8.2, J4′-H,5′-H
=
3
3
3
7.6, J4′-H,6′-H = 1.8, 1 H, 4′-H), 7.45 (dd, J6′-H,5′-H = 7.6, J6′-H,4′-H = 1.8, 1 H, 6′-H). 13C NMR
4
3
4
2
(100.6 MHz, CDCl3): 27.76 (C(CH3)3), 67.47 (CH2-1), 82.30 (C(CH3)3), 115.75 (d, JCF = 22.1,
CH-3′), 123.97 (d, JCF = 12.1, C-1′), 124.10 (d, JCF = 3.6, CH-5′), 125.55 (d, JCF = 5.1,
CH-2), 126.63 (d, JCF = 3.6, CH-3), 127.61 (d, JCF = 3.6, CH-6′), 129.34 (d, JCF = 8.8,
CH-4′), 153.28 (CO carbon ate), 160.34 (d, JCF = 250.3, CF-2′). 19F NMR (376.5 MHz, CDCl3):
2
4
4
3
3
3
1
–118.21. IR (CHCl3): 2979 (m ), 1743 (s, CO carbon ate), 1489 (m ), 1457 (m ), 1370 (m ), 1256
(s), 1163 (s), 969 (m ), 858 (m ), 755 (m ). MS (CI-NH3, 150 °C), m/z (%): 522 ([2 M – NH4+],
1), 404 ([2 M + NH4+] – t-BuOH – CO2, 3), 270 ([M + NH4+], 95), 214 ([M + NH4+] –
CH2=C(CH3)2, 20), 169 ([M + NH4+] – Boc, 20), 152 (MH+ – Boc, 22), 135 (MH+ – Boc – OH,
5), 52 (100). For C14H17FO3 calculated: 66.65% C, 6.79% H; foun d: 66.77% C, 6.91% H.
tert-Butyl (E)-3-(3′-fluorophenyl)prop-2-en-1-yl carbonate (4h ). Th e crude product obtain ed by
procedure C was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with a m ixture of
h exan es an d AcOEt (99.2:0.8) to furn ish 4h as a yellowish oil (103 m g, 40%). 1H NMR
3
4
(400.1 MHz, CDCl3): 1.50 (s, 9 H, t-Bu), 4.72 (dd, J1-H,2-H = 6.3, J1-H,3-H = 1.3, 2 H, 1-H),
3
3
3
4
6.29 (dt, J2-H,3-H = 15.9, J2-H,1-H = 6.3, 1 H, 2-H), 6.63 (dt, J3-H,2-H = 15.9, J3-H,1-H = 1.3,
1 H, 3-H), 6.94 (dddd, JHF = 8.5, J4′-H,5′-H = 8.4, J4′-H,6′-H = 2.5, J4′-H,2′-H = 0.9, 1 H, 4′-H),
3
3
4
4
3
4
4
3
7.08 (ddd, J2′-H,F = 10.1, J2′-H,4′-H = 2.5, J2′-H,6′-H = 1.9, 1 H, 2′-H), 7.14 (ddd, J6′-H,5′-H = 7.8,
4J6′-H,2′-H = 1.9, J6′-H,4′-H = 0.9, 1 H, 6′-H), 7.27 (ddd, J5′-H,4′-H = 8.4, J5′-H,6′-H = 7.8, J5′-H,F
=
4
3
3
4
6.0, 1 H, 5′-H). 13C NMR (100.6 MHz, CDCl3): 27.75 (C(CH3)3), 67.02 (CH2-1), 82.35
2
2
4
(C(CH3)3), 113.06 (d, JCF = 21.8, CH-2′), 114.84 (d, JCF = 21.4, CH-4′), 122.50 (d, JCF = 2.8,
3
4
CH-6′), 124.38 (CH-2), 130.02 (d, JCF = 8.5, CH-5′), 132.93 (d, JCF = 2.5, CH-3), 138.51
(d, JCF = 7.8, C-1′), 153.25 (CO carbon ate), 163.00 (d, JCF = 245.4, CF-3′). 19F NMR
(376.5 MHz, CDCl3): –113.84. IR (CHCl3): 2980 (m ), 1741 (s, CO carbon ate), 1584 (m ), 1370
(m ), 1276 (s), 1255 (s), 1161 (s), 1117 (m ), 966 (m ), 859 (m ). MS (CI-NH3, 150 °C), m/z (%):
522 ([2 M + NH4+], 15), 404 ([2 M + NH4+] – t-BuOH – CO2, 25), 386 (10), 310 (10), 270
([M + NH4+], 100), 169 ([M + NH4+] – Boc, 5), 152 (MH+ – Boc, 5), 135 (MH+ – Boc – OH, 2),
52 (5). For C14H17FO3 calculated: 66.65% C, 6.79% H; foun d: 66.49% C, 6.81% H.
3
1
tert-Butyl (E)-3-(4′-fluorophenyl)prop-2-en-1-yl carbonate (4i). Th e crude product obtain ed by
procedure C was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with a m ixture of
h exan es an d AcOEt (99:1) to give 4i as a yellowish oil (72 m g, 29%). Th e crude product ob-
tain ed by procedure E was ch rom atograph ed on a colum n of silica gel (5 × 15 cm ) with a
m ixture of h exan es an d AcOEt (100:0 to 98.5:1.5) to afford 4i as a colorless oil (3.273 g,
3
4
65%). 1H NMR (400.1 MHz, CDCl3): 1.50 (s, 9 H, t-Bu), 4.70 (dd, J1-H,2-H = 6.5, J1-H,3-H
=
3
3
3
1.2, 2 H, 1-H), 6.21 (dt, J2-H,3-H = 15.9, J2-H,1-H = 6.5, 1 H, 2-H), 6.63 (dt, J3-H,2-H = 15.9,
4J3-H,1-H = 1.2, 1 H, 3-H), 6.94 (dd, J3′-H,2′-H = 8.8, J3′-H,F = 8.7, 2 H, 3′-H an d 5′-H), 7.28 (dd,
3
3
4J2′-H,F = 5.4, J2′-H,3′-H = 8.8, 2 H, 2′-H an d 6′-H). 13C NMR (100.6 MHz, CDCl3): 27.76
3
2
6
(C(CH3)3), 67.32 (CH2-1), 82.26 (C(CH3)3), 115.51 (d, JCF = 21.7, CH-3′), 122.64 (d, JCF
2.2, CH-2), 128.19 (d, JCF = 8.1, CH-2′), 132.34 (d, JCF = 3.2, C-1′), 133.23 (CH-3), 153.30
(CO carbon ate), 162.56 (d, JCF = 247.6, CF-4′). 19F NMR (376.5 MHz, CDCl3): –114.15. IR
=
3
4
1
(n eat): 2981 (m ), 2936 (w), 1740 (s, CO carbon ate), 1601 (m ), 1510 (s, CF), 1370 (m ), 1275
(s), 1255 (s), 1159 (s), 850 (m ). MS (CI-NH3, 150 °C), m/z (%): 522 ([2 M + NH4+], 10), 404
([2 M + NH4+] – t-BuOH – CO2, 100), 348 (10), 270 ([M + NH4+], 40), 169 ([M + NH4+] – Boc,
7), 152 (MH+ – Boc, 9), 135 (MH+ – Boc – OH, 8), 52 (1). For C14H17FO3 calculated: 66.65% C,
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

724
Štambaský, Malkov, Kočovský:
6.79% H; foun d: 66.39% C, 6.95% H. Th e crude product obtain ed by procedure D was ch ro-
m atograph ed on a colum n of silica gel (3 × 10 cm ) with h exan es to yield th e correspon din g
stilben e derivate (73 m g); con tin ued elution with a m ixture of h exan es an d AcOEt (100:0 to
98.5:1.5) gave 4i as a colorless oil (65 m g, 27%).
tert-Butyl (E)-3-(2′,4′-difluorophenyl)prop-2-en-1-yl carbonate (4j). Th e crude product obtain ed
by procedure C was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with a m ixture
of h exan es an d AcOEt (99:1 to 98.5:1.5) to afford 4j as a yellowish oil (31 m g, 11%). Th e
crude product obtain ed by procedure E was ch rom atograph ed on a colum n of silica gel (5 ×
15 cm ) with a m ixture of h exan es an d AcOEt (100:0 to 98.5:1.5) to furn ish 4j as a colorless
3
oil (4.32 g, 80%). 1H NMR (400.1 MHz, CDCl3): 1.50 (s, 9 H, t-Bu), 4.72 (dd, J1-H,2-H = 6.3,
3
3
3
4J1-H,3-H = 1.1, 2 H, 1-H), 6.31 (dt, J2-H,3-H = 16.1, J2-H,1-H = 6.3, 1 H, 2-H), 6.74 (dt, J3-H,2-H
=
4
3
4
16.1, J3-H,1-H = 1.1, 1 H, 3-H), 6.79 (ddd, JHF = 11.4 an d 10.8, J3′-H,5′-H = 2.4, 1 H, 3′-H),
6.84 (dddd, JHF = 11.3, J5′-H,6′-H = 8.7, J5′-H,3′-H = 2.4, JHF = 1.0, 1 H, 5′-H), 7.41 (ddd,
3J6′-H,5′-H = 8.7, JHF = 8.5 an d 6.4, 1 H, 6′-H). 13C NMR (100.6 MHz, CDCl3): 27.77
(C(CH3)3), 67.35 (CH2-1), 82.37 (C(CH3)3), 104.09 (t, JCF = 25.6, CH-3′), 111.52 (dd, JCF
21.5, JCF = 3.6, CH-5′), 125.23 (dd, JCF = 5.1, JCF = 2.1, CH-2), 125.74 (dd, JCF = 2.9, JCF
1.5, C-3), 128.48 (dd, JCF = 9.5 an d 5.2, CH-6′), 137.50 (d, JCF = 25.6, C-1′), 153.26 (CO
carbon ate), 162.40 (d, JCF = 250.1, CF), 162.52 (d, JCF 250.2, CF). 19F NMR (376.5 MHz,
CDCl3): –110.66 (d, JFF = 7.9), –113.92 (d, JFF = 7.9). IR (n eat): 2981 (m ), 2934 (m ), 1742 (s,
CO carbon ate), 1615 (m ), 1503 (s, CF), 1370 (m ), 1275 (s), 1255 (s), 1161 (s), 966 (m ),
853 (m ). MS (CI-NH3, 150 °C), m/z (%): 288 ([M + NH4+], 30), 187 ([M + NH4+] – Boc, 5),
170 ([M + NH4+] – t-BuOH – CO2, 5), 153 ([M + NH4+] – t-BuOH – CO2 – NH3, 5), 52 (100).
For C14H16F2O3 calculated: 62.22% C, 5.97% H; foun d: 62.35% C, 6.15% H.
3
3
4
5
4
2
2
=
=
4
4
6
3
5
3
2
1
1
4
4
tert-Butyl (E)-3-(3′-methoxyphenyl)prop-2-en-1-yl carbonate (4k). Th e crude product obtain ed
by procedure C was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with a m ixture
of h exan es an d AcOEt (99.2:0.8) to give iodo-3-m eth oxyben zen e 5k (366 m g, 51% recov-
ered). Con tin ued elution with a m ixture of h exan es an d AcOEt (98.5:1.5) furn ish ed 4k as a
yellowish oil (73 m g, 25%). 1H NMR (400.1 MHz, CDCl3): 1.50 (s, 9 H, t-Bu), 3.81 (s, 3 H,
3
4
3
3
CH3O), 4.72 (dd, J1-H,2-H = 6.4, J1-H,3-H = 1.3, 2 H, 1-H), 6.29 (dt, J2-H,3-H = 15.9, J2-H,1-H
=
3
3
4
6.4, 1 H, 2-H), 6.64 (d, J3-H,2-H = 15.9, 1 H, 3-H), 6.82 (ddd, J4′-H,5′-H = 8.1, J4′-H,2′-H = 2.5,
4J4′-H,6′-H = 0.9, 1 H, 4′-H), 6.92 (dd, J2′-H,4′-H = 2.5, J2′-H,6′-H = 1.7, 1 H, 2′-H), 6.98 (ddd,
4
4
3J6′-H,5′-H = 7.9, J6′-H,2′-H = 1.7, J6′-H,4′-H = 0.9, 1 H, 6′-H), 7.24 (dd, J5′-H,4′-H = 8.1, J5′-H,6′-H
=
4
4
3
3
7.9, 1 H, 5′-H). 13C NMR (100.6 MHz, CDCl3): 27.77 (C(CH3)3), 55.18 (CH3O), 67.35
(CH2-1), 82.22 (C(CH3)3), 111.83 (CH-2′), 113.77 (CH-4′), 119.30 (CH-6′), 123.22 (CH-2),
129.54 (CH-5′), 134.22 (CH-3), 137.62 (C-1′), 153.31 (CO carbon ate), 159.76 (CH-3′). IR
(n eat): 2979 (m ), 2938 (m ), 1740 (s, CO carbon ate), 1598 (m ), 1580 (m ), 1369 (m ), 1275 (s),
1255 (s), 1159 (s), 857 (m ). MS (CI-NH3, 150 °C), m/z (%): 546 ([2 M + NH4+], 18), 428
([2 M + NH4+] – t-BuOH – CO2, 63), 282 ([M + NH4+], 100), 181 ([M + NH4+] – Boc, 45), 164
(MH+ – Boc, 40), 147 (MH+ – Boc – OH, 10), 52 (25). For C15H20O4 calculated: 68.16% C,
7.63% H; foun d: 68.03% C, 7.80% H.
tert-Butyl (E)-3-(3′-nitrophenyl)prop-2-en-1-yl carbonate (4l). Th e crude product obtain ed by
procedure B was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with a m ixture of
h exan es an d AcOEt (98.5:1.5) to afford iodo-3-n itroben zen e 5l (562 m g, 73% recovered).
Con tin ued elution with a m ixture of h exan es an d AcOEt (97.5:2.5) furn ish ed 4l as a yellow-
ish oil (134 m g, 43% of th eory, 57% based on th e recovered iodide): 1H NMR (400.1 MHz,
3
4
CDCl3): 1.49 (s, 9 H, t-Bu), 4.74 (dd, J1-H,2-H = 6.0, J1-H,3-H = 1.4, 2 H, 1-H), 6.42 (dt,
3J2-H,3-H = 16.0, J2-H,1-H = 6.0, 1 H, 2-H), 6.70 (dt, J3-H,2-H = 16.0, J3-H,1-H = 1.4, 1 H, 3-H),
3
3
4
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

Preparation of Boc-Protected Cinnamyl-Type Alcohols
725
3
3
3
4
7.48 (dd, J5′-H,4′-H = 8.1, J5′-H,6′-H = 7.8, 1 H, 5′-H), 7.67 (ddd, J6′-H,5′-H = 7.8, J6′-H,2′-H = 1.8,
4J6′-H,4′-H = 0.9, 1 H, 6′-H), 8.08 (ddd, J4′-H,5′-H = 8.1, J4′-H,2′-H = 2.2, J4′-H,6′-H = 0.9, 1 H,
3
4
4
4′-H), 8.21 (dd, J2′-H,4′-H = 2.2, J2′-H,6′-H = 1.8, 1 H, 2′-H). 13C NMR (100.6 MHz, CDCl3):
27.69 (C(CH3)3), 66.53 (CH2-1), 82.45 (C(CH3)3), 121.14 (CH-2′), 122.49 (CH-4′), 126.40
(CH-2), 129.48 (C-5′), 131.23 (CH-3), 132.27 (C-6′), 137.93 (C-1′), 148.52 (C-3′), 153.13 (CO
carbon ate). IR (n eat): 2981 (m ), 2935 (m ), 1742 (s, CO carbon ate), 1531 (s, C-N), 1369 (m ,
N-O), 1351 (s, N-O), 1276 (s), 1255 (s), 1160 (s), 966 (m ), 859 (m ), 732 (m ). MS (CI-NH3,
150 °C), m/z (%): 576 ([2 M + NH4+], 5), 458 ([2 M + NH4+] – t-BuOH – CO2, 1), 297 ([M +
NH4+], 100), 241 (3), 52 (23). For C14H17NO5 calculated: 60.21% C, 6.14% H, 5.02% N;
foun d: 60.13% C, 6.15% H, 4.88% N.
4
4
tert-Butyl (E)-3-(3′,5′-dimethylphenyl)prop-2-en-1-yl carbonate (4m ). Th e crude product ob-
tain ed by procedure C was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with a
m ixture of h exan es an d AcOEt (99:1) to yield 3,5-dim eth yliodoben zen e 5m (252 m g, 35%
recovered). Con tin ued elution with a m ixture of h exan es an d AcOEt (99:1) afforded 4m as
a yellowish oil (87 m g, 33%). 1H NMR (400.1 MHz, CDCl3): 1.51 (s, 9 H, t-Bu), 2.31 (s, 6 H,
3
4
3
3
CH3), 4.71 (dd, J1-H,2-H = 6.5, J1-H,3-H = 1.2, 2 H, 1-H), 6.27 (dt, J2-H,3-H = 15.9, J2-H,1-H
=
3
4
6.5, 1 H, 2-H), 6.61 (dt, J3-H,2-H = 15.9, J3-H,1-H = 1.2, 1 H, 3-H), 6.91 (s, 1 H, 4′-H), 7.02 (s,
2 H, 2′-H an d 6′-H). 13C NMR (100.6 MHz, CDCl3): 21.19 (CH3), 27.76 (C(CH3)3), 67.55
(CH2-1), 82.09 (C(CH3)3), 122.44 (CH-2′), 124.52 (CH-2′ an d CH-6′), 129.77 (CH-4′), 134.64
(CH-3), 136.08 (C-1′), 137.98 (C-3′ an d C-5′), 153.35 (CO carbon ate). IR (n eat): 2979 (m ),
2920 (w), 1740 (s, CO carbon ate), 1602 (w), 1369 (m ), 1274 (s), 1254 (s), 1163 (s), 853 (m ).
MS (CI-NH3, 150 °C), m/z (%): 542 ([2 M + NH4+], 15), 424 ([2 M + NH4+] – t-BuOH – CO2,
100), 280 ([M + NH4+], 42), 179 ([M + NH4+] – Boc, 40), 162 (MH+ – Boc, 52), 145 (MH+
–
Boc – OH, 30), 52 (30). For C16H22O3 calculated: 73.25% C, 8.45% H; foun d: 73.06% C,
8.39% H.
tert-Butyl (E)-3-(naphthalen-1′-yl)prop-2-en-1-yl carbonate (4n ). Th e crude product obtain ed
by procedure C was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with a m ixture
of h exan es an d AcOEt (99:1) to give 1-iodon aph th alen e 5n (629 m g, 81% recovered). Con -
tin ued elution with a m ixture of h exan es an d AcOEt (98.5:1.5) afforded 4n as a yellowish oil
(93 m g, 32% of th eory, 56% based on th e recovered iodide). 1H NMR (400.1 MHz, CDCl3):
3
4
3
1.54 (s, 9 H, t-Bu), 4.85 (dd, J1-H,2-H = 6.4, J1-H,3-H = 1.3, 2 H, 1-H), 6.34 (dt, J2-H,3-H = 15.6,
3J2-H,1-H = 6.4, 1 H, 2-H), 7.44 (dt, J3-H,2-H = 15.6, J3-H,1-H = 1.3, 1 H, 3-H), 7.46 (m , 1 H,
3
4
3′-H), 7.50 (m , 1 H, 6′-H), 7.52 (m , 1 H, 8′-H), 7.61 (d, JHH = 7.2, 1 H, 4′-H), 7.81 (d, JHH
8.2, 1 H, 2′-H), 7.86 (dd, JHH = 7.71, J6′-H,8′-H = 2.0, 1 H, 6′-H), 8.11 (dd, JHH = 7.2, J8′-H,6′-H
=
=
4
4
2.0, 1 H, 8′-H). 13C NMR (100.6 MHz, CDCl3): 27.77 (C(CH3)3), 67.52 (CH2-1), 82.23
(C(CH3)3), 123.68 (CH-7′), 124.12 (CH-4′), 125.51 (CH-2), 125.79 (CH-8′), 126.11 an d 126.12
(CH-3′ an d CH-6′), 128.33 (CH-2′), 128.47 (CH-5′), 131.07 (C-10′), 131.64 (CH-3), 133.50
(C-1′), 133.95 (C-9′), 153.35 (CO carbon ate). IR (n eat): 2979 (m ), 1740 (s, CO carbon ate),
1369 (m ), 1276 (s), 1254 (s), 1160 (s), 857 (m ), 791 (m ), 777 (m ). MS (CI-NH3, 150 °C), m/z
(%): 586 ([2 M + NH4+], 10), 468 ([2 M + NH4+] – t-BuOH – CO2, 65), 302 ([M + NH4+], 30),
201 ([M + NH4+] – Boc, 25), 184 (MH+ – Boc, 25), 167 (MH+ – Boc – OH, 100), 52 (10). For
C
18H20O3 calculated: 76.03% C, 7.09% H; foun d: 76.16% C, 6.92% H.
tert-Butyl (E)-3-(thiophen-2′-yl)prop-2-en-1-yl carbonate (4o). Th e crude product obtain ed by
procedure C was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with a m ixture of
h exan es an d AcOEt (99:1) to yield 4o as a yellowish oil (77 m g, 31%). Th e crude product
obtain ed by procedure E was ch rom atograph ed on a colum n of silica gel (5 × 15 cm ) with a
m ixture of h exan es an d AcOEt (100:0 to 99:1) to produce 4o as a colorless oil (3.07 g, 64%).
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

726
Štambaský, Malkov, Kočovský:
3
4
1H NMR (400.1 MHz, CDCl3): 1.50 (s, 9 H, t-Bu), 4.67 (dd, J1-H,2-H = 6.5, J1-H,3-H = 1.3, 2 H,
3
3
3
4
1-H), 6.12 (dt, J2-H,3-H = 15.7, J2-H,1-H = 6.5, 1 H, 2-H), 6.79 (dt, J3-H,2-H = 15.7, J3-H,1-H
1.3, 1 H, 3-H), 6.96 (dd, J4′-H,5′-H = 5.0, J4-H,3′-H = 3.6, 1 H, 4′-H), 6.99 (dd, J3′-H,4′-H = 3.6,
=
3
3
3
4J3′-H,5′-H = 1.1, 1 H, 3′-H), 7.18 (dd, J5′-H,4′-H = 5.0, J5′-H,3′-H = 1.1, 1 H, 5′-H). 13C NMR
(100.6 MHz, CDCl3): 27.75 (C(CH3)3), 67.08 (CH2-1), 82.23 (C(CH3)3), 122.29 (CH-2), 124.94
(CH-5′), 126.50 (CH-3′), 127.34 (CH-4′), 127.53 (CH-3), 141.13 (C-1′), 153.26 (CO carbon -
ate). IR (n eat): 2980 (m ), 2933 (w), 1741 (s, CO carbon ate), 1650 (w), 1369 (m ), 1274 (s),
1254 (s), 1161 (s), 956 (m ), 857 (m ), 700 (m ). MS (CI-NH3, 150 °C), m/z (%): 380 ([2 M +
NH4+] – t-BuOH – CO2, 1), 258 ([M + NH4+], 5), 157 ([M + NH4+] – Boc, 5), 140 (MH+ – Boc,
5), 123 (MH+ – Boc – OH, 25), 52 (100). For C12H16O3S calculated: 59.97% C, 6.71% H;
foun d: 59.75% C, 6.96% H.
3
4
tert-Butyl (E)-3-(thiophen-3′-yl)prop-2-en-1-yl carbonate (4p ). Th e crude product obtain ed by
procedure C was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with a m ixture of
h exan es an d AcOEt (99:1) to afford 4p as a yellowish oil (110 m g, 44%). 1H NMR (400.1 MHz,
3
4
CDCl3): 1.50 (s, 9 H, t-Bu), 4.68 (dd, J1-H,2-H = 6.6, J1-H,3-H = 1.3, 2 H, 1-H), 6.14 (dt,
3J2-H,3-H = 15.8, J2-H,1-H = 6.6, 1 H, 2-H), 6.67 (ddt, J3-H,2-H = 15.8, J3-H,1-H = 1.3, J3-H,4′-H
=
3
3
4
4
4
4
3
0.6, 1 H, 3-H), 7.19 (dd, J2′-H,4′-H = 2.9, J2′-H,5′-H = 1.3, 1 H, 2′-H), 7.20 (dd, J5′-H,4′-H = 5.1,
3
4
4
4J5′-H,2′-H = 1.3, 1 H, 5′-H), 7.27 (ddd, J4′-H,5′-H = 5.1, J4′-H,2′-H = 2.9, J4′-H,3-H = 0.6, 1 H,
4′-H). 13C NMR (100.6 MHz, CDCl3): 27.73 (C(CH3)3), 67.40 (CH2-1), 82.15 (C(CH3)3),
122.59 (CH-2), 123.10 (CH-2′), 124.91 (CH-5′), 126.13 (CH-4′), 128.62 (CH-3), 138.78 (C-3′),
153.27 (CO carbon ate). IR (NaCl, n eat): 2981 (m ), 1741 (s, CO carbon ate), 1369 (m ), 1275 (s),
1254 (s), 1163 (s). MS (EI, 150 °C), m/z (%): 240 (M+, 5), 205 (20), 184 (M+ – (CH3)2C=CH2,
50), 166 (M+ – t-BuOH, 100), 140 (M+ – (CH3)2C=CH2 – CO2, 20), 123 (30), 121 (40), 119 (25),
83 (40). HRMS (EI): 240.0822 (C12H16O3S (M+) requires 240.0820).
tert-Butyl (E)-3-(pyridne-3′-yl)prop-2-en-1-yl carbonate (4q). Th e crude product obtain ed by
procedure C was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with a m ixture of
h exan es an d AcOEt (60:40) to furn ish 4q as a brown oil (44 m g, 18%). Th e crude product
obtain ed by procedure E was ch rom atograph ed on a colum n of silica gel (5 × 15 cm ) with
AcOEt to afford 4q as a brown oil (2.22 g, 48%). 1H NMR (400.1 MHz, CDCl3): 1.45 (s, 9 H,
3
4
3
3
t-Bu), 4.68 (dd, J1-H,2-H = 6.2, J1-H,3-H = 1.4, 2 H, 1-H), 6.31 (dt, J2-H,3-H = 16.0, J2-H,1-H
=
3
4
3
6.2, 1 H, 2-H), 6.60 (dt, J3-H,2-H = 16.0, J3-H,1-H = 1.4, 1 H, 3-H), 7.19 (dd, J5′-H,4′-H = 8.0,
3J5′-H,6′-H = 4.8, 1 H, 5′-H), 7.64 (ddd, J4′-H,5′-H = 8.0, J4′-H,2′-H = 2.1, J4′-H,6′-H = 1.6, 1 H,
3
4
4
3
4
4
4′-H), 8.43 (dd, J6′-H,5′-H = 4.8, J6′-H,4′-H = 1.6, 1 H, 6′-H), 8.55 (d, J2′-H,4′-H = 2.1, 1 H, 2′-H).
13C NMR (100.6 MHz, CDCl3): 27.62 (C(CH3)3), 66.77 (CH2-1), 82.26 (C(CH3)3), 123.31
(CH-5′), 125.26 (CH-2), 130.20 (CH-3), 131.68 (C-3′), 132.87 (CH-4′), 148.34 (CH-2′), 148.93
(CH-6′), 153.08 (CO carbon ate). IR (n eat): 2980 (w), 1744 (s, CO carbon ate), 1280 (s), 1255
(m ), 1161 (m ). MS (EI, 150 °C), m/z (%): 236 (MH+, 100), 180 (MH+ – (CH3)2C=CH2, 20), 120
(10), 118 (MH+ – (CH3)2C=CH2 – H2O, 10). HRMS (EI): 236.1289 (C13H18O3N (MH+) requires
236.1287). For C13H17NO3 calculated: 66.36% C, 7.28% H, 5.95% N; foun d: 66.03% C,
7.35% H, 5.89% N.
Methyl 2-acetoxy-5-(E)-3′-tert-butoxycarbonyloxyprop-1′-en-1′-yl benzoate (4r). Th e crude prod-
uct obtain ed by procedure B was ch rom atograph ed on a colum n of silica gel (3 × 10 cm )
with a m ixture of h exan es an d AcOEt (98.5:1.5) to yield th e deacetylated iodide (192 m g);
con tin ued elution with a 95:5 m ixture gave th e startin g iodide 5r (195 m g, 20% recovered).
Fin ally elution with a 90:10 m ixture afforded 4r (84 m g, 22%) as a yellow oil. 1H NMR
(400.1 MHz, CDCl3): 1.48 (s, 9 H, t-Bu), 2.32 (s, 3 H, CH3CO), 3.85 (s, 3 H, CH3O), 4.70 (dd,
4
3
3
3J3′-H,2′-H = 6.2, J3′-H,1′-H = 1.0, 2 H, 3′-H), 6.29 (dt, J2′-H,1′-H = 15.9, J2′-H,3′-H = 6.2, 1 H,
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

Preparation of Boc-Protected Cinnamyl-Type Alcohols
727
3
4
3
2′-H), 6.64 (dt, J1′-H,2′-H = 15.9, J1′-H,3′-H = 1.0, 1 H, 1′-H), 7.04 (d, J3-H,4-H = 8.4, 1 H, 3-H),
7.54 (dd, J4-H,3-H = 8.4, J4-H,6-H = 2.2, 1 H, 4-H), 8.01 (d, J6-H,4-H = 2.2, 1 H, 6-H). 13C NMR
(100.6 MHz, CDCl3): 20.86 (CH3CO), 27.67 (C(CH3)3), 52.15 (CH3O), 66.88 (CH2-3), 82.26
(C(CH3)3), 123.12 (C-1), 123.19 (CH-3), 124.53 (CH-2′), 129.79 (CH-6), 131.46 (CH-4),
132.00 (CH-1′), 134.28 (C-5), 150.07 (C-2), 153.16 (CO carbon ate), 164.54 (CO ben zoate),
169.55 (CO acetate). IR (NaCl, CHCl3): 2980 (m ), 1740 (s), 1731 (s), 1369 (s), 1275 (s), 1187
(s), 1081 (s). MS (EI, 150 °C), m/z (%): 350 (M+, 1), 319 (4), 294 (M+ – (CH3)2C=CH2, 14),
252 (100), 220 (30), 191 (30), 159 (25), 158 (18), 103 (15). HRMS (EI): 350.1367 (C18H22O7
(M+) requires 350.1366). For C17H22O7 calculated: 61.71% C, 6.33% H; foun d: 61.53% C,
6.47% H.
3
4
4
tert-Butyl (E)-3-(4′-methoxyphenyl)prop-2-en-1-yl carbonate (4s). Th e crude product obtain ed
by procedure D was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with a m ixture
of h exan es an d AcOEt (98.5:1.5) to give 4s as a colorless oil (88 m g, 35%), followed by th e
correspon din g stilben e derivative (21 m g). 1H NMR (400.1 MHz, CDCl3): 1.50 (s, 9 H, t-Bu),
3
4
3
3.81 (s, 3 H, CH3O), 4.70 (dd, J1-H,2-H = 6.7, J1-H,3-H = 1.2, 2 H, 1-H), 6.16 (dt, J2-H,3-H
=
3
3
4
15.8, J2-H,1-H = 6.7, 1 H, 2-H), 6.62 (dt, J3-H,2-H = 15.8, J3-H,1-H = 1.2, 1 H, 3-H), 6.85 (d,
3J3′-H,2′-H = 8.8, 2 H, 3′-H), 7.33 (d, J2′-H,3′-H = 8.8, 2 H, 2′-H). 13C NMR (100.6 MHz, CDCl3):
3
27.78 (C(CH3)3), 55.26 (CH3O), 67.74 (CH2-1), 82.11 (C(CH3)3), 113.97 (CH-3′), 120.54
(CH-2), 127.88 (CH-2′), 128.93 (C-1′), 134.25 (CH-3), 153.37 (CO carbon ate), 159.56 (C-4′).
IR (n eat): 2979 (m ), 1742 (s, CO carbon ate), 1610 (m ), 1514 (m ), 1370 (m ), 1275 (s), 1253 (s),
1164 (s), 1034 (m ), 849 (m ). MS (CI-NH3, 150 °C), m/z (%): 282 ([M + NH4+], 0.5), 264 (M+,
1), 208 (5), 175 (20), 147 ([M + NH4+] – NH3 – t-BuOH – CO2, 100). For C15H20O4 calculated:
68.16% C, 7.63% H; foun d: 68.32% C, 7.89% H.
tert-Butyl (E)-3-(4′-acetyloxyphenyl)prop-2-en-1-yl carbonate (4t). Th e crude product obtain ed
by procedure D was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with a m ixture
of h exan es an d AcOEt (98.5:1.5) to yield th e startin g acetate 7t (46 m g, 28% recovered).
Con tin ued elution with a 92.5:7.5 m ixture afforded 4t (75 m g, 36% based on th e recovered
startin g acetate) as a colorless oil, th e correspon din g stilben e derivative (8 m g) was eluted
with an 85:15 m ixture. 1H NMR (400.1 MHz, CDCl3): 1.50 (s, 9 H, t-Bu), 2.29 (s, 3 H,
3
4
3
3
CH3CO2), 4.70 (dd, J1-H,2-H = 6.4, J1-H,3-H = 1.2, 2 H, 1-H), 6.24 (dt, J2-H,3-H = 15.9, J2-H,1-H
=
3
4
3
6.4, 1 H, 2-H), 6.64 (dt, J3-H,2-H = 15.9, J3-H,1-H = 1.2, 1 H, 3-H), 7.04 (d, J3′-H,2′-H = 8.6, 2 H,
3′-H), 7.39 (d, J2′-H,3′-H = 8.6, 2 H, 2′-H). 13C NMR (100.6 MHz, CDCl3): 21.06 (CH3CO2),
3
27.73 (C(CH3)3), 67.25 (CH2-1), 82.19 (C(CH3)3), 121.67 (CH-3′), 123.13 (CH-2), 127.57
(CH-2′), 133.27 (CH-3), 133.94 (C-1′), 150.34 (C-4′), 153.26 (CO carbon ate), 169.28 (CO ace-
tate). IR (n eat): 2981 (m ), 1740 (s, CO carbon ate), 1507 (m ), 1370 (m ), 1275 (s), 1255 (s),
1194 (s), 1164 (s). MS (CI-NH3, 150 °C), m/z (%): 602 ([2 M + NH4+], 1), 484 ([2 M + NH4+] –
t-BuOH – CO2, 2), 310 ([M + NH4+], 10), 175 ([M + NH4+] – NH3 – t-BuOH – CO2, 100).
For C16H20O5 calculated: 65.74% C, 6.90% H; foun d: 65.60% C, 7.02% H.
tert-Butyl (E)-3-(pyridin-2′-yl)prop-2-en-1-yl carbonate (4u ). Th e crude product obtain ed by
procedure E was ch rom atograph ed on a colum n of silica gel (5 × 15 cm ) with AcOEt to af-
3
ford 4u as a brown oil. 1H NMR (400.1 MHz, CDCl3): 1.46 (s, 9 H, t-Bu), 4.74 (d, J1-H,2-H
=
3
3
3
4.7, 2 H, 1-H), 6.69 (d, J3-H,2-H = 15.8, 1 H, 3-H), 6.75 (dt, J2-H,3-H = 15.8, J2-H,1-H = 4.7,
3
3
4
1 H, 2-H), 7.09 (ddd, J5′-H,4′-H = 7.6, J5′-H,6′-H = 4.8, J5′-H,3′-H = 1.0, 1 H, 5′-H), 7.24 (ddd,
4
5
3
3
3J3′-H,4′-H = 7.8, J3′-H,5′-H = 1.0, J3′-H,6′-H = 0.9, 1 H, 3′-H), 7.58 (ddd, J4′-H,3′-H = 7.8, J4′-H,5′-H
=
4
3
4
5
7.6, J4′-H,6′-H = 1.8, 1 H, 4′-H), 8.51 (ddd, J6′-H,5′-H = 4.8, J6′-H,4′-H = 1.8, J6′-H,3′-H = 0.9, 1 H,
6′-H). 13C NMR (100.6 MHz, CDCl3): 27.66 (C(CH3)3), 66.57 (CH2-1), 82.13 (C(CH3)3),
121.74 (CH-3′), 122.37 (CH-5′), 127.49 (CH-3), 132.66 (CH-2), 136.37 (CH-4′), 149.46
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

728
Štambaský, Malkov, Kočovský:
(CH-6′), 153.15 (CO carbon ate), 154.48 (C-2′). IR (n eat): 2980 (w), 1741 (s, CO carbon ate),
1278 (s), 1254 (s), 1161 (s). MS (CI-isobutan e, 150 °C), m/z (%): 236 (MH+, 100), 180 (MH+
–
(CH3)2C=CH2, 20), 120 (MH+ – (CH3)2C=CH2 – H2O, 40). HRMS (CI-isobutan e): 236.1289
(C13H18O3N (MH+) requires 236.1287). For C13H17NO3 calculated: 66.36% C, 7.28% H,
5.95% N; foun d: 66.22% C, 7.27% H, 6.07% N.
tert-Butyl (E)-3-(pyridin-4′-yl)prop-2-en-1-yl carbonate (4v). A solution of th e allyl alcoh ol 9v
(60 m g, 0.44 m m ol) in THF (2 m l) was slowly added to a suspen sion of sodium h ydride
(54 m g, 1.30 m m ol, 60% suspen sion in m in eral oil, 3 × wash ed with dry THF) in THF (3 m l)
at room tem perature an d th e m ixture was stirred for 1 h . Th e resultin g solution was slowly
added to a solution of Boc an h ydride (226 m g, 1.04 m m ol) in THF (7 m l) at room tem pera-
ture an d th e m ixture was stirred at room tem perature overn igh t. Th e reaction was quen ch ed
with brin e (5 m l), th e m ixture was diluted with eth er (100 m l), wash ed with brin e (3 × 50 m l),
dried (Na2SO4), an d evaporated. Th e residue was ch rom atograph ed on a colum n of silica gel
(3 × 10 cm ) with a m ixture of h exan es an d AcOEt (60:40) to furn ish 4v as a yellow oil (50 m g,
3
4
48%). 1H NMR (400.1 MHz, CDCl3): 1.49 (s, 9 H, t-Bu), 4.73 (dd, J1-H,2-H = 5.7, J1-H,3-H
=
3
3
3
1.2, 2 H, 1-H), 6.48 (dt, J2-H,3-H = 16.0, J2-H,1-H = 5.7, 1 H, 2-H), 6.59 (dt, J3-H,2-H = 16.0,
4J3-H,1-H = 1.2, 1 H, 3-H), 7.22 (d, J3′-H,2′-H = 6.0, 2 H, 3′-H an d 5′-H), 8.54 (d, J2′-H,3′-H = 6.0,
2 H, 2′-H an d 6′-H). 13C NMR (100.6 MHz, CDCl3): 27.71 (C(CH3)3), 66.47 (CH2-1), 82.53
(C(CH3)3), 120.96 (CH-3′ an d CH-5′), 127.94 (CH-2), 131.01 (CH-3), 143.47 (C-4′), 150.16
(CH-2′ an d CH-6′), 153.11 (CO carbon ate). IR (n eat): 2980 (m ), 1742 (s, CO carbon ate), 1596
(m ), 1369 (m ), 1277 (s), 1255 (s), 1162 (s), 1119 (m ), 849 (m ). MS (EI, 150 °C), m/z (%): 235
3
3
(M+, 10), 179 (M+ – (CH3)2C=CH2, 45), 135 (M+ – (CH3)2C=CH2 – CO2, 10), 118 (MH+
–
(CH3)2C=CH2 – CO2 – H2O, 30), 28 (100). HRMS (EI): 235.1207 (C13H17NO3 (M+) requires
235.1208). For C13H17NO3 calculated: 66.36% C, 7.28% H, 5.95% N; foun d: 66.20% C,
7.34% H, 5.81% N.
tert-Butyl (E)-3-(N-methylpyrrol-2′-yl)prop-2-en-1-yl carbonate (4w ). Th e crude product ob-
tain ed by procedure E was ch rom atograph ed on a colum n of n eutral alum in a (3 × 15 cm )
with a m ixture of h exan es, AcOEt an d Et3N (74:25:1) to give 4w as a brown oil (200 m g,
3
31%). 1H NMR (400.1 MHz, C6D6): 1.35 (s, 9 H, t-Bu), 2.72 (s, 3 H, CH3), 4.60 (dd, J1-H,2-H
=
4
3
3
6.6, J1-H,3-H = 1.2, 2 H, 1-H), 5.94 (dt, J2-H,3-H = 15.7, J2-H,1-H = 6.6, 1 H, 2-H), 6.16 (dd,
3J4′-H,3′-H = 3.7, J4′-H,5′-H = 2.6, 1 H, 4′-H) 6.20 (dd, J5′-H,4′-H = 2.6, J5′-H,3′-H = 1.6, 1 H, 5′-H),
3
3
4
3
4
3
4
6.31 (dt, J3-H,2-H = 15.7, J3-H,1-H = 1.2, 1 H, 3-H), 6.41 (dd, J3′-H,4′-H = 3.7, J3′-H,5′-H = 1.6, 1 H,
3′-H). 13C NMR (100.6 MHz, C6D6): 27.76 (C(CH3)3), 33.32 (CH3), 67.92 (CH2-1), 81.16
(C(CH3)3), 108.30 (CH-3′), 108.47 (CH-4′), 119.72 (CH-2), 123.58 (CH-5′), 123.85 (CH-3),
130.53 (C-2′), 154.17 (CO carbon ate). MS (EI, 150 °C), m/z (%): 237 (M+, 80), 181 (M+
–
(CH3)2C=CH2, 80), 137 (M+ – (CH3)2C=CH2 – CO2, 52), 120 (80), 57 (100). HRMS (EI):
237.1362 (C13H19NO3 (M+) requires 237.1365).
Pinacolyl 1-(tert-butyloxycarbonyl)prop-2-en-1-ol-3-yl boronate (6). Cycloh exen e (164 m g,
2.00 m m ol) was added to a m ixture of a 1 M solution of boran e in THF (1.0 m l, 1.0 m m ol)
an d THF (1 m l) at 0 °C an d th e m ixture was stirred for 1.5 h . Th e resultin g solution was
evaporated in vacuum to form a wh ite solid, to wh ich n eat pin acolboran e (1.41 g, 11.0 m m ol)
was added. Carbon ate 13 (1.56 g, 10.0 m m ol) was th en slowly added an d th e reaction m ix-
ture h eated spon tan eously. Th e resultin g m ixture was stirred at room tem perature overn igh t,
th e reaction was quen ch ed with water (2 m l) an d th e m ixture was stirred for 1 h . Th e result-
in g suspen sion was extracted with AcOEt (3 × 20 m l), th e com bin ed organ ic layers were
dried (Na2SO4) an d evaporated, yieldin g boron ate 6 (2.70 g, 95%): b.p. 110–111 °C at
270 Pa. 1H NMR (400.1 MHz, CDCl3): 1.20 (s, 12 H, CH3), 1.42 (s, 9 H, t-Bu), 4.58 (dd,
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

Preparation of Boc-Protected Cinnamyl-Type Alcohols
729
4
3
4
3J1-H,2-H = 4.8, J1-H,3-H = 1.8, 2 H, 1-H), 5.63 (dt, J3-H,2-H = 18.1, J3-H,1-H = 1.8, 1 H, 3-H),
6.55 (dt, J2-H,3-H = 18.1, J2-H,1-H = 4.8, 1 H, 2-H). 13C NMR (100.6 MHz, CDCl3): 24.65
(C(CH3)2), 27.65 (C(CH3)3), 67.76 (CH2-1), 82.03 (C(CH3)3), 83.27 (C(CH3)2), 120.25 (CH-3),
145.66 (CH-2), 153.13 (CO carbon ate). IR (CHCl3): 2980 (s), 1744 (s), 1648 (m ), 1458 (w),
1370 (m ), 1350 (m ), 1329 (m ), 1278 (s), 1255 (s), 1165 (m ), 1145 (s), 1118 (m ). MS (CI), m/z
(%): 285 (M + H+, 9), 284 (M+, 2), 229 (M + H+ – t-Bu, 100), 228 (M+ – t-Bu, 25), 185 (M +
H+ – t-Bu – CO2, 7), 119 (20), 101 (35). HRMS (CI): 285.1871 (C14H26BO5 (M + H)+ requires
285.1873). For C14H25BO5 calculated: 59.18% C, 8.87% H; foun d: 59.32% C, 8.83% H.
tert-Butyl prop-2-en-1-yl carbonate (8) 28. Fraction distillation of th e crude product obtain ed
by procedure A yielded 8 as a colorless oil (7.89 g, 50%): b.p. 40 °C at 270 Pa. 1H NMR
(400.1 MHz, CDCl3): 1.46 (s, 9 H, t-Bu), 4.53 (ddd, J1-H,2-H = 5.8, J1-H,3-Ha = 1.4, J1-H,3-Hb
1.3, 2 H, 1-H), 5.22 (ddd, J3-Hb,2-H = 10.5, J3-Hb,3-Ha = 2.8, J3-Hb,1-H = 1.3, 1 H, 3-Hb), 5.31
(ddd, J3-Ha,2-H = 17.2, J3-Ha,3-Hb = 2.8, J3-Ha,1-H = 1.4, 1 H, 3-Ha), 5.90 (ddt, J2-H,3-Ha = 17.2,
3J2-H,3-Hb = 10.5, J2-H,1-H = 5.8, 1 H, 2-H). For C8H14O3 calculated: 60.74% C, 8.92% H;
3
3
3
4
4
=
3
2
4
3
2
4
3
3
foun d: 60.70% C, 8.96% H.
(E)-3-(Pyridin-4′yl)prop-2-en-1-ol (9v). n-BuLi (1.1 m l, 2.2 m m ol, 2 M solution in pen tan e)
was slowly added to a solution of trieth yl ph osph on oacetate 12 (450 m g, 2.01 m m ol) in THF
(5 m l) at –83 °C. After stirrin g for 5 m in , pyridin -4-carbaldeh yde 11v (214 m g, 2.00 m m ol)
was slowly added an d th e resultin g m ixture was stirred at –83 °C for an addition al 10 m in
an d th en at room tem perature for 2 h . Th e reaction was quen ch ed with brin e (5 m l), th e
m ixture was diluted with eth er (100 m l) an d wash ed with brin e (3 × 50 m l), dried (Na2SO4),
an d evaporated. Th e crude eth yl ester 10v was dissolved in THF (5 m l), cooled to –83 °C an d
DIBAL-H (3.2 m l, 4.8 m m ol, 1.5 M solution in toluen e) was slowly added an d th e resultin g
m ixture was stirred at th is tem perature for an addition al 2 h . Th e reaction was quen ch ed
with MeOH (5 m l) an d th en a saturated aqueous solution of potassium -sodium tartrate
(10 m l) was added. Th e resultin g m ixture was stirred at 40 °C an d a solid potassium -sodium
tartrate (approxim ately 2 g) was added in portion s, un til th e solution becam e h om ogen eous.
Th e resultin g m ixture was diluted with eth er (100 m l), wash ed with an aqueous saturated
solution of potassium -sodium tartrate (3 × 50 m l), dried (Na2SO4), an d evaporated. Th e resi-
due was ch rom atograph ed on a colum n of silica gel (3 × 10 cm ) with AcOEt to afford 9v as
a wh ite solid (105 m g, 39%): m .p. 90–91 °C (CHCl3). 1H NMR (400.1 MHz, CDCl3): 2.52 (s,
3
1 H, OH), 4.39 (m , 2 H, 1-H), 6.58–6.60 (m , 2 H, 2-H an d 3-H), 7.24 (d, J3′-H,2′-H = 6.2, 2 H,
3
3′-H an d 5′-H), 8.52 (d, J2′-H,3′-H = 6.2, 2 H, 2′-H an d 6′-H). 13C NMR (100.6 MHz, CDCl3):
62.86 (CH2-1), 120.95 (CH-3′ an d CH-5′), 127.66 an d 133.94 (CH-2 an d CH-3), 144.30
(C-4′), 149.99 (CH-6′). IR (CHCl3): 3019 (m ), 1220 (m ), 1211 (m ), 784 (m ). MS (EI, 150 °C),
m/z (%): 135 (M+, 75), 117 (M+ – H2O, 20), 106 (85), 93 (100). HRMS (EI): 135.0686
(C8H9NO (M+) requires 135.0684).
tert-Butyl prop-2-yn-1-yl carbonate (13). Fraction distillation of th e crude product obtain ed
by procedure A gave 13 as a colorless liquid (25.60 g, 82%): b.p. 47–49 °C at 270 Pa.
4
1H NMR (400.1 MHz, CDCl3): 1.47 (s, 9 H, t-Bu), 2.50 (t, J3-H,1-H = 2.5, 1 H, 3-H), 4.64 (d,
4J1-H,3-H = 2.5, 2 H, 1-H). 13C NMR (100.6 MHz, CDCl3): 27.6 (C(CH3)3), 54.2 (CH2-1), 75.2
(CH-3), 77.2 (C-2), 82.9 (C(CH3)3), 152.6 (CO carbon ate). IR (CHCl3): 3296, 2983, 1747,
1395, 1371, 1280, 1256, 1158, 1097. MS (CI), m/z (%): 157 (M + H+, 100), 139 (5), 119 (5),
101 (20), 81 (22). HRMS (CI): 157.0862 (C8H13O3 (M + H)+ requires 157.0865). For C8H12O3
calculated: 61.52% C, 7.74% H; foun d: 61.54% C, 7.80% H.
1-(tert-Butyloxycarbonyl)prop-2-en-1-ol-3-yl boronic acid (15). Cycloh exen e (165 m g, 2.01 m m ol)
was added to a m ixture of a 1 M solution of boran e in THF (1.0 m l, 1.0 m m ol) an d THF (1 m l)
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

730
Štambaský, Malkov, Kočovský:
at 0 °C an d th e m ixture was stirred for 1.5 h . Th e resultin g solution was evaporated in vac-
uum to form a wh ite solid, to wh ich n eat catech olboran e (1.34 g, 11.2 m m ol) an d th en car-
bon ate 13 (1.50 g, 9.6 m m ol) were added at room tem perature (spon tan eous h eatin g is
desired for h igh yield) an d th e resultin g m ixture was stirred at room tem perature overn igh t.
Th e reaction was quen ch ed with water (10 m l) an d th e m ixture was stirred for 2 h . Th e re-
sultin g suspen sion was filtered off, yieldin g wh ite solid of 15 (710 m g, 36%). Th e filtrate
was extracted with AcOEt (3 × 20 m l). Com bin ed organ ics layers were dried (Na2SO4) an d
evaporated. Th e residue was ch rom atograph ed on a colum n of silica gel (5 × 5 cm ) with a
m ixture of h exan es an d AcOEt (80:20), wh ich eluted catech ol. Con tin ued elution with
AcOEt afforded boron ic acid 15 as a wh ite foam (504 m g, 26%). Th e com bin ed yield of
boron ic acid 15 was 1.210 g (62%). 1H NMR (400.1 MHz, CDCl3): 1.48 (s, 9 H, t-Bu), 4.69
3
4
3
4
(dd, J1-H,2-H = 4.5, J1-H,3-H = 1.7, 2 H, 1-H), 5.76 (dt, J3-H,2-H = 17.9, J3-H,1-H = 1.7, 1 H,
3-H), 6.91 (dt, J2-H,3-H = 17.9, J2-H,1-H = 4.5, 1 H, 2-H). 13C NMR (100.6 MHz, CDCl3): 27.70
(C(CH3)3), 67.49 (CH2-1), 82.40 (C(CH3)3), 122.45 (CH-3), 149.18 (CH-2), 153.15 (CO car-
bon ate). IR (CHCl3): 3328 (m ), 2977 (w), 1748 (s), 1645 (w), 1394 (m ), 1349 (m ), 1279 (m ),
1248 (m ), 1159 (m ), 1138 (m ), 1113 (m ), 1074 (m ). MS (EI), m/z (%): 384 (3 (M + H+ – H2O –
t-Bu), 20), 322 (3 (M + H+ – H2O – t-Bu – H2O·CO2), 10), 278 (3 (M + H+ – H2O – t-Bu –
3
3
H2O·CO2 – CO2), 10), 216 (7), 177 (8). HRMS (EI): 384.0844 (C12H15O12B3 trim er (M + H+
–
H2O – t-Bu) requires 384.0842). For C8H15BO5 calculated: 47.56% C, 7.48% H; foun d:
47.68% C, 7.34% H.
Prop-2-en-1-ol-3-yl boronic acid (16) 12. Neat catech olboran e (13.25 g, 110.49 m m ol) was
slowly added to n eat propargyl alcoh ol (2.76 g, 50.80 m m ol) at room tem perature over a pe-
riod of 15 m in . After th e addition h as been com pleted, th e m ixture was h eated at 70 °C for
1 h . Wh ite precipitate th at was form ed durin g th e course of th e reaction was dissolved in a
sm all am oun t of a m ixture of MeOH an d CH2Cl2 (1:1) an d ch rom atograph ed on a colum n
of silica gel (5 × 5 cm ): a m ixture of h exan es an d AcOEt (50:50) eluted catech ol; con tin ued
elution with a m ixture of CH2Cl2 an d MeOH (90:10) furn ish ed boron ic acid 16 as a wh ite
3
4
foam (2.08 g, 40%). 1H NMR (400.1 MHz, CD3OD): 4.10 (dd, J1-H,2-H = 4.2, J1-H,3-H = 1.9, 2 H,
3
4
3
3
1-H), 5.80 (dt, J3-H,2-H = 17.8, J3-H,1-H = 1.9, 1 H, 3-H), 6.60 (dt, J2-H,3-H = 17.8, J2-H,1-H
4.2, 1 H, 2-H). 13C NMR (100.6 MHz, CD3OD): 64.78 (CH2-1), 123.10 (CH-3), 151.75 (CH-2).
=
Supporting information available. 1H NMR spectra for som e of th e key com poun ds. Th ese
supplem en tary data are available free of ch arge via doi:10.1135/cccc20080705.
We thank the University of Glasgow for a studentship to J. Štambaský.
REFERENCES AND NOTES
1. For general review of palladium complexes in allylic substitution: a) Godleski S. A. in:
Comprehensive Organic Synthesis, Vol. 4 (B. M. Trost, I. Fleming and M. F. Semmelhack,
Eds), pp. 585–661. Pergamon, Oxford 1991; b) Frost C. G., Howarth J., Williams J. M. J.:
Tetrahedron: Asymmetry 1992, 3, 1089; c) Trost B. M., VanVranken D. L.: Chem. Rev.
1996, 96, 395; d) Negishi E. (Ed.): Handbook of Organopalladium Chemistry for Organic
Synthesis, Vols I and II. J. Wiley & Sons, New York 2002.
2. For reversed regioselectivity to branched products in Pd-catalyzed allylic substitution:
a) Prétôt R., Pfaltz A.: Angew. Chem. Int. Ed. 1998, 37, 323; b) Hayashi T., Kawatsura M.,
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

Preparation of Boc-Protected Cinnamyl-Type Alcohols
731
Uozumi Y.: J. Am. Chem. Soc. 1998, 120, 1681; c) You S. L., Zhu X. Z., Luo Y. M., Hou
X. L., Dai L. X.: J. Am. Chem. Soc. 2001, 123, 7471; d) Hou X. L., Sun N.: Org. Lett. 2004,
6, 4399; e) Zheng W. H., Sun N., Hou X. L.: Org. Lett. 2005, 7, 5151.
3. a) Dvořák D., Starý I., Kočovský P.: J. Am. Chem. Soc. 1995, 117, 6130; b) Malkov A. V.,
Baxendale I. R., Dvořák D., Mansfield D. J., Kočovský P.: J. Org. Chem. 1999, 64, 2737;
c) Malkov A. V., Spoor P., Vinader V., Kočovský P.: Tetrahedron Lett. 2001, 42, 509;
d) Glorius F., Neuburger M., Pfaltz A.: Helv. Chim. Acta 2001, 84, 3178. For a recent
overview, see the following: e) Belda O., Moberg C.: Acc. Chem. Res. 2004, 37, 159.
4. Lloyd-Jones G. C., Pfaltz A.: Angew. Chem. Int. Ed. 1995, 34, 462.
5. a) Zhang S. W., Mitsudo T., Kondo T., Watanabe Y.: J. Organomet. Chem. 1995, 485, 55;
b) Trost B. M., Fraisse P. L., Ball Z. T.: Angew. Chem. Int. Ed. 2002, 41, 1059.
6. a) Evans P. A., Leahy D. K.: J. Am. Chem. Soc. 2002, 124, 7882; b) Hayashi T., Okada A.,
Suzuka T., Kawatsura M.: Org. Lett. 2003, 5, 1713.
7. For a review, see: Takeuchi R.: Synlett 2002, 1954.
8. Bricout H., Carpentier J. F., Mortreux A.: Tetrahedron Lett. 1996, 37, 6105.
9. Blacker A. J., Clarke M. l., Loft M. S., Mahon M. F., Humphries M. E., Williams J. M. J.:
Chem. Eur. J. 2000, 6, 353.
10. Karlström A. S. E., Bäckvall J. E. in: Modern Organocopper Chemistry (M. Krause, Ed.),
pp. 259–288. Wiley–VCH, Wienheim 2002.
11. a) Houlihan F., Bouchard F., Frechet J. M. J., Willson C. G.: Can. J. Chem. 1985, 63, 153;
b) Chen C. T., Kuo J. H., Li C. H., Barhate N. B., Hon S. W., Li T. W., Chao S. D., Liu
C. C., Li Y. C., Chang I. H., Lin J. S., Liu C. J., Chou Y. C.: Org. Lett. 2001, 3, 3729;
c) Hudlicky T., Rinner U., Gonzalez D., Akgun H., Schilling S., Siengalewicz P., Martinot
T. A., Pettit G. R.: J. Org. Chem. 2002, 67, 8726; d) Alonso E., Guijarro D., Martínez P.,
Ramón D. J., Yus M.: Tetrahedron 1999, 55, 11027; e) Basel Y., Hassner A.: J. Org. Chem.
2000, 65, 6368; f) Basel Y., Hassner A.: Synthesis 2001, 4, 550.
12. a) Roush W. R., Champoux J. A., Peterson B. C.: Tetrahedron Lett. 1996, 37, 8989;
b) Frank S. A., Chen H., Kunz R. K., Schnaderbeck M. J., Roush W. R.: Org. Lett. 2000, 2,
2691.
13. a) Kobayashi Y., Murugesh M. G., Nakano M., Takahisa E., Usmani S. B., Ainai T.: J. Org.
Chem. 2002, 67, 7110; b) Organ M. G., Ghasemi H.: J. Org. Chem. 2004, 69, 695.
14. Shirakawa K., Arase A., Hoshi M.: Synthesis 2004, 11, 1814.
15. We have found difficult to constantly reproduce the yield of the free boronic acid.
We propose, this was caused by separation difficulties rather than by reaction
parameters.
16. Frank S. A., Chen H., Kunz R. K., Schnaderbeck M. J., Roush W. R.: Org. Lett. 2000, 2,
2691.
17. No decomposition was detected when stored at room temperature up to 1 month and
at 4 °C more than 1 year.
18. a) Berrée F., Bleis P. G. L., Carboni B.: Tetrahedron Lett. 2002, 43, 4935; b) Guiles J. W.,
Johnson S. G., Murray W. V.: J. Org. Chem. 1996, 61, 5169; c) Shimizu M., Kitagawa H.,
Kurahashi T., Hiyama T.: Angew. Chem. Int. Ed. 2001, 40, 4283; d) Arterburn J. B.,
Corona C., Rao K. V., Carlson K. E., Katzenellenbogen J. A.: J. Org. Chem. 2003, 68,
7063; e) Reed M. A., Chang M. T., Snieckus V.: Org. Lett. 2004, 6, 2297; f) Murata M.,
Watanabe S., Masuda Y.: Tetrahedron Lett. 1999, 40, 2585.
19. a) Pears D. A., Smith S. C.: Aldrichimica Acta 2005, 38, 23; b) Ramarao C., Ley S. V.,
Smith S. C., Shirley I. M., DeAlmeida N.: Chem. Commun. 2002, 1132.
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732

732
Štambaský, Malkov, Kočovský:
20. a) Barder T. E., Walker S. D., Martinelli J. R., Buchwald S. L.: J. Am. Chem. Soc. 2005,
127, 4685; b) Raheem I. T., Goodman S. N., Jacobsen E. N.: J. Am. Chem. Soc. 2004, 126,
706.
21. Filler R., Lin S., Zhang Z.: J. Fluorine Chem. 1995, 74, 69.
22. a) Chatterjee A. K., Choi T. L., Sanders D. P., Grubbs R. H.: J. Am. Chem. Soc. 2003, 125,
11360; b) Connon S. J., Blechert S.: Angew. Chem. Int. Ed. 2003, 42, 1900.
23. a) Hallberg A., Westerlund C.: Chem. Lett. 1982, 1993; b) Bumagin N. A., Bumagina I. G.,
Beletskaya I. P.: Dokl. Chem. 1984, 274, 39; c) Bumagin N. A., Andryukhova N. P.,
Beletskaya I. P.: Bull. Acad. Sci. U.S.S.R., Div. Chem. Sci. 1987, 36, 1561; d) Mckean D. R.,
Parrinello G., Renaldo A. F., Stille J. K.: J. Org. Chem. 1987, 52, 422; e) Denmark S. E.,
Wang Z.: Synthesis 2000, 7, 999; f) Lee H. M., Nolan S. P.: Org. Lett. 2000, 2, 2053;
g) Amatore M., Gosmini C., Perichon J.: Eur. J. Org. Chem. 2005, 6, 989; h) Clarke M. L.:
Adv. Synth. Catal. 2005, 347, 303.
24. Takacs J. M., Helle M. A., Seely F. L.: Tetrahedron Lett. 1986, 27, 1257.
25. For the sample spectrum of a crude reaction mixture, see the Supporting Information.
26. Iwasaki M., Kobayashi Y., Li J. P., Matsuzaka H., Ishii Y., Hidai M.: J. Org. Chem. 1991,
56, 1922.
27. Large sterically demanding ortho substituents were not investigated.
28. Stoner E. J., Peterson M. J., Allen M. S., DeMattei J. A., Haight A. R., Leanna M. R., Patel
S. R., Plata D. J., Premchandran R. H., Rasmussen M.: J. Org. Chem. 2003, 68, 8847.
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 5, pp. 705–732