Iridium-catalyzed selective N-allylation of hydrazines

Article abstract of DOI:10.1016/j.tet.2005.03.105

A highly chemo- and regioselective iridium-catalyzed allylic amination is described. The reaction of various hydrazones and hydrazides with allylic carbonates proceeds at ambient temperature in the presence of an [Ir(COD)Cl]₂/pyridine catalyst,

Full text of DOI:10.1016/j.tet.2005.03.105

Tetrahedron 61 (2005) 6298–6308
Iridium-catalyzed selective N-allylation of hydrazines
*
Robert Matunas, Amy J. Lai and Chulbom Lee
Department of Chemistry, Princeton University, Princeton, NJ 08544, USA
Received 11 December 2004; revised 15 February 2005; accepted 4 March 2005
Available online 10 May 2005
Abstract—A highly chemo- and regioselective iridium-catalyzed allylic amination is described. The reaction of various hydrazones and
hydrazides with allylic carbonates proceeds at ambient temperature in the presence of an [Ir(COD)Cl]2/pyridine catalyst, ammonium iodide,
and diethylzinc to afford the corresponding N-allylation products in high yields with excellent chemo- and regioselectivities. Only the more
nucleophilic nitrogen of a given hydrazine derivative undergoes the C–N bond formation to yield a branched allylic isomer as the exclusive
product.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
selective alkylation at one of the two available nitrogens
while avoiding overalkylation (Eq. 1).3 Moreover, such
methods are only applicable, for the most part, with primary
electrophiles due to the lower reactivity of secondary alkyl
halides and competing elimination pathways. In this regard,
reductive amination5 is particularly valuable for the
installation of secondary alkyl chains, but limited only to
cases where the requisite imine formation is possible. Thus,
a methodology that would allow for the easy installation of
branched alkyl groups to a hydrazine scaffold in one step
with selectivity for a particular nitrogen would be of
potential synthetic value.
Hydrazines and their derivatives are an important class of
compounds that have found wide utility in organic
synthesis.1,2 While hydrazines have traditionally been
employed as reagents for the derivatization and characteri-
zation of carbonyl compounds, the N–N linkage has been
used as a key structural motif of various bioactive active
agents in recent years. In particular, an increasing number of
N–N bond containing heterocycles and peptidomimetics
have made their ways to commercial applications as
pharmaceutical and agricultural agents.3,4
(1)
Our approach to the selective alkylation of hydrazines is the
formation of the C–N bond using h3-allylmetal chemistry as
outlined in Scheme 1.6–13 Based on findings in zinc(II)
alkoxide mediated allylic etherification reactions,14,15 we
wondered whether the ‘zinc effect’ would also be viable for
the N-allylation reactions of hydrazones 2 and hydrazides 3.
For the synthesis of substituted hydrazine derivatives, a
number of methods have been developed over the years
largely making use of SN2 type displacement. These
alkylative approaches, however, typically involve tedious
synthetic sequences requiring extensive use of protecting
groups because of the inherent difficulty in achieving
Scheme 1. Strategy for N-allylation of hydrazones and hydrazines.
Keywords: Iridium; Catalysis; Hydrazones; Hydrazides; Hydrazines; Amination; Allylation.
*
Corresponding author. Tel.: C1 609 258 6253; fax: C1 609 258 6746; e-mail: cblee@princeton.edu
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.03.105

R. Matunas et al. / Tetrahedron 61 (2005) 6298–6308
6299
Although our prior work on allylic etherification exploited
palladium catalysis, we chose to explore the use of an
iridium catalyst for this endeavor, as such catalysts had been
shown to exhibit a pronounced regiochemical preference for
the formation of branched products.16–19 It was also hoped
that the use of diethylzinc as a basic mediator in this
reaction would overcome the inherent problem of chemo-
selectivity, allowing for the selective delivery of an
al0lylic electrophile to one nitrogen over the other (N vs
N -allylation). Described herein are our results towards
meeting these challenges.
as substrates lacking one, such as simple phenylhydrazones,
were unreactive (data not shown). The reaction tolerated an
aryl bromide (2i) and a terminal alkyne (2j), and also fared
well with an aromatic allylic carbonate (1b). Most notably,
only the branched isomer of the desired product was formed
in all cases examined.
Encouraged by the results of hydrazones, we endeavored to
explore the feasibility of using the same catalytic system for
the allylation of hydrazide 3a. As summarized in Table 3,
the desired N-allylation product 5a could be obtained as a
single regioisomer, with substitution at the primary nitrogen
(N0-position). In all cases, little to no dialkylation was
observed. In contrast to the reaction of hydrazones, the use
of only 0.25 equiv of Et2Zn, instead of 0.50 equiv, provided
a higher yield (entries 1 vs 2). There was a substantial
background reaction (13%) in the absence of Et2Zn,
presumably due to the greater nucleophilicity of hydrazides
relative to hydrazones (entry 3), while the iridium catalyst
was indispensable for the reaction (entry 6). In order to test
the possibility that the latent nucleophilicity of the
hydrazide might be sufficient to promote the alkylation
without recourse to Et2Zn as base, the reaction was
performed under zinc free conditions (entries 7 and 8).
Although the use of simple bases, Cs2CO3 and i-Pr2NEt,
improved the yield by a marginal amount relative to the
background reaction (entries 3 vs 7 and 8), the lack of
substantial reactivity highlighted the unique nature and role
of Et2Zn in this reaction.
2. Results and discussion
Initial studies were focused on the model reaction between
acetophenone-derived hydrazone 2a and allylic carbonate
1a, in which various reaction parameters were probed to
identify an effective catalytic system (Table 1). Guided by
literature precedents,12,16,18 we chose [Ir(COD)Cl]2 as the
precatalyst while employing pyridine and Et2Zn as the
ligand and base, respectively.20 Gratifyingly, these con-
ditions adopted from our previous studies on allylic
etherification proved effective to give rise to the desired
N-allylation product 4a with complete regioselectivity
(entry 1). While THF was found to be an optimal solvent,
a set of control experiments clearly indicated the importance
of each component of the reaction system (entries 3–6), in
which the effect of 1 equiv of NH4I on the yield of the
reaction was particularly noteworthy.21
Having established working conditions, we surveyed the
scope of the reaction with a variety of hyrazines and allylic
carbonates (Table 4). Similar to the reaction of hydrazones,
the t-Boc-, Cbz- and Ts-protected hydrazines 3a, 3b and 3c
participated well in the reaction, while the acetate-protected
hydrazine 3d failed to react under these conditions (entry 4).
Also in accord with the hydrazones, hydrazines lacking
an electron withdrawing substituent gave no reaction
under these conditions. Good yields were uniformly
obtained in the reactions of structurally diverse allylic
carbonates and hydrazides (entries 5–8). In0 particular, it
was noteworthy that a highly selective (N vs N ) allylation of
N-acyl-N0-alkyl hydrazines could be achieved to form
N0,N0-dialkyl hydrazides, although dialkylation was not
observed to any serious extent in other reactions (entries 1–6
vs 7 and 8).
Table 1. Development of Ir-catalyzed N-allylation of hydrazonesa
Entry
[Ir(COD)Cl]2/
pyridine
Et2Zn
(equiv)
NH4I
(equiv)
% Yield
1
2.5 mol%/5 mol%
5.0 mol%/10 mol%
2.5 mol%/5 mol%
2.5 mol%/5 mol%
2.5 mol%/5 mol%
—
0.5
0.5
0.5
—
—
0.5
1.0
1.0
—
1.0
—
76
89
12
0
0
0
2b
3
4
5
6
1.0
a All reactions were performed at 25 8C in THF (0.4 mL) with 0.30 mmol
(1.5 equiv) of 2a and 0.20 mmol (1.0 equiv) of 1a.
b No reaction in dioxane. 40% yield in MeCN.
The new method was further extended to the synthesis of
N–N bond-containing heterocycles via an intramolecular
N-allylation reaction. Compound 6, containing hydrazone
and allylic carbonate moieties within the same molecule,
was thus prepared (Scheme 2, vide infra) and tested for ring
closure (Eq. 2). Upon subjection to our standard reaction
conditions, hydrazone 6 underwent a smooth cyclization to
give rise to the desired tetrahydropyridazine 7 in 88% yield.
Finally, the utility of the N-allylated products was briefly
explored through several transformations (Eqs. 3–5).
Hydrazone 4h, originally derived from acetophenone,
could be converted to hydrazines 10 and 11 by standard
hydrolysis22 and reductive amination5,23 reactions, respect-
ively. Simple hydrogenation25 of 4g furnished the fully
saturated N,N0-dialkyl hydrazide 12.
With conditions for the allylic amination established, we
further examined the scope of the reaction with a wide range
of substrates. As illustrated in Table 2, a variety of
hydrazones derived from ketones and aldehydes partici-
pated well in the reaction. In addition to the t-Boc-protected
hydrazone 2a used in the initial study, both Cbz- and
Ts-protected hydrazones 2b and 2c also proved competent
reaction partners (entries 2, 3 and 8). Interestingly, the
reaction of acetate 2d worked poorly under these conditions,
giving the product only in low yield as the main component
of an inseperable mixture of products (entry 4). The
presence of an electron withdrawing group was necessary,

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R. Matunas et al. / Tetrahedron 61 (2005) 6298–6308
Table 2. Ir(I)-Catalyzed N-allylation of hydrazones with allylic carbonatesa
Entry
1
Hydrazone
Allylic carbonate
Product
%Yield
89
1a
2a
2b
2c
2d
4a
4b
4c
4d
2
3
4
5
1a
1a
1a
1a
86
92
17
88
2e
4e
4f
6
7
1a
1a
82
86
2f
2g
4g
8
1a
1a
1a
75
41
71
2h
2i
4h
4i
9
10
2j
4j
4k
4l
11
12
2a
90
83
1b
1c
2a
a All reactions performed at room temperature in THF (0.4 mL) with 0.30 mmol (1.5 equiv) of hydrazone, 0.20 mmol allylic carbonate, 0.15 mmol of Et2Zn
(0.50 equiv with respect to hydrazone), 0.20 mmol of NH4I (1.0 equiv with respect to electrophile), 5 mol% [Ir(COD)Cl]2, and 10 mol% pyridine.
(2)

R. Matunas et al. / Tetrahedron 61 (2005) 6298–6308
Table 3. Development of Ir-catalyzed N-allylation of hydrazinesa
6301
(5)
Entry
[Ir(COD)Cl]2/
pyridine
Et2Zn
(equiv)
NH4I
(equiv)
% Yield
1
2
3
4
5.0 mol%/10 mol%
5.0 mol%/10 mol%
2.5 mol%/5 mol%
2.5 mol%/5 mol%
2.5 mol%/5 mol%
—
0.50
0.25
—
0.50
—
0.50
—
—
1.0
1.0
1.0
—
74
93
13
!2
!2
0
19
19
3. Conclusion
In summary, we have developed a highly chemo- and
regioselective iridium-catalyzed method for the N-allylation
of hydrazones and hydrazines with allylic carbonates.
The reaction provides the branched, N-allylated products
in good yields under mild reaction conditions. Crucial to the
success of the reaction is the utilization of diethylzinc as
base, as well as ammonium iodide as a halide additive. The
amination reactions of hydrazones and hydrazides described
herein can provide rapid access to differentially substituted
hydrazines without recourse to protecting group manipu-
lation. Such expedient access to these compounds may be
useful in further applications, such as the preparation of
novel peptidomimetics or heterocycles.
5
—
6
1.0
1.0
1.0
7b
8c
5.0 mol%/10 mol%
5.0 mol%/10 mol%
a All reactions were performed at 25 8C in THF (0.4 mL) with 0.20 mmol of
1a and 0.30 mmol (1.5 equiv) of 3a.
b Cs2CO3 (1.0 equiv) was used as base.
c Diisopropylethylamine (1.0 equiv) was used as base.
4. Experimental
4.1. General
Unless otherwise noted, all reactions were conducted in
Table 4. Ir(I)-Catalyzed N-allylation of hydrazines with allylic carbonatesa
Entry
Hydrazine
Electrophile
Product
%Yield
93
1
3a
1a
5a
5b
2
3
4
1a
1a
86
57
0
3b
5c
3c
1a
3d
5d
1b
5
6
7
3a
3a
88
82
85
5e
5f
1d
1a
3e
3f
5g
8
1a
82
5i
a All reactions performed at room temperature in THF (0.4 mL) with 0.30 mmol (1.5 equiv) of hydrazine, 0.20 mmol allylic carbonate, 0.075 mmol of Et2Zn
(0.25 equiv with respect to hydrazine), 0.20 mmol of NH4I (1.0 equiv with respect to electrophile), 5 mol% [Ir(COD)Cl]2, and 10 mol% pyridine.

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R. Matunas et al. / Tetrahedron 61 (2005) 6298–6308
flame-dried glassware under an argon atmosphere using
anhydrous solvent (either distilled or passed through an
activated alumina column or activated molecular sieves
column). Commercially available reagents were used with-
out further purification. Thin layer chromatography (TLC)
was performed using EM Science silica gel 60 F254 plates
and visualized using UV light, anisaldehyde, ceric sulfate or
potassium permanganate stains. Flash chromatography was
performed on EM Science silica gel 60 (40–63 mm) using
the indicated solvent system. 1H and 13C NMR spectra were
recorded in CDCl3, unless otherwise noted, on a Varian
Mercury 300 MHz, a Varian Inova 400 MHz or a Varian
7.39 (m, 5H), 5.25 (s, 2H), 2.35 (q, JZ8.0 Hz, 2H), 2.20 (q,
JZ8.0 Hz, 2H), 1.14 (t, JZ7.5 Hz, 3H), 1.10 (t, JZ8.0 Hz,
3H); 13C NMR (125 MHz, CDCl3): d 159.8, 154.2, 136.2,
128.8, 128.7, 128.6, 67.6, 30.2, 21.6, 11.3, 9.8; HRMS
(DCI-MS) [MC] Calcd for C13H19N2O2 235.1447, found
235.1442.
4.2.3. N0-[1-(4-Bromo-phenyl)-ethylidene]-hydrazine-
carboxylic acid t-butyl ester (2i). Following the same
procedure as 2a, the reaction of t-butyl carbazate (661 mg,
5.0 mmol) with p-bromoacetophenone (1.49 g, 7.5 mmol)
in hexane (10 mL) gave hydrazone 2g (1.07 g, 68%) as a
white solid after recrystallization from EtOH. Mp
167–168 8C. IR (film) 3190, 2980, 1730, 1700, 1530,
1140 cmK1; 1H NMR (400 MHz, CDCl3): d 7.76 (br s, 1H),
7.62 (d, JZ6.8 Hz, 2H), 7.45 (d, JZ7.6 Hz, 2H), 2.13
(s, 3H), 1.51 (s, 9H); 13C NMR (100 MHz, CDCl3): d 152.8,
146.3, 137.1, 131.6, 128.0, 123.6, 81.8, 28.5, 12.6; HRMS
(DCI-MS) [MC] Calcd for C13H18N2O2Br 313.0552, found
313.0540.
1
Inova 500 MHz spectrometer. Chemical shifts in H NMR
spectra were reported in parts per million (ppm) on the d
scale from an internal standard of residual chloroform
(7.27 ppm). Data for 1H NMR are reported as follows:
chemical shift, multiplicity (s, singlet; d, doublet; t, triplet;
q, quartet; m, multiplet), coupling constant in Hertz (Hz),
and integration. Data for 13C NMR spectra are reported in
terms of chemical shift in ppm from the central peak of
CDCl3 (77.23 ppm). Infrared (IR) spectra were recorded on
a Nicolet 730 FT-IR spectrometer and reported in frequency
of the absorption (cmK1). High resolution mass spectra
(HRMS) were obtained from the Princeton University Mass
Spectrometry Facility and UCR Mass Spectrometry
Facility.
4.2.4. N0-Pent-4-ynylidene-hydrazinecarboxylic acid
t-butyl ester (2j). To a solution of hex-5-ynal29 (192 mg,
2.0 mmol) was added t-butyl carbazate (264 mg, 2.0 mmol).
The reaction mixture was allowed to stir at room
temperature until deemed complete by TLC. At this time,
the reaction mixture was diluted with EtOAc, dried over
Na2SO4, and concentrated in vacuo. Purification of the
crude material by chromatography on deactivated (Et3N)
silica gel (4:1, then 2:1 hexanes/EtOAc), gave the desired
hydrazone 2j (172 mg, 41%) as a white crystalline solid. Mp
93–95 8C. IR (film) 3291, 3248, 3046, 2979, 2932, 1707,
4.2. Representative procedure for the preparation of
hydrazones
To a suspension of t-butyl carbazate (5.4 g, 41 mmol) in
hexanes (50 mL) was added acetophenone (7.2 mL,
61 mmol) dropwise. The reaction mixture was then heated
to reflux for 8 h. After cooling to ambient temperature, the
resulting precipitate was collected by suction filtration,
washed with additional cold hexanes, and allowed to air dry
under aspiration to afford the known hydrazone 2a24 (8.8 g,
91%). Other known hydrazones 2c,25 2d,26 2e,27 2f,28 and
2g28 were also prepared following this procedure.
1537, 1368, 1251, 1167 cmK1 1H NMR (300 MHz,
;
CDCl3): d 7.86 (br s, 1H), 7.25 (t, JZ5.0 Hz, 1H), 2.50
(m, 2H), 2.39 (m, 2H), 1.97 (t, JZ2.4 Hz, 1H), 1.47 (s, 9H);
13C NMR (75 MHz, CDCl3): d 152.7, 145.1, 83.0, 81.4,
69.6, 31.2, 28.5, 16.4; HRMS (DCI-MS) [MC] Calcd for
C10H17N2O2 197.1290, found 197.1292.
4.3. General procedure for the preparation of allylic
carbonates
4.2.1. N0-(1-Phenyl-ethylidene)-hydrazinecarboxylic
acid benzyl ester (2b). Following the same procedure as
2a, the reaction of benzylcarbazate (831 mg, 5.0 mmol)
with acetophenone (901 mg, 7.5 mmol) in hexane (10 mL)
gave hydrazone 2b (1.1 g, 98%). Recrystallization from
EtOH gave analytically pure hydrazone 2b as flocculent
white crystals (1.06 g, 79%). Mp 134–135 8C. IR (film)
To a solution of allylic alcohol in dry THF at K78 8C was
added n-BuLi dropwise. After stirring for 30 min, a solution
of Boc2O in THF was added. The reaction mixture was
allowed to warm to room temperature, and was then
quenched with saturated aqueous NH4Cl. The aqueous layer
was extracted with EtOAc, and the combined organic
phases were washed with water and brine, dried over
Na2SO4, and concentrated in vacuo. Purification by flash
column chromatography gave the pure allylic carbonates
1a–c.30
3200, 3050, 1700, 1730, 1540, 1230 cmK1 1H NMR
;
(500 MHz, CDCl3): d 7.92 (br s, 1H), 7.79 (m, 2H), 7.46
(m, 2H), 7.42 (m, 6H), 5.32 (br s, 2H), 2.22 (s, 3H); 13C
NMR (100 MHz, CDCl3): d 153.8, 149.1, 138.2, 136.2,
129.5, 128.9, 128.7, 128.6, 126.6, 67.8, 13.2; HRMS (DEI-
MS) [MC] Calcd for C12H16N2O2 268.1212, found
268.1205.
4.3.1. Carbonic acid t-butyl ester 1,1-dimethyl-allyl ester
(1d). Following the general procedure, the reaction of
2-methyl-but-3-en-2-ol (1.78 g, 20.7 mmol) with Boc2O
(4.51 g, 20.7 mmol) and n-BuLi (2.5 M in hexane, 9.1 mL,
22.7 mmol) in dry THF (40 mL) gave the desired allylic
carbonate 1d (2.75 g, 71%) as a clear, colorless oil. IR (film)
4.2.2. N0-(1-Ethyl-propylidene)-hydrazinecarboxylic
acid benzyl ester (2h). Following the same procedure as
2a, the reaction of benzylcarbazate (0.83 g, 5.0 mmol) with
3-pentanone (0.79 mL, 0.65 g, 7.5 mmol) in hexane
(10 mL) gave hydrazone 2h (1.1 g, 98%) as a white solid.
The product was used without further purification. Mp 39–
43 8C. IR (film) 3250, 2970, 1720, 1530, 1460, 1230,
2982, 2936, 1741, 1368, 1285, 1126 cmK1 1H NMR
;
(500 MHz, CDCl3): d 6.13 (dd, JZ17.5, 11.0 Hz, 1H),
5.21 (d, JZ18.0 Hz, 1H), 5.14 (d, JZ11.0 Hz, 1H), 1.51 (s,
3H), 1.49 (s, 9H), 1.47 (s, 3H); 13C NMR (75 MHz, CDCl3):
1
1040 cmK1; H NMR (500 MHz, CDCl3): d 7.70 (s, 1H),

R. Matunas et al. / Tetrahedron 61 (2005) 6298–6308
6303
Scheme 2. Preparation of hydrazone 6.
d 152.1, 142.5, 113.2, 81.7, 81.6, 28.1, 26.6; LRMS (EI) m/z
130 (53), 85 (33), 71 (100).
added a solution of DMSO (1.2 mL, 17 mmol) in DCM
(5 mL). After 5 min, a solution of the alcohol 15 (1.5 g,
6.8 mmol) in DCM (10 mL) was added. After a further
15 min, Et3N (3.7 mL, 34 mmol) was added, and the
reaction mixture then allowed to warm to room temperature.
H2O was then added, and the aqueous layer was extracted
with additional DCM. The combined DCM layers were
successively washed with 0.1 M HCl, H2O, saturated
NaHCO3, H2O, and brine; dried over Na2SO4; and
concentrated in vacuo to give aldehyde 16 (1.40 g, 96%)
as an orange oil. The crude product was used without further
purification in the subsequent Grignard addition. IR (film)
4.3.2. Carbonic acid t-butyl ester 4-(t-butyl-dimethyl-
silanyloxy)-1-vinyl-butyl ester (14). To a solution of 6-(t-
butyl-dimethyl-silanyloxy)-hex-1-en-3-ol31 (13, 5.9 g,
26 mmol) in dry THF (25 mL) under argon at K78 8C
was added n-BuLi (2.5 M in hexane, 11.3 mL, 28 mmol)
dropwise. After stirring 3 min, a solution of Boc2O (5.6 g,
26 mmol) in THF (25 mL) was added. The reaction was
allowed to proceed at K78 8C for 30 min, and then the ice
bath was removed. On warming to room temperature, the
reaction was quenched with saturated NH4Cl, and the bulk
of the THF was concentrated in vacuo. The remaining
phases were partitioned between EtOAc and water, and the
aqueous layer was extracted with additional EtOAc. The
combined organic layers were washed with H2O and brine,
dried over Na2SO4, and concentrated in vacuo. The
resulting crude oil was purified by chromatography
(hexane/EtOAc, 40:1/20:1) to give the desired allylic
carbonate 14 (6.6 g, 77%) as a colorless, sticky oil. IR (film)
3087, 2955, 2858, 1742, 1276, 1235, 1169, 1100 cmK1; 1H
NMR (400 MHz, CDCl3): d 5.77 (ddd, JZ17.2, 10.4,
6.4 Hz, 1H), 5.25 (d, JZ17.2 Hz, 1H), 5.16 (d, JZ10.8 Hz,
1H), 4.98 (q, JZ6.7 Hz, 1H), 3.60 (m, 2H), 1.67 (m, 1H),
1.54 (m, 2H), 1.45 (s, 9H), 0.86 (s, 9H), 0.01 (s, 6H); 13C
NMR (100 MHz, CDCl3): d 153.2, 163.6, 117.3, 82.1, 78.0,
62.8, 30.9, 28.5, 28.0, 26.1, 18.5, K5.1.
2928, 2936, 2826, 2727, 1740, 1370, 1275, 1255, 1163 cmK1
;
1H NMR (300 MHz, CDCl3): d 9.77 (s, 1H), 5.77 (ddd, JZ
17.1, 10.5, 6.3 Hz, 1H), 5.30 (d, JZ17.4 Hz, 1H), 5.22 (d,
JZ10.5 Hz, 1H), 5.04 (q, JZ6.1 Hz, 1H), 2.54 (t, JZ
7.4 Hz, 2H), 1.98 (q, JZ7.0 Hz, 2H), 1.48 (s, 9H); 13C NMR
(100 MHz, CDCl3): d 201.2, 153.0, 135.7, 117.9, 82.5, 76.8,
39.6, 28.0, 26.6.
4.3.5. Carbonic acid t-butyl ester 4-hydroxy-4-phenyl-1-
vinyl-butyl ester (17). To a solution of the crude aldehyde
16 (1.4 g, 6.5 mmol) in dry Et2O (7 mL) under argon at 0 8C
was added PhMgCl (1.8 M in THF, 4.5 mL, 8.2 mmol)
dropwise. The reaction was completed within 15 min (by
TLC), and then quenched by addition of saturated NH4Cl.
The aqueous layer was extracted with EtOAc, and the
combined organic phases were washed with H2O, saturated
NaHCO3, H2O, and brine; dried over Na2SO4; and
concentrated in vacuo to give a crude yellow oil.
Purification by chromatography (hexanes/EtOAc, 7.5:1/
5:1) gave the desired alcohol 17 (0.91 g, 46% over 2 steps)
as a clear, colorless oil. The alcohol was characterized as a
mixture of diastereomers. IR (film) 3416, 2980, 2934, 2868,
4.3.3. Carbonic acid t-butyl ester 4-hydroxy-1-vinyl-
butyl ester (15). To a solution of allylic carbonate 14 (6.5 g,
20 mmol) in dry THF (20 mL) under argon was added
TBAF (1.0 M in THF, 25 mL, 25 mmol). The reaction was
complete (by TLC) after 4 h, at which time saturated NH4Cl
was added. The aqueous layer was then extracted with
EtOAc, and the combined organic layers were then washed
with H2O and brine, dried over Na2SO4, and concentrated in
vacuo to give a crude oil. Purification by chromatography
(hexane/EtOAc, 4:1/2:1) gave primary alcohol 15 (4.0 g,
95%) as a clear, colorless oil. IR (film) 3363, 2981, 2937,
1
1739, 1369, 1276, 1255, 1162 cmK1; H NMR (400 MHz,
CDCl3): d 7.31 (m, 4H), 7.25 (m, 1H), 5.74 (ddd, JZ17.2,
10.8, 6.8 Hz, 1H), 5.23 (d, JZ17.6 Hz, 1H), 5.16 (d, JZ
10.4 Hz, 1H), 5.15 (d, JZ10.4 Hz, 1H; diastereomer), 5.00
(m, 1H), 4.66 (m, 1H), 1.95 (d, JZ3.6 Hz, 1H), 1.65–1.85
(m, 3H), 1.60 (m, 1H), 1.45 (s, 9H); 13C NMR (100 MHz,
CDCl3): d 153.2, 144.6, 136.3, 128.7, 127.8, 126.0
(diastereomer), 126.0, 117.5, 82.2, 78.0, 77.7 (diaster-
eomer), 74.4, 74.3 (diastereomer), 34.8, 34.5 (diaster-
eomer), 30.8, 30.6 (diastereomer), 28.0.
2874, 1740, 1370, 1277, 1255, 1163 cmK1 1H NMR
;
(400 MHz, CDCl3): d 5.78 (ddd, JZ17.2, 10.4, 6.8 Hz,
1H), 5.26 (d, JZ17.2 Hz, 1H), 5.17 (d, JZ10.4 Hz, 1H),
5.00 (q, JZ6.8 Hz, 1H), 3.64 (q, JZ6.0 Hz, 1H), 1.5–1.8
(m, 4H), 1.45 (s, 9H), 1.42 (t, JZ5.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d 136.3, 117.4, 82.3, 77.8, 62.6, 30.8,
28.4, 28.0.
4.3.6. Carbonic acid t-butyl ester 4-oxo-4-phenyl-1-vinyl-
butyl ester (18). To a suspension of PCC (436 mg,
2.0 mmol) and NaOAc (33 mg, 0.40 mmol) in DCM
(2 mL) was added a solution of alcohol 17 (394 mg,
1.35 mmol) in DCM (2 mL). After 1 h, an additional
145 mg of PCC was added, and the stirring was continued
4.3.4. Carbonic acid t-butyl ester 4-oxo-1-vinyl-butyl
ester (16). To a solution of oxalyl chloride (0.74 mL,
8.5 mmol) in dry DCM (20 mL) under argon at K60 8C was

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R. Matunas et al. / Tetrahedron 61 (2005) 6298–6308
for an hour before 20 mL of Et2O was added. The reaction
mixture was then filtered through florisil and concentrated in
vacuo to give the crude ketone 18 (377 mg, 96%) as a clear,
colorless oil. This material was used for the next reaction
without further purification. IR (film) 3087, 3082, 2980,
2934, 1740, 1688, 1369, 1275, 1255, 1161 cmK1; 1H NMR
(300 MHz, CDCl3): d 7.95 (d, JZ7.8 Hz, 2H), 7.56 (t, JZ
7.4 Hz, 1H), 7.45 (t, JZ7.6 Hz, 2H), 5.84 (ddd, JZ17.1,
10.5, 6.3 Hz, JZ1H), 5.32 (d, JZ17.1 Hz, 1H), 5.23 (d, JZ
10.5 Hz, 1H), 5.13 (q, JZ6.3 Hz, 1H), 3.06 (t, JZ7.5 Hz,
2H), 2.12 (q, JZ7.1 Hz, 2H), 1.47 (s, 9H); 13C NMR
(100 MHz, CDCl3): d 199.2, 153.1, 137.0, 136.1, 133.3,
128.8, 128.2, 117.6, 82.4, 34.1, 28.6, 28.0.
28.6; HRMS (EI-MS) [MCKi-C4H8] Calcd for
C10H14N2O2 194.1055, found 194.1052.
4.4. Representative procedure for allylic amination
To a solution of hydrazone 2a (70 mg, 0.30 mmol) and
allylic carbonate 1a (40 mg, 0.20 mmol) in dry THF
(0.2 mL) under argon was added Et2Zn (1.0 M in hexanes,
0.15 mL, 0.15 mmol). The resulting solution was allowed to
stir at 25 8C for 8 h to ensure complete consumption of
Et2Zn. After this time, NH4I (29 mg, 0.20 mmol) was
added, followed by a solution of [Ir(COD)Cl2] (6.7 mg,
5 mol%) and pyridine (1.6 mL, 10 mol%) in THF (0.2 mL).
After the reaction was deemed complete by TLC (typically
less than 30 min), the reaction mixture was concentrated in
vacuo and the resulting residue was purified by flash column
chromatography to give the desired allylic amination
product 4a (56 mg, 89%) as a clear, colorless oil.
4.3.7. Carbonic acid 4-(t-butoxycarbonyl-hydrazono)-4-
phenyl-1-vinyl-butyl ester t-butyl ester (6). To a solution
of the crude ketone 18 (370 mg, 1.3 mmol) in hexane
(2 mL) was added t-butyl carbazate (250 mg, 1.9 mmol).
After refluxing overnight, the solution was cooled to room
temperature. Concentration of the solvent in vacuo and
purification by chromatography (10:1 hexanes/EtOAc) gave
three fractions of material: the desired (E)-hydrazone 6
(239 mg, 46%), a mixture of (E) and (Z) isomers (224 mg,
43%), and the undesired (Z)-isomer (50 mg, 10%), all as
thick colorless liquids. Charaterization of the (E)-isomer. IR
(film) 3238, 2980, 2933, 1742, 1528, 1494, 1368, 1273,
1252, 1163 cmK1; 1H NMR (400 MHz, CDCl3): d 7.85 (br
s, 1H), 7.74 (m, 2H), 7.32 (m, 3H), 5.82 (ddd, JZ17.2, 10.8,
6.4 Hz, 1H), 5.33 (d, JZ17.2 Hz, 1H), 5.27 (d, JZ10.8 Hz,
1H), 5.05 (q, JZ6.3 Hz, 1H), 2.65 (t, JZ8.4 Hz, 2H), 1.87
(m, 2H), 1.54 (s, 9H), 1.48 (s, 9H); 13C NMR (100 MHz,
CDCl3): d 153.0, 153.0, 149.8, 137.0, 135.5, 129.4, 128.6,
126.4, 118.3, 82.8, 81.6, 77.0, 60.2, 28.5, 28.0, 21.7; HRMS
(EI-MS) [MC] Calcd for C22H32N2O2 404.2311, found
404.2294. Characterization of the minor (Z)-isomer. IR
(film) 3366, 2979, 2933, 1744, 1714, 1483, 1368, 1275,
1255, 1161 cmK1; 1H NMR (400 MHz, CDCl3): d 7.56 (br
s, 1H), 7.47 (t, JZ7.2 Hz, 2H), 7.40 (t, JZ7.2 Hz, 1H), 7.17
(d, JZ6.8 Hz, 2H), 5.73 (ddd, JZ17.2, 10.8, 6.8 Hz, 1H),
5.23 (d, JZ17.2 Hz, 1H), 5.15 (d, JZ10.4 Hz, 1H), 5.00 (q,
JZ6.4 Hz, 1H), 2.60 (m, 2H), 1.87 (q, JZ7.6 Hz, 2H), 1.43
(s, 18H); 13C NMR (100 MHz, CDCl3): d 153.1, 152.8,
136.1, 133.8, 129.8, 129.6, 127.1, 117.5, 82.2, 81.3, 77.5,
34.2, 31.0, 28.4, 28.0.
4.4.1. N0-(1-Phenyl-ethylidene)-N-(1-vinyl-butyl)-hydra-
zinecarboxylic acid t-butyl ester (4a). IR (film) 2960,
1
2930, 1690, 1370, 1300, 1160 cmK1; H NMR (500 MHz,
CDCl3): d 7.81 (m, 2H), 7.39 (m, 3H), 6.04 (br m, 1H), 5.22
(d, JZ17.4 Hz, 1H), 5.13 (dq, JZ10.2, 0.9 Hz, 1H), 4.68
(br m, 1H), 2.22 (s, 3H), 1.30–1.74 (m, 4H), 1.46 (s, 9H),
0.92 (t, JZ7.4 Hz, 3H); 13C NMR (125 MHz, CDCl3): d
152.4, 138.4, 138.1, 130.3, 128.5, 127.2, 116.5, 80.8, 62.5,
34.9, 28.7, 19.7, 17.3, 14.2; HRMS (DCI-MS) [MC] Calcd
for C19H29N2O2 317.2229, found 317.2221.
4.4.2. N0-(1-Phenyl-ethylidene)-N-(1-vinyl-butyl)-hydra-
zinecarboxylic acid benzyl ester (4b). Following the
representative procedure, the reaction of hydrazone 2b
(80 mg, 0.30 mmol) with allylic carbonate 1a (40 mg,
0.20 mmol) gave 4b (60 mg, 86%) as a clear, colorless
oil. IR (film) 3066, 3033, 2958, 2872, 1703, 1283 cmK1; 1H
NMR (500 MHz, CDCl3): d 7.85 (d, JZ7.0 Hz, 2H), 7.43
(m, 3H), 7.36 (m, 5H), 6.05 (br m, 1H), 5.21 (m, 4H), 4.80
(br m, 1H), 2.20 (s, 3H), 1.76 (m, 1H), 1.62 (m, 1H), 1.36
(m, 2H), 0.93 (t, JZ7.0 Hz, 3H); 13C NMR (125 MHz,
CDCl3): d 171.5, 153.1, 138.0, 137.6, 136.7, 130.6, 128.8,
128.6, 128.3, 127.2, 116.9, 67.6, 62.2, 34.7, 19.7, 17.3, 14.2;
HRMS (DCI-MS) [MC] Calcd for C22H27N2O2 351.2072,
found 351.2074.
4.4.3. N0-(1-Phenyl-ethylidene)-N-(1-vinyl-butyl)-N-p-
toluenesulfonylhydrazine (4c). Following the representa-
tive procedure, the reaction of hydrazone 2c (86 mg,
0.30 mmol) with allylic carbonate 1a (40 mg, 0.20 mmol)
gave 4c (68 mg, 92%) as a clear, colorless oil. IR (film)
3069, 3028, 2959, 2931, 2872, 1959, 1351, 1296, 1163,
4.3.8. N0-(3-Phenyl-propyl)-hydrazinecarboxylic acid
t-butyl ester (3e). To a solution of N0-(3-phenyl-propyl-
idene)-hydrazinecarboxylic acid t-butyl ester 2f (267 mg,
1.1 mmol) in MeOH (5 mL) at 0 8C was added NaCNBH3
(135 mg, 2.2 mmol), along with a few drops of AcOH to
achieve a pH of 4–5. After 15 min, the ice bath was
removed. Upon completion of the reaction (by TLC),
saturated NaHCO3 was added, and the aqueous layer was
extracted with EtOAc. The combined EtOAc layers were
washed with brine, dried over Na2SO4, and concentrated in
vacuo to give a colorless oil. Purification by chromato-
graphy (hexanes/EtOAc, 4:1/2:1) gave alkyl hydrazide 3e
(114 mg, 46%). IR (film) 3316, 2977, 2934, 2863, 1711,
1
1089 cmK1; H NMR (500 MHz, CDCl3): d 7.93 (d, JZ
7.0 Hz, 2H), 7.67 (d, JZ7.0 Hz, 2H), 7.52 (t, JZ7.5 Hz,
1H), 7.47 (t, JZ7.5 Hz, 2H), 7.27 (d, JZ8.0 Hz, 2H), 5.68
(ddd, JZ18.5, 10.5, 7.5 Hz, 1H), 4.93 (d, JZ17.5 Hz, 1H),
4.83 (d, JZ10.5 Hz, 1H), 4.43 (m, 1H), 2.66 (s, 3H), 2.45
(s, 3H), 1.33 (m, 4H), 0.88 (t, JZ7.0 Hz, 3H); 13C NMR
(125 MHz, CDCl3): d 178.8, 143.7, 137.6, 135.5, 135.1,
131.3, 129.3, 129.2, 128.7, 127.6, 117.2, 65.0, 35.6, 21.9,
19.6, 18.3, 14.0; HRMS (EI-MS) [MC] Calcd for
C21H26N2O2S 370.1715, found 370.1707.
1
1454, 1367, 1284, 1234, 1155 cmK1; H NMR (300 MHz,
CDCl3): d 7.27 (m, 2H), 7.17 (m, 3H), 6.01 (br s, 1H), 3.95
(br s, 1H), 2.87 (t, JZ8.7 Hz, 2H), 2.67 (t, JZ7.8 Hz, 2H),
1.76 (m, 2H), 1.46 (s, 9H); 13C NMR (75 MHz, CDCl3): d
157.0, 142.2, 128.6, 128.6, 126.0, 80.7, 51.7, 33.5, 29.7,
4.4.4. Acetic acid N0-(1-phenyl-ethylidene)-N-(1-vinyl-

R. Matunas et al. / Tetrahedron 61 (2005) 6298–6308
6305
butyl)-hydrazide (4d). Following the representative pro-
cedure, the reaction of hydrazone 2d (53 mg, 0.30 mmol)
with allylic carbonate 1a (40 mg, 0.20 mmol) gave of 4d
(9 mg, 17%) as a clear, colorless oil. IR (film) 3072, 2959,
4.4.8. N0-(1-Ethyl-propylidene)-N-(1-vinyl-butyl)-hydra-
zinecarboxylic acid benzyl ester (4h). Following the
representative procedure, the reaction of hydrazone 2h
(60 mg, 0.30 mmol) with allylic carbonate 1a (40 mg,
0.20 mmol) gave 4h (61 mg, 75%) as a clear, colorless
oil. IR (film) 3068, 3033, 2961, 2936, 2874, 1702,
2931, 2872, 1651, 1446, 1379, 1301 cmK1 1H NMR
;
(500 MHz, CDCl3): d 7.20–7.40 (m, 5H), 5.82 (m, 1H),
5.27 (d, JZ18.0 Hz, 1H), 5.16 (d, JZ10.5 Hz, 1H), 4.40 (br
m, 1H), 2.33 (s, 3H), 1.88 (s, 3H), 1.81 (m, 1H), 1.63 (m,
1H), 1.40 (m, 2H), 0.96 (t, JZ7.5 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d 167.8, 136.6, 131.5, 128.8, 128.4,
127.3, 117.9, 59.7, 33.8, 21.9, 19.7, 17.2, 14.1; HRMS
(EI-MS) [MC] Calcd for C16H22N2O 258.17321, found
258.1719.
1
1287 cmK1; H NMR (400 MHz, CDCl3): d 7.30 (m, 5H),
5.86 (br m, 1H), 5.15 (d, JZ17.6 Hz, 1H), 5.09 (m, 3H),
4.60 (m, 1H), 2.36 (q, JZ7.6 Hz, 2H), 2.19 (m, 2H), 1.60
(m, 1H), 1.51 (m, 1H), 1.26 (sextet, JZ7.2 Hz, 2H), 1.08 (t,
JZ7.6 Hz, 3H), 0.94 (t, JZ7.6 Hz, 3H), 0.87 (t, JZ7.2 Hz,
3H); 13C NMR (75 MHz, CDCl3): d 183.2, 153.5, 137.4,
136.8, 128.6, 128.3, 128.2, 117.0, 67.4, 61.4, 34.4, 28.5,
24.4, 19.6, 14.1, 11.3, 10.3; HRMS (EI-MS) [MC] Calcd
for C19H28N2O2 316.2151, found 316.2144.
4.4.5. N0-Benzylidene-N-(1-vinyl-butyl)-hydrazinecar-
boxylic acid t-butyl ester (4e). Following the representa-
tive procedure, the reaction of hydrazone 2e (66 mg,
0.30 mmol) with allylic carbonate 1a (40 mg, 0.20 mmol)
gave 4e (53 mg, 88%) as a clear, colorless oil. IR (film)
3078, 2961, 2933, 2873, 1699, 1368, 1292, 1156 cmK1; 1H
NMR (500 MHz, CDCl3): d 8.90 (br s, 1H), 7.71 (d, JZ
7.5 Hz, 2H), 7.39 (m, 3H), 6.06 (ddd, JZ17.5, 10.5, 7.0,
1H), 5.19 (d, JZ17.0 Hz, 1H), 4.82 (q, JZ7.0 Hz, 1H), 1.94
(m, 1H), 1.67 (m, 1H), 1.56 (s, 9H), 1.37 (m, 2H), 0.96 (t,
JZ7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 153.4,
151.6, 138.6, 136.1, 129.8, 128.7, 127.4, 115.8, 81.5, 62.8,
35.0, 28.6, 18.2, 14.0; HRMS (FAB-MS) [MC] Calcd for
C18H26N2O2 302.1994, found 302.2007.
4.4.9. N0-[1-(4-Bromo-phenyl)-ethylidene]-N-(1-vinyl-
butyl)-hydrazinecarboxylic acid t-butyl ester (4i). Fol-
lowing the representative procedure, the reaction of
hydrazone 2i (94 mg, 0.30 mmol) with allylic carbonate
1a (40 mg, 0.20 mmol) gave 4i (32 mg, 41%) as a clear,
colorless oil. IR (film) 2961, 2931, 2873, 1699, 1304,
1
1158 cmK1; H NMR (500 MHz, CDCl3): d 7.73 (d, JZ
8.5 Hz, 2H), 7.53 (d, JZ8.5 Hz, 2H), 6.04 (br m, 1H), 5.23
(d, JZ17.5 Hz, 1H), 5.16 (d, JZ10.5 Hz, 1H), 4.69 (br m,
1H), 2.21 (s, 3H), 1.72 (m, 1H), 1.59 (m, 1H), 1.49 (s, 9H),
1.35 (m, 2H), 0.94 (t, JZ7.2 Hz, 3H); 13C NMR (125 MHz,
CDCl3): d 168.8, 152.2, 138.0, 137.2, 131.7, 128.7, 124.8,
116.5, 81.0, 62.2, 34.9, 28.6, 19.7, 17.1, 14.2; HRMS
(EI-MS) [MC] Calcd for C19H27N2O2Br 394.1255, found
394.1260.
4.4.6. N0-(3-Phenyl-propylidene)-N-(1-vinyl-butyl)-
hydrazinecarboxylic acid t-butyl ester (4f). Following
the representative procedure, the reaction of hydrazone 2f
(74 mg, 0.30 mmol) with allylic carbonate 1a (40 mg,
0.20 mmol) gave 4f (54 mg, 82%) as a clear, colorless oil.
IR (film) 3064, 3027, 2960, 2932, 2873, 1697, 1454, 1367,
4.4.10. N0-Pent-4-ynylidene-N-(1-vinyl-butyl)-hydra-
zinecarboxylic acid t-butyl ester (4j). Following the
representative procedure, the reaction of hydrazone 2j
(42 mg, 0.30 mmol) with allylic carbonate 1a (40 mg,
0.20 mmol) gave 4j (40 mg, 71%) as a clear, colorless oil.
IR (film) 3313, 2961, 2933, 2873, 1697, 1368, 1293,
1
1294, 1162 cmK1; H NMR (300 MHz, CDCl3): d 7.96 (t,
JZ5.1 Hz, 1H), 7.28 (m, 2H), 7.20 (m, 3H), 5.88 (ddd, JZ
16.8, 11.1, 6.9 Hz, 1H), 5.09 (d, JZ17.1 Hz, 1H), 5.08 (d,
JZ11.1 Hz, 1H), 4.59 (dt, JZ8.7, 6.8 Hz, 1H), 2.88 (t, JZ
7.6 Hz, 2H), 2.67 (m, 2H), 1.66 (m, 1H), 1.48 (m, 1H), 1.47
(s, 9H), 1.25 (sextet, JZ7.4 Hz, 2H), 0.88 (t, JZ7.4 Hz,
3H); 13C NMR (75 MHz, CDCl3): d 160.8, 153.9, 141.3,
138.3, 128.6, 126.2, 115.8, 81.0, 60.8, 35.2, 34.5, 32.5, 28.6,
19.5, 14.0; HRMS (EI-MS) [MC] Calcd for C20H30N2O2
330.2307, found 330.2294.
1
1161 cmK1; H NMR (400 MHz, CDCl3): d 8.03 (t, JZ
4.4 Hz, 1H), 5.90 (ddd, JZ17.2, 10.4, 6.8 Hz, 1H), 5.08 (m,
2H), 4.60 (m, 1H), 2.53 (m, 2H), 2.42 (m, 2H), 1.94 (t, JZ
2.8 Hz, 1H), 1.74 (m, 1H), 1.52 (m, 1H), 1.45 (s, 9H), 1.26
(sextet, JZ7.4 Hz, 2H), 0.88 (t, JZ7.4 Hz); 13C NMR
(75 MHz, CDCl3): d 157.6, 153.7, 138.3, 115.8, 83.6, 81.2,
69.0, 61.0, 34.6, 62.7, 28.6, 19.4, 15.7, 14.0; HRMS (DCI-
MS) [MC] Calcd for C16H26N2O2 278.1994, found
278.1998.
4.4.7. N0-(1-Ethyl-propylidene)-N-(1-vinyl-butyl)-hydra-
zinecarboxylic acid t-butyl ester (4g). Following the
representative procedure, the reaction of hydrazone 2g
(60 mg, 0.30 mmol) with allylic carbonate 1a (40 mg,
0.20 mmol) gave 4g (49 mg, 86%) as a clear, colorless oil.
IR (film) 3077, 2974, 2936, 2875, 1698, 1636, 1460, 1367,
4.4.11. N-(1-Phenyl-allyl)-N0-(1-phenyl-ethylidene)-
hydrazinecarboxylic acid t-butyl ester (4k). Following
the representative procedure, the reaction of hydrazone 2a
(70 mg, 0.30 mmol) with allylic carbonate 1b (47 mg,
0.20 mmol) gave 4k (63 mg, 90%) as a clear, colorless oil.
1
1302, 1253, 1166 cmK1; H NMR (300 MHz, CDCl3): d
IR (film) 3062, 2976, 2929, 1696, 1366, 1300, 1163 cmK1
;
5.87 (br m, 1H), 5.15 (d, JZ17.4 Hz, 1H), 5.09 (d, JZ
10.2 Hz, 1H), 4.53 (m, 1H), 2.39 (q, JZ7.5 Hz, 2H), 2.24
(m, 2H), 1.20–1.60 (m, 4H), 1.43 (s, 9H), 1.34 (t, JZ7.5 Hz,
3H), 1.02 (t, JZ7.5 Hz, 3H), 0.90 (t, JZ7.5 Hz, 3H); 13C
NMR (125 MHz, CDCl3; imine carbonyl not observed due
to quadrupolar broadening): d 152.9, 137.8, 116.6, 80.3,
61.1, 34.4, 28.6, 28.5, 25.0, 24.1, 19.7, 14.1, 11.5, 10.4;
HRMS (EI-MS) [MC] Calcd for C16H30N2O2 282.2307,
found 282.2295.
1H NMR (400 MHz, CDCl3): d 7.74 (d, JZ6.4 Hz, 2H),
7.44 (d, JZ7.6 Hz, 2H), 7.33 (m, 5H), 7.22 (t, JZ7.6 Hz,
1H), 6.34 (ddd, JZ17.6, 9.6, 7.2 Hz, 1H), 5.89 (d, JZ
6.8 Hz, 1H), 5.29 (d, JZ16.8 Hz, 1H), 5.28 (d, JZ10.8 Hz,
1H), 2.14 (s, 3H), 1.42 (s, 9H); 13C NMR (75 MHz, CDCl3):
d 171.2, 152.2, 140.4, 138.2, 136.5, 130.3, 128.4, 128.2,
128.4, 127.4, 127.2, 118.0, 81.1, 65.7, 28.6, 17.4; HRMS
(DCI-MS) [MC] Calcd for C22H27N2O2 351.2072, found
351.2069.

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R. Matunas et al. / Tetrahedron 61 (2005) 6298–6308
4.4.12. N-(1-Phenethyl-allyl)-N0-(1-phenyl-ethylidene)-
hydrazinecarboxylic acid t-butyl ester (4l). Following
the representative procedure, the reaction of hydrazone 2a
(70 mg, 0.30 mmol) with allylic carbonate 1c (52 mg,
0.20 mmol) gave 4l (63 mg, 83%) as a clear, colorless oil.
7.35 (m, 5H), 6.00 (br s, 1H), 5.92 (ddd, JZ17.6, 10.4,
7.6 Hz, 1H), 5.27 (d, JZ17.2 Hz, 1H), 5.16 (d, JZ10.0 Hz,
1H), 4.62 (br d, JZ6.4 Hz, 1H), 4.21 (br s, 1H), 1.42 (s, 9H);
13C NMR (75 MHz, CDCl3): d 156.8, 140.7, 138.5, 128.8,
128.1, 127.9, 117.5, 80.7, 67.4, 28.6; HRMS (DCI-MS)
[MC] Calcd for C14H21N2O2 249.1603, found 249.1612.
IR (film) 3026, 2976, 2930, 1700, 1366, 1302, 1162 cmK1
;
1H NMR (300 MHz, CDCl3): d 7.83 (m, 2H), 7.40 (m, 3H),
7.26 (m, 2H), 7.18 (m, 3H), 6.09 (br m, 1H), 5.23 (d, JZ
17.1 Hz, 1H), 5.17 (d, JZ11.1 Hz, 1H), 4.70 (m, 1H), 2.63
(t, JZ7.8 Hz, 2H), 2.26 (s, 3H), 2.06 (m, 1H), 1.91 (m, 1H),
1.45 (s, 9H); 13C NMR (75 MHz, CDCl3): d 170.3, 152.4,
142.2, 138.3, 137.8, 130.4, 128.8, 128.6, 128.5, 127.2,
126.1, 116.9, 81.0, 61.9, 34.8, 32.9, 28.6, 17.4; HRMS
(EI-MS) [MC] Calcd for C24H30N2O2 378.2307, found
378.2288.
4.4.17. N0-(1,1-Dimethyl-allyl)-hydrazinecarboxylic acid
t-butyl ester (5f). Following the representative procedure,
the reaction of hydrazine 3a (40 mg, 0.30 mmol) with allylic
carbonate 1d (37 mg, 0.20 mmol) gave 5f (33 mg, 82%) as a
sticky colorless oil. IR (film) 3270, 3225, 2980, 2930, 1710,
1
1455, 1365, 1280, 1255, 1165 cmK1; H NMR (500 MHz,
CDCl3): d 5.91 (br s, 1H), 5.80 (dd, JZ17.0, 10.5 Hz, 1H),
5.10 (d, JZ17.0 Hz, 1H), 5.09 (d, JZ10.5 Hz, 1H), 3.82 (br
s, 1H), 1.46 (s, 9H), 1.17 (s, 6H); 13C NMR (125 MHz,
CDCl3): d 157.2, 144.0, 113.7, 80.4, 58.6, 28.6, 24.8; HRMS
(DCI-MS) [MC] Calcd for C10H21N2O2 201.1603, found
201.1599.
4.4.13. N0-(1-Vinyl-butyl)-hydrazinecarboxylic acid
t-butyl ester (5a). Following the representative procedure,
the reaction of hydrazine 3a (40 mg, 0.30 mmol) with allylic
carbonate 1a (40 mg, 0.20 mmol) gave 5a (40 mg, 93%) as a
clear, colorless oil. IR (film) 3320, 2960, 1720, 1460, 1370,
4.4.18. N0-(3-Phenyl-propyl)-N0-(1-vinyl-butyl)-hydra-
zinecarboxylic acid t-butyl ester (5g). Following the
representative procedure, the reaction of hydrazine 3e
(52 mg, 0.30 mmol) with allylic carbonate 1a (40 mg,
0.20 mmol) gave 5g (44 mg, 86%) as a clear, colorless oil.
IR (film) 3234, 3064, 3026, 2959, 2931, 2871, 1743, 1695,
1
1280, 1250, 1170 cmK1; H NMR (400 MHz, CDCl3): d
6.10 (br s, 1H), 5.55 (ddd, JZ8.4, 10.0, 6.8 Hz, 1H), 5.12 (d,
JZ17.2 Hz, 1H), 5.11 (d, JZ10.4 Hz, 1H), 3.89 (br s, 1H),
3.34 (br m, 1H), 1.41 (s, 9H), 1.2–1.4 (m, 4H), 0.87 (t, JZ
7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3): d 156.9, 139.4,
117.9, 80.5, 63.8, 35.3, 28.6, 19.1, 14.3; HRMS (DCI-MS)
[MC] Calcd for C11H23N2O2 215.1760, found 215.1759.
1
1392, 1633, 1171 cmK1; H NMR (300 MHz, CDCl3): d
7.10–7.30 (m, 5H), 5.56 (ddd, JZ17.4, 10.5, 9.0 Hz, 1H),
5.22 (dd, JZ10.2, 2.0 Hz, 1H), 5.10 (dd, JZ17.1, 1.8 Hz,
1H), 4.90 (br s, 1H), 3.08 (br m, 1H), 2.72 (br m, 3H), 2.53
(br m, 1H), 1.78 (m, 2H), 1.64 (m, 1H), 1.46 (m, 1H), 1.46
(s, 9H), 1.38 (m, 2H), 0.90 (t, JZ6.9 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d 155.6, 142.7, 136.1, 128.8, 128.4,
125.8, 118.9, 79.6, 69.0, 54.5, 34.3, 33.4, 29.2, 28.6, 19.6,
14.3; HRMS (EI-MS) [MC] Calcd for C20H32N2O2
332.2463, found 332.2467.
4.4.14. N0-(1-Vinyl-butyl)-hydrazinecarboxylic acidbenzyl
ester (5b). Following the representative procedure, the
reaction of hydrazine 3b (50 mg, 0.30 mmol) with allylic
carbonate 1a (40 mg, 0.20 mmol) gave 5b (43 mg, 86%) as
a clear oil. IR (film) 3320, 3070, 3030, 2960, 2930, 2870,
1
1720, 1460, 1260 cmK1; H NMR (300 MHz, CDCl3): d
7.35 (m, 5H), 6.21 (br s, 1H), 5.58 (dt, JZ17.7, 9.0 Hz, 1H),
5.15 (m, 4H), 3.96 (br s, 1H), 3.39 (br s, 1H), 1.47 (m, 1H),
1.33 (m, 3H), 0.90 (t, JZ6.6 Hz, 3H); 13C NMR (125 MHz,
CDCl3): d 157.4, 139.1, 136.4, 128.8, 128.5, 128.4, 118.3,
67.3, 63.9, 35.2, 19.1, 14.3; HRMS (DCI-MS) [MC] Calcd
for C14H21N2O2 249.1603, found 249.1596.
4.4.19. N0-Isopropyl-N0-(1-vinyl-butyl)-hydrazinecarb-
oxylic acid t-butyl ester (5i). Following the representative
procedure, the reaction of hydrazine 3f32 (75 mg,
0.30 mmol) with allylic carbonate 1a (40 mg, 0.20 mmol)
gave 5g (56 mg, 85%) as a colorless, viscous oil.
Characterized as a mixture of rotamers. IR (film) 3236,
3126, 3075, 2968, 2933, 2873, 1750, 1695, 1392, 1365,
4.4.15. N0-(1-Vinyl-butyl)-N-p-toluenesulfonyl hydrazine
(5c). Following the representative procedure, the reaction of
hydrazine 3c (56 mg, 0.30 mmol) with allylic carbonate 1a
(40 mg, 0.20 mmol) gave 5c (31 mg, 57%) as a clear,
colorless oil. IR (film) 3230, 2950, 2930, 2870, 1320,
1
1174 cmK1; H NMR (300 MHz, CDCl3): d 5.68 (m, 1H),
5.10 (m, 3H), 2.8–8.2 (br m, 2H), 1.55 (m, 1H), 1.41 (s, 9H),
1.41 (m, 1H), 1.33 (m, 2H), 1.00 (d, JZ6.3 Hz, 6H), 0.84 (t,
JZ7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3): d 158.2,
156.3, 139.0, 137.3, 135.8, 118.3, 117.7, 116.7, 79.9, 79.4,
68.1, 66.2, 64.1, 54.4, 52.7, 51.2, 34.6, 34.3, 28.5, 28.0,
21.3, 19.4, 14.3; HRMS (EI-MS) [MC] Calcd for
C14H28N2O2 256.2150, found 256.2138.
1
1160 cmK1; H NMR (500 MHz, CDCl3): d 7.83 (d, JZ
8.5 Hz, 2H), 7.33 (d, JZ9.0 Hz, 2H), 6.01 (br s, 1H), 5.37
(dt, JZ17.0, 10.0 Hz, 1H), 5.20 (dd, JZ10.5, 1.5 Hz, 1H),
5.02 (d, JZ17.0 Hz, 1H), 3.80 (br s, 1H), 2.87 (q, JZ
8.5 Hz, 1H), 2.45 (s, 3H), 1.36 (m, 1H), 1.22 (m, 3H), 0.80
(t, JZ7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3): d 144.3,
137.5, 135.9, 129.8, 128.5, 119.5, 63.6, 34.9, 21.8, 19.0,
14.0; HRMS (DCI-MS) [MC] Calcd for C13H21N2O2S
269.1323, found 169.1334.
4.4.20. 3-Phenyl-6-vinyl-5,6-dihydro-4H-pyridazine-1-
carboxylic acid t-butyl ester (7). Following the repre-
sentative procedure, the reaction of hydrazine 6 (40 mg,
0.10 mmol) gave 7 (25 mg, 88%) as a clear, colorless oil. IR
(film) 3083, 3062, 2978, 2933, 1727, 1698, 1397, 1333,
1153 cmK1; 1H NMR (400 MHz, CDCl3): d 7.77 (d, 8.2 Hz,
2H), 7.32 (m, 3H), 5.72 (ddd, JZ16.9, 10.5, 4.0 Hz, 1H),
5.14 (d, JZ10.5 Hz, 1H), 5.01 (d, JZ16.3 Hz, 1H), 4.99 (br
m, 1H), 2.62 (d, JZ17.7, 5.1 Hz, 1H), 2.38 (ddd, JZ17.9,
12.9, 6.9 Hz, 1H), 1.99 (m, 2H), 1.54 (s, 9H); 13C NMR
4.4.16. N0-(1-Phenyl-allyl)-hydrazinecarboxylic acid
t-butyl ester (5e). Following the representative procedure,
the reaction of hydrazine 3a (40 mg, 0.30 mmol) with allylic
carbonate 1b (47 mg, 0.20 mmol) gave 5e (44 mg, 88%) as a
clear oil. IR (film) 3315, 2978, 1715, 1454, 1367, 1277,
1
1253, 1162 cmK1; H NMR (400 MHz, CDCl3): d 7.25–

R. Matunas et al. / Tetrahedron 61 (2005) 6298–6308
6307
(125 MHz, CDCl3): d 153.4, 146.0, 138.0, 135.2, 129.0,
128.5, 125.5, 115.9, 81.5, 51.9, 28.5, 21.8, 18.9; HRMS
(EI-MS) [MC] Calcd for C17H22N2O2 286.1681, found
286.1668.
79.8, 59.8, 35.2, 28.6, 28.4, 26.1, 24.1, 20.0, 14.3, 11.5,
10.4; HRMS (EI-MS) [MC] Calcd for C16H34N2O2
286.2620, found 286.2633.
4.4.21. N-(1-Vinyl-butyl)-hydrazinecarboxylic acid benzyl
ester (10). To a solution of hydrazone 4b (35 mg,
0.10 mmol) in EtOH (2 mL) was added 37% HCl dropwise
(0.5 mL). After 10 min, the reaction mixture was diluted
with H2O and washed with EtOAc. The aqueous layer was
then brought to a basic pH (ca. 14) with NaOH and extracted
with EtOAc. The combined EtOAc layers were then dried
over Na2SO4 and concentrated in vacuo to give a crude
residue. Purification by chromatography (hexanes/EtOAc,
4:1) gave hydrazine 10 (17.4 mg, 68%) as a clear, colorless
oil. IR (film) 3341, 3223, 6038, 3034, 2958, 2933, 2873,
Acknowledgements
The authors thank Princeton University for startup research
funding and the support from Summer Undergraduate
Research Program (SURP) for A.J.L.
References and notes
1699, 1404, 1298, 1096 cmK1 1H NMR (300 MHz,
;
CDCl3): d 7.33 (m, 5H), 5.83 (ddd, JZ16.8, 10.8, 6.4 Hz,
1H), 5.15 (s, 2H), 5.09 (d, JZ10.4 Hz, 1H), 5.08 (d, JZ
18.4 Hz, 1H), 4.52 (br m, 1H), 3.71 (br s, 2H), 1.73 (m, 1H),
1.48 (m, 1H), 1.24 (sextet, JZ7.4 Hz, 2H), 0.88 (t, JZ
7.4 Hz, 3H); 13C NMR (75 MHz, CDCl3): d 158.2, 137.4,
136.7, 128.7, 128.4, 128.2, 116.1, 67.9, 59.5, 33.6, 19.6,
14.0; HRMS (EI-MS) [MC] Calcd for C14H20N2O2
248.1524, found 248.1516.
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4.4.22. N0-(1-Phenyl-ethyl)-N-(1-vinyl-butyl)-hydrazine-
carboxylic acid benzyl ester (11). To a solution of
hydrazone 4b (70 mg, 0.2 mmol) in MeOH (0.5 mL) at
0 8C was added NaCNBH3 (25 mg, 0.4 mmol), along with a
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zide 11 (64 mg, 90%) as a clear, sticky oil, which was
characterized as a 1:1 mixture of diastereomers. IR (film)
3291, 3065, 3032, 2959, 2931, 2872, 1699, 1454, 1390,
1292, 1095, 670 cmK1; 1H NMR (300 MHz, CDCl3): d 7.30
(m, 10H), 5.85 (m, 1H), 5.46 (m, 1H), 5.17 (s, 4H), 4.90 (m,
4H), 4.20 (m, 4H), 1.55 (m, 2H), 1.32 (m, 8H), 1.11 (m, 4H),
0.80 (t, JZ7.2 Hz, 3H), 0.69 (t, JZ7.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d 158.3, 144.3, 144.0, 138.2, 137.9,
136.6, 128.8, 128.5, 128.4, 128.3, 128.0, 128.0, 127.6,
116.2, 116.0, 67.8, 67.8, 64.1, 63.1, 59.6, 34.6, 21.8, 21.5,
19.8, 19.7, 14.1, 14.0; HRMS (EI-MS) [MC] Calcd for
C22H28N2O2 352.2150, found 352.2140.
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added to a solution of the hydrazone 4g (35 mg, 0.12 mmol)
in EtOH (1 mL), and the reaction mixture was put under a
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2969, 2934, 2875, 1693, 1460, 1366, 1329, 1178, 1152,
1104 cmK1; 1H NMR (500 MHz, CDCl3): d 4.20 (br s, 1H),
2.40 (q, JZ7.3 Hz, 2H), 2.27 (br m, 2H), 1.45 (s, 9H), 1.2–
1.8 (m, 8H), 1.15 (t, JZ7.5 Hz, 3H), 1.06 (t, JZ7.6 Hz,
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