Alkylation of Aldehyde (Arenesulfonyl)hydrazones with Trialkylboranes

Article abstract of DOI:10.1021/jo962089q

(Arenesulfonyl)hydrazone derivatives of aryl aldehydes are readily alkylated by trialkylboranes in the presence of base to generate new organoboranes that may be converted to the corresponding substituted alkanes or alcohols depending upon the reaction conditions chosen. Both tosyl- and trisylhydrazone derivatives can be utilized in the reaction, which tolerates a variety of functional groups, making it a versatile alternative to both the Grignard and Suzuki-coupling reactions.

Full text of DOI:10.1021/jo962089q

3688
J . Org. Chem. 1997, 62, 3688-3695
Alk yla tion of Ald eh yd e (Ar en esu lfon yl)h yd r a zon es w ith
Tr ia lk ylbor a n es
George W. Kabalka,* J ohn T. Maddox, Ekaterini Bogas, and Shane W. Kelley
Departments of Chemistry and Radiology, University of Tennessee, Knoxville, Tennessee 37996-1600
Received November 7, 1996X
(Arenesulfonyl)hydrazone derivatives of aryl aldehydes are readily alkylated by trialkylboranes in
the presence of base to generate new organoboranes that may be converted to the corresponding
substituted alkanes or alcohols depending upon the reaction conditions chosen. Both tosyl- and
trisylhydrazone derivatives can be utilized in the reaction, which tolerates a variety of functional
groups, making it a versatile alternative to both the Grignard and Suzuki-coupling reactions.
Sch em e 1
In tr od u ction
Alkylation of carbonyl compounds by organometallic
reagents is one of the most useful reactions in synthetic
organic chemistry. Typically, only active alkylmetals
such as the organomagnesium,1 organolithium,2 or orga-
nozinc3 reagents can be utilized to achieve this transfor-
mation. Trialkylboranes do not routinely alkylate car-
bonyl compounds, although a few exceptions are known.4
The 1,2-addition of a trialkylborane to a carbonyl com-
pound would be a valuable addition to organic methodol-
ogy. The use of an organoborane reagent would eliminate
many side reactions (enolization, condensation, etc.) that
are associated with the strongly basic, traditional orga-
nometallic reagents5 since organoboron reagents are not
basic. In addition, most organoboranes are stable to
protic solvents such as alcohols and water. Using orga-
noboranes, a wide variety of functional groups6 could then
be incorporated early in the synthetic sequence. Finally,
chiral organoborane reagents could be used to induce
asymmetry in the product molecule, which is not easily
accomplished with traditional organometallics.7
carbonyl. We now wish to report the results of a detailed
study of this new reaction.
Resu lts a n d Discu ssion
Syn th esis of Ar yl Ald eh yd e (Ar en esu lfon yl)h y-
d r a zon es 1. Two hydrazone derivatives were utilized
in this study: tosylhydrazones 1 (Ar ) Ts) and trisylhy-
drazones 1 (Ar ) Tris; 2,4,6-triisopropylbenzenesulfonyl).
Tosyl-9 and trisylhydrazones10 are stable, crystalline
solids that were prepared according to literature proce-
dures and purified by recrystallization from a minimum
quantity of hot ethanol.
Syn th esis of Ar yla lk a n es 3. Hydrazone 1 is readily
alkylated by trialkylboranes in the presence of base. The
reaction generates a new trialkylborane 2 that can be
protonolyzed to the corresponding alkane 3 or oxidized
to the corresponding alcohol 4 (Scheme 1). It had been
noted earlier that trialkylboranes capable of yielding
stable carbanions after deboronation, e.g., 2, are readily
protonolyzed by base.11 In this study, it was found that
nucleophilic bases such as sodium hydroxide (NaOH) and
tetrabutylammonium hydroxide (Bu4NOH) produced ex-
cellent yields of 3 (Scheme 1). Heating the tosylhydra-
zone reactions to reflux in THF allowed them to proceed
to completion in a reasonable time. Table 1 contains a
summary of the reactions in which 3 was produced from
1 and tributylborane in the presence of these two bases.
Bu4NOH provided the highest yields of 3 in the shortest
We recently reported the initial results of a study
involving the alkylation of aryl aldehyde (arenesulfonyl)-
hydrazones using trialkylboranes to produce the corre-
sponding alkanes or alcohols in excellent yields upon
workup (Scheme 1).8 The oxidative reaction sequence is
the equivalent of a 1,2-addition of a trialkylborane to a
X Abstract published in Advance ACS Abstracts, May 1, 1997.
(1) (a) Kharasch, M. S.; Reinmuth, O. Grignard Reactions of Non-
Metallic Substances; Prentice-Hall: New York, 1954. (b) Blomberg,
C.; Hartog, F. A. Synthesis 1977, 18. (c) Larock, R. C. Comprehensive
Organic Transformations; VCH: New York, 1989; pp 553-567.
(2) Wakefield, B. J . Organolithium Methods; Academic Press: New
York, 1988.
(3) (a) Knochel, P.; Singer, R. D. Chem. Rev. 1993, 93, 2117. (b)
Furukawa, J .; Kawabata, N. Adv. Organomet. Chem. 1974, 12, 103.
(4) (a) Miyaura, N.; Itoh, M.; Suzuki, A.; Brown, H. C.; Midland, M.
M.; J acob, P., III. J . Am. Chem. Soc. 1972, 94, 6549. (b) Negishi, E.;
Chiu, K.; Yosida, T. J . Org. Chem. 1975, 40, 1676. (c) Negishi, E.;
Abramovitch, A.; Merrill, R. E. J . Chem. Soc., Chem. Commun. 1975,
138. (d) Review: Negishi, E. J . Organomet. Chem. 1976, 108, 281. (e)
Okada, K.; Hosoda, Y.; Oda, M. Tetrahedron Lett. 1986, 27, 6213. (f)
Mikhailov, B. M.; Baryshnikova, T. K.; Shashkov, A. S. J . Organomet.
Chem. 1981, 219, 301.
(5) Eicher, T. In The Chemistry of the Carbonyl Group; Patai, S.,
Ed.; Interscience Publishers: New York, 1966; p 638.
(6) Brown, H. C.; Kramer, G. W.; Levy, A. B.; Midland, M. M.
Organic Syntheses via Boranes; Wiley-Interscience: New York, 1975;
p 11.
(7) See, for example: (a) Eleveld, M. B.; Hogeveen, H. Tetrahedron
Lett. 1984, 25, 5187. (b) Mukaiyama, T.; Soai, K.; Sato, T.; Shimizu,
H.; Suzuki, K. J . Am. Chem. Soc. 1979, 101, 1455. (c) Mazaleyrat, J .
P.; Cram, D. J . J . Am. Chem. Soc. 1981, 103, 4585. (d) Oguni, N.;
Omi, T. Tetrahedron Lett. 1984, 25, 2823. (e) J oshi, N. N.; Srebnik,
M.; Brown, H. C. Tetrahedron Lett. 1989, 30, 5551.
(8) (a) Kabalka, G. W.; Maddox, J . T.; Bogas, E. J . Org. Chem. 1994,
59, 5530. (b) Kabalka, G. W.; Maddox, J . T.; Bogas, E.; Tejedor, D.;
Ross, E. J . Synth. Commun. 1996, 26, 999.
(9) Kabalka, G. W.; Hutchins, R.; Natale, N. R.; Yang, D. T. C.;
Broach, V. Organic Syntheses; Wiley: New York, 1988; Collect. Vol.
VI, pp 293-298.
(10) (a) Cusack, N. J .; Reese, C. B.; Risius, A. C.; Roozpeikar, B.
Tetrahedron 1976, 32, 2157. (b) Dudman, C. C.; Reese, C. B. Synthesis
1982, 419.
(11) Weinheimer, A. J .; Marsico, W. E. J . Org. Chem. 1962, 27, 1926.
S0022-3263(96)02089-0 CCC: $14.00 © 1997 American Chemical Society

Alkylation of Aldehyde (Arenesulfonyl)hydrazones
J . Org. Chem., Vol. 62, No. 11, 1997 3689
Ta ble 1. Syn th esis of Ar yla lk a n es 3 fr om Tosylh yd r a zon es 1
entry
tosylhydrazone
product
base
time (h)
% yield 3a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
1a (X ) H)
3a
3a
3a
3b
3b
3c
3c
3d
3e
3f
3f
3g
3g
3h
3h
3i
Bu4NOH
Bu4NOH
NaOH
Bu4NOH
NaOH
Bu4NOH
NaOH
Bu4NOH
Bu4NOH
Bu4NOH
NaOH
Bu4NOH
NaOH
Bu4NOH
NaOH
Bu4NOH
NaOH
Bu4NOH
NaOH
1
1
1
80
78b
83
90
89
83
83
89
93
94
99
94
90
89
88
92
93
98
90
91
89
91
1a (X ) H)
1a (X ) H)
1b (X ) 4-methyl)
1b (X ) 4-methyl)
1c (X ) 4-methoxy)
1c (X ) 4-methoxy)
1d (X ) 3-methoxy)
1e (X ) 2-methoxy)
1f (X ) 4-chloro)
1f (X ) 4-chloro)
1g (X ) 4-bromo)
1g (X ) 4-bromo)
1h (X ) 3-bromo)
1h (X ) 3-bromo)
1i (X ) 2-bromo)
1i (X ) 2-bromo)
1j (X ) 4-nitro)
1
17
1.5
17
2.5
2
1
1.5
1
1
1
1
1
1
1
1
1
1
24
3i
3j
3j
3k
3k
3l
1j (X ) 4-nitro)
1k (X ) 3-nitro)
1k (X ) 3-nitro)
1l (X ) 2,4,6-trimethyl)
Bu4NOH
NaOH
Bu4NOH
a
b
Isolated yields based on starting tosylhydrazones. Tosylhydrazone prepared in situ.
Ta ble 2. Syn th esis of Ar yla lk a n es 3 fr om
Tr isylh yd r a zon es 1
Sch em e 2
time
(h)
%
entry
tosylhydrazone
product
T (°C) yield 3a,b
1
2
3
4
5
6
7
8
9
1o (X ) H)
3a
3b
3c
3f
3g
3h
3i
1
1
1.5
1
1
0.5
0.5
0.5
0.5
reflux
reflux
reflux
rt
rt
rt
rt
rt
rt
98
88
81
93
93
96
92
95
96
1p (X ) 4-methyl)
1q (X ) 4-methoxy)
1t (X ) 4-chloro)
1u (X ) 4-bromo)
1v (X ) 3-bromo)
1w (X ) 2-bromo)
1x (X ) 4-nitro)
1y (X ) 3-nitro)
3j
3k
time, although the use of NaOH provides a simple
alternative.
a
b
Isolated yields based on starting trisylhydrazones. Bu4NOH
used as base in all reactions!
Excellent yields were obtained using either Bu4NOH
or NaOH with a variety of substituents present on the
ring. The aryl aldehyde tosylhydrazones may be pre-
pared beforehand or synthesized and used in situ without
a significant decrease in the yield of the final product
(Table 1, entries 1 and 2). Tosylhydrazones containing
both electron-withdrawing and electron-donating sub-
stituents produced excellent yields of alkane, although
reactants containing electron-donating groups required
longer reaction times. Substitution at the ortho position
did not significantly affect the overall reaction yields.
The reaction may also be extended to aromatic het-
erocycles. Both 2-pentylpyrrole and 2-pentylfuran were
produced in good yields (Scheme 2). The slightly lower
yields are presumably due to the increased electron
density in the heterocyclic rings as compared to the
substituted benzene derivatives. This makes formation
of the anion (after deboronation) less favorable, which
results in an incomplete hydrolysis under the reaction
conditions.
The aryl aldehyde trisylhydrazones produce compa-
rable yields of 3 under milder reaction conditions (Table
2). Trisylhydrazones with electron-withdrawing substit-
uents are sufficiently reactive to produce the product
alkane at room temperature. Trisylhydrazones with
electron-donating substituents, however, must be heated
to reflux to produce good yields of alkane.
At present, the reaction appears limited to aryl alde-
hyde derivatives. Preliminary experiments involving
tosyl derivatives of aliphatic aldehydes have been unsuc-
cessful, and only modest alkylation yields have been
observed in reactions involving trisylhydrazones.12
Syn th esis of Ar yl Alcoh ols 4. Oxidation of inter-
mediate 2 produces alcohol 4 if a non-nucleophilic base
is utilized (Scheme 1). The use of a non-nucleophilic base
minimizes the deboronation of 2 and subsequent proto-
nolysis to 3. Several bases were surveyed for use in this
new reaction. Triethylamine, diisopropylethylamine, di-
ethylamine, Proton Sponge (1,8-bis(dimethylamino)-
naphthalene), and lutidine were examined. These hin-
dered bases were not sufficiently basic to remove the
sulfonamide proton from the tosylhydrazone in the initial
step of the reaction.
The strong kinetic bases, butyllithium, lithium hex-
amethyldisilazide (LiHMDS), and sodium hydride, pro-
duced modest yields of the desired alcohol after oxidation.
The chief drawback to their use is that they form
tosylhydrazone anion salts that precipitate from solution,
impeding further reaction with the trialkylborane. The
hindered base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)
produced a 43% yield of the desired alcohol product after
7 h at room temperature. Simply heating the reaction
to reflux increased the yield of product to 73% in 1 h.
(12) The trisylhydrazone of heptanal was prepared and (without
isolation) was added to a solution of tributylborane and DBU. Diazene
11 was isolated from the reaction mixture (after protonolysis) along
with a 14% yield of the desired product, undecane.

3690 J . Org. Chem., Vol. 62, No. 11, 1997
Kabalka et al.
Ta ble 3. Syn th esis of Ar yl Alcoh ols 4 fr om
Tosylh yd r a zon es 1: Oxid a tion w ith Sod iu m P er bor a te
Ta ble 4. Syn th esis of Ar yl Alcoh ols 4 fr om
Tosylh yd r a zon es 1: Oxid a tion w ith P er a cetic Acid
time
%
%
Time
(h)
%
%
entry
tosylhydrazone
1a (X ) H)
products (h) yield 4a yield 3a
entry Tosylhydrazone Products
Yield 4a Yield 3a
1
2
3
4
5
6
7
8
4a /3a
4b/3b
4c/3c
4d /3d
4e/3e
4g/3g
4j/3j
0.5
1.5
3
1.5
1.5
1
73
83
71
76
86
30
0
15b
5b
1
2
3
4
5
6
7
1a (X ) H)
4a /3a
4f/3f
4g/3g
4h /3h
4i/3i
0.5
0.5
1
1
1
74
80
80
78
80
0
17
1b (X ) 4-methyl)
1c (X ) 4-methoxy)
1d (X ) 3-methoxy)
1e (X ) 2-methoxy)
1g (X ) 4-bromo)
1j (X ) 4-nitro)
1f (X ) 4-chloro)
1g (X ) 4-bromo)
1h (X ) 3-bromo)
1i (X ) 2-bromo)
1j (X ) 4-nitro)
1k (X ) 3-nitro)
15b
17
8b
15
14
70
87
0
18
17b
84
4j/3j
4k /3k
1
1
1
1
62
23
1l (X ) 2,4,6-trimethyl) 4l/3l
90
a
b
Isolated yield based on starting tosylhydrazone. GC yield.
a
b
Isolated yield based on tosylhydrazone. GC yield.
Ta ble 5. Syn th esis of Ar yl Alcoh ols 4 fr om
Tosylh yd r a zon es 1: Oxid a tion w ith TMANO
Thus, DBU is sufficiently basic to produce the tosylhy-
drazone anion necessary for reaction with the trialkyl-
borane. It is also non-nucleophilic and does not proto-
nolyze the intermediate organoborane 2. Consequently,
DBU was chosen as the standard base for this study.
time
(h)
%
%
entry
tosylhydrazone
products
yield 4a yield 3a
1
2
3
1a (X ) H)
1j (X ) 4-nitro)
1k (X ) 3-nitro)
4a /3a
4j/3j
4k /3k
0.5
1
1
83
0
64
84
24
The alcohol synthesis involves, in the last step, the
oxidation of intermediate 2 to alcohol 4 (Scheme 1).
Compound 2, a benzylic organoborane, is particularly
susceptible to protonolysis to form 3. Consequently, the
use of the classic sodium hydroxide-hydrogen peroxide
oxidation procedure must be avoided to maximize the
yield of the desired alcohol.13
a
Isolated yield based on tosylhydrazone.
derivatives (Table 4, entries 3-5) demonstrate, again, that
the regiochemistry of the substituent has little effect on
the yield of the reaction.
The 3-nitro derivative (Table 4, entry 7) produced a
relatively low yield of alcohol 4k compared to the other
entries, presumably due to the electron-withdrawing
properties of the nitro group. In fact, when the nitro
group was para to the original carbonyl group (Table 4,
entry 6), only the alkane product was produced. Both
oxidizing procedures (NaBO3‚4H2O and peracetic acid)
produced only alkane 3j from the 4-nitro substrate. Use
of an anhydrous oxidant, trimethylamine N-oxide
(TMANO),16 also resulted in exclusive production of
alkane 3j (Table 5). Apparently, the 4-nitro group
stabilizes the incipient benzylic anion involved in the
protonolysis of the intermediate organoborane to such an
extent that it becomes the primary reaction pathway. Use
of the anhydrous TMANO oxidation also did not enhance
the yield of alcohol 4k obtained from the 3-nitro deriva-
tive 1k (Table 5, entry 3). It did, however, increase the
yield of alcohol 4a produced from benzaldehyde tosylhy-
drazone, 1a (Table 5, entry 1).
The aryl aldehyde trisylhydrazones were then inves-
tigated as substrates for the alcohol synthesis. These
derivatives produced alcohol 4 in excellent yield and
proceeded under very mild conditions. Whereas the tosyl
derivatives required heating to reflux in THF, the trisyl
derivatives reacted at room temperature to give compa-
rable or enhanced yields of product (Table 6).
The standard oxidizing procedures were also utilized
for the trisylhydrazone reactions. Both sodium perborate
(Table 6, entries 1-5 and 9) and peracetic acid (Table
6, entries 6-8) were used as oxidants. Good yields of
alcohol 4 were obtained when either electron-withdraw-
ing or electron-donating groups were present in the
trisylhydrazone starting materials. The hindered 2,4,6-
trimethyl derivative 1z also produced an excellent yield
of alcohol 4l.
Sodium perborate (NaBO3‚4H2O) is a stable, easily
handled, solid oxidant that has been shown to be an
efficient oxidizing agent for trialkylboranes.14 Perborate
oxidations proceed at room temperature under conditions
less stringent than the classical peroxide procedure. Use
of this oxidant produced the desired alcohol, 4, in good
yields from most tosylhydrazone substrates (Table 3).
Minor amounts of alkane 3 are produced as a byproduct
since water is added along with the sodium perborate,
and some hydrolysis occurs.
Both the methoxy- and methyl-substituted tosylhydra-
zones produce good yields of alcohol 4. The results from
reactions utilizing the isomeric methoxy derivatives
(Table 3, entries 3-5) demonstrate that the reaction is
insensitive to substituent regiochemistry. The hindered
2,4,6-trimethyl derivative (Table 3, entry 8), prepared
from mesitaldehyde, produced an excellent yield of
alcohol 4l, which suggests that the reaction is also
insensitive to steric effects in the tosylhydrazone. The
4-bromobenzaldehyde (1g) and 4-nitrobenzaldehyde (1j)
tosylhydrazones produced the corresponding alkanes as
the major products. Electron-withdrawing substituents
in the para position presumably stabilize the benzylic
anion leading to the formation of alkane (Table 3, entries
6 and 7). Thus, less basic oxidants were investigated.
Peracetic acid has been used to successfully oxidize
water-sensitive organoboranes.15 The use of peracetic
acid increased the yield of 4 dramatically (Table 4). For
example, the use of peracetic acid reversed the result
obtained with sodium perborate for the 4-bromo deriva-
tive (Table 4, entry 3, versus Table 3, entry 6). Several
substrates bearing electron-withdrawing groups were
oxidized with peracetic acid, and most gave excellent
yields of alcohol 4 with the remainder of product being
alkane 3. The results obtained utilizing the three bromo
An anomalous result was obtained when bromine was
present in the ortho position (Table 6, entry 8). Instead
of alcohol 4i, a good yield of the corresponding alkane 3i
was isolated. It was initially hypothesized that the
increased basicity of the trisyl anion, together with the
ortho effect of the electron-withdrawing substituent,
(13) Brown, H. C.; Sharp, R. L. J . Am. Chem. Soc. 1966, 88, 5851.
(14) Kabalka, G. W.; Shoup, T. M.; Goudgaon, N. M. J . Org. Chem.
1989, 54, 5930.
(15) Kidwell, R. L.; Murphy, M.; Darling, S. D. Organic Syntheses;
Wiley: New York, 1973; Collect. Vol. V, pp 918-921.
(16) Soderquist, J . A.; Najafi, M. R. J . Org. Chem. 1986, 51, 1330.

Alkylation of Aldehyde (Arenesulfonyl)hydrazones
J . Org. Chem., Vol. 62, No. 11, 1997 3691
Ta ble 6. Syn th esis of Ar yl Alcoh ols 4 fr om
Tr isylh yd r a zon es 1
Sch em e 3
entry
trisylhydrazone
1o (X ) H)
1p (X ) 4-methyl)
1q (X ) 4-methoxy)
1r (X ) 3-methoxy)
1s (X ) 2-methoxy)
1u (X ) 4-bromo)
1v (X ) 3-bromo)
product time (h) % yield 4a
1
2
3
4
5
6
7
8
9
4a
4b
4c
4d
4e
4g
4h
4i
2
2
3
1
1
1
1
1
1
90b
87b
80b
76b
88b
86c
83c
1w (X ) 2-bromo)
1z (X ) 2,4,6-trimethyl)
0c,d
91b
4l
Isolated yield based on starting hydrazone. b Sodium perborate
a
used as oxidant. c Peracetic acid was used as oxidant. 89% yield
d
of alkane product isolated. e 82% yield of alkane product isolated.
Ta ble 7. Rea ction of p-Tolu a ld eh yd e Tosylh yd r a zon e
w ith Va r iou s Tr ia lk ylbor a n es
5a,b (%)
6a,c (%)
Sch em e 4
entry
R
products
1
2
3
4
5
6
-CH2(CH2)3CH2Cl
-CH2(CH2)3CH2CN
-CH2(CH2)9COOCH3
-Chxe
5a a /6a a
5bb/6bb
5cc/6cc
5d d /6d d
5ee/6ee
5ff/6ff
75
72
75
68
51
91d
98
89
71
62
80
-CH(CH3)CH2CH3
-Phf
a
b
Isolated yields. Oxidized using sodium perborate. c Bu4NOH
used as the base. Two equivalents of Bu4NOH. e Chx ) cyclo-
d
hexyl. f From triphenylboron.
contributed to the production of alkane product. How-
ever, when this concept was tested by preparing the
intermediate organoborane that would be formed from
the reaction of 2-bromobenzaldehyde tosylhydrazone
with base and then treating it with the trisyl anion, none
of alkane 3i was observed. Current research is directed
at clarifying these unusual results.
starting tosylhydrazone would generate an anion (7,
Scheme 3). The trialkylborane would then react with this
anion to form an electron-rich organoborane complex that
would spontaneously undergo a 1,2-boratropic shift,17
expelling nitrogen and the p-toluenesulfinate anion, to
produce the new organoborane 2. The new benzylic
borane would then be hydrolyzed to the corresponding
alkane 3 or oxidized to alcohol 4. Alternatively, the
reaction could proceed via a diazo mechanism (Scheme
4). Removal of a proton from the aryl aldehyde tosylhy-
drazone would generate the anion, which could then
decompose to the intermediate diazo compound, 8, prior
to reacting with the trialkylborane. The borate complex,
once formed, would undergo a spontaneous 1,2-boratropic
shift, expelling nitrogen, to generate trialkylborane 2.
Reactions of R-diazocarbonyl compounds with trialkylbo-
ranes are known.18 The difficulty in elucidating which
mechanism is operative lies in the fact that they differ
only in the timing of the tosyl group loss.
F u n ction a lized Or ga n obor a n es. Organoboranes
have been particularly useful in organic synthesis be-
cause of their exceptional tolerance of a wide variety of
functional groups. An advantage of this new reaction is
that functionalized alkyl groups can thus be incorporated
into the alcohol or alkane product. As noted previously,
this is difficult to achieve using traditional organometallic
reagents. Table 7 contains examples of functionalized
organoboranes that were reacted with p-tolualdehyde
tosylhydrazone, 1b, and the yields of the respective
product alkanes and alcohols obtained. Entries 1-3
(Table 7) demonstrate that halo, cyano, and ester groups
are readily tolerated using this methodology and good
yields of either the corresponding alcohol or alkane are
obtained. Entries 4 and 5 (Table 7) reveal that secondary
alkyl groups may also be utilized. Finally, entry 6 (Table
7) shows that a phenyl group can be transferred. In this
case, production of the corresponding alcohol is difficult
to achieve due to the ready protonolysis of the intermedi-
ate organoborane with two electronegative aromatic
groups attached to the benzylic carbon.
(17) For reviews, see: Matteson, D. In The Chemistry of the Metal-
Carbon Bond; Hartley, F. R., Ed.; Wiley: New York, 1984; pp 307-
409. Pelter, A.; Smith; Brown, H. C. Borane Reagents; Academic
Press: New York, 1988; pp 256-301.
(18) (a) Hooz, J .; Morrison, G. F. Can. J . Chem. 1970, 48, 868. (b)
Hooz, J .; Linke, S. J . Am. Chem. Soc. 1968, 90, 5936. (c) Hooz, J .;
Linke, S. J . Am. Chem. Soc. 1968, 90, 6891.
Mech a n ism of th e Rea ction . There are two possible
mechanistic courses for the new reaction. In the first,
the anion mechanism, removal of a proton from the

3692 J . Org. Chem., Vol. 62, No. 11, 1997
Kabalka et al.
Sch em e 5
results suggest that either the reaction proceeds via the
anion mechanism or the reaction of the trialkylborane
with the diazo intermediate is more efficient than the
cycloaddition with dimethyl maleate.
The reaction of trialkylboranes with diazo compound
8 was then investigated. Compound 8a (X ) H) was
prepared in 90% yield from benzaldehyde trisyl-
hydrazone.10b The diazo compound was then reacted with
tributylborane under a variety of conditions. In the first
series of experiments, a solution of tributylborane in THF
was added directly to 8a . Vigorous gas evolution was
observed, and several products were formed but little of
the desired alcohol 4a was obtained after oxidation.
Then, a solution of 8a in THF was added dropwise to a
solution of tributylborane in THF; in this case, 37% of
the alcohol product was isolated after oxidation. When
the dropwise addition reaction was conducted in the
presence of DBU, 55% of 4a was isolated after oxidation.
This is much lower than the 90% yield typically produced
under the normal trisylhydrazone reaction conditions. A
2-fold excess of 8a was necessary to produce 93% of the
desired product 4a . It is therefore possible to obtain the
desired alkylation reaction via reaction of the diazo
intermediate with tributylborane, but a 2-fold excess is
necessary to obtain a yield comparable to that observed
in the in-situ reaction.
Benzaldehyde trisylhydrazone was then mixed with
DBU in THF to determine if the diazo compound is
produced under the normal reaction conditions. After 2
h at room temperature, very little starting material was
consumed and a small amount of the diazo compound
formed. To eliminate the possibility that tributylborane,
a Lewis acid, catalyzes the formation of the diazo
intermediate, tribromoborane was added to a mixture of
benzaldehyde trisylhydrazone and DBU. Tribromobo-
rane had no effect on the formation of the diazo com-
pound, and disappearance of the starting material was
not observed.
Both the tosyl and trisyl reactions were monitored by
11B NMR. Immediate formation of an intermediate was
detected at room temperature in both cases upon addition
of DBU to the reaction mixture. This was evidenced by
an upfield shift of the 11B resonance. In the trisylhydra-
zone reaction mixture, the boron resonance shifted from
85 to 18 ppm, while in the tosylhydrazone reactions, a
shift to 37 ppm was observed. The borate intermediate
then disappeared, and a new resonance appeared at 8
ppm in both reactions. The reaction was repeated using
the diazo compound. 8a was slowly added to a solution
of tributylborane and DBU in THF at -78 °C. 11B-NMR
analysis revealed a resonance at -4 ppm. When the
reaction mixture was allowed to come to rt, a new
resonance was observed at 1 ppm. These results differ
from those obtained in the hydrazone reactions and
suggest that the hydrazone reactions do not proceed via
the diazo mechanism.
Con clu sion s. The development of a new alkylation
reaction that is the synthetic equivalent of the 1,2-
addition of a trialkylborane to a carbonyl compound has
been achieved. Both aryl aldehyde tosylhydrazones and
trisylhydrazones are readily alkylated with trialkylbo-
ranes in the presence of base to produce the correspond-
ing substituted arylalkanes or alcohols. Several func-
tional groups may be present in either the hydrazone or
the trialkylborane. The trisylhydrazones react more
readily than the corresponding tosylhydrazones, produc-
ing either the alkane or alcohol products in excellent
Tosylhydrazones have been used to generate diazo
compounds,19 and the generation of an aryl diazo com-
pound, such as that shown in Scheme 4, is possible under
the conditions employed in this new reaction. When
p-tolualdehyde tosylhydrazone was treated with DBU in
the absence of an organoborane under the standard
reaction conditions, a deep red color formed that can be
attributed to the formation of a diazo compound. In fact,
when pentane extracts of this reaction mixture were
examined by IR, a sharp band at 2050 cm-1 was noted.
The characteristic IR band of aryl diazo compounds has
been reported to be in the range 2020-2060 cm-1 19c
The
.
reaction, however, does not go to completion, and as
evidenced by TLC, starting tosylhydrazone was still
present after the typical reaction period of 1 h. Recovery
of the starting material was verified by flash chroma-
tography, which resulted in a 29% recovery of p-tolual-
dehyde tosylhydrazone. p-Toluenesulfonohydrazide was
also detected, which indicates that decomposition of the
starting hydrazone also took place.
Dimethyl maleate was then used to probe the reaction
mechanism. Dimethyl maleate reacts with aryl diazo
compounds via a 1,3-dipolar cycloaddition to generate
trans-5-aryl-4,5-dihydro-1H-pyrazole-3,4-dicarboxylic acid
dimethyl esters (10, Scheme 5).20 Reaction of p-tolual-
dehyde tosylhydrazone, 1b, with dimethyl maleate and
DBU in the absence of trialkylborane in refluxing THF,
produced a 76% isolated yield of 10b. When the reaction
was run in the presence of trialkylborane (Scheme 5), an
80% isolated yield of alcohol (trialkylborane reaction) was
produced after oxidation and none of pyrazoline 10b was
detected. In an attempt to enhance the rate of the
maleate reaction, it was repeated but modified such that
the solution containing 1b, the borane, and dimethyl
maleate was heated to reflux prior to the addition of base.
Once again, a 77% yield of alcohol was produced. These
(19) (a) Creary, X. Organic Syntheses; Wiley: New York, 1990;
Collect. Vol. VII, pp 438-443. (b) Woulfman, D. S.; Yousefian, S.;
White, J . M. Synth. Commun. 1988, 18, 2349. (c) J on´czyk, A.;
Włostowska, J . Synth. Commun. 1978, 8, 569. (d) Kaufman, G. M.;
Smith, J . A.; Vander Stouw, G. G.; Shechter, H. J . Am. Chem. Soc.
1965, 87, 935. (e) Farnum, D. G. J . Org. Chem. 1963, 28, 870.
(20) J ones, W. M. J . Am. Chem. Soc. 1959, 81, 5153.

Alkylation of Aldehyde (Arenesulfonyl)hydrazones
J . Org. Chem., Vol. 62, No. 11, 1997 3693
refrigerator overnight, and the resulting solid was collected
by vacuum filtration and washed with 3 × 5 mL of cold
methanol. The products were recrystallized from hot ethanol.
The physical and spectral properties of previously reported
compounds were in accord with literature values. The physical
data from newly prepared derivatives are presented below.
yields at room temperature. The reaction thus provides
a useful alternative to both the Grignard and transition-
metal-catalyzed coupling reactions such as the Suzuki
reaction.21
4-Meth ylben za ld eh yd e tr isylh yd r a zon e (1p ): 1H-NMR
(DMSO-d6) δ 11.61 (s, 1H), 7.89 (s, 1H), 7.41 (d, 2H, J ) 8.0
Hz), 7.17 (d, 2H, J ) 8.0 Hz), 4.23 (sept, 2H, J ) 6.7 Hz), 2.88
(sept, 1H, J ) 6.7 Hz), 2.27 (s, 3H), 1.21 (d, 12H, J ) 6.7 Hz),
1.17 (d, 6H, J ) 7.1 Hz); 13C-NMR (DMSO-d6) δ 152.58, 150.37,
144.94, 139.60, 132.56, 131.15, 129.26, 126.47, 123.53, 33.29,
29.14, 24.67, 23.33, 20.86. Anal. Calcd for C23H32N2O2S: C,
68.96; H, 8.05; N, 6.99. Found: C, 68.93; H, 8.06; N, 7.04.
4-Met h oxyb en za ld eh yd e t r isylh yd r a zon e (1q ): 1H-
NMR (DMSO-d6) δ 11.49 (s, 1H), 7.88 (s, 1H), 7.47 (d, 2H, J )
8.6 Hz), 7.22 (s, 2H), 6.92 (d, 2H, J ) 8.6 Hz), 4.24 (sept, 2H,
J ) 6.6 Hz), 3.74 (s, 3H), 2.88 (sept, 1H, J ) 6.8 Hz), 1.21 (d,
12H, J ) 6.7 Hz), 1.16 (d, 6H, J ) 6.9 Hz); 13C-NMR (DMSO-
d6) δ 160.58, 152.53, 150.38, 144.88, 132.61, 128.06, 126.45,
123.49, 114.17, 55.22, 33.30, 29.14, 24.68, 23.32. Anal. Calcd
for C23H32N2O3S: C, 66.31; H, 7.74; N, 6.72. Found: C, 66.49;
H, 7.67; N, 6.95.
3-Meth oxyben za ld eh yd e tr isylh yd r a zon e (1r ): 1H-NMR
(DMSO-d6) δ 11.75 (s, 1H), 7.91 (s, 1H), 7.31-7.23 (m overlap-
ping s, 3H), 7.10-7.08 (m, 2H), 6.94-6.90 (m, 1H), 4.26 (sept,
2H, J ) 6.7 Hz), 3.73 (s, 3H), 2.90 (sept, 1H, J ) 6.8 Hz), 1.24
(d, 12H, J ) 6.7 Hz), 1.20 (d, 6H, J ) 6.9 Hz); 13C-NMR (CDCl3)
δ 159.73, 153.44, 151.29, 146.12, 134.70, 131.20, 129.49,
123.82, 120.58, 116.96, 110.71, 55.20, 34.13, 29.96, 24.79,
23.47. Anal. Calcd for C23H32N2O3S: C, 66.31; H, 7.74; N,
6.72. Found: C, 66.24; H, 7.78; N, 6.72.
Exp er im en ta l Section
All melting points are uncorrected. Elemental analyses
were performed by Atlantic Microlabs, Norcross, GA.
All glassware, syringes, and needles were dried in an oven
heated to 250 °C for at least 12 h and cooled under argon prior
to use. All solvents were dried and distilled prior to use.22
Reactions were magnetically stirred and monitored by TLC.
Products were purified by flash chromatography using 230-
400 mesh ASTM 60 Å silica gel.23
Tributylborane, triphenylborane, and p-toluenesulfonohy-
drazide were purchased from Aldrich Chemical Co. and used
without further purification. 2,4,6-Triisopropylbenzenesulfono-
hydrazide was prepared from 2,4,6-triisopropylbenzenesulfonyl
chloride according to the literature procedure.10a 5-Chloro-1-
pentene (Fairfield Chemical Co.), 5-hexenitrile (Acros Chemi-
cal Co.), and methyl 10-undecenoate (Eastman Chemical Co.)
were hydroborated according to published procedures to gener-
ate the functionalized trialkylboranes listed in Table 5.24-26
Gen er a l P r oced u r e for th e Syn th esis of Ar yl Ald eh yd e
Tosylh yd r a zon es. To a solution of p-toluenesulfonohy-
drazide (5.62 g, 30.2 mmol) in absolute ethanol (17 mL) was
added the aldehyde (26.6 mmol). The reaction mixture was
stirred and heated to reflux for 10 min. The mixture was
cooled, and the precipitated product was collected and recrys-
tallized from hot ethanol.
2-Meth oxyben za ld eh yd e tr isylh yd r a zon e (1s): 1H-NMR
(DMSO-d6) δ 11.61 (s, 1H), 8.26 (s, 1H), 7.58-7.55 (m, 1H),
7.35-7.29 (m, 1H), 7.22 (s, 2H), 7.03-6.86 (m, 1H), 4.23 (sept,
2H, J ) 6.7 Hz), 3.78 (s, 3H), 2.88 (sept, 1H, J ) 6.8 Hz), 1.20
(d, 12H, J ) 6.8 Hz), 1.17 (d, 6H, J ) 6.2 Hz); 13C-NMR (CDCl3)
δ 157.76, 153.27, 151.36, 142.38, 131.41, 126.43, 123.79,
121.88, 120.58, 110.93, 55.15, 30.03, 24.90, 24.82, 23.55. Anal.
Calcd for C23H32N2O3S: C, 66.31; H, 7.74; N, 6.72. Found: C,
66.17; H, 7.69; N, 6.79.
The yields and melting points of the tosylhydrazone prod-
ucts are presented in Table 8 (Supporting Information). The
physical and spectral properties of previously reported com-
pounds were in accord with literature values and are sum-
marized in Table 9 (Supporting Information). The physical
data from newly prepared derivatives are presented below.
3-Meth oxyben za ld eh yd e tosylh yd r a zon e (1d ): 1H-NMR
(acetone-d6) δ 10.14 (s, 1H), 7.95 (s, 1H), 7.85 (d, 2H, J ) 8.2
Hz), 7.37 (d, 2H, J ) 8.2 Hz), 7.28 (t, 1H, J ) 7.8 Hz), 7.20-
7.13 (m, 2H), 6.96-6.90 (m, 1H), 3.78 (s, 3H), 2.36 (s, 3H); 13C-
NMR (CDCl3) δ 159.67, 147.87, 144.22, 135.17, 134.53, 129.64,
129.54, 127.86, 120.43, 116.64, 111.40, 55.26, 21.50. Anal.
Calcd for C15H16N2O3S: C, 59.19; H, 5.30; N, 9.20. Found: C,
59.26; H, 5.34; N, 9.25.
1
4-Ch lor oben za ld eh yd e tr isylh yd r a zon e (1t): H-NMR
(DMSO-d6) δ 11.83 (s, 1H), 7.91 (s, 1H), 7.54 (d, 2H, J ) 8.6
Hz), 7.43 (d, 2H, J ) 8.6 Hz), 7.23 (s, 2H), 4.22 (sept, 2H, J )
6.7 Hz), 2.89 (sept, 1H, J ) 6.9 Hz), 1.89 (overlapping doublets,
J ) 7.0, 7.1 Hz); 13C-NMR (DMSO-d6) δ 152.70, 150.37, 143.48,
134.23, 132.77, 132.44, 128.79, 128.08, 123.58, 33.29, 29.16,
24.65, 23.32. Anal. Calcd for C22H29N2SO2Cl: C, 62.77; H,
6.94; N, 6.65. Found: C, 62.92; H, 6.93; N, 6.73.
2-P yr r oleca r boxa ld eh yd e tosylh yd r a zon e (1m ): 1H-
NMR (DMSO-d6) δ 11.22 (br s, 1H), 7.77 (d, 2H, J ) 8.2 Hz),
7.72 (s, 1H), 7.36 (d, 2H, J ) 8.2 Hz), 6.83 (d, 1H, ) 1.1 Hz),
6.33 (s, 1H), 6.05 (m, 1H), 2.34 (s, 3H); 13C-NMR (DMSO-d6) δ
142.99, 140.26, 136.48, 129.41, 127.23, 126.53, 122.08, 112.76,
108.99, 20.93. Anal. Calcd for C12H13N3O2S: C, 54.74; H, 4.98;
N, 15.96. Found: C, 54.63; H, 5.02; N, 15.93.
1
4-Br om oben za ld eh yd e tr isylh yd r a zon e (1u ): H-NMR
(DMSO-d6) δ 11.80 (s, 1H), 7.92 (s, 1H), 7.52 (m, 4H), 7.22 (s,
2H), 4.25 (sept, 2H, J ) 6.6 Hz), 2.90 (sept, 1H, J ) 6.7 Hz),
1.23 (d, 12H, J ) 6.6 Hz), 1.20 (d, 6H, J ) 6.7 Hz); 13C-NMR
(DMSO-d6) δ 152.52, 150.30, 143.40, 133.07, 132.40, 131.53,
128.20, 123.40, 122.87, 33.29, 29.09, 24.60, 23.26. Anal. Calcd
for C22H29N2O2SBr: C, 56.77; H, 6.28; N, 6.02. Found: C,
56.58; H, 6.19; N, 6.11.
1
2-F u r a ld eh yd e tosylh yd r a zon e (1n ): H-NMR (DMSO-
d6) δ 11.42, (s, 1H), 7.80-7.70 (m, 4H), 7.38 (d, 2H, J ) 8.1
Hz), 6.79 (d, 1H, J ) 3.3 Hz), 6.54 (m, 1H), 2.34 (s, 3H); 13C-
NMR (DMSO-d6) δ 148.55, 145.00, 143.43, 136.88, 136.09,
129.65, 127.12, 113.80, 111.95, 20.94. Anal. Calcd for
C12H12N2O3S: C, 54.53; H, 4.58; N, 10.60. Found: C, 54.66;
H, 4.64; N, 10.68.
Gen er a l P r oced u r e for Syn t h esis of Ar yl Ald eh yd e
Tr isylh yd r a zon es. To a stirred solution of 2,4,6-triisopro-
pylbenzenesulfonohydrazide (3.28 g, 11.0 mmol) in anhydrous
1
3-Br om oben za ld eh yd e tr isylh yd r a zon e (1v): H-NMR
(DMSO-d6) δ 11.93 (s, 1H), 7.89 (s, 1H), 7.74 (s, 1H), 7.52 (t,
2H, J ) 8.3 Hz), 7.32 (t, 1H, J ) 7.9 Hz), 7.24 (s, 2H), 4.22
(sept, 2H, J ) 6.7 Hz), 2.89 (sept, 1H, J ) 6.9 Hz), 1.21 (d,
12H, J ) 6.7 Hz), 1.18 (d, 6H, J ) 6.8 Hz); 13C-NMR (DMSO-
d6) δ 152.79, 150.40, 142.88, 136.24, 132.26, 130.88, 128.14,
126.05, 123.59, 122.07, 33.29, 29.19, 24.65, 23.31. Anal. Calcd
for C22H29N2O2SBr: C, 56.77; H, 6.28; N, 6.02. Found: C,
56.84; H, 6.23; N, 6.06.
methanol (45 mL) was added the aldehyde (9.97 mmol).
A
solid immediately precipitated, and the mixture was stirred
at room temperature for 1 h. The mixture was placed in a
2-Br om oben za ld eh yd e tr isylh yd r a zon e (1w ): 1H-NMR
(acetone-d6) δ 10.71 (s, 1H), 8.41 (s, 1H), 7.86-7.82 (m, 1H),
7.60-7.56 (m, 1H), 7.39-7.24 (m overlapping s, 4H), 4.36 (sept,
2H, J ) 6.8 Hz), 2.93 (sept, 1H, J ) 6.9 Hz), 1.27 (d, 12H, J )
6.8 Hz), 1.21 (d, 6H, J ) 6.9 Hz); 13C-NMR (acetone-d6) δ
154.01, 151.88, 144.50, 133.90, 133.83, 133.46, 132.16, 128.53,
127.86, 124.58, 124.10, 34.70, 30.51, 25.09, 23.70. Anal. Calcd
for C22H29N2O2SBr: C, 56.77; H, 6.28; N, 6.02. Found: C,
56.88; H, 6.33; N, 6.10.
(21) Ishiyama, T.; Abel, S.; Miyaura, N.; Suzuki, A. Chem. Lett. 1992,
691.
(22) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals, 3rd ed.; Pergamon: New York, 1988.
(23) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.
(24) Brown, H. C.; Kabalka, G. W.; Rathke, M. W. J . Am. Chem.
Soc. 1967, 89, 4530.
(25) Kabalka, G. W.; Hedgecock, H. C. J . Org. Chem. 1975, 40, 1776.
(26) Kabalka, G. W.; Gooch, E. E.; J . Org. Chem. 1981, 46, 2582.

3694 J . Org. Chem., Vol. 62, No. 11, 1997
Kabalka et al.
4-Nitr oben za ld eh yd e tr isylh yd r a zon e (1x): 1H-NMR
(acetone-d6) δ 11.19 (s, 1H), 8.24 (d, 2H, J ) 8.8 Hz), 7.86 (d,
2H, J ) 8.8 Hz), 7.32 (s, 2H), 4.36 (sept, 2H, J ) 6.7 Hz), 2.94
(sept, 1H, J ) 6.8 Hz), 1.28 (overlapping doublets, 18 H, J )
6.6, 6.7 Hz); 13C-NMR (acetone-d6) δ 154.25, 152.02, 149.21,
143.58, 143.49, 141.27, 133.51, 128.43, 124.73, 34.81, 30.63,
25.16, 23.77. Anal. Calcd for C22H29N3O4S; C, 61.23; H, 6.78;
N, 9.74. Found: C, 61.13; H, 6.83; N, 9.82.
temperature for 1 h. A small amount of sodium thiosulfate
solution was then added to destroy any excess peracid. The
reaction mixture was transferred to a separatory funnel,
extracted with ether (3 × 10 mL), washed with saturated
sodium bicarbonate solution and then with brine, and dried
over anhydrous MgSO4. The solvent was removed under
reduced pressure, and the crude product was purifed via flash
chromatography as described previously.
3-Nitr oben za ld eh yd e tr isylh yd r a zon e (1y): 1H-NMR
(DMSO-d6) δ 12.10 (s, 1H), 8.37 (s, 1H), 8.17 (d, 1H, J ) 7.9
Hz), 8.05 (s, 1H), 7.94 (d, 1H, J ) 7.7 Hz), 7.66 (t, 1H, J ) 7.9
Hz), 7.24 (s, 2H), 4.24 (sept, 2H, J ) 6.7 Hz), 2.89 (sept, 1H,
J ) 6.9 Hz), 1.23 (d, 12H, J ) 6.7 Hz), 1.17 (d, 6H, J ) 6.8
Hz); 13C-NMR (DMSO-d6) δ 152.83, 150.43, 148.12, 142.33,
135.64, 133.09, 132.29, 130.35, 123.92, 123.62, 120.04, 33.29,
29.19, 24.64, 23.31. Anal. Calcd for C22H29N3SO4: C, 61.23;
H, 6.77; N, 9.74. Found: C, 61.24; H, 6.72; N, 10.00.
2,4,6-Tr im eth ylben za ld eh yd e tr isylh yd r a zon e (1z): 1H-
NMR (DMSO-d6) δ 11.53 (s, 1H), 8.17 (s, 1H), 7.21 (s, 2H),
6.79 (s, 2H), 4.18 (sept, 2H, J ) 6.6 Hz), 2.88 (sept, 1H, J )
6.8 Hz), 2.15 (s, 3H), 2.09 (s, 6H), 1.17 (overlapping doublets,
18H, J ) 6.75 Hz); 13C-NMR (DMSO-d6) δ 152.77, 150.31,
144.70, 138.09, 136.71, 129.24, 128.08, 123.50, 33.44, 30.73,
29.03, 24.67, 23.43, 20.64, 20.30. Anal. Calcd for
C25H36N2O2S: C, 70.05; H, 8.46; N, 6.54. Found: C, 70.15; H,
8.50; N, 6.49.
Gen er a l P r oced u r e for Syn th esis of Ar yla lk a n es 3.
The aldehyde tosylhydrazone (3.00 mmol) was dissolved in 17
mL of THF contained in an argon-flushed, 50 mL round-
bottomed flask equipped with a side arm, reflux condenser,
and stirring bar. Tributylborane (3.0 mmol, 3.0 mL of a 1.0
M solution in THF) was added via syringe, followed by NaOH
(3.0 mmol, 1.0 mL of a 3.0 M solution in H2O) or Bu4NOH (3.0
mmol, 1.0 mL of a 3.0 M solution in MeOH). The reaction
was heated to gentle reflux under argon and monitored by TLC
for the disappearance of starting material. At the end of the
reaction, as indicated by TLC, water (10 mL) was added to
the reaction, and the mixture was allowed to cool to room
temperature. The product 3 was extracted into ether. The
combined organic layer were dried over anhydrous MgSO4 and
filtered, and the solvent was removed in vacuo. The crude
product was purified by flash chromatography.
Oxid a tion w ith TMANO. The reaction vessel was cooled
to room temperature, and TMANO (10 mmol, 5.0 mL of a 2.0
M solution in CHCl3) was added. The mixture was then heated
to reflux and allowed to remain at that temperature for 23 h.
The mixture was then cooled and transferred to a separatory
funnel, extracted with ether, washed with brine, and dried over
anhydrous MgSO4. The solvent was removed, and the crude
product was purified via flash chromatography as described
previously.
1-(3-Nitr op h en yl)p en ta n -1-ol (4k ): 1H-NMR (CDCl3/TMS)
δ 8.23-7.47 (m, 4H), 4.80 (t, 1H, J ) 6.5 Hz), 2.16 (br s, 1H),
1.86-1.71 (m, 2H), 1.44-1.28 (m, 4H), 0.90 (t, 3H, J ) 6.8
Hz); 13C-NMR (CDCl3) δ 148.38, 147.08, 131.98, 129.31, 122.34,
120.86, 73.57, 39.02, 27.66, 22.49, 13.92. Anal. Calcd for
C11H15O3N: C, 63.14; H, 7.23; N, 6.69. Found: C, 62.98; H,
7.38; N, 6.42. The alkane product, 1-nitro-3-pentylbenzene
(3j), was also isolated to give 0.13 g (23% yield).
6-Ch lor o-1-p -t olylh exa n -1-ol (5a a ): 1H-NMR (CDCl3/
TMS) δ 7.22 (d, 2H, J ) 8.1 Hz), 7.15 (d, 2H, J ) 7.9 Hz), 4.62
(t, 1H, J ) 6.6 Hz), 3.50 (t, 2H, J ) 6.7 Hz), 2.34 (s, 3H), 1.89
(br s, 1H), 1.84-1.65 (m, 4H), 1.50-1.21 (m, 4H); 13C-NMR
(CDCl3) δ 141.77, 137.22, 129.13, 125.79, 74.30, 44.95, 38.73,
32.49, 26.75, 25.10, 21.06. Anal. Calcd for C13H19OCl: C,
68.86; H, 8.45. Found: C, 68.77; H, 8.57.
7-Hydr oxy-7-p-tolylh eptan en itr ile (5bb): 1H-NMR (CDCl3/
TMS) δ 7.22 (d, 2H, J ) 8.1 Hz), 7.16 (d, 2H, J ) 8.1 Hz),
4.67-4.59 (dd, 1H, J ) 6.1, 6.9 Hz), 2.38-2.27 (singlet and d,
5H, J ) 7.0 Hz), 1.87-1.57 (m, 5H), 1.55-1.24 (m, 4H); 13C-
NMR (CDCl3) δ 141.64, 137.32, 129.16, 125.76, 119.67, 74.21,
38.51, 28.49, 25.26, 24.96, 21.06, 17.02; IR (cm-1, neat) 3450,
2950, 2855, 2250, 1518, 1460, 1425; GCMS m/ z 199 (M -
H2O).
12-H yd r oxy-12-p -t olyld od eca n oic a cid m et h yl est er
1
The yields of 3 are presented in Tables 1 and 2. The
physical and spectral properties of all products that had been
previously reported were in accord with literature values and
are summarized in the Supporting Information.
(5cc): H-NMR (CDCl3/TMS) δ 7.22 (d, 2H, J ) 8.0 Hz), 7.14
(d, 2H, J ) 8.0 Hz), 4.61 (t, 1H, J ) 6.7 Hz), 3.65 (s, 3H), 2.34
(s, 3H), 2.29 (t, 2H, J ) 7.6 Hz), 1.91 (br s, 1H), 1.86-1.17 (m,
18H); 13C-NMR (CDCl3) δ 174.29, 141.99, 137.04, 129.04,
125.82, 74.48, 51.37, 39.00, 34.07, 29.45, 29.34, 29.17, 29.09,
25.81, 24.90, 21.05. Anal. Calcd for C20H32O3: C, 74.96; H,
10.06. Found: C, 75.05; H, 10.14.
Gen er a l P r oced u r e for Syn th esis of Ar yl Alcoh ols 4.
The aldehyde tosylhydrazone (3.00 mmol) was dissolved in 17
mL of THF contained in an argon-flushed, 50 mL, round-
bottomed flask equipped with a side arm, reflux condenser,
and stirring bar. Tributylborane (3.0 mmol, 3.0 mL of a 1.0
M solution in THF) was added via syringe, followed by DBU
(0.45 mL, 3.0 mmol). The reaction was heated to a gentle
reflux until the tosylhydrazone disappeared as evidenced by
TLC. The reaction mixture was then oxidized by one of the
following methods.
The yields of 4 are presented in Tables 3-7. The spectral
properties of all products that had been previously reported
were in accord with literature values and are summarized in
the Supporting Information. The physical data for new
compounds are presented below.
Oxid a tion w ith Sod iu m P er bor a te. The reaction vessel
was placed in a room-temperature water bath. Distilled water
(10 mL) and sodium perborate (1.38 g, 8.97 mmol) were then
added. The reaction was stirred vigorously for 2 h. The
reaction mixture was transferred to a separatory funnel and
the product extracted into ether. The extracts were washed
with brine and dried over anhydrous MgSO4. The solvent was
removed under reduced pressure, and the crude product was
purified via flash chromatography as described previously.
1-Ch lor o-6-p-tolylh exa n e (6a a ): 1H-NMR (CDCl3/TMS) δ
7.07 (s, 4H), 3.51 (t, 2H, J ) 6.7 Hz), 2.56 (t, 2H, J ) 7.6 Hz),
2.31 (s, 3H), 1.76 (qt, 2H, J ) 7.0 Hz), 1.61 (qt, 2H, J ) 7.5
Hz), 1.56-1.30 (m, 4H); 13C-NMR (CDCl3) δ 139.47, 135.04,
128.94, 128.24, 45.07, 35.33, 32.55, 31.36, 28.48, 26.73, 20.96.
Anal. Calcd for C13H19Cl: C, 74.09; H, 9.09. Found: C, 74.26;
H, 9.24.
1
7-p-Tolylh ep ta n en itr ile (6bb): H-NMR (CDCl3/TMS) δ
7.13-7.01 (m, 4H), 2.57 (t, 2H, J ) 7.6 Hz), 2.31 (singlet and
t, 5H, J ) 7.0 Hz), 1.68-1.30 (m, 8H); 13C-NMR (CDCl3) δ
139.24, 135.13, 128.97, 128.22, 35.25, 31.14, 28.51, 28.30,
25.29, 20.96, 17.07. Anal. Calcd for C14H19N: C, 83.53; H,
9.51; N, 6.96. Found: C, 83.41; H, 9.55; N, 6.82.
12-p-Tolyld od eca n oic a cid m eth yl ester (6cc): 1H-NMR
(CDCl3/TMS) δ 7.07 (s, 4H), 3.66 (s, 3H), 2.55 (t, 2H, J ) 7.7
Hz), 2.31 (s overlapping t, 3H and 2H, J ) 7.5 Hz), 1.70-1.50
(m, 4H), 1.26 (br s, 14 H); 174.28, 139.83, 134.88, 128.86,
128.23, 51.37, 35.49, 34.09, 31.60, 29.52, 29.40, 29.36, 29.21,
29.12, 24.93, 20.94; 13C-NMR (CDCl3) δ. Anal. Calcd for
C20H32O2: C, 78.90; H, 10.59. Found: C, 78.67; H, 10.68.
p-Ben zyltolu en e (6ff): 1H-NMR (CDCl3/TMS) δ 7.29-7.00
(m, 9H), 3.90 (s, 2H), 2.28 (s, 3H); 13C-NMR (CDCl3) δ 141.38,
141.23, 135.45, 129.10, 128.83, 128.39, 127.12, 125.93, 41.50,
20.94. Anal. Calcd for C14H14: C, 92.26; H, 7.74. Found: C,
92.06; H, 7.68.
Oxid a tion w ith P er a cetic Acid . The reaction vessel was
placed in an ice-water bath. Peracetic acid (10 mmol, 2.2 mL
of a 32 wt % solution in acetic acid) was added slowly over the
course of 8 min. After the addition was complete, the ice bath
was removed and the reaction mixture allowed to stir at room

Alkylation of Aldehyde (Arenesulfonyl)hydrazones
J . Org. Chem., Vol. 62, No. 11, 1997 3695
tr a n s-5-p-Tolyl-4,5-d ih yd r o-1H-p yr a zole-3,4-d ica r box-
ylic Acid Dim eth yl Ester (10b).27 Dimethyl maleate 9
(0.435 g, 3.02 mmol) and 1b (0.866 g, 3.00 mmol) were added
to a flame-dried, argon-flushed, 50 mL, round-bottom flask
equipped with a side arm, reflux condenser, stir bar, argon
inlet, and mercury bubbler. Dry THF (20 mL) was then added
followed by DBU (0.45 mL, 3.0 mmol) and the reaction heated
to reflux for 1.5 h. The reaction was then cooled to room
temperature and distilled water (10 mL) added. The reaction
mixture was transferred to a separatory funnel, extracted with
ether, washed with brine, and dried over anhydrous MgSO4.
Solvent was removed under reduced pressure, and the crude
product was flash chromatographed using 7 in. of silica gel in
a 40 mm column with 25% EtOAc/hexanes to give 0.63 g (76%
yield) of 10b: 1H-NMR (CDCl3/TMS) δ 7.17 (s, 4H), 5.22 (d,
1H, J ) 9.3 Hz), 4.02 (d, 1H, J ) 9.3 Hz), 3.85 (s, 3H), 3.78 (s,
3H), 2.35 (s, 3H), 1.29-1.21 (br s, 1H); 13C-NMR (CDCl3) δ
170.86, 162.24, 138.63, 137.85, 136.24, 129.79, 126.10, 70.43,
57.93, 52.80, 52.25, 21.08.
Com p etition Exp er im en t. The competition experiment
was performed in the same manner as the synthesis of 1-p-
tolylpentan-1-ol, 4b, reported previously with the only differ-
ence being the addition of dimethyl maleate (0.433 g, 3.00
mmol) at the beginning of the reaction.
Ack n ow led gm en t. We wish to thank the Depart-
ment of Energy and the Robert H. Cole Foundation for
support of this research.
Su ppor tin g In for m ation Available: Melting points (Table
8) of all the (arenesulfonyl)hydrazones and 1H NMR and 13C
NMR data (Table 9) for all alkane and alcohol products not
described in the Experimental Section (7 pages). This material
is contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
(27) For the preparation and spectra of compounds similar to 10b
see: (a) Hassner, A.; Michelson, M. J . J . Org. Chem. 1962, 27, 3974.
(b) J ones, W. M. J . Am. Chem. Soc. 1959, 81, 3776, 5153. (c) J ones,
W. M.; Sanderfer, P. O.; Baarda, D. G. J . Org. Chem. 1967, 32, 1367.
J O962089Q