Synthesis of 2H-chromenes through the reduction of chromones with 9-BBN

Article abstract of DOI:10.1246/bcsj.74.967

Chromones were regioselectively reduced to 2H-1-benzopyrans through the 1,2-addition of 9-borabicyclo-[3.3.1]nonane. Although transition-metal complexes did not have a catalytic effect on the reaction, only by using palladium(II) chloride, could both 2H-1-benzopyran and dihydro-1-benzopyran be obtained to a similar extent. Also, the reduction of chromone using other organoboranes led not to 2H-1-benzopyran, but rather to chromanone through the reduction of only an olefin moiety.

Full text of DOI:10.1246/bcsj.74.967

c. Jpn.
© 2001 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 74, 967—970 (2001)
967
e Chemical
ciety of Ja-
n
e Chemical
ciety of Ja-
n
Synthesis of 2H-Chromenes through the Reduction of Chromones with
9-BBN
Reduction of Chromones with 9-BBN
T. Eguchi et al.
Tetsuya Eguchi and Yukio Hoshino*
01
7
0
Division of Chemical and Materials Engineering, Graduate School of Engineering, Muroran Institute of Technology,
Mizumoto-cho, Muroran 050-8585
SJA8
09-2673
368
torber
(Received October 18, 2000)
Chromones were regioselectively reduced to 2H-1-benzopyrans through the 1,2-addition of 9-borabicyclo-
[3.3.1]nonane. Although transition-metal complexes did not have a catalytic effect on the reaction, only by using palla-
dium(II) chloride, could both 2H-1-benzopyran and dihydro-1-benzopyran be obtained to a similar extent. Also, the re-
duction of chromone using other organoboranes led not to 2H-1-benzopyran, but rather to chromanone through the re-
duction of only an olefin moiety.
00
00
.3
2H-1-Benzopyrans (2, 2H-Chromenes), which have been
well-known as natural pigments, have broadly served as im-
portant intermediates to synthesize many natural products. In
particular, anthocyanins (2-aryl-2H-1-benzopyrans) are be-
coming increasingly noteworthy because of their health-pro-
moting effects found in vegetables, fruits, fruit juices, and red
wines. 2 are also employed as intermediates to produce many
medicinal reagents, such as antimicrobiral, antitumor, antiul-
cer, anti-HIV, antituberculer agent, and venom antidotes.1 In
spite of several reports concerning methods for the synthesis of
chromenes,2 general strategies for the syntheses which can ef-
ficiently afford various substituted chromene systems are still
required.
Recently, on the other hand, organic syntheses using orga-
noboranes have been dramatically developed. Among them, 9-
borabicyclo[3.3.1]nonane (9-BBN) has been known to reduce
rapidly and quantitatively conjugated aldehydes and ketones to
the corresponding allylic alcohols in tetrahydrofuran in excel-
lent purities.3 In addition, even cyclic enones, such as 2-cyclo-
pentene-1-one and 2-cyclohexene-1-one, are also cleanly re-
duced to the desired allylic alcohols without an incidental
attack at the double bond. Unlike more conventional reagents,
such as aluminum hydride and diisobutylaluminum hydride
(DIBAH), a mildness in the reactivity of 9-BBN, tolerates the
presence of almost any other functional groups, such as ester,
amide, carboxylic acid, nitro, halogen, and nitrile. In the
course of our investigations on the synthesis of 2 by the reduc-
tion of 4H-1-benzopyran-4-ones (chromones, 1), we decided
to examine the scope of the hydroboration route to 2. An arti-
cle concerning the reductions of 2H-1-benzopyran-2-ones
(coumarins) and 1a with diborane has already been reported by
Still and Goldsmith.4 In this case, 1a was treated with dibo-
rane and reduced at both the carbonyl group and the olefin
moiety to afford 2,3-dihydro-1-benzopyran-3-ol. It was also
suggested that the reduction of 1a proceeded through a step in-
volving hydride addition to a pyrylium salt intermediate to
yield 2a. From it, it can be assumed that this reaction can be
completed at the stage of the formation of 2a by means of con-
trolling the amount of hydride ion, Hꢀ. Thus the authors car-
ried out the reaction of 1 with 9-BBN, instead of diborane, be-
ing able to donate only a hydride ion, and succeeded in
obtaining moderate-satisfactory results. In this article, we de-
scribe the obtained results (Scheme 1).
Results and Discussion
Reduction of 1a with 9-BBN. The reductions of 1a (1
mmol) were carried out with varying amounts of 9-BBN at
room temperature followed by the treatment of alkaline hydro-
gen peroxide, the obtained results are summarized in Table 1.
As shown in the table, 3 molar amounts of 9-BBN (Run 4)
showed the greatest yield upon this reaction. No reduction oc-
curred in the absence of 9-BBN (Run 1) to give salicylic acid
resulting from a chromone ring cleavage. In the case using a
large excess of 9-BBN (Run 5), a remarkable decrease in the
yield of 2a was observed, which should be recognized to be
due to a further reduction, such as in the case of diborane.4 H.
C. Brown and his coworkers5 have already reported on the hy-
droboration of allyl-substituted 2-butenyl (crotyl) derivatives
with diborane, and proposed that the reaction proceeded
through double hydroborations and a subsequent elimination
Scheme 1.

968 Bull. Chem. Soc. Jpn., 74, No. 5 (2001)
Table 1.
Reduction of Chromone (1a) with 9-BBNa)
Run
Reduction of Chromones with 9-BBN
(47%) was merely observed. Accordingly, the authors consid-
er at present that the reaction presumably proceeded through
the pyrylium intermediate, though this is still not clear in de-
tail.
Amount of 9-BBN
Yield of 2ab)
mmol
%
—
7
1
2
3
4
5
0
1
2
3
5
On the other hand, one is often confronted with reactions
promoted by some transition-metal catalysts, particularly by
palladium complexes, where organoboranes participate.6
Thus, the hydroborations were conducted in the presence of
some palladium and rhodium catalysts, those results are given
in Table 2. It is apparent that these catalysts have practically a
negative effect, rather than positive one, on this reduction. In
the case of using palladium(II) chloride [PdCl2] as a catalyst,
dihydro-1-benzopyran (chroman) also reduced at olefin moiety
was obtained in 31% yield, as well as 2a. From these facts, it
may be reasonable to consider that palladium catalyses accel-
erate the reaction so powerfully that a further reduction of 2a
once produced proceeds through the formation of a π-allyl
type complex followed by some side reaction, for example,
such as a ring cleavage.
44
79
53
a) All the reactions were carried out under a nitrogen atmo-
sphere at room temperature, using 1 mmol of 1a.
b) GLC yields based on the substrate.
of borane moieties by heating, resulting in double-bond migra-
tion. If the present reaction occured via the same pathway,
though not heated, the reaction scheme may be pictured as fol-
lows (Scheme 2(a)). An alternative aspect is a participation of
pyrylium salt intermediate, as mentioned in the foregoing sec-
tion. In this case, the first hydroboration occurs at the carbonyl
group of substrate followed by the elimination of a borate moi-
ety, resulting in the formation of pyrylium intermediate. Then,
the second one proceeds at the C2–C3-position of the intermedi-
ate with the borane moiety on the C3-position. A subsequent
elimination of the borane moiety is presumably induced by the
coordination of base with the boron atom, facilitanting heterol-
ysis of the boron–carbon bond, yielding the olefin, as shown in
Scheme 2(b). Actually, the reaction solution was initially col-
ored pale yellow, and finally dark red to suggest the presence
of ionic species. However we were puzzled by the discrepancy
in the optimum amount of 9-BBN (three molar amounts).
Only two molar amounts of borane are required in both reac-
tion schemes. As a possibility, a part of 9-BBN may be con-
sumed by a side reaction, such as a ring cleavage, though this
is not clear at the present stage. Furthermore, since Brown et
al5 carried out eliminations in the presence of mathanol, acetic
acid, and methanesulfonic acid after hydroboration, to deter-
mine whether acids would increase the rate, the authors con-
ducted the same experiment by the addition of methanesulfon-
ic acid after hydroboration. But, a decrease in the yield of 2a
Reactions Using Other Boranes. For the purpose of
comparing various boron compounds, as well as 9-BBN, the
Table 2.
Reduction of Chromone (1a) with 9-BBN in the
Presence of Transition Metal Catalystsa)
Yield of 2ac)
Run
Catalystb)
%
1
2
3
4
[Pd(PPh3)4] (0.03)
PdCl2 (0.1)
57
24d)
54
47
[PdCl2(dppf)]e) (0.03)
RhCl3•3H2O (0.1)
a) All the reactions were carried out under a nitrogen atmo-
sphere at room temperature, using 1 mmol of 1a and 3
mmol of 9-BBN.
b) Figure in parenthese indicate the added amount in a
mmol-unit.
c) GLC yields based on the substrate.
d) Chroman was also obtained 31% yield.
e) dppf: 1,1′-bis(diphenylphosphino)ferrocene.
Scheme 2.

T. Eguchi et al.
Bull. Chem. Soc. Jpn., 74, No. 5 (2001) 969
Scheme 3.
representative hydroborating reagents, such as bis(1,2-dimeth-
ylpropyl)borane (disiamylborane), 1,3,2-benzodioxaborole
(catecholborane) and dicyclohexylborane, were attempted in
reactions with 1a. While 2a was not obtained in every case, di-
hydro-1-benzopyran-4-one (chromanone) reduced only at ole-
fin moiety of 1a was given in 33, 12, and 31% yields, respec-
tively. Although no definitive evidence could be detected, 9-
BBN seems clearly to be specific for this reduction, compared
with the other one-hydride donor boranes, such as the above-
mentioned ones.
In general, catecholborane is thought to be far less reactive
than dialkylboranes, and to be more favorable to the hydrobo-
ration of a carbon-carbon triple bond than to that of a double
bond. Although the reactivities both of disiamylborane and di-
cyclohexylborane should be essentially regarded as being com-
parable to that of 9-BBN, these stabilities and regioselectivities
seem to be slightly less than those of the latter. Additionally,
while disiamyl- and dicyclohexylborane have bulky alkyl
groups around the boron atom, that in 9-BBN is comparatively
exposed.7 Thus, a predominance of 9-BBN toward the ring
system, such as 1, may arise from this steric reason. In the
former three cases, the formations of chromanone in low yield
would be due to the 1,4-addition of boranes toward the carbon-
yl group followed by elimination of the borane moiety to give
the enol, which would immediately isomerize to the ketone
(Scheme 3).
substituent effect was observed, more or less, depending upon
its position and on the electronic property. 6-OMe-derivative
(1b, Entry 1 in Table 3) gave a desired product (2b) in the
highest yield among them, whereas 7-OMe-derivative (1g, En-
try 6 in Table 3) provided 2g in fairly low yield. These results
seem to be due to a difference of the stability between the ben-
zopyrylium salts formed as an intermediate in the present reac-
tion. Similarly, it may be assumed that the lower yields of Cl-
derivatives (2e, 2j, Entries 4 and 9 in Table 3) and NO2-deriva-
tives (2f, 2k, Entries 5 and 10 in Table 3) are due to the lability
of the intermediates resulting from the presence of an electron-
withdrawing group. By introducing a methyl group (Entries 3,
7, 8, and 12 in Table 3), there is a tendency to diminish the
yields of 2 to a certain extent, compared to that in the case of
unsubstituted chromone. The lower yield of 2m can be recog-
nized to arise from a decrease in the basicity of the carbonyl
group of 1m, as already reported in our earlier study concern-
ing the basicity of chromones,8 resulting in a difficulty con-
cerning the addition of 9-BBN in the initial stage of the reac-
tion. However, both basicities of 1d and 1h are slightly greater
than that of 1a.8 Thus, the low yields of 2d and 2h should be
considered to be due to another reason, such as a thermody-
namic one, though this is still not clear. A steric hindrance of
isoflavone (1l) against the carbonyl group must be greater than
that of 1m. Accordingly, it seems reasonable to assume that
the higher yield of 2l compared with that of 2m is due to an in-
crease in the stability of the pyrylium intermediate by means of
the introduction of a phenyl group at the C3-position, spreading
the conjugated system.
Substituent Effect. For twelve derivatives (1b–1m),
which introduced some substituents on the condensed benzene
ring or C3-position of 1a, the reductions were carried out under
the same conditions in order to examine the generality of this
reaction. The obtained results are summarized in Table 3. A
Conclusion
Although its reaction mechanism is still not clear in detail,
the reduction of chromones with 9-BBN has been demonstrat-
ed to proceed regioselectively to give the corresponding 2H-1-
benzopyrans, while reactions using reductants, such as di-
siamylborane, catecholborane, and dicyclohexylborane, af-
forded chromanone in low yield.
Table 3.
Reduction of Substituted Chromones (1b–1m)
with 9-BBNa)
Yield of 2b)
%
Entry
Substituent
1
2
3
4
5
6
7
8
9
6-OMe
6-Ph
6-Me
6-Cl
6-NO2
7-OMe
7-Me
8-Me
8-Cl
93 (2b)
52 (2c)
55 (2d)
37 (2e)
10 (2f)
19 (2g)
51 (2h)
62 (2i)
30 (2j)
12 (2k)
61 (2l)
47 (2m)
Experimental
All of the reactions were carried out under a nitrogen atmo-
sphere. The melting points were determined by using a Yanaco
micro-melting-point apparatus and are uncorrected. The IR spec-
tra were recorded on a JASCO-IRA-1 spectrometer by means of a
KBr pellet or neat. 1H NMR spectra were obtained with a JEOL
JNM-EX270 Fourier Transform NMR spectrometer (270 MHz),
and are reported in δ units using tetramethylsilane as an internal
standard. Mass spectra were taken on a JEOL-JMS-D300. GLC
analyses were performed on a Hitachi-263-30 instrument with Sil-
icone SE-30 (2 m) on Uniport B using hexadecane as an internal
standard. THF was purified by distillation from diphenylketyl un-
der a nitrogen atmosphere before use. Column chromatography
was performed using a Wakogel C-200 (silica gel).
10
11
12
8-NO2
3-Ph
3-Me
a) All the reactions were carried out under a nitrogen
atmosphere at room temperature, using 1 mmol of sub-
strate and 3 mmol of 9-BBN. b) Isolated yields based on
the substrate.
Boranes. 9-Borabicyclo[3.3.1]nonane in THF and 1,3,2-ben-

970 Bull. Chem. Soc. Jpn., 74, No. 5 (2001)
Reduction of Chromones with 9-BBN
zodioxaborole in THF from Aldrich Chemical Co. were used di-
rectly. Other dialkylboranes were prepared via the hydroboration
of appropriate alkenes with diborane, and were transferred to a
main reaction flask with double-ended needles under a nitrogen
atmosphere.
MS Found: m/z 208.0890. Calcd for C15H12O: M, 208.0888.
General Procedure. To a solution of chromone (1a, 146 mg,
1 mmol) in THF was added dropwise 6 mL (3.0 mmol) of a 0.5 M
(1 M ꢁ 1 mol dmꢀ3) 9-BBN solution in THF for 1 h. The result-
ing mixture was stirred overnight at room temperature. Then, 2
mL of 3M aqueous sodium hydroxide and 2 mL of 30% hydrogen
peroxide were added with cooling, if necessary, and the mixture
was stirred for 6 h at room temperature, following by acidification
with dilute hydrochloric acid and extracted three times with ether.
The combined extracts were washed with 2 M aqueous sodium
hydroxide, water, and brine, and the ethereal layer was dried with
anhydrous magnesium sulfate. After removal of the solvent, the
residue was chromatographed on a silica-gel column (benzene/
hexanes ꢁ 1:9) to give the reduced product, 2H-chromene (2a),
as a colorless liquid.
Transition Metal Catalysts.
Tetrakis(triphenylphosphine)-
palladium(0)9 and dichloro[1,1′-bis-(diphenylphosphino)-ferroce-
ne]palladium(II)10 were prepared according to reported proce-
dures. Rhodium(III) chloride trihydrate was commercially avail-
able grade, and was used without further purification.
Materials. Solvents were commercially available grade and
were purified by ordinary procedures before use. Chromones (1a–
1m) were prepared according to known procedures,11 and were
1
identified by means of IR and H NMR spectra. 2H-Chromenes,
isolated in the present reactions, were identified on the basis of
values given in the literature,2,12 except for the following deriva-
tives.
6-Phenyl-2H-chromene (2c): Mp 64.1–65.6 ˚C; IR (KBr)
1230 (–O–), 1480 cmꢀ1(–CꢁC–); 1H NMR (CDCl3) δ 4.78 (dd, J
ꢁ 1.7, 2.0 Hz, 2H, C2–H), 5.82 (m, 1H, C3–H), 6.49 (d, J ꢁ 9.6
Hz, 1H, C4–H), and 6.83–7.55 (m, 8H, aromatic). MS Found: m/z
208.0882. Calcd for C15H12O: M, 208.0888.
6-Methyl-2H-chromene (2d): IR (neat) 1250 (–O–), 1510
cmꢀ1 (–CꢁC–); 1H NMR (CDCl3) δ 2.24 (s, 3H, –CH3), 4.78 (dd,
J ꢁ 2.0, 2.0 Hz, 2H, C2–H), 5.76 (m, 1H, C3–H), 6.38 (d, J ꢁ 9.9
Hz, 1H, C4–H), and 6.65–6.91 (m, 3H, aromatic). MS Found: m/z
146.0733. Calcd for C10H10O: M, 146.0732.
7-Methyl-2H-chromene (2h): IR (neat) 1250 (–O–), 1510
cmꢀ1 (–CꢁC–); 1H NMR (CDCl3) δ 2.27 (s, 3H, –CH3), 4.79 (dd,
J ꢁ 2.0, 2.0 Hz, 2H, C2–H), 5.70 (m, 1H, C3–H), 6.39 (d, J ꢁ 9.8
Hz, 1H, C4–H), and 6.60–6.86 (m, 3H, aromatic). MS Found: m/z
146.0728. Calcd for C10H10O: M, 146.0732.
References
1
a) J. L. Ingham, In “Progress in the Chemistry of Organic
Natural Products,” ed by W. Herz, H. Grisebach, and G. W. Kirby,
Springer, Wien (1983), Vol. 43, pp. 1–266; b) T. A. Engler, K. O.
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2
a) U. Rao and K. K. Balasubramanian, Tetrahedron Lett.,
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3
S. Krishnamurthy and H. C. Brown, J. Org. Chem., 42,
1197 (1977).
4
W. C. Still, Jr. and D. J. Goldsmith, J. Org. Chem., 35,
8-Methyl-2H-chromene (2i): IR (neat) 1210 (–O–), 1470
cmꢀ1 (–CꢁC–); 1H NMR (CDCl3) δ 2.17 (s, 3H, –CH3), 4.83 (dd,
J ꢁ 1.9, 1.7 Hz, 2H, C2–H), 5.76 (m, 1H, C3–H), 6.41 (m, 1H, C4–
H), and 6.73–6.98 (m, 3H, aromatic). MS Found: m/z 146.0720.
Calcd for C10H10O: M, 146.0732.
2282 (1970).
5
H. C. Brown and R. M. Gallivan, Jr., J. Am. Chem. Soc., 90,
2906 (1968).
6
7
N. Miyaura and A. Suzuki, Chem. Rev., 95, 2457 (1995).
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8-Chloro-2H-chromene (2j): IR (neat) 1230 (–O–), 1575
3002 (1985).
1
cmꢀ1 (–CꢁC–); H NMR (CDCl3) δ 4.95 (dd, J ꢁ 3.3, 2.0 Hz,,
8
Y. Hoshino, S. Takeda, M. Hamada, and N. Takeno, Nippon
2H, C2–H), 5.80 (m, 1H, C3–H), 6.40 (m, 1H, C4–H), and 6.75–
7.17 (m, 3H, aromatic). MS Found: m/z 166.0183. Calcd for
C9H7ClO: M, 166.0185.
8-Nitro-2H-chromene (2k): Mp 53.0–53.5 ˚C; IR (KBr)
1230 (–O–), 1520 cmꢀ1 (–CꢁC–); 1H NMR (CDCl3) δ 5.01 (dd, J
ꢁ 3.3, 2.0 Hz,, 2H, C2–H), 5.91 (m, 1H, C3–H), 6.46 (m, 1H, C4–
H), and 6.88–7.70 (m, 3H, aromatic). MS Found: m/z 177.0433.
Calcd for C9H7NO3: M, 177.0426.
Kagaku kaishi, 1982, 1492.
9
D. R. Coulson, Inorg. Synth., 1972, 121.
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3-Phenyl-2H-chromene (2l): Mp 89.5–90.0 ˚C; IR (KBr)
1
1220 (–O–), 1590 cmꢀ1 (–CꢁC–); H NMR (CDCl3) δ 5.17 (s,
2H, C2–H), 6.81 (s, 1H, C4–H), and 6.81–7.46 (m, 9H, aromatic).