Boron-complexation strategy for use with 1-acyldipyrromethanes

Article abstract of DOI:10.1021/jo0492620

1-Acyldipyrromethanes are important precursors in rational syntheses of diverse porphyrinic compounds. 1-Acyldipyrromethanes are difficult to purify, typically streaking upon chromatography and giving amorphous powders upon attempted crystallization. A solution to this problem has been achieved by reacting the 1-acyldipyrromethane with a dialkylboron triflate (e.g., Bu ₂B-OTf or 9-BBN-OTf) to give the corresponding B,B-dialkyl-B-(1- acyldipyrromethane)boron(III) complex. The reaction is selective for a 1-acyldipyrromethane in the presence of a dipyrromethane. The 1-acyldipyrromethane-boron complexes are stable to routine handling, are soluble in common organic solvents, are hydrophobic, crystallize readily, and chromatograph without streaking. The 1-acyldipyrromethane can be liberated in high yield from the boron complex upon treatment with 1-pentanol. Alternatively, the 1-acyldipyrromethane-boron complex can be used in the formation of a trans-A₂B₂-porphyrin. In summary, the boron-complexation strategy has broad scope and greatly facilitates the isolation of 1-acyldipyrromethanes.

Full text of DOI:10.1021/jo0492620

Bor on -Com p lexa tion Str a tegy for Use w ith 1-Acyld ip yr r om eth a n es
Kannan Muthukumaran,† Marcin Ptaszek,† Bruce Noll,‡ W. Robert Scheidt,*,‡ and
J onathan S. Lindsey*,†
Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204, and
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556
jlindsey@ncsu.edu; scheidt.1@nd.edu
Received April 30, 2004
1-Acyldipyrromethanes are important precursors in rational syntheses of diverse porphyrinic
compounds. 1-Acyldipyrromethanes are difficult to purify, typically streaking upon chromatography
and giving amorphous powders upon attempted crystallization. A solution to this problem has been
achieved by reacting the 1-acyldipyrromethane with a dialkylboron triflate (e.g., Bu2B-OTf or 9-BBN-
OTf) to give the corresponding B,B-dialkyl-B-(1-acyldipyrromethane)boron(III) complex. The reaction
is selective for a 1-acyldipyrromethane in the presence of a dipyrromethane. The 1-acyldipyr-
romethane-boron complexes are stable to routine handling, are soluble in common organic solvents,
are hydrophobic, crystallize readily, and chromatograph without streaking. The 1-acyldipyr-
romethane can be liberated in high yield from the boron complex upon treatment with 1-pentanol.
Alternatively, the 1-acyldipyrromethane-boron complex can be used in the formation of a trans-
A2B2-porphyrin. In summary, the boron-complexation strategy has broad scope and greatly facilitates
the isolation of 1-acyldipyrromethanes.
CHART 1
In tr od u ction
Rational syntheses of a variety of porphyrinic com-
pounds bearing diverse patterns of meso-substituents
have been developed recently. The porphyrinic com-
pounds include porphyrins,1-3 chlorins,4 corroles,5 and
bilanes.6 The syntheses begin with dipyrromethanes (1)
and, depending on desired substitution pattern, also
employ 1-acyldipyrromethanes (2) and 1,9-diacyldipyr-
romethanes (3) (Chart 1).1,2 1-Acyldipyrromethanes are
readily prepared from the corresponding dipyrromethane,
and 1,9-diacyldipyrromethanes can be prepared by 9-acy-
lation of a 1-acyldipyrromethane or by 1,9-diacylation of
a dipyrromethane. Although the acylation procedures
work reasonably well, purification is difficult owing to
the lack of crystallinity of the acyldipyrromethanes.
Accordingly, the mixture containing the acyldipyr-
romethane is usually separated by chromatography,
which can be tedious owing to the tendency of the
acyldipyrromethanes to streak on chromatographic me-
dia.
One of our objectives over the past few years has been
to increase the scale of porphyrin syntheses, which
entails decreasing if not eliminating reliance on chroma-
tography for purification. Toward this goal, we recently
developed a simple procedure for isolating a 1,9-diacyl-
dipyrromethane from the diacylation reaction mixture by
forming a dialkyltin complex (Chart 2, 4).7 Dipyr-
romethanes, 1-acyldipyrromethanes, or 1,8-diacyldipyr-
romethanes did not give tin complexes. The tin complex
of a 1,9-diacyldipyrromethane was hydrophobic and
crystalline, greatly facilitating isolation. In addition, the
tin complex readily underwent decomplexation upon
treatment with dilute trifluoroacetic acid. The availability
of the tin-complexation procedure has enabled routine
synthesis of multigram quantities of 1,9-diacyldipyr-
romethanes.
† North Carolina State University.
‡ University of Notre Dame.
(1) Rao, P. D.; Dhanalekshmi, S.; Littler, B. J .; Lindsey, J . S. J . Org.
Chem. 2000, 65, 7323-7344.
(2) Rao, P. D.; Littler, B. J .; Geier, G. R., III; Lindsey, J . S. J . Org.
Chem. 2000, 65, 1084-1092.
(3) Littler, B. J .; Ciringh, Y.; Lindsey, J . S. J . Org. Chem. 1999, 64,
2864-2872.
(4) Taniguchi, M.; Ra, D.; Mo, G.; Balasubramanian, T.; Lindsey, J .
S. J . Org. Chem. 2001, 66, 7342-7354.
(5) (a) Guilard, R.; Gryko, D. T.; Canard, G.; Barbe, J .-M.; Koszarna,
B.; Brandes, S.; Tasior, M. Org. Lett. 2002, 4, 4491-4494. (b) Gryko,
D. T. Eur. J . Org. Chem. 2002, 1735-1743. (c) Decre´au, R. A.; Collman,
J . P. Tetrahedron Lett. 2003, 44, 3323-3327. (d) Gryko, D. T.; Tasior,
M.; Koszarna, B. J . Porphyrins Phthalocyanines 2003, 7, 239-248.
(6) Lee, C.-H.; Li, F.; Iwamoto, K.; Dadok, J .; Bothner-By, A. A.;
Lindsey, J . S. Tetrahedron 1995, 51, 11645-11672.
(7) Tamaru, S.-I.; Yu, L.; Youngblood, W. J .; Muthukumaran, K.;
Taniguchi, M.; Lindsey, J . S. J . Org. Chem. 2004, 69, 765-777.
10.1021/jo0492620 CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/08/2004
5354
J . Org. Chem. 2004, 69, 5354-5364

Boron-Complexation for 1-Acyldipyrromethanes
CHART 2
CHART 3
SCHEME 1
The beneficial impact of the tin-complexation procedure
prompted us to explore an analogous method for isolating
a 1-acyldipyrromethane from the mixture formed upon
1-acylation of a dipyrromethane. The synthesis of a
1-acyldipyrromethane (2) is achieved by treatment of a
dipyrromethane (1) with EtMgBr in THF at room tem-
perature followed by addition of a pyridyl thioester (5)
in THF at -78 °C.2 The product mixture consists of
unreacted dipyrromethane (1), the 1-acyldipyrromethane
(2), and pyridyl thioester and/or other byproducts (Scheme
1). A suitable complexation aid for application to such a
mixture must meet several criteria, including the follow-
ing: (1) afford reaction with diverse 1-acyldipyr-
romethanes, (2) resist complex formation with other
species in the reaction mixture, particularly the dipyr-
romethane, (3) yield a crystalline solid, (4) exhibit suf-
ficient stability for routine handling, and (5) undergo
decomplexation under mild conditions to liberate the
1-acyldipyrromethane in pure form.
A number of metal complexes of 2-acylpyrroles are
known, as shown in Chart 3. Pyrrole-2-carboxaldehyde
forms a stable coordination complex (A) in conjunction
with acetylacetone and copper(II), nickel(II), palladium-
(II), or platinum(II).8 Pyrrole-2-acyl species and imino
derivatives therefrom also form complexes with various
metals or coordination centers (B,9 C,10 D,11 E,10 and F 12).
We began our search for suitable metal complexes of
1-acyldipyrromethanes on the basis of the known com-
plexes of 2-acylpyrroles. Note that 1-acyldipyrromethanes
and 2-acylpyrroles each contain the same R-acylpyrrole
motif.
In this paper, we report the development of a boron-
complexation strategy for the isolation and purification
of 1-acyldipyrromethanes formed upon acylation of dipyr-
romethanes. We also describe use of the 1-acyldipyr-
romethane-boron complexes in porphyrin-forming reac-
tions following similar procedures employed with 1-acyldi-
pyrromethanes. The ability to complex the 1-acyldipyr-
romethane greatly facilitates purification and enables
synthesis of 1-acyldipyrromethanes at the multigram
scale.
Resu lts a n d Discu ssion
(8) Mehta, P.; Mehta, R. K. J . Indian Chem. Soc. 1984, LXI, 571-
572.
(9) Hu¨bler, K.; Hu¨bler, U. Z. Anorg. Allg. Chem. 2000, 626, 1224-
1236.
(10) Dawson, D. M.; Walker, D. A.; Thornton-Pett, M.; Bochmann,
M. J . Chem. Soc., Dalton Trans. 2000, 459-466.
(11) Adams, H.; Bailey, N. A.; Fenton, D. E.; Moss, S.; Rodriguez
de Barbarin, C. O. J . Chem. Soc., Dalton Trans. 1986, 693-699.
(12) Bacchi, A.; Bonardi, A.; Carcelli, M.; Mazza, P.; Pelagatti, P.;
Pelizzi, C.; Pelizzi, G.; Solinas, C.; Zani, F. J . Inorg. Biochem. 1998,
69, 101-112.
Id en tifica tion of Su ita ble 1-Acyld ip yr r om eth a n e-
Coor d in a tion Com p lexes. A variety of metal reagents
were examined as potential complexation aids for 1-acyl-
dipyrromethanes. The metal reagents include Mg(OAc)2‚
4H2O, Sc(OTf)3, TiF4, MnCl2, Mn(OAc)2, FeBr3, Fe(OAc)2,
Fe(acac)3, Co(OAc)2‚4H2O, Ni(OAc)2‚4H2O, Cu(OAc)2‚
H2O, Zn(OAc)2‚2H2O, GeI4, MoCl3, RuCl3‚H2O, Pd(OAc)2,
Pd(CH3CN)2Cl2, Ag(OTf), CdCl2, InCl3, In(OAc)3, SnF4,
J . Org. Chem, Vol. 69, No. 16, 2004 5355

Muthukumaran et al.
resistant to decomplexation.13-15 2-Ketopyrroles are also
known to form stable boron-difluoride complexes (G,
Chart 3).15 A dialkylboron complex of a 2-iminopyrrole
also is known (H, Chart 3).16
SCHEME 2
We thought that boron complexes with B,B-dialkyl
substituents might afford the appropriate balance of
stability and susceptibility to decomplexation for our
studies. A variety of compounds containing N-(dialkyl-
boryl)pyrrole17-25 or N-(diarylboryl)pyrrole26 motifs have
been prepared. Thus, reaction of 2a and Bu2B-OTf in
CH2Cl2 containing TEA at room temperature afforded the
corresponding boron complex 6a -BBu 2 in 93% yield
(Scheme 3). The boron complex was readily isolated by
passage through a pad of silica. The generality of the
complexation of 1-acyldipyrromethane 2a with various
boron reagents was examined. The complex of 2a with
9-BBN gave an orange-yellow solid, whereas the boron
complex with dibutyl or dimethyl substituents gave an
orange oil. On the other hand, no complex was obtained
with BF3‚O(Et)2 or B-bromocatechol borane. Owing to the
high yield and formation of a crystalline product, we
primarily used 9-BBN complexes for further study.
The selectivity of boron complexation was examined
next. Dipyrromethane 1a did not give a boron complex
(TLC analysis). However, a trace amount of a byproduct,
tentatively assigned as dipyrrin-boron complex 7 on the
basis of 1H NMR and absorption spectroscopy, was
observed. The reaction of 1,9-diacyldipyrromethane 3a 1
and Bu2B-OTf in CH2Cl2 containing TEA at room tem-
perature afforded the corresponding bis-boron complex
3a -(BBu 2)2 (Scheme 4). Thus, the complexation process
is selective for the R-acylpyrrole motif but does not
distinguish 1-acyl versus 1,9-diacyldipyrromethanes.
SbCl5, TeCl4, CeI3, EuCl3, Dy(OTf)3, Yb(OTf)3, Tl(OAc),
and BiCl3. The conditions employed treatment of a
methanolic solution of 2a 2 (100 mM) with the metal
reagent (50 mM) at room temperature for 1 h. Most of
the reagents examined gave multiple components. A
readily isolable complex was obtained only with Cu-
(OAc)2‚H2O, affording Cu -2a as a green precipitate
(Scheme 2). Although the formation of Cu -2a was prom-
ising, copper was found to have three limitations as a
complexing agent: (1) the Cu -2a complex underwent
decomplexation upon silica TLC; (2) formation of the
complex was quite substrate-selective; a copper complex
was obtained for 1-p-toluoyl-5-phenyldipyrromethane
(2a ) but not with 1-pentafluorobenzoyl-5-(pentafluorophe-
nyl)dipyrromethane (2e)1; and (3) the Cu -2a complex was
an amorphous solid rather than a crystalline product.
1-Acyldipyr r om eth an e-Bor on Com plexes. To meet
the objectives of broad applicability and formation of
crystalline products, we turned to investigate boron
complexes. The first boron derivative of a dipyrromethane
species apparently was reported by Treibs et al.,13 who
reacted BF3-etherate with a dipyrrin to obtain a difluo-
roboron-dipyrrin complex. A wide variety of such di-
fluoroboron-dipyrrin (BODIPY) derivatives have been
prepared owing to their high fluorescence yields.14 The
boron-difluoride complexes of dipyrrins are exceptionally
The generality of the complexation with 9-BBN-OTf
was examined with various 1-acyldipyrromethanes
(Scheme 5). The requisite 1-acyldipyrromethanes 2a ,2
2d ,7 2e,1 2f,2 2g,1 2h ,7 and 2i27 are known compounds,
whereas 2b and 2c were prepared herein following the
general method.2 In each case, the resulting boron
complex was hydrophobic and easily isolated by passage
of the mixture through a pad of silica. The complexation
of 1-acyldipyrromethanes 2a -d and 2g with 9-BBN-OTf
(15) Chen, J .; Burghart, A.; Wan, C.-W.; Thai, L.; Ortiz, C.; Reiben-
spies, J .; Burgess, K. Tetrahedron Lett. 2000, 41, 2303-2307.
(16) Minkin, V. I.; Korobov, M. S.; Nivorozhkin, L. E.; Kompan, O.
E.; Borodkin, G. S.; Olekhnovich, R. Ya. Russ. J . Coord. Chem. 1998,
24, 152-161.
(17) Ko¨ster, R.; Bellut, H.; Hattori, S.; Weber, L. Liebigs Ann. Chem.
1968, 720, 32-57.
(18) Bellut, H.; Ko¨ster, R. Liebigs Ann. Chem. 1970, 738, 86-96.
(19) Bellut, H.; Miller, C. D.; Ko¨ster, R. Synth. Inorg. Met.-Org.
Chem. I 1971, 83-91.
(20) Kerschl, S.; Wrackmeyer, B. J . Chem. Soc., Chem. Commun.
1986, 403-404.
(13) Treibs, A.; Kreuzer, F.-H. Liebigs Ann. Chem. 1968, 718, 208-
223.
(21) Wrackmeyer, B.; Maisel, H. E.; Schwarze, B.; Milius, W.; Ko¨ster,
R. J . Organomet. Chem. 1997, 541, 97-107.
(14) (a) Wagner, R. W.; Lindsey, J . S. Pure Appl. Chem. 1996, 68,
1373-1380. Corrigendum: Wagner, R. W.; Lindsey, J . S. Pure Appl.
Chem. 1998, 70 (8), p. i. (b) Burghart, A.; Kim, H.; Welch, M. B.;
Thoresen, L. H.; Reibenspies, J .; Burgess, K. J . Org. Chem. 1999, 64,
7813-7819. (c) Kim, H.; Burghart, A.; Welch, M. B.; Reibenspies, J .;
Burgess, K. Chem. Commun. 1999, 1889-1890. (d) Burghart, A.;
Thoresen, L. H.; Chen, J .; Burgess, K.; Bergstro¨m, F.; J ohansson, L.
B.-Å. Chem. Commun. 2000, 2203-2204. (e) Chen, J .; Burghart, A.;
Derecskei-Kovacs, A.; Burgess, K. J . Org. Chem. 2000, 65, 2900-2906.
(f) Ambroise, A.; Kirmaier, C.; Wagner, R. W.; Loewe, R. S.; Bocian,
D. F.; Holten, D.; Lindsey, J . S. J . Org. Chem. 2002, 67, 3811-3826.
(g) Gabe, Y.; Urano, Y.; Kikuchi, K.; Kojima, H.; Nagano, T. J . Am.
Chem. Soc. 2004, 126, 3357-3367.
(22) Wrackmeyer, B.; Schwarze, B. J . Organomet. Chem. 1997, 534,
181-186.
(23) Wrackmeyer, B.; Schwarze, B. J . Organomet. Chem. 1997, 534,
207-211.
(24) Wrackmeyer, B.; Schwarze, B.; Milius, W. J . Organomet. Chem.
1997, 545-546, 297-308.
(25) Wrackmeyer, B.; Schwarze, B.; Milius, W.; Boese, R.; Parch-
ment, O. G.; Webb, G. A. J . Organomet. Chem. 1997, 552, 247-254.
(26) (a) Cornelissen-Gude, C.; Retting, W. J . Phys. Chem. A 1999,
103, 4371-4377. (b) Kehr, G.; Fro¨hlich, R.; Wibbeling, B.; Erker, G.
Chem. Eur. J . 2000, 6, 258-266.
(27) Tomizaki, K.-Y.; Lysenko, A. B.; Taniguchi, M.; Lindsey, J . S.
Tetrahedron 2004, 60, 2011-2023.
5356 J . Org. Chem., Vol. 69, No. 16, 2004

Boron-Complexation for 1-Acyldipyrromethanes
SCHEME 3
SCHEME 5
SCHEME 4
a
The product partially decomplexed upon chromatography
(silica, CH2Cl2).
ent) with 9-BBN-OTf or Bu2B-OTf gave a stable complex
(6h -BBN or 6h -BBu 2) in excellent yield. However, reac-
tion of 2i (1-pentafluorobenzoyl substituent) with 9-BBN-
OTf gave a complex (6i-BBN) that proved unstable,
whereas the reaction of 2i with BBu2-OTf gave 6i-BBu 2
in 89% yield. Thus, the presence of the pentafluorophenyl
group is potentially deleterious only at the 1-acyl position.
It is noteworthy that among the complexes examined
herein, almost all 9-BBN complexes of 1-acyldipyr-
romethanes were solids (the all-pentyl 6c-BBN was the
one exception), whereas almost all dibutylboron com-
plexes of 1-acyldipyrromethanes were oils (6f-BBu 2 was
the one exception). Regardless of state, the boron com-
plexes typically are yellow-orange, whereas the uncom-
plexed 1-acyldipyrromethanes are off-white solids. The
1-acyldipyrromethane-boron complexes are stable to
water and routine handling. Unlike 1-acyldipyrro-
methanes, the 1-acyldipyrromethane-boron complexes
gave 6a -BBN-6d -BBN and 6g-BBN in excellent yields
(87-97%). The reaction of 2e or 2f with 9-BBN-OTf gave
complete reaction (TLC analysis), but partial decomplex-
ation occurred upon passage through a silica pad, afford-
ing a mixture of 2e and 6e-BBN or 2f and 6f-BBN.
Isolation of the unstable mesityl-substituted complex 6f-
BBN was circumvented by reaction of 2f with Bu2B-OTf,
which gave 6f-BBu 2 as a stable product in 89% yield.
The same approach with the pentafluorophenyl-substi-
tuted 2e gave 6e-BBu 2, which was isolated in pure form
by silica pad separation but underwent facile decomplex-
ation to 2e upon further handling.
To check the effect of the presence of a single pen-
tafluorophenyl group at the 5-position or 1-acyl position,
boron complexation reactions of 2h and 2i were investi-
gated. The reaction of 2h (5-pentafluorophenyl substitu-
J . Org. Chem, Vol. 69, No. 16, 2004 5357

Muthukumaran et al.
the boron atom, R-carbonyl, and pyrrole unit. Selected
bond lengths and angles are shown in Supporting Infor-
mation. The C-O bond length (1.298 Å) is longer than
for that in 2-benzoylpyrrole (1.234 Å),29 suggesting some
enolate character. At the same time, the C-C bond
between the carbonyl carbon and the R-carbon of the
acylpyrrole (1.402 Å) is significantly shorter than that
in 2-benzoylpyrrole (1.445 Å),29 suggesting partial mul-
tiple bond character. Similar structural features were
reported for the 2-ketopyrrole-BF2 complex.15 Coordi-
nation of the carbonyl group and the pyrrolic nitrogen
atom to the boron atom effectively masks two groups that
can participate in hydrogen bonding. The ensheathed
R-acylpyrrole motif is the source of the striking change
in physical properties (polarity, crystallinity) upon con-
version of a 1-acyldipyrromethane to the corresponding
dialkylboron complex.
F IGUR E 1. ORTEP drawing of the X-ray structure of 6a -
BBN. The diethyl ether solvate molecule is also illustrated.
All ellipsoids are contoured at the 50% level, and hydrogens
are omitted for clarity.
Bor on Com p lexa t ion a s P u r ifica t ion Aid for
1-Acyld ip yr r om eth a n es. An integrated procedure con-
sisting of 1-acylation and subsequent boron complexation
was developed. The two steps are carried out as follows:
(i) The dipyrromethane (1) is treated with 2.0 molar
equiv of EtMgBr followed by 1.0 molar equiv of a
Mukaiyama reagent30 (5). The reaction mixture is
quenched with aqueous NH4Cl, and the organic layer is
separated and concentrated, affording the crude product
2 (vide infra). Note that the use of boron complexation
to isolate the 1-acyldipyrromethane enables use of a
stoichiometric quantity of EtMgBr, rather than an excess
as employed previously to ensure complete consumption
of the Mukaiyama reagent.2
(ii) The residue (2) is dissolved in CH2Cl2 and treated
with TEA and R2B-OTf at room temperature for 1 h.
Passage of the reaction mixture over a pad of silica using
CH2Cl2/hexanes as eluant readily affords the boron
complex.
In this manner, each member in a series of dipyr-
romethanes (1a -f,31 1g32) was reacted with the appropri-
ate Mukaiyama reagent (5a -e,2 5f ) followed by boron
complexation with Bu2B-OTf or 9-BBN-OTf. The corre-
sponding boron complexes of 2a -c and 2f-h were readily
obtained in good yield, whereas that of 2d was prepared
by a slightly modified procedure (Scheme 6).
A slight modification to the general boron-complexation
method was explored to further streamline workup. The
modification entails use of a solvent for complexation that
results in precipitation of the 1-acyldipyrromethane-
boron complex. Thus, the reaction of 2a with 9-BBN-OTf
in the presence of TEA in toluene afforded a precipitate,
which largely consisted of 6a -BBN and the TfOH‚TEA
salt. Washing with water and methanol afforded the
desired 1-acyldipyrromethane-boron complex 6a -BBN.
This procedure was employed with 8.88 g of 2a , affording
a precipitate (9.63 g, 52%) of analytically pure 6a -BBN.
Silica pad separation of the filtrate afforded additional
can be precipitated/crystallized from CH2Cl2/hexanes, are
relatively nonpolar, and do not streak upon chromatog-
raphy.
Ch a r a cter iza tion . The spectral changes upon boron
complexation of a 1-acyldipyrromethane include the
appearance of the characteristic absorption at ca. 340-
390 nm. The 13C NMR spectra show the downfield shift
1
(∼8 ppm) of the carbonyl carbon. The H NMR spectra
show (1) disappearance of the NH resonance of the
acylpyrrole unit, (2) a ∼0.4 ppm upfield shift of the
unsubstituted pyrrolic NH resonance, (3) a downfield
shift (∼0.2 ppm) of the meso-proton, (4) a downfield shift
(∼1 ppm) of the â-protons of the acylpyrrole, and (5)
multiplets from the diastereotopic alkyl moieties attached
to the boron atom. An example of a boron complex with
freely rotating alkyl substituents is provided by 6a -BMe2,
where a distinct singlet (0.04, 0.15 ppm) is observed
owing to the different magnetic environment for each
methyl group (syn or anti with respect to the meso-
substituent). In the rigid 9-BBN complexes, a further
difference in magnetic environment stems from whether
the alkyl boron groups are proximal or distal to the
R-carbonyl unit. For example, in 6a -BBN, the 9-BBN
bridgehead protons give two partially overlapping mul-
tiplets (centered at ∼0.7 ppm) and the remaining meth-
ylene protons give complex multiplets in the low-field
region (1.6-2.4 ppm).
The 11B NMR spectra of selected samples (6a -BBN-
6d -BBN, and 6g-BBN) each showed a single peak at ∼13
ppm relative to the 11B standard, BF3‚O(Et)2 (0 ppm). For
comparison, the boron signal in the unacylated N-(9-
borabicyclo[3.3.1]non-9-yl)pyrrole appears at 59.9 ppm.23
The relative upfield shift of the dialkylboron acylated
pyrrole complex is characteristic of organoboron species
with coordination in the lone p orbital of the boron atom.28
Elemental analyses for some of the boron complexes were
satisfactory while others showed unsatisfactory results
for carbon. This discrepancy may stem from solvent
inclusion in the crystal lattice of the boron complexes.
However, FABMS analysis of each complex was satisfac-
tory.
(29) English, R. B.; McGillivray, G.; Smal, E. Acta Crystallogr. 1980,
B36, 1136-1141.
(30) Araki, M.; Sakata, S.; Takei, H.; Mukaiyama, T. Bull. Chem.
Soc. J pn. 1974, 47, 1777-1780.
(31) Laha, J . K.; Dhanalekshmi, S.; Taniguchi, M.; Ambroise, A.;
Lindsey, J . S. Org. Process Res. Dev. 2003, 7, 799-812.
(32) Cho, W.-S.; Kim, H.-J .; Littler, B. J .; Miller, M. A.; Lee, C.-H.;
Lindsey, J . S. J . Org. Chem. 1999, 64, 7890-7901.
(33) Geier, G. R., III; Callinan, J . B.; Rao, P. D.; Lindsey, J . S. J .
Porphyrins Phthalocyanines 2001, 5, 810-823.
X-ray structural analysis was performed on 6a -BBN
(Figure 1). Complexation results in near coplanarity of
(28) Wrackmeyer, B. Annu. Rep. NMR Spectrosc. 1988, 20, 61-203.
5358 J . Org. Chem., Vol. 69, No. 16, 2004

Boron-Complexation for 1-Acyldipyrromethanes
SCHEME 6
material (1.77 g), giving an overall yield of 62%. This
procedure is well suited for synthesis at the multigram
level. No change in solvent was required for use with 2d ;
the boron complex 6d -BBN precipitated upon formation
in CH2Cl2. Note that dipyrromethanes 1a -f were pre-
pared by a streamlined procedure with minimal or no
reliance on chromatography,31 and 1g was prepared
herein by the same procedure; accordingly, the overall
route to form a 1-acyldipyrromethane can now be imple-
mented with limited or no use of chromatography.
Decom p lexa tion of 1-Acyld ip yr r om eth a n e-Bo-
r on Com p lex. A simple method for decomplexation of
the 1-acyldipyrromethane-boron complexes was inves-
tigated using 6a -BBN as a test case. The cleavage of the
B-N bond in alkyl or arylamines has been achieved with
acids,34,35 bases,35 or ethanolamine.35 The similar cleav-
age of N-(dialkylboron)pyrroles has been achieved with
acids19,24 or ethanol.24 Given the potential lability of the
1-acyldipyrromethane to acidic conditions, we focused on
neutral reaction conditions. Smooth decomplexation was
obtained in refluxing solvents composed of H2O/THF or
ROH/THF, where ROH is methanol, neopentyl glycol,
ethanolamine, poly(ethylene glycol), 1,3-propanediol, pen-
taerythritol, or poly(vinyl alcohol). In many cases, isola-
tion could be achieved in nearly pure form without
chromatography. A key factor in choice of alcohol is to
avoid chromatography altogether for separation of the
1-acyldipyrromethane and the derivative formed upon
reaction of ROH and the dibutylboron or 9-BBN species.
We found that 1-pentanol generally afforded superior
results. Accordingly, treatment of 6a -BBN with excess
1-pentanol in refluxing THF for 1 h followed by solvent
removal, trituration with hot hexanes for 5 min, and
recrystallization/precipitation from CH2Cl2/hexanes af-
forded 2a in 83% yield (Scheme 7).
Application of these decomplexation conditions to 6a -
BBN, 6b-BBN, and 6d -BBN afforded 2a , 2b, and 2d ,
respectively, in excellent yields (Scheme 7). The boron
complex 6f-BBu 2 was decomplexed with neat 1-pentanol
at 80 °C for 1 h followed by the workup procedure
described above. Decomplexation of 6c-BBN with 1-pen-
tanol in THF at reflux for 1 h afforded 2c, which was
isolated upon passage through a pad of alumina.
Use of 1-Acyld ip yr r om eth a n e-Bor on Com p lexes
in P or p h yr in F or m a tion . The reduction of a 1-acyl-
dipyrromethane affords the corresponding dipyrro-
methane-1-carbinol, which upon self-condensation and
oxidation affords the trans-A2B2 porphyrin.2,33 The 1-acyl-
dipyrromethane-boron complexes were examined as
precursors to trans-A2B2 porphyrins, thereby avoiding the
(34) Bar-Haim, G.; Kol, M. J . Org. Chem. 1997, 62, 6682-6683.
(35) Bar-Haim, G.; Kol, M. Tetrahedron Lett. 1998, 39, 2643-2644.
J . Org. Chem, Vol. 69, No. 16, 2004 5359

Muthukumaran et al.
SCHEME 7
of the crude reaction mixtures. For comparison, the
reaction of the uncomplexed 1-acyldipyrromethane 2a
affords porphyrin 8 in 25% yield.33
Con clu sion
Advances in porphyrin chemistry stem both from
identification of new routes and from development of
refined syntheses of critical intermediates. 1-Acyldipyr-
romethanes are essential intermediates in the synthesis
of trans-A2B2, trans-AB2C, cis-A2B2, cis-AB2C, and ABCD
porphyrins; diverse chlorins; A2B, AB2, and ABC corroles;
and bilanes. The boron-complexation strategy provides
a facile method for the isolation of a 1-acyldipyr-
romethane from the crude acylation mixture. Formation
of the boron complex alters the structure by blocking the
pyrrolic nitrogen and carbonyl oxygen atoms, thereby
ensheathing sites that can engage in hydrogen bonding.
The resulting 1-acyldipyrromethane-boron complex is
typically less polar than the corresponding 1-acyldipyr-
romethane, has high solubility in organic solvents, chro-
matographs as a sharp band, and crystallizes readily. The
boron-complexation strategy can be used for the purifica-
tion of a wide variety of 1-acyldipyrromethanes. The
1-acyldipyrromethane-boron complexes can be decom-
plexed to give the 1-acyldipyrromethanes in excellent
yields. Alternatively, reduction of a 1-acyldipyrromethane-
boron complex followed by self-condensation of the re-
sulting dipyrromethane-carbinol affords the correspond-
ing trans-A2B2 porphyrin. The ability to isolate and
handle 1-acyldipyrromethanes as dialkylboron complexes
should increase the scale of 1-acyldipyrromethane syn-
theses and facilitate the preparation of a wide variety of
porphyrinic compounds.
SCHEME 8
Exp er im en ta l Section
Non com m er cia l Com p ou n d s. Dipyrromethanes 1a -f
were prepared as described in the literature and analyzed for
purity by gas chromatography.31 1-Acyldipyrromethanes 2a ,2
2d ,7 2e,1 2f,2 2g,1 2h ,7 2i;27 1,9-diacyldipyrromethane 3a ;1 and
the Mukaiyama reagents 5a -e2 and 5f 5 were prepared as
described in the literature.
5-[4-(Tr im et h ylsilylet h yn yl)p h en yl]d ip yr r om et h a n e
(1g). Following a standard procedure,31 a solution of 4-(tri-
methylsilylethynyl)benzaldehyde (7.00 g, 35.0 mmol) in pyrrole
(347 mL) was degassed for 10 min. Then InCl3 (1.11 g, 5.00
mmol) was added. The mixture was stirred at room temper-
ature under argon. After 1.5 h, NaOH (6.00 g, 0.15 mol, 20-
40 mesh beads) was added, and the stirring was continued
for an additional 45 min. The mixture was filtered, and the
filtrate was concentrated under high vacuum. The resulting
oil was triturated with hexanes (50 mL), and the volatile
components were evaporated. This procedure was repeated
four times, affording a white solid. Crystallization from ethanol
afforded off-white crystals (7.66 g, 69%): mp 122-123 °C (lit.32
120 °C). 1H NMR spectral data are consistent with reported
values:32 1H NMR δ 0.26 (s, 9H), 5.45 (s, 1H), 5.88-5.92 (m,
2H), 6.13-6.19 (m, 2H), 6.67-6.71 (m, 2H), 7.14 (d, J ) 8.0
Hz, 2H), 7.42 (d, J ) 8.0 Hz, 2H), 7.83-7.90 (br, 2H). Anal.
Calcd for C18H20N2: C, 75.42; H, 6.96; N, 8.80. Found: C, 75.40;
H, 6.88; N, 8.75.
boron-decomplexation procedure. Thus, the boron com-
plex 6a -BBu 2 was treated with NaBH4 in THF/methanol
for 40 min. TLC analysis indicated complete consumption
of 6a -BBu 2 and formation of a new polar spot. The
reaction mixture was worked up in the standard way and
the product was subjected to acid-catalyzed self-conden-
sation [Yb(OTf)3 in CH2Cl2]33 followed by oxidation with
DDQ. Porphyrin 8 was obtained in 26% yield (Scheme
8). The boron complex 6a -BBN was treated similarly,
affording porphyrin 8 in 17% yield. In both cases, no other
porphyrin species were observed upon LD-MS36 analysis
1-(4-Meth ylben zoyl)d ip yr r om eth a n e (2b). Following a
standard procedure2 (but with a 500 mM solution of 1b rather
than 1 M owing to limited solubility), a solution of 1b (0.731
g, 5.00 mmol) in THF (10 mL) at room temperature under
argon was treated with EtMgBr (12.5 mL, 12.5 mmol, 1.0 M
solution in THF) for 10 min. The solution was cooled to -78
(36) (a) Fenyo, D.; Chait, B. T.; J ohnson, T. E.; Lindsey, J . S. J .
Porphyrins Phthalocyanines 1997, 1, 93-99. (b) Srinivasan, N.; Haney,
C. A.; Lindsey, J . S.; Zhang, W.; Chait, B. T. J . Porphyrins Phthalo-
cyanines 1999, 3, 283-291.
5360 J . Org. Chem., Vol. 69, No. 16, 2004

Boron-Complexation for 1-Acyldipyrromethanes
°C. Then a solution of 5a (1.15 g, 5.00 mmol) in THF (5.0 mL)
was added. The reaction mixture was stirred at -78 °C for 10
min and at room temperature for 20 min. Standard workup
and chromatography [silica, CH2Cl2/ethyl acetate (9:1)] af-
forded a pale brown solid (0.812 g, 62%): mp 172-174 °C; 1H
NMR δ 2.43 (s, 3H), 4.09 (s, 2H), 6.03-6.06 (m, 1H), 6.08-
6.12 (m, 1H), 6.14-6.18 (m, 1H), 6.51-6.55 (m, 1H), 6.80-
6.86 (m, 1H), 7.27 (d, J ) 8.0 Hz, 2H), 7.76 (d, J ) 8.0 Hz,
2H), 9.25-9.28 (br, 1H), 10.94-10.98 (br, 1H); 13C NMR δ 21.8,
26.8, 106.4, 108.3, 110.3, 117.7, 123.1, 128.2, 129.3, 130.7,
136.0, 141.2, 142.7, 185.6. Anal. Calcd for C17H16N2O: C, 77.25;
H, 6.10; N, 10.60. Found: C, 76.52; H, 5.89; N, 10.33.
1-Hexa n oyl-5-p en tyld ip yr r om eth a n e (2c). Following a
standard procedure,2 a solution of 1c (1.08 g, 5.00 mmol) in
THF (5.0 mL) under argon at room temperature was treated
with EtMgBr (12.5 mL, 12.5 mmol, 1.0 M solution in THF)
for 10 min. The solution was cooled to -78 °C, and then a
solution of 5f (1.05 g, 5.00 mmol) in THF (5.0 mL) was added.
The reaction mixture was stirred at -78 °C for 10 min and at
room temperature for 20 min. Standard workup and chroma-
tography [silica, CH2Cl2/ethyl acetate (9:1)] afforded a light
yellow oil (0.986 g, 63%): 1H NMR δ 0.81-0.90 (m, 6H), 1.22-
1.37 (m, 10H), 1.68-1.76 (m, 2H), 2.00-2.06 (m, 2H), 2.74 (t,
J ) 7.6 Hz, 2H), 4.05 (t, J ) 7.6 Hz, 1H), 6.02-6.06 (m, 1H),
6.08-6.14 (m, 2H), 6.64-6.68 (m, 1H), 6.88-6.91 (m, 1H),
8.94-8.98 (br, 1H), 10.16-10.20 (br, 1H); 13C NMR δ 14.1, 14.2,
22.7, 26.2, 27.7, 31.85, 31.87, 33.8, 38.1, 38.3, 105.0, 108.1,
108.5, 117.3, 119.5, 131.1, 133.0, 144.8, 191.9. Anal. Calcd for
which upon concentration afforded an orange oil (0.344 g,
91%): 1H NMR δ 0.04 (s, 3H), 0.15 (s, 3H), 2.48 (s, 3H), 5.66
(s, 1H), 5.87-5.92 (m, 1H), 6.15-6.19 (m, 1H), 6.43 (d, J )
4.0 Hz, 1H), 6.70-6.75 (m, 1H), 7.24-7.38 (m, 8H), 7.84-7.88
(br, 1H), 8.11 (d, J ) 8.0 Hz, 2H); 13C NMR δ 6.8, 22.1, 44.1,
107.9, 108.6, 117.5, 118.3, 119.3, 127.3, 128.1, 128.8, 128.9,
129.95, 129.99, 132.0, 133.1, 141.4, 145.5, 150.1, 176.1; FABMS
obsd 381.2158 [(M + H)+], calcd 381.2138 (C25H25BN2O). Anal.
Calcd for C25H25BN2O: C, 78.96; H, 6.63; N, 7.37. Found: C,
78.66; H, 6.60; N, 7.28. λabs 393 nm.
10-(9-Bor a bicyclo[3.3.1]n on -9-yl)-1-(4-m eth ylben zoyl)-
5-p h en yld ip yr r om eth a n e (6a -BBN). A solution of 2a (0.680
g, 2.00 mmol) in CH2Cl2 (4 mL) was treated with TEA (0.670
mL, 4.80 mmol) followed by 9-BBN-OTf (8.00 mL, 4.00 mmol,
0.5 M in hexanes). After 30 min, the mixture was passed
through a pad of silica (4 × 8 cm) eluting with CH2Cl2. The
product eluted as a fast-moving yellow band, which upon
concentration afforded a yellow-orange solid (0.863 g, 94%):
mp 187 °C (dec); 1H NMR δ 0.66-0.71 (m, 2H), 1.65-1.84 (m,
6H), 1.95-2.25 (m, 6H), 2.48 (s, 3H), 5.83-5.86 (m, 1H), 6.01
(s, 1H), 6.13-6.17 (m, 1H), 6.41 (d, J ) 4.0 Hz, 1H), 6.69-
6.73 (m, 1H), 7.18 (d, J ) 8.0 Hz, 2H), 7.22-7.38 (m, 6H),
7.83-7.87 (br, 1H), 8.11 (d, J ) 8.0 Hz, 2H); 13C NMR δ 22.0,
23.8, 25.1, 25.9, 26.4, 30.5, 30.8, 34.48, 34.54, 44.7, 108.1, 108.5,
117.4, 118.2, 120.8, 127.0, 128.1, 128.4, 128.6, 129.7, 129.9,
132.3, 134.8, 142.1, 145.0, 151.9, 174.4; 11B NMR δ 12.34;
FABMS obsd 460.2674 [M+], calcd 460.2686 (C31H33BN2O).
Anal. Calcd for C31H33BN2O: C, 80.87; H, 7.22; N, 6.08.
Found: C, 78.96; H, 7.13; N, 5.85. λabs 381 nm.
C
20H30N2O: C, 76.39; H, 9.62; N, 8.91. Found: C, 76.15; H,
9.80; N, 8.77.
10-(9-Bor a bicyclo[3.3.1]n on -9-yl)-1-(4-m eth ylben zoyl)-
d ip yr r om eth a n e (6b-BBN). Following the procedure for 6a -
BBN, reaction of 2b (0.529 g, 2.00 mmol) afforded a yellow-
orange solid (0.696 g, 91%): mp 147 °C (dec); 1H NMR δ 0.71-
0.78 (m, 2H), 1.67-1.75 (m, 4H), 1.76-1.91 (m, 4H), 1.98-
2.14 (m, 2H), 2.16-2.26 (m, 2H), 2.48 (s, 3H), 4.34 (s, 2H),
6.03-6.06 (m, 1H), 6.16-6.18 (m, 1H), 6.36 (d, J ) 4.0 Hz,
1H), 6.69-6.72 (m, 1H), 7.29 (d, J ) 4.0 Hz, 1H), 7.36 (d, J )
8.0 Hz, 2H), 7.90-7.94 (br, 1H), 8.11 (d, J ) 8.0 Hz, 2H); 13C
NMR δ 22.1, 24.0, 25.2, 26.8, 29.5, 31.5, 34.5, 107.1, 108.7,
117.5, 118.3, 120.7, 128.2, 128.7, 129.8, 129.9, 135.3, 145.0,
149.5, 174.1; 11B NMR δ 12.74; FABMS obsd 384.2395 [M+],
calcd 384.2373 (C25H29BN2O). Anal. Calcd for C25H29BN2O: C,
78.13; H, 7.61; N, 7.29. Found: C, 78.17; H, 7.58; N, 7.09. λabs
380 nm.
10-(9-Bor a bicyclo[3.3.1]n on -9-yl)-1-h exa n oyl-5-p en tyl-
d ip yr r om eth a n e (6c-BBN). Following the procedure for 6a -
BBN, reaction of 2c (0.529 g, 2.00 mmol) afforded an orange
oil (0.758 g, 87%): 1H NMR δ 0.55-0.64 (m, 2H), 0.82-0.94
(m, 6H), 1.19-1.54 (m, 12H), 1.62-1.91 (m, 8H), 1.96-2.17
(m, 6H), 2.81 (t, J ) 8.0 Hz, 2H), 4.43 (t, J ) 8.0 Hz, 1H),
6.03-6.06 (m, 1H), 6.13-6.17 (m, 1H), 6.39 (d, J ) 4.0 Hz,
1H), 6.62-6.67 (m, 1H), 7.05 (d, J ) 4.0 Hz, 1H), 7.76-7.80
(br, 1H); 13C NMR δ 14.1, 14.2, 22.5, 22.6, 22.7, 24.0, 25.0, 25.8,
26.3, 27.6, 30.7, 30.8, 31.5, 31.7, 32.2, 34.19, 32.22, 36.4, 39.2,
105.2, 108.5, 117.0, 117.57, 117.63, 133.5, 136.5, 154.8, 184.3;
11B NMR δ 13.22; FABMS obsd 434.3481 [M+], calcd 434.3468
(C28H43BN2O). Anal. Calcd for C28H43BN2O: C, 77.41; H, 9.98;
N, 6.45. Found: C, 75.22; H, 9.90; N, 6.40. λabs 345 nm.
10-(9-Bor abicyclo[3.3.1]n on -9-yl)-1-(4-m eth oxyben zoyl)-
5-(4-m eth oxyp h en yl)d ip yr r om eth a n e (6d -BBN). Follow-
ing the procedure for 6a -BBN, reaction of 2d (0.773 g, 2.00
mmol) afforded a yellow-brown solid (0.986 g, 97%): mp 72-
73 °C; 1H NMR δ 0.64-0.74 (m, 2H), 1.62-1.86 (m, 6H), 1.98-
2.24 (m, 6H), 3.79 (s, 3H), 3.92 (s, 3H), 5.82-5.87 (m, 1H), 5.96
(s, 1H), 6.12-6.17 (m, 1H), 6.40 (d, J ) 4.0 Hz, 1H), 6.69-
6.72 (m, 1H), 6.84 (d, J ) 8.0 Hz, 2H), 7.05 (d, J ) 8.0 Hz,
2H), 7.10 (d, J ) 8.0 Hz, 2H), 7.30 (d, J ) 4.0 Hz, 1H), 7.84-
7.88 (br, 1H), 8.21 (d, J ) 8.0 Hz, 2H); 13C NMR δ 24.0, 25.2,
26.0, 26.5, 30.6, 30.9, 34.6, 34.7, 44.0, 55.4, 55.8, 107.9, 108.6,
114.0, 114.7, 117.4, 117.8, 120.5, 123.5, 129.6, 130.0, 133.0,
134.4, 134.5, 151.7, 158.6, 164.4, 173.8; 11B NMR δ 12.69;
FABMS obsd 506.2749 [M+], calcd 506.2741 (C32H35BN2O3).
Scr een in g P r otocol for Meta l Com p lexa tion of 1-Acyl-
d ip yr r om eth a n es. A solution of 2a (0.017 g, 0.050 mmol) in
methanol (0.5 mL) was treated with a solution of a metal
reagent (0.025 mmol) in methanol (0.5 mL). The mixture was
stirred at room temperature for 1 h. The reaction was
monitored visually for precipitate formation. The reaction
mixture was examined by TLC (silica, CH2Cl2/ethyl acetate,
9:1) and by absorption spectroscopy.
Bis[1-(4-m et h ylb en zoyl)-5-p h en yld ip yr r om et h a n -10-
yl]cop p er (II) (Cu -2a ). A solution of 2a (0.25 mmol, 85 mg)
in methanol (2.5 mL) was treated with a warm solution of Cu-
(OAc)2‚H2O (0.30 mmol, 26 mg) in methanol (1 mL). The
mixture was stirred at room temperature for 20 min. The
resulting precipitate was filtered. The filtered material was
washed with methanol and dried in vacuo to afford a green
powder (75 mg, 81%): Anal. Calcd for C46H38CuN4O2: C, 74.42;
H, 5.16; N, 7.55. Found: C, 73.93; H, 5.22; N, 7.40. λabs 380
nm.
10-(Dibu tylbor yl)-1-(4-m eth ylben zoyl)-5-p h en yld ip yr -
r om eth a n e (6a -BBu 2). A solution of 2a (0.340 g, 1.00 mmol)
in CH2Cl2 (2 mL) was treated with TEA (0.335 mL, 2.40 mmol)
followed by Bu2B-OTf (2.00 mL, 2.00 mmol, 1.0 M in CH2Cl2).
After 30 min, the mixture was passed through a pad of silica
(4 × 8 cm) eluting with CH2Cl2. The product eluted as a fast-
moving yellow band, which upon concentration afforded an
orange oil (0.431 g, 93%): 1H NMR δ 0.36-0.52 (m, 2H), 0.61
(t, J ) 7.2 Hz, 3H), 0.65-1.18 (m, 13H), 2.47 (s, 3H), 5.60 (s,
1H), 5.85-5.88 (m, 1H), 6.13-6.17 (m, 1H), 6.45 (d, J ) 4.0
Hz, 1H), 6.68-6.72 (m, 1H), 7.20-7.38 (m, 8H), 7.79-7.83 (br,
1H), 8.11 (d, J ) 8.0 Hz, 2H); 13C NMR δ 14.3, 14.4, 22.2, 22.6,
22.7, 26.17, 26.24, 27.1, 27.5, 44.2, 107.9, 108.8, 117.4, 117.8,
119.3, 127.3, 128.0, 128.77, 128.83, 129.98, 130.01, 132.2,
134.2, 141.5, 145.4, 150.1, 176.5; FABMS obsd 465.3074 [(M
+ H)+], calcd 465.3077 (C31H37BN2O). Anal. Calcd for C31H37
-
BN2O: C, 80.17; H, 8.03; N, 6.03. Found: C, 79.98; H, 8.06;
N, 5.95. λabs 393 nm.
10-(Dim eth ylbor yl)-1-(4-m eth ylben zoyl)-5-ph en yldipyr -
r om eth a n e (6a -BMe2). A solution of 2a (0.340 g, 1.00 mmol)
in CH2Cl2 (2 mL) was treated with TEA (0.335 mL, 2.40 mmol)
followed by Me2B-Br (0.390 mL, 1.00 mmol). After 30 min, the
mixture was passed through a pad of silica (4 × 8 cm) eluting
with CH2Cl2. The product eluted as a fast-moving yellow band,
J . Org. Chem, Vol. 69, No. 16, 2004 5361

Muthukumaran et al.
Anal. Calcd for C32H35BN2O3: C, 75.89; H, 6.97; N, 5.53.
Found: C, 74.75; H, 7.37; N, 5.01. λabs 388 nm.
145.6, 146.1, 177.6; FABMS obsd 555.2627 [(M + H)+], calcd
555.2606 (C31H32BF5N2O). Anal. Calcd for C31H32BF5N2O: C,
67.16; H, 5.82; N, 5.05. Found: C, 67.00; H, 5.78; N, 4.91. λabs
386 nm.
10-(Dibu tylbor yl)-1-(p en ta flu or oben zoyl)-5-p en ta flu o-
r op h en yld ip yr r om eth a n e (6e-BBu 2). Following the proce-
dure for 6a -BBu 2, reaction of 2e (0.506 g, 1.00 mmol) afforded
an orange oil (0.608 g, 97%): 1H NMR δ 0.13-0.35 (m, 2H),
0.58-1.39 (m, 16H), 5.94 (s, 1H), 6.00 (s, 1H), 6.15-6.20 (m,
1H), 6.61 (d, J ) 4.0 Hz, 1H), 6.74-6.80 (m, 1H), 7.04-7.10
(m, 1H), 8.05-8.09 (br, 1H); 13C NMR δ 14.1, 14.3, 20.9, 21.4,
26.0, 26.2, 26.9, 27.4, 33.5, 33.9, 108.5, 109.2, 109.4, 111.3,
118.8, 119.6, 119.7, 119.8, 122.1, 122.3, 127.0, 136.9 (m), 138.0,
139.6 (m), 142.1 (m), 142.9 (m), 143.9 (m), 144.4 (m), 145.5
(m), 146.4 (m), 147.0 (m), 150.6, 166.0. This compound partially
decomplexed to 2e upon handling as a result of exposure to
moisture.
10-(Dib u t ylb or yl)-1-(4-iod ob en zoyl)-5-m esit yld ip yr -
r om eth a n e (6f-BBu 2). Following the procedure for 6a -BBu 2,
reaction of 2f (0.494 g, 1.00 mmol) afforded a yellow-orange
solid (0.548 g, 89%): mp 53-54 °C; 1H NMR δ -0.25- -0.17
(m, 1H), 0.24-0.39 (m, 2H), 0.55-0.98 (m, 13H), 1.14-1.27
(m, 2H), 2.15 (s, 6H), 2.62 (s, 3H), 5.88 (s, 1H), 5.90-5.93 (m,
1H), 6.16-6.20 (m, 1H), 6.50 (d, J ) 4.0 Hz, 1H), 6.66-6.70
(m, 1H), 6.83 (s, 2H), 7.17 (d, J ) 4.0 Hz, 1H), 7.80-7.84 (br,
1H), 7.85-7.94 (m, 4H); 13C NMR δ 14.3, 14.5, 20.9, 21.2, 21.8,
26.1, 26.2, 27.3, 27.5, 40.1, 101.9, 108.0, 108.9, 116.8, 117.0,
122.8, 130.0, 130.1, 130.6, 130.9, 134.8, 135.3, 136.9, 137.2,
138.6, 153.0, 174.7; FABMS obsd 619.2390 [(M + H)+], calcd
619.2357 (C33H40BIN2O). Anal. Calcd for C33H40BIN2O: C,
64.09; H, 6.52; N, 4.53. Found: C, 64.08; H, 6.62; N, 4.40. λabs
404 nm.
10-(Dib u t ylb or yl)-1-(p e n t a flu or ob e n zoyl)d ip yr r o-
m eth a n e (6i-BBu 2). Following the procedure for 6a -BBu 2,
reaction of 2i (0.340 g, 1.00 mmol) afforded an orange oil (0.412
g, 89%): 1H NMR δ 0.58-0.68 (m, 2H), 0.74-0.92 (m, 10H),
1.00-1.08 (m, 2H), 1.16-1.30 (m, 4H), 4.09 (s, 2H), 6.04-6.09
(m, 1H), 6.14-6.20 (m, 1H), 6.45 (d, J ) 4.0 Hz, 1H), 6.70-
6.75 (m, 1H), 7.01-7.06 (m, 1H), 7.90-7.93 (br, 1H); 13C NMR
δ 14.4, 22.0, 26.2, 27.3, 107.6, 109.1, 117.8, 120.21, 120.26,
120.30, 121.9, 126.9, 137.5, 152.1, 164.1; FABMS obsd 465.2179
[(M + H)+], calcd 465.2137 (C24H26BF5N2O). Anal. Calcd for
C24H26BF5N2O: C, 62.09; H, 5.64; N, 6.03. Found: C, 61.31;
H, 5.63; N, 5.93. λabs 382 nm.
Acyla tion -Bor on Com p lexa tion P r oced u r e, Exem p li-
fied for 6a -BBN. A solution of EtMgBr (20.0 mL, 20.0 mmol,
1.0 M in THF) was added slowly to a solution of 1a (2.22 g,
10.0 mmol) in THF (10 mL) under argon. The resulting
mixture was stirred at room temperature for 10 min and then
cooled to -78 °C. A solution of S-2-pyridyl 4-methylbenzothio-
ate (5a , 2.29 g, 10.0 mmol) in THF (10 mL) was added. The
solution was stirred at -78 °C for 10 min and then warmed
to room temperature. The reaction mixture was quenched by
addition of saturated aqueous NH4Cl (40 mL). The mixture
was extracted with ethyl acetate (30 mL). The organic layer
was washed (water and brine), dried (Na2SO4), and filtered.
The filtrate was concentrated. The crude product (a red-orange
oil) thus obtained was dissolved in CH2Cl2 (20 mL) and treated
with TEA (3.35 mL, 24.0 mmol) followed by 9-BBN-OTf (40
mL, 20.0 mmol, 0.5 M in hexane) with stirring at room
temperature. A precipitate formed that largely consisted of the
salt of TEA and triflic acid. After 1 h, the mixture was poured
onto a pad of silica (4 × 8 cm) eluting with CH2Cl2. The product
eluted as a fast-moving yellow band, which upon concentration
afforded a yellow-orange solid (3.12 g, 67%) with satisfactory
characterization data (mp, 1H NMR spectrum, and FABMS)
as reported above.
Note: The use of boron complexation to isolate the 1-acyl-
dipyrromethane enables use of stoichiometric quantities of
reagents rather than excess as employed previously. Thus, the
1-acylation of dipyrromethanes was conducted with slight
modification to the standard procedure. Previously, 2.5 molar
equiv of EtMgBr was used for the acylation of dipyrromethane
(1) with 1.0 molar equiv of a Mukaiyama reagent (5) in order
to avoid cochromatography of the unreacted 5 and the product
2.2 (The unreacted Mukaiyama reagent is consumed by
EtMgBr, affording the ketone.30) Given that the 1-acyldipyr-
romethane is to be isolated as a boron complex, complete
consumption of the Mukaiyama reagent is not necessary.
Sca le-Up P r oced u r e. A solution of EtMgBr (80.0 mL, 80.0
mmol, 1.0 M in THF) was added slowly to a solution of 1a
(8.88 g, 40.0 mmol) in THF (40 mL) under argon. The resulting
mixture was stirred at room temperature for 10 min and then
cooled to -78 °C. A solution of S-2-pyridyl 4-methylbenzothio-
ate (5a , 9.16 g, 40.0 mmol) in THF (40 mL) was added. The
solution was stirred at -78 °C for 10 min and then warmed
to room temperature. The reaction mixture was quenched by
addition of saturated aqueous NH4Cl. The mixture was
extracted with ethyl acetate. The organic layer was dried (Na2-
SO4) and filtered. The filtrate was concentrated. The crude
product (a red-orange oil) thus obtained was dissolved in
toluene (80 mL) and treated with TEA (13.4 mL, 96.0 mmol)
followed by 9-BBN-OTf (160 mL, 80.0 mmol, 0.5 M in hexanes)
with stirring at room temperature. A precipitate formed
immediately, which largely consisted of the title compound and
the salt of TEA and triflic acid. After 1 h, the mixture was
filtered through a Bu¨chner funnel using coarse filter paper.
The filtered material was washed with water, washed with
methanol, and then dried in vacuo to afford a yellow powder
(9.63 g, 52%). The filtrate was concentrated and passed
10-(9-Bor a bicyclo[3.3.1]n on -9-yl)-1-(4-br om oben zoyl)-
5-[4-(2-tr im eth ylsilyl)eth yn ylph en yl]dipyr r om eth an e (6g-
BBN). Following the procedure for 6a -BBN, reaction of 2g
(0.529 g, 2.00 mmol) afforded a yellow-orange solid (1.19 g,
96%): mp 172 °C (dec); 1H NMR δ 0.24 (s, 9H), 0.64-0.73 (m,
2H), 1.64-1.85 (m, 6H), 1.94-2.09 (m, 4H), 2.12-2.24 (m, 2H),
5.83 (s, 1H), 6.00 (s, 1H), 6.13-6.18 (m, 1H), 6.39 (d, J ) 4.0
Hz, 1H), 6.71-6.75 (m, 1H), 7.09 (d, J ) 8.0 Hz, 2H), 7.32 (d,
J ) 4.0 Hz, 1H), 7.40 (d, J ) 8.0 Hz, 2H), 7.68-7.74 (m, 2H),
7.82-7.86 (br, 1H), 8.02-8.10 (m, 2H); 13C NMR δ 0.18, 23.8,
25.1, 25.9, 26.6, 30.7, 30.8, 34.6, 44.8, 94.7, 104.9, 108.4, 108.8,
117.9, 118.7, 121.6, 122.1, 128.4, 129.2, 129.7, 131.0, 131.7,
132.4, 132.6, 132.7, 135.1, 142.4, 152.5, 173.2; 11B NMR δ
13.98; FABMS obsd 620.2057 [M+], calcd 620.2030 (C35H38
-
BBrN2OSi). Anal. Calcd for C35H38BBrN2OSi: C, 67.64; H,
6.16; N, 4.51. Found: C, 67.41; H, 6.26; N, 4.43. λabs 388 nm.
10-(9-Bor a bicyclo[3.3.1]n on -9-yl)-1-(4-m eth ylben zoyl)-
5-(p en ta flu or op h en yl)d ip yr r om eth a n e (6h -BBN). Follow-
ing the procedure for 6a -BBN, reaction of 2h (0.430 g, 1.00
mmol) afforded a yellow-orange solid (0.512 g, 93%): mp 154-
156 °C (dec); 1H NMR δ 0.58-0.64 (m, 1H), 0.68-0.74 (m, 1H),
1.58-1.85 (m, 6H), 1.94-2.24 (m, 6H), 2.50 (s, 3H), 5.79 (s,
1H), 6.12-6.18 (m, 1H), 6.30 (s, 1H), 6.60 (d, J ) 4.0 Hz, 1H),
6.62-6.68 (m, 1H), 7.38 (d, J ) 4.0 Hz, 1H), 7.39 (d, J ) 8.0
Hz, 2H), 7.75-7.78 (br, 1H), 8.15 (d, J ) 8.0 Hz, 2H); 13C NMR
δ 22.2, 23.9, 25.1, 26.3, 27.2, 29.8, 31.3, 34.67, 34.71, 36.3,
106.9, 109.2, 117.4, 118.3, 120.56, 120.60, 120.64, 127.9, 129.6,
130.07, 130.14, 135.9, 136.8 (m), 139.4 (m), 142.0 (m), 144.4
(m), 145.8, 146.4, 146.9 (m), 175.9; FABMS obsd 550.2229 [M+],
calcd 550.2215 (C31H28BF5N2O). Anal. Calcd for C31H28
-
BF5N2O: C, 67.65; H, 5.13; N, 5.09. Found: C, 68.05; H, 5.23;
N, 4.92. λabs 377 nm.
10-(Dib u t ylb or yl)-1-(4-m et h ylb en zoyl)-5-(p en t a flu o-
r op h en yl)d ip yr r om eth a n e (6h -BBu 2). Following the pro-
cedure for 6a -BBu 2, reaction of 2h (0.430 g, 1.00 mmol)
afforded an orange oil (0.497 g, 90%): 1H NMR δ 0.16-0.35
(m, 2H), 0.54-1.25 (m, 16H), 2.48 (s, 3H), 5.94-6.02 (m, 2H),
6.14-6.18 (m, 1H), 6.57 (d, J ) 4.0 Hz, 1H), 6.72-6.78 (m,
1H), 7.24 (d, J ) 4.0 Hz, 1H), 7.38 (d, J ) 8.0 Hz, 2H), 8.06-
8.10 (br, 1H), 8.12 (d, J ) 8.0 Hz, 2H); 13C NMR δ 14.2, 14.4,
21.5, 21.8, 22.2, 26.1, 26.3, 27.1, 27.6, 33.7, 107.9, 109.0, 117.4,
118.3, 119.68, 119.72, 119.76, 127.7, 128.0, 130.1, 130.2, 135.0,
5362 J . Org. Chem., Vol. 69, No. 16, 2004

Boron-Complexation for 1-Acyldipyrromethanes
through a silica pad eluting with CH2Cl2/hexanes, affording
1.77 g of the title compound. The combined yield is 11.4 g (62%)
afforded crude 2h . Boron complexation with TEA (3.35 mL,
24.0 mmol) and 9-BBN-OTf (40.0 mL, 20.0 mmol, 0.5 M in
hexanes) in CH2Cl2 followed by passage through a pad of silica
[CH2Cl2/hexanes (1:1)] afforded yellow crystals (3.17 g, 58%)
with satisfactory characterization data (mp, 1H NMR, and
elemental analysis) as reported above.
1
and the characterization data are satisfactory (mp, H NMR,
13C NMR, and FABMS spectra) as reported above.
10-(9-Bor a bicyclo[3.3.1]n on -9-yl)-1-(4-m eth ylben zoyl)-
d ip yr r om eth a n e (6b-BBN). Following the acylation-com-
plexation procedure, reaction of 1b (1.46 g, 10.0 mmol) with
EtMgBr (20.0 mL, 20.0 mmol, 1.0 M in THF) followed by
treatment with 5a (2.29 g, 10.0 mmol) afforded crude 2b. Boron
complexation with TEA (3.35 mL, 24.0 mmol) and 9-BBN-OTf
(40.0 mL, 20.0 mmol, 0.5 M in hexanes) in CH2Cl2 followed by
passage through a pad of silica [CH2Cl2/hexanes (1:1)] afforded
a solid, which upon trituration with hexanes afforded yellow
crystals (2.30 g, 60%) with satisfactory characterization data
Decom p lexa tion P r oced u r e, Exem p lified for 6a -BBN
f 2a . A solution of 6a -BBN (0.230 g, 0.500 mmol) in THF
(0.8 mL) was treated with 1-pentanol (0.2 mL). The reaction
mixture was heated at reflux. After 1 h, TLC (silica/CH2Cl2)
examination showed almost complete consumption of boron
complex 6a -BBN. The mixture was concentrated to dryness,
and the resulting oily residue was treated with 5 mL of
hexanes. The oil solidified upon standing for 5 min. The
mixture was heated gently under reflux for 5 min (the solid
dissolved completely). The mixture was cooled, affording a
precipitate upon standing for a few hours. The solvent was
decanted. The solid was dissolved in a minimal amount of CH2-
Cl2 (∼0.2 mL), and the title compound was precipitated upon
addition of hexanes. The precipitate was collected and dried
in vacuo to afford a dark-yellow powder (0.118 g, 66%). The
hexanes solution was concentrated to half of the starting
volume. The resulting precipitate was filtered, dissolved in a
minimal volume of CH2Cl2, and precipitated upon addition of
hexanes, affording an additional 0.030 g of title compound. The
combined yield (0.148 g) is 83%: mp 64-65 °C (lit.2 70-72
°C); 1H NMR (CDCl3) δ 2.42 (s, 3H), 5.54 (s, 1H), 5.99 (s, 1H),
6.04-6.08 (m, 1H), 6.16-6.20 (m, 1H), 6.72 (s, 1 H), 6.79-
6.83 (m, 1H), 7.36-7.22 (m, 8H), 7.75 (d, J ) 8.0 Hz, 2H),
7.97-8.00 (br, 1H) 9.34-9.37 (br, 1H); FABMS obsd 340.1593
[M+], calcd 340.1576 (C23H20N2O).
1
(mp, H NMR, and elemental analysis) as reported above.
10-(9-Bor a bicyclo[3.3.1]n on -9-yl)-1-h exa n oyl-5-p en tyl-
d ip yr r om eth a n e (6c-BBN). Following the acylation-com-
plexation procedure, reaction of 1c (2.16 g, 10.0 mmol) with
EtMgBr (20.0 mL, 20.0 mmol, 1.0 M in THF) followed by
treatment with 5f (2.09 g, 10.0 mmol) afforded crude 2c. Boron
complexation with TEA (3.35 mL, 24.0 mmol) and 9-BBN-OTf
(40.0 mL, 20.0 mmol, 0.5 M in hexanes) in CH2Cl2 followed by
passage through a pad of silica [CH2Cl2/hexanes (1:1)] afforded
an orange oil (2.59 g, 60%) with satisfactory characterization
data (1H NMR and 13C NMR spectra and FABMS) as reported
above.
10-(9-Bor abicyclo[3.3.1]n on -9-yl)-1-(4-m eth oxyben zoyl)-
5-(4-m eth oxyp h en yl)d ip yr r om eth a n e (6d -BBN). Follow-
ing the acylation-complexation procedure, reaction of 1d (2.45
g, 10.0 mmol) with EtMgBr (20.0 mL, 20.0 mmol, 1.0 M in
THF) followed by treatment with 5b (2.45 g, 10.0 mmol)
afforded crude 2d . Boron complexation with TEA (3.35 mL,
24.0 mmol) and 9-BBN-OTf (40.0 mL, 20.0 mmol, 0.5 M in
hexanes) in CH2Cl2 afforded a yellow-orange precipitate. The
precipitate was filtered and dissolved in 50 mL of CH2Cl2. The
solution was washed with water and brine, dried (Na2SO4),
and concentrated to dryness. The resulting yellow solid was
stirred in Et2O for 1 min, filtered, washed with Et2O and
hexanes, dissolved in 20 mL of CH2Cl2, and concentrated to
dryness, affording yellow crystals (2.81 g, 56%). The filtrates
(from reaction mixture and stirring in Et2O) were combined,
concentrated, and filtered through a pad of silica CH2Cl2/
hexanes (1:1), affording additional product (0.52 g). The total
yield is 3.33 g (66%), and the characterization data are
Notes: High ratios of 1-pentanol/THF can be used and
result in faster reaction (20 min) but can cause interference
upon crystallization. In most cases, it is important to remove
1-pentanol completely because of the high solubility of 1-acyl-
dipyrromethanes in 1-pentanol.
1-(4-Meth ylben zoyl)d ip yr r om eth a n e (2b). Following the
decomplexation procedure, a sample of 6b-BBN (0.74 g, 2.0
mmol) was dissolved in THF (3 mL) and 1-pentanol (1 mL)
was added. The mixture was refluxed for 1 h, concentratedm
and treated with 5 mL of hexanes. The resulting precipitate
was filtered, washed with hexanes, and dried under vacuo to
give pale yellow crystals (0.43 g, 81%) with satisfactory
1
characterization data (mp, H NMR, and elemental analysis)
1
satisfactory (mp, H NMR, and elemental analysis).
as described above.
10-(Dib u t ylb or yl)-1-(4-iod ob en zoyl)-5-m esit yld ip yr -
r om eth a n e (6f-BBu 2). Following the acylation-complexation
procedure, reaction of 1f (2.64 g, 10.0 mmol) with EtMgBr (20.0
mL, 20.0 mmol, 1.0 M in THF) followed by treatment with 5d
(2.29 g, 10.0 mmol) afforded crude 2f. Boron complexation with
TEA (3.35 mL, 24.0 mmol) and dibutylboron triflate (20.0 mL,
20.0 mmol, 1.0 M in CH2Cl2) in CH2Cl2 followed by passage
through a pad of silica [CH2Cl2/hexanes (1:2)] afforded a
golden-yellow amorphous powder (4.23 g, 68%) with satisfac-
tory characterization data (mp, 1H NMR, and elemental
analysis) as reported above.
1-Hexa n oyl-5-p en tyld ip yr r om eth a n e (2c). Following the
decomplexation procedure, reaction of 6c-BBN (0.869 g, 2.00
mmol) with 1-pentanol (1.00 mL, 10.0 mmol) in THF at reflux
afforded a crude product. The crude product was passed
through a pad of alumina [CH2Cl2 f CH2Cl2/ethyl acetate (4:
1)] affording a light yellow oil (0.514 g, 82%) with satisfactory
characterization data (1H NMR, elemental analysis) as de-
scribed above.
1-(4-Met h oxyb en zoyl)-5-(4-m et h oxyp h en yl)d ip yr r o-
m eth a n e (2d ). Following the decomplexation procedure, a
suspension of 6d -BBN (1.01 g, 2.00 mmol) in THF (3.2 mL)
and 1-pentanol (0.8 mL) was refluxed for 1.5 h. The mixture
was concentrated, and the residue was dissolved in a small
volume of CH2Cl2 and treated with hexanes. An oily precipitate
was formed. The solvent was decanted. The residue was dried
under vacuum, washed thoroughly with hexanes, and dried
again to afford a pale brown amorphous powder (0.610 g,
78%): mp 58-61 °C (dec) (lit.7 113-114 °C). The 1H NMR data
and elemental analysis data were consistent with those for
the same compound obtained by a different route.7
10-(9-Bor a bicyclo[3.3.1]n on -9-yl)-1-(4-br om oben zoyl)-
5-[4-(tr im eth ylsilyleth yn yl)p h en yl]d ip yr r om eth a n e (6g-
BBN). Following the acylation-complexation procedure, reac-
tion of 1g (3.18 g, 10.0 mmol) with EtMgBr (20.0 mL, 20.0
mmol, 1.0 M in THF) followed by treatment with 5e (2.93 g,
10.0 mmol) afforded crude 2g. Boron complexation with TEA
(3.35 mL, 24.0 mmol) and 9-BBN-OTf (40.0 mL, 20.0 mmol,
0.5 M in hexanes) in CH2Cl2 followed by passage through a
pad of silica [CH2Cl2/hexanes (1:1)] afforded orange-yellow
crystals (4.38 g, 71%) with satisfactory characterization data
1-(4-Iod ob en zoyl)-5-m esit yld ip yr r om et h a n e (2f). A
sample of 6f-BBu 2 (1.24 g, 2.00 mmol) was dissolved in
1-pentanol (4.0 mL). The solution was heated at 70-80 °C.
After 1 h the mixture was concentrated, and 20 mL of hexanes
was added. The mixture was heated at reflux for 2 min and
then cooled to room temperature. After standing overnight at
-15 °C, the precipitate was collected, dissolved in a minimum
1
(mp, H NMR, and elemental analysis) as reported above.
10-(9-Bor a bicyclo[3.3.1]n on -9-yl)-1-(4-m eth ylben zoyl)-
5-(p en ta flu or op h en yl)d ip yr r om eth a n e (6h -BBN). Follow-
ing the acylation-complexation procedure, reaction of 1h (3.12
g, 10.0 mmol) with EtMgBr (20.0 mL, 20.0 mmol, 1.0 M in
THF) followed by treatment with 5a (2.29 g, 10.0 mmol)
J . Org. Chem, Vol. 69, No. 16, 2004 5363

Muthukumaran et al.
volume of CH2Cl2, and precipitated with hexanes. The pre-
cipitate was collected and dried in vacuo to afford a dark
60 min, DDQ (0.085 g, 0.375 mmol) was added. The mixture
was stirred at room temperature for 1 h. TEA was added, and
the entire reaction mixture was passed through a pad of silica
and eluted with CH2Cl2 until the eluant was no longer purple.
The resulting porphyrin-containing solution was concentrated
by rotary evaporation to give a purple solid. The solid was
triturated with methanol and dried in vacuo, affording a
crystalline purple solid (0.021 g, 26%). The characterization
data (1H NMR, LDMS, and UV-vis spectra) were consistent
with the reported values.2
5,15-Bis(4-m eth ylp h en yl)-10,20-d ip h en ylp or p h yr in (8)
fr om 6a -BBN. Following the porphyrin formation procedure
for 8 from 6a -BBu 2, reaction of 6a -BBN (0.460 g, 1.00 mmol)
afforded a purple solid (0.054 g, 17%) with satisfactory
characterization data (1H NMR, LDMS, and UV-vis spectra).
1
powder (0.639 g, 65%): mp 166-170 °C (lit.2 163 °C). The H
NMR and elemental analysis data were consistent with those
for the same compound obtained by a different route.2
5,15-Bis(4-m eth ylp h en yl)-10,20-d ip h en ylp or p h yr in (8)
fr om 6a -BBu 2. A sample of 1-acyldipyrromethane-boron
complex 6a -BBu 2 (0.116 g, 0.250 mmol) was dissolved in dry
THF/methanol (3:1, 6 mL) at room temperature in a round-
bottomed flask fitted with a vented rubber septum and flooded
with argon. The septum was removed as needed to add NaBH4
(0.238 g, 6.25 mmol, 25 mol equiv) in small portions with rapid
stirring. The progress of the reduction was monitored by TLC
analysis [alumina, CH2Cl2/ethyl acetate (3:2)] of reaction
aliquots. After the reaction was complete (about 40 min), the
reaction mixture was poured into a stirred mixture of satu-
rated aqueous NH4Cl and CH2Cl2. The organic phase was
separated, washed with water, dried (Na2SO4), and concen-
trated under reduced pressure to yield the monocarbinol as a
foamlike solid. To the flask containing the dipyrromethane-
moncarbinol (0.250 mmol assuming quantitative reduction)
was added reagent-grade CH2Cl2 (50 mL). The mixture was
stirred for 5 min to achieve dissolution, and then Yb(OTf)3
(0.010 g, 0.016 mmol, 0.32 mM) was added. The reaction was
monitored by absorption spectroscopy [by injecting a 50 µL
reaction aliquot into a solution of DDQ (300 µL, 0.01 M in
toluene); then 50 µL of the resulting oxidized mixture was
dissolved in CH2Cl2/EtOH (3:1, 3 mL), and the absorption
spectrum was recorded]. After acid-catalyzed condensation for
Ack n ow led gm en t. This work was supported by
grants from the NIH to J .S.L. (GM36238) and to W.R.S.
(GM38401). Mass spectra were obtained at the Mass
Spectrometry Laboratory for Biotechnology at North
Carolina State University. Partial funding for the
facility was obtained from the North Carolina Biotech-
nology Center and the NSF.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
each new compound and crystallographic data for 6a -BBN.
This material is available free of charge via the Internet at
http://pubs.acs.org.
J O0492620
5364 J . Org. Chem., Vol. 69, No. 16, 2004