Aluminum tris(2,6-diphenylphenoxide)-ArCOCl complex for nucleophilic dearomatic functionalization [6]

Full text of DOI:10.1021/ja0014382

10216
J. Am. Chem. Soc. 2000, 122, 10216-10217
Aluminum Tris(2,6-diphenylphenoxide)-ArCOCl
Complex for Nucleophilic Dearomatic
Functionalization
Susumu Saito, Toshihiko Sone, Masaaki Murase, and
Hisashi Yamamoto*
Figure 1. Molecular structure of ATPH.
Graduate School of Engineering, Nagoya UniVersity
CREST, Japan Science and Technology Corporation (JST)
Chikusa, Nagoya 464-8603, Japan
ReceiVed April 25, 2000
Recently, we demonstrated the nucleophilic dearomatization
of benzaldehyde (PhCHO) complexed with aluminum tris(2,6-
diphenylphenoxide) (ATPH) (Figure 1),1 which proceeded smoothly
with a variety of nucleophiles.2 Unfortunately, however, conjugate
addition to the ATPH-PhCHO complex did not proceed effectively
with smaller nucleophiles (Scheme 1). For example, MeLi and
the lithium enolates of methyl acetate undergo 1,2-addition
predominantly. The lithium enolates of several ketones, methyl
propionate, tert-butyl acetate, PhLi, and vinyl- and allyllithiums
give equal amounts of 1,2- and 1,6-adducts. In sharp contrast,
treatment of a toluene solution of ATPH (1.1 equiv) with benzoyl
chloride (PhCOCl; 1.0 equiv) at -78 °C, followed by addition
of MeLi (3.0 equiv)3 and workup with concentrated HCl gives
1,6- and 1,4-adducts 1a and 1b in a ratio of 2.6:1 in 99% isolated
yield (Scheme 1).
Figure 2. Conjugate addition of various nucleophiles using the ATPH-
PhCOCl. The values in parentheses are ratios of 1,6- and 1,4-adducts,
1
which were determined by H NMR analysis. Combined yields of 1,6-
and 1,4-adducts are indicated. Acids and esters are obtained with the
following conditions: -78 °C to room temperature; acid, concentrated
HCl; ester, Et2O solution of HCl, followed by MeOH.
Nucleophiles that add in a 1,6-manner to ATPH-PhCOCl
include Grignard reagents (i-PrMgBr and t-BuMgCl), which are
ineffective for the conjugate addition to the ATPH-PhCHO
complex. Figure 2 shows that enhanced regioselectivities (1,6-
vs 1,2-addition) are achieved with the ATPH-PhCOCl complex.
Addition products can be isolated as acids or esters by altering
workup conditions. In each of these cases, 1,2-adduct could not
1
be detected by H NMR analysis.
Insight regarding the change in product distribution in the two
types of complexes may be derived from a comparison of their
X-ray crystal structures. The X-ray crystal structure of ATPH-
PhCHO, Figure 3a,4 shows one face of the extended π-system to
be relatively exposed, at least in the region distal to the carbonyl
group. On the other hand, the X-ray crystal structure of ATPH-
PhCOCl,4 Figure 3b, revealed that two of the phenyl rings (black)
of ATPH and the flat PhCOCl form a sandwich structure,
rendering the CdO highly congested. The CdO of ATPH-
PhCOCl has a single bond-like character. The Al-OdC bond of
1.235(4) Å is longer than that of Al-OdCHPh (1.14(1) Å).5 This
is consistent with the FT-IR measurement of the ATPH-PhCOCl
and ATPH-PhCHO complexes in solution (CD2Cl2, -40 °C). The
frequency of the carbonyl of ATPH-PhCOCl is shifted to a lower
frequency as a result of enhanced conjugation relative to that of
the free substrates by 42 cm-1.6 The ATPH-PhCHO complex,
Figure 3. The X-ray crystal structures of (a) ATPH-PhCHO and (b)
ATPH-PhCOCl.
Scheme 1
(1) (a) Saito, S.; Yamamoto, H. Chem. Commun. 1997, 1585. (b) Yama-
moto, H.; Saito, S. Pure Appl. Chem. 1999, 71, 235. (c) Saito, S.; Yamamoto,
H. Chem. Eur. J. 1999, 5, 1959.
(2) For preliminary results concerning nucleophilic addition to aromatic
rings using ATPH, see: (a) Maruoka, K.; Ito, M.; Yamamoto, H. J. Am. Chem.
Soc. 1995, 117, 9091. (b) Saito, S.; Shimada, K.; Yamamoto, H. Marigorta,
E. M.; Fleming, I. Chem. Commun. 1997, 1299. (c) Saito, S.; Sone, T.;
Yamamoto, H. Synlett 1999, 81.
on the other hand, exhibits no detectable shift. In fact, the
π-deficiency of PhCOCl is significantly enhanced by complex-
(3) The use of less nucleophile (1.1-2.5 equiv) gives the corresponding
product in lower yield.
(4) The single-crystal structures of ATPH-PhCHO and ATPH-PhCOCl were
established for the first time in this paper. See Supporting Information for
details.
(5) The average bond length of CdO in free RCOCl is ca. 1.18 Å. The
CdO of RCHO has a similar average length of ca. 1.22 Å. See also ref 1 in
the Supporting Information.
(6) For benzoyl chlorides, an unequal intensity of doublet is usually seen
in the CdO region. A second band is due to the Fermi resonance involving
the stretch of the overtone of the Ph-C which interacts with the carbonyl
stretch. IR frequency: PhCHO (1708 cm-1); ATPH-PhCHO (1708 cm-1);
PhCOCl (1770 (CdO stretch) and 1728 ((due to the Fermi resonance) cm-1);
ATPH-PhCOCl (1728 cm-1). See also ref 2 in the Supporting Information.
10.1021/ja0014382 CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/27/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 41, 2000 10217
Scheme 2
Figure 4. Schematic depiction of the induced conformational changes
of ATPH as a “molecular tweezer” for effective inclusion of PhCOCl.
The three benzene rings correspond to the darkened phenyls in Figure
3b.
ation with ATPH. 13C NMR measurements (75 MHz, CD2Cl2,
-30 °C) show downfield shifts (∆δ) for the carbonyl carbon from
free to bound substrates of 9.49 ppm for ATPH-PhCHO and 18.0
ppm for ATPH-PhCOCl.7 The π-stacking between two π-donors
(ATPH phenyls) and one π-acceptor (complexed PhCOCl)
involving the carbonyl carbon may act as a “molecular tweezer”8
to stabilize the ATPH-PhCOCl complex (Figure 4). The interac-
tion does not seem to be the primary binding force, but rather is
induced upon intrinsic Lewis acid-base complexation.9 This
aspect was further demonstrated by a 13C NMR (CD2Cl2, -78
°C to room temperature) competition experiment using a 1:1:1
mixture of ATPH, PhCHO, and PhCOCl. The analysis shows
Scheme 3
KPhCOCl/KPhCHO ) ([ATPH‚PhCOCl]/[ATPH‚PhCHO])([PhCHO]free
/
[PhCOCl]free) < 3.5 × 10-3 10
,
suggesting that PhCOCl forms
complexes that are less stabilized than those of PhCHO by more
than 14 kJ mol-1 (at 298 K). It should be emphasized that the
relative destabilization, i.e., the higher reactivity of ATPH-
PhCOCl, compared with ATPH-PhCHO, might be compensated
for to some extent by the formation of the “molecular tweezer”.
When t-BuLi was used for the tert-butylation of ATPH-
PhCHO, the 1,6-adduct, but no 1,4-adduct, was produced.2a This
could be ascribed to the distinctive structure of ATPH-PhCHO,
which is not driven to π-sandwiching (Figure 3a). The two ortho
positions of ATPH-PhCHO are sterically encumbered to an equal
degree, while one of the two ortho positions (the asterisked ortho
position: 1,4-addition site) of ATPH-PhCOCl is sterically
deshielded due to the sandwich structure (Figure 3b). Alkyllithi-
ums are prone to 1,4-addition with ATPH-PhCOCl in the order
MeLi >BuLi > s-BuLi > t-BuLi,11 although they show a general
preference for 1,6-selectivity. Unexpectedly, we observed com-
plete regiochemical reversal according to the size of RLi upon
addition to acid chloride complexes 12 and 14: 1,6-selectivity
predominated with t-BuLi to give 13c and 15d, whereas MeLi
underwent 1,4-addition exclusively to give 13a,b and 15a,b
(Scheme 2).
(7) 13C NMR (75 MHz, CD2Cl2, -30 °C) chemical shifts: PhCHO (191.9
ppm); ATPH-PhCHO (201.4 ppm); PhCOCl (168.0 ppm); and ATPH-PhCOCl
(185.0 ppm). We can exclude the species [PhCtO+][ATPH‚Cl-] to account
for this significant downfield shift, since a single crystal of ATPH-PhCOCl
was grown in CH2Cl2-hexane at -20 °C to give the structure shown in Figure
3b.
(8) The two phenyl rings of ATPH which form the π-sandwich are separated
by ca. 7.0 Å. This value is identical to the distance in “molecular tweezers”
which can include aromatic guests by interactions between two π-donors and
one π-acceptor, see: Zimmerman, S. C.; VanZyl, C. M.; Hamilton, G. S. J.
Am. Chem. Soc. 1989, 111, 1373. See also ref 3 in the Supporting Information.
(9) Zimmerman (ref 8) pointed out that cooperative π-stacking with an
electron donor-acceptor component can contribute to complex stability if
hydrophobic forces or hydrogen bonding is present. In our case, the Lewis
acid-base coordination may substitute for these forces and bonding.
Scheme 4
As shown in Figure 3b, complex 12 should orient itself so that
the m-methyl substituted carbon occupies the less-congested meta
site which is marked with an asterisk. Attack at both ortho
positions of 12 is unfavorable, and hence bulky t-BuLi suffers
1,6-addition to give 13c exclusively (Scheme 2). This observation
is in contrast to the formation of 1,6-adduct 15d accompanied
by a small amount of 1,4-adduct 15c. The ratio of two different
1,4-adducts 13a,b could be explained along similar lines (Scheme
2): the asterisked ortho position, which is less congested than
the other ortho position, is selectively methylated.
The ATPH-â-naphthaldehyde complex (X ) H, Scheme 3)
did not undergo conjugate addition even with t-BuLi. However,
the reaction proceeded smoothly with the use of acid chloride
complex 16. Of particular interest is the novel 1,8-selectivity to
give 17a (Scheme 3). In marked contrast, 1,4-addition predomi-
nated with the lithium enolate of 2-methylpropionate to give 18b
in 66% yield (Scheme 3).
Another striking advantage of the present method can be seen
in the reaction of 4-chlorobenzoic acid chloride 19 with t-BuMgBr
(3equiv) (Scheme 4). This facilitates a tandem 1,6-addition-
chloride elimination-rearomatization-1,4-addition sequence, i.e.,
in situ double conjugate addition, to give 20a and 20b in 73%
yield.
(10) Although we encountered an experimental limit for measuring KPhCOCl
/
KPhCHO, the preferred order of binding to ATPH is PhCO2Me > PhCOCl, and
the relative binding constant of PhCO2Me and PhCHO is KPhCOOMe/KPhCHO
)
3.5 × 10-3. In these competition experiments using ATPH, we always observed
a set of two chemical shifts, each corresponding to free and bound substrates,
due to slow exchange at the NMR time scale.
Supporting Information Available: Experimental procedures and
analytical and spectral data for all new compounds (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
(11) Exposure of ATPH-PhCOCl to these nucleophiles gives 1,6- and 1,4-
product ratios of 2.6:1 (MeLi), 4.5:1 (n-BuLi), 14:1 (s-BuLi), and 39:1 (t-
BuLi). A similar regiochemical trend was obtained previously using the
ATPH-R-naphthaldehyde complex (see ref 2a).
JA0014382