Fluorine-assisted selective alkylation to fluorinated epoxides and carbonyl compounds: Implication of pentacoordinate trialkylaluminum complexes

Full text of DOI:10.1021/ja964113n

5754
J. Am. Chem. Soc. 1997, 119, 5754-5755
Scheme 1
Fluorine-Assisted Selective Alkylation to
Fluorinated Epoxides and Carbonyl Compounds:
Implication of Pentacoordinate Trialkylaluminum
Complexes
Takashi Ooi, Naoko Kagoshima, and Keiji Maruoka*
first experimental evidence of the intervention of pentacoordi-
nate trialkylaluminum complexes B as plausible intermediates
(Scheme 1).
Department of Chemistry, Graduate School of Science
Hokkaido UniVersity, Sapporo 060, Japan
Alkylation of terminal or 1,2-disubstituted epoxides normally
provides a regioisomeric mixture of corresponding ring opening
alcohols. For instance, treatment of 3-phenyl-1,2-epoxypropane
(1, X ) H) with Me2AlCtCPh (1.5 equiv) in toluene at -78
to -20 °C gave rise to a mixture of 1,5-diphenyl-4-pentyn-2-
ol (2, X ) H, R ) Ph) and 2-benzyl-4-phenyl-3-butyn-1-ol (3,
X ) H, R ) Ph) (64% combined yield) in a ratio of 1.1:1 (entry
2 in Table 1). In marked contrast, however, reaction of its fluoro
analogue, 3-(2-fluorophenyl)-1,2-epoxypropane (1, X ) F) with
Me2AlCtCPh under similar reaction conditions afforded 1-(2-
fluorophenyl)-5-phenyl-4-pentyn-2-ol (2, X ) F, R ) Ph) as a
sole isolable product in 61% yield (entry 1 in Table 1).8 The
metal effect on the regioselectivity for the present alkynylation
was also examined. Attempted reaction of fluoro epoxide 1
(X ) F) with PhCtCMgBr or PhCtCTiCl(OPri)2 furnished
halohydrine 4a or 4b, respectively, as a sole isolable product.9
Use of PhCtCLi for the substrate 1 (X ) F) gave less
ReceiVed December 2, 1996
Organoaluminum compounds have found numerous applica-
tions in organic synthesis.1 Many of the reaction characteristics
of organoaluminums associated with the availability of the
empty p orbital of aluminum which makes these compounds
electrophilic or Lewis acidic. Accordingly, organoaluminums
(AlX3) react readily with a variety of neutral or negatively
charged Lewis bases (L) to form the corresponding tetracoor-
dinate complexes of type A. Although pentacoordination of
type B (X ) Et; L ) phosphine) in 1:1 Et3Al/diphosphine
complexes has been previously claimed with Ph2PPPh2, MeN-
(PPh2)2, and EtN(PPh2)2,2 recent evidence obtained on the
Me3Al/Ph2PCH2PPh2 complex only points to a highly fluxional
molecule in solution with tetracoordinate aluminum species of
type C even at -80 °C.3 Recently, several restricted examples
on neutral pentacoordinate, trigonal bipyramidal aluminum
complexes of type D (X ) halogen, hydrogen, alkyl; L )
nitrogen or phosphine), where ligands L occupy two axial
positions, have been isolated and characterized.4 However, little
is known about the existence of another pentacoordinate
organoaluminum complex B,5 and its nature still remains elusive
despite its potential importance in the mechanistic as well as
synthetic points of view. In this context, we have been
interested for some time in the possibility of forming a
previously uncertain pentacoordinate organoaluminum complex
B and its synthetic application to, for example, chelation-
controlled reactions. Among various metals to be chelated,
aluminum has exceedingly high affinity toward fluorine as
evident from the bond strengths in several diatomic molecules
of metal-fluorine.6,7 The combination of this characteristic
property with the well-known high oxygenophilicity of alumi-
num suggests that fluorine-assisted selective transformation of
oxygen-containing organofluorine substrates seems to be quite
suitable for our purpose. Here, we report such a selective
alkylation with fluoro epoxides and fluoro carbonyl compounds
as model substrates of our case study, which represents the
satisfactory results.10 These and other selected examples are
included in Table 1, which clearly demonstrates the efficiency
of the nucleophilic ring opening of fluoro epoxides with organo-
aluminum alkynides via the chelation between fluorine and
aluminum, thereby permitting the otherwise difficult regiose-
lective functionalization. A terminal epoxide with a fluorine
atom on the aliphatic carbon chain underwent smooth alkyny-
lation with excellent selectivity in spite of its conformational
flexibility (entry 5). For 1,2-trans-disubstituted epoxides, a high
level of regioselectivity was observed as well (entries 7 and 9).
Even a δ-fluoro epoxide showed moderate selectivity (entry 11
vs 12).
Although the hypothetical participation of neighboring fluo-
rine atom in organoaluminum complexes with fluoro epox-
ides, i.e., the existence of pentacoordinate trialkylaluminum
complexes of type B, is strongly implicated by the above
alkynylation experiments, more direct and physical evidence
was obtained by carrying out low-temperature 13C and 27Al
(6) For example, the bond strengths in several diatomic molecules of
metal-fluorine follow: Al-F, 663.6 ( 6.3 kJ/mol; Li-F, 577 ( 21
kJ/mol; Ti-F, 569 ( 34 kJ/mol; Si-F, 552.7 ( 2.1 kJ/mol; Sn-F,
466.5 ( 13 kJ/mol; Mg-F, 461.9 ( 5.0 kJ/mol. See: Weast, R. C.
Handbook of Chemistry and Physics, 65th ed.; CRC Press: New York,
1984-1985.
(1) (a) Mole, T.; Jeffery, E. A. Organoaluminum Compounds; Elsevier:
Amsterdam, 1972. (b) Negishi, E. Organometallics in Organic Synthesis;
John Wiley & Sons: New York, 1980. (c) Zweifel, G.; Miller, J. A. Org.
React. 1984, 32, 375. (d) Maruoka, K.; Yamamoto, H. Angew. Chem., Int.
Ed. Engl. 1985, 24, 668. (e) Maruoka, K.; Yamamoto, H. Tetrahedron 1988,
44, 5001.
(2) Clemens, D. F.; Sisler, H. H.; Brey, W. S., Jr. Inorg. Chem. 1966, 5,
527.
(3) Schmidbaur, H.; Lauteschlager, S.; Muller, G. J. Organomet. Chem.
1985, 281, 25. For this argument, see: ref 4e.
(7) For the synthetic utility of forming the strong Al-F bonds, see: (a)
Posner, G. H.; Ellis, J. W.; Ponton, J. J. Fluorine Chem. 1981, 19, 191. (b)
Posner, G. H.; Haines, S. R. Tetrahedron Lett. 1985, 26, 1823.
(8) Use of exactly 1 equiv of Me2AlCtCPh under similar reaction
conditions gave desired regioisomer 2 with excellent selectivity (>99:<1),
but the yield of 2 was a little bit lower (56%) compared to that with 1.5
equiv of Me2AlCtCPh.
(4) (a) Heitsch, C. W.; Nordman, C. E.; Parry, P. W. Inorg. Chem. 1963,
2, 508. (b) Palenick, G. Acta Crystallogr. 1964, 17, 1573. (c) Beattie, I. R.;
Ozin, G. A. J. Chem. Soc. A 1968, 2373. (d) Bennett, F. R.; Elms, F. M.;
Gardiner, M. G.; Koutsantonis, G. A.; Raston, C. L.; Roberts, N. K.
Organometallics 1992, 11, 1457. (e) Muller, G.; Lachmann, J.; Rufinska,
A. Ibid. 1992, 11, 2970. (f) Fryzuk, M. D.; Giesbrecht, G. R.; Olovsson,
G.; Rettig, S. J. Ibid. 1996, 15, 4832.
(9) For preparation of the alkynyltitanium reagent, PhCtCTiCl(OPri)2
from PhCtCLi and Cl2Ti(OPri)2, see: Tabusa, F.; Yamamda, T.; Suzuki,
K.; Mukaiyama, T. Chem. Lett. 1984, 405.
(10) The ring opening reaction of epoxide 1 (X ) H or F) was carried
out with 1.5 equiv of PhCtCLi in toluene at 25 °C for 42 h giving the
secondary alcohol 2 (X ) H or F; R ) Ph) exclusively in only 8-9%
yield. Attempted reaction of trans-1,2-disubstituted epoxide under similar
reaction conditions resulted in the almost total recovery of the starting
epoxide (cf. entry 7 in Table 1).
(5) For an intramolecular version of inorganic aluminum complex B,
see: Rutherford, D.; Atwood, D. A. Organometallics 1996, 15, 4417.
S0002-7863(96)04113-3 CCC: $14.00 © 1997 American Chemical Society

Communications to the Editor
J. Am. Chem. Soc., Vol. 119, No. 24, 1997 5755
Table 1. Regioselective Alkylation of Fluoro Epoxides with
Organoaluminum Alkynides
C-7 at δ 45.27/46.52 and 47.93 (d, J ) 4 Hz)/48.01 (d, J ) 4
Hz), respectively, shifted downfield to δ 52.85/54.10 and 57.87
(d, J ) 3.6 Hz)/58.07 (d, J ) 3.6 Hz), respectively, and the
uncomplexed, diastereomeric C-F carbon C-9 at δ 90.40 (d, J
) 167 Hz) and 90.66 (d, J ) 167 Hz) shifted upfield to δ 88.95
(d, J ) 169 Hz) and 89.07 (d, J ) 169 Hz), respectively. Since
these 13C NMR data may not rigorously rule out the possibility
of the involvement of a fluxional complex F, we further carried
out the low-temperature 27Al NMR analysis of several trialkyl-
aluminum complexes.12 The original signal of Me3Al appeared
at δ 153 in CD2Cl2 at -50 °C. Addition of fluorobenzene to
Me3Al in CD2Cl2 showed the Al signal at δ 152, while the
coordination of epoxide 1 (X ) H) to Me3Al caused significant
downfield shift to δ 195. However, when Me3Al was com-
plexed with fluoro epoxide 1 (X ) F), the upfield shift of the
Al signal in the complex E relative to the non-fluoro epoxide
1 (X ) H)/Me3Al complex was observed at δ 182. Moreover,
the Al signal of the epoxide 5 (X ) H)/Me3Al complex at δ
167 significantly shifted upfield to δ 146 in the spectrum of
fluoro epoxide 5 (X ) F)/Me3Al complex probably due to the
formation of a six-membered chelate as well as the participation
of more basic alkyl fluoride compared to the case of epoxide 1
(X ) F). The data presented herein, together with alkynylation
experiments, argue against the possibility of fluxional orga-
noaluminum complexes with fluoro epoxides by a rapid metal
site exchange as shown in F.
a
Our concept is also applicable to the selective alkylation of
carbonyl compounds with organoaluminum reagents. Indeed,
treatment of an equimolar mixture of 2-fluorobenzaldehyde and
4-fluorobenzaldehyde in toluene at -78 °C with Me2AlCtCPh
(1 equiv) resulted in formation of two different propargyl
alcohols 6 and 7 (X ) F, R ) Ph; 58% combined yield) in a
ratio of 9.2:1. The selectivity is lowered by switching the metals
a Unless otherwise specified, the reaction was carried out in toluene
with 1.5 equiv of reagent under the given reaction condition. b Isolated
yield. c Determined by capillary GLC, HPLC, and/or 300-MHz 1H
NMR analysis. d The regio- and stereochemical assignment of alkylation
products were made by independent syntheses, i.e., the carbonyl
alkylation of aldehydes with propargylic Grignard reagents (Ishiguro,
M.; Ikeda, N.; Yamamoto, H. J. Org. Chem. 1982, 47, 2225). e Ratio
of trans/cis ) 2.7:1. f Ratio of trans/cis ) 8.3:1. g Syn/anti ratio of the
major regioisomer ) 4.3:1. h Syn/anti ratios of each regioisomer are
41:1 and 1:4.6, respectively. i Two equivalents of aluminum alkynide
was used.
NMR studies of these aluminum complexes. The original
signals of epoxide carbons C-1 and C-2 in 1 (X ) F) occurred
at δ 46.27 and 50.83, respectively, and the signal of the fluorine
bearing aromatic carbon C-5 appeared at δ 161.09 (d, J ) 245
Hz). When 1 (X ) F) was complexed with Me3Al in a 1:1.1
of PhCtC-M from Al to Mg (3.7:1), Ti (2.7:1),9,13 and Li
(1.8:1). The similar tendency is also observed with BuCtC-M
(M ) AlMe2 or Li). The high affinity of aluminum to fluorine
compared to other halogens is evident from the discrimination
experiment between chloro analogues with Me2AlCtCPh,
which shows only moderate selectivity (2.4:1).
Acknowledgment. This work was partially supported by a Grant-
in-Aid for Scientific Research from the Ministry of Education, Science,
Sports and Culture, Japan.
molar ratio in CD2Cl2 at -78 °C, the significant downfield shift
of epoxide carbons C-1 and C-2 in structure E was observed at
δ 53.60 and 59.67, respectively, with concomitant upfield shift
of C-F carbon C-5 at δ 160.08 (d, J ) 246 Hz) by 13C NMR
analysis at -78 °C; this supported the expected chelate
formation of aluminum with fluoro epoxide 1 (X ) F). It should
be added that the upfield shift of fluorine bearing carbon was
also observed in the 13C NMR measurement of fluorobenzene
with Me3Al (1.1 equiv) in CD2Cl2 at -78 °C, where the original
peak of the C-F carbon at δ 162.77 (d, J ) 245 Hz) shifted to
δ 161.61 (d, J ) 245 Hz).11 Similarly, epoxide 5 (X ) F)/
Me3Al chelate complex in CD2Cl2 at -78 °C showed that the
original signals of free, diastereomeric epoxide carbons C-6 and
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(12) Benn, R.; Rufinska, A. Angew. Chem., Int. Ed. Engl. 1986, 25, 861.
The 27Al NMR chemical shifts are highly dependent on the ligands and
structural types of organoaluminum compounds and on the coordination
number of the Al atom. However, as the general tendency, the higher
coordination number of the Al atom in organoaluminum compounds always
causes the more upfield shift. See also: van Vliet, M. R. P.; Buysingh, P.;
van Koten, G.; Vrieze, K.; Kojic-Prodic, B.; Spek, A. L. Organometallics
1985, 4, 1701. See: refs 4e,f and 5.
(11) The similar upfield effect is observed in several metal complexes
of fluorinated macrocycles: Plenio, H.; Diodone, R. J. Am. Chem. Soc.
1996, 118, 356.
(13) Reaction of an equimolar mixture of 2-fluoro- and 4-fluorobenzal-
dehyde with (PhCtC)2Ti(OPri)2 in toluene at -78 °C gave 6 and 7 in a
ratio of 1.7:1.