Utility of a diene-tricarbonyliron complex as a mobile chiral auxiliary: Regio- and stereocontrolled functionalization of acyclic diene ligands

Article abstract of DOI:10.1021/ja991889q

Stereoselective construction of contiguous stereogenic centers of acyclic compounds by using the Fe(CO)₃ moiety as a mobile chiral auxiliary is described. Although the reactions of acyclic (pentadienyl)iron(1+) cations with nucleophiles generally occur in a stereoselective but nonregioselective manner, giving rise to several regioisomers, O-acyl and O-phosphoryl cyanohydrin Fe(CO)₃ complexes 2-5 undergo regio-and stereoselective 1,5- nucleophilic substitution with several heteroatomic nucleophiles, giving the 6-substituted hepta-2,4-dienonitrile Fe(CO)₃ complexes 6 and 7, that is, 1,2-migration products of the Fe(CO)₃ group. These products were obtained as single products, even if the starting materials 3-5 were a mixture of diastereomers. The (2E,4E)/(2E,4Z) selectivity of the 1,5-substituted products (6/7) is strongly dependent on the Lewis acid catalyst, triphenylcarbenium perchlorate (TrClO₄) giving 6 (method A) and BF₃·etherate giving 7 (method B), respectively. Furthermore, by applying iterative 1,5-nucleophilic substitution to 6, both 6,7-anti-disubstituted (2E,4E)-adduct anti-10 and 6,7-syn-disubstituted (2E,4Z)-one syn-11 were synthesized stereoselectively by switching the reaction conditions (method A and method B). The third introduction of the ethylsulfanyl group into anti-10 proceeded efficiently by the same treatment of 10 with ethanethiol and TrClO₄ to afford the 6,7-anti-7,8-anti-trisubstituted (2E,4E)-adduct 19. Further manipulation successfully converted 19 to the N-Boc-O-Me derivative 24 of anti-2,3-amino alcohol 25, which had been isolated from a marine sponge.

Full text of DOI:10.1021/ja991889q

J. Am. Chem. Soc. 1999, 121, 9143-9154
9143
Utility of a Diene-Tricarbonyliron Complex as a Mobile Chiral
Auxiliary: Regio- and Stereocontrolled Functionalization of Acyclic
Diene Ligands
Yoshiji Takemoto,*,† Naoki Yoshikawa,‡ Yasutaka Baba,‡ Chuzo Iwata,‡ Tetsuaki Tanaka,‡
Toshiro Ibuka,† and Hirofumi Ohishi§
Contribution from the Graduate School of Pharmaceutical Sciences, Kyoto UniVersity, Sakyo-ku,
Kyoto 606-8501, Japan, Graduate School of Pharmaceutical Sciences, Osaka UniVersity,
1-6 Yamada-oka, Suita, Osaka 565-0871, Japan, and Osaka UniVersity of Pharmaceutical Sciences,
4-20-1, Nasahara, Takatsuki, Osaka 569-1094, Japan
ReceiVed June 7, 1999
Abstract: Stereoselective construction of contiguous stereogenic centers of acyclic compounds by using the
Fe(CO)3 moiety as a mobile chiral auxiliary is described. Although the reactions of acyclic (pentadienyl)-
iron(1+) cations with nucleophiles generally occur in a stereoselective but nonregioselective manner, giving
rise to several regioisomers, O-acyl and O-phosphoryl cyanohydrin Fe(CO)3 complexes 2-5 undergo regio-
and stereoselective 1,5-nucleophilic substitution with several heteroatomic nucleophiles, giving the 6-substituted
hepta-2,4-dienonitrile Fe(CO)3 complexes 6 and 7, that is, 1,2-migration products of the Fe(CO)3 group. These
products were obtained as single products, even if the starting materials 3-5 were a mixture of diastereomers.
The (2E,4E)/(2E,4Z) selectivity of the 1,5-substituted products (6/7) is strongly dependent on the Lewis acid
catalyst, triphenylcarbenium perchlorate (TrClO4) giving 6 (method A) and BF3‚etherate giving 7 (method B),
respectively. Furthermore, by applying iterative 1,5-nucleophilic substitution to 6, both 6,7-anti-disubstituted
(2E,4E)-adduct anti-10 and 6,7-syn-disubstituted (2E,4Z)-one syn-11 were synthesized stereoselectively by
switching the reaction conditions (method A and method B). The third introduction of the ethylsulfanyl group
into anti-10 proceeded efficiently by the same treatment of 10 with ethanethiol and TrClO4 to afford the
6,7-anti-7,8-anti-trisubstituted (2E,4E)-adduct 19. Further manipulation successfully converted 19 to the N-Boc-
O-Me derivative 24 of anti-2,3-amino alcohol 25, which had been isolated from a marine sponge.
Introduction
very promising. Thus far, several elegant reactions such as
nucleophilic or electrophilic addition4a,b to cyclodiene-Mo-
(CO)2Cp or -Fe(CO)2P(OPh)3 complexes and [6π + 4π]
cycloaddition4c,d of cycloheptatriene-Cr(CO)3 complexes have
been developed and successfully applied to the asymmetric
synthesis of the segments of macrocyclic antibiotics. However,
these reactions have been restricted only to cyclic polyene metal
complexes.5
To extend the applicability of the transition-metal complexes
for multiple functionalization, we have recently begun to
investigate the iterative use of acyclic (η4-1,3-diene)Fe(CO)3
complexes with concurrent 1,2-migration of the metal on the
ligand (Scheme 1).6 The use of acyclic diene-iron complexes
Owing to their biological action and structural interest, highly
functionalized acyclic compounds, which are a constituent of
macrolides and macrolactams, are attracting increasing atten-
tion.1 With the aim of synthesizing these natural products,
numerous new reactions and concepts for acyclic stereocontrol
have been developed recently in organic chemistry.2 Among
these efforts, the use of a transition-metal complex offers a
unique opportunity for attaining the synthesis of stereodefined
organic molecules.3 Due to their high ability of stereo- and
regiochemical control, transition-metal-mediated construction
of contiguous stereogenic centers onto the ligand seems to be
* Corresponding author. E-mail: takemoto@pharm.kyoto-u.ac.jp.
† Kyoto University.
(4) (a) Pearson, A. J.; Blystone, S. L.; Nar, H.; Pinkerton, A. A.; Roden,
B. A.; Yoon, J. J. Am. Chem. Soc. 1989, 111, 134-144. (b) Pearson, J. P.;
Mallik, S.; Mortezaei, R.; Perry, M. W. D.; Shively, R. J., Jr.; Youngs, W.
J. J. Am. Chem. Soc. 1990, 112, 8034-8042. (c) Rigby, J. H.; Ateeq, H.
S.; Charles, N. R.; Cuisiat, S. V.; Ferguson, M. D.; Henshilwood, J. A.;
Krueger, A. C.; Ogbu, C. O.; Short, K. M.; Heeg, M. J. J. Am. Chem. Soc.
1993, 115, 1382-1396. (d) Rigby, J. H.; Fales, K. R. Tetrahedron Lett.
1998, 39, 5717-5720.
(5) (a) Stephenson, G. R.; Alexander, R. P.; Morley, C.; Howard, P. W.
Philos. Trans. R. Soc. London A 1988, 326, 545-556. (b) Pearson, A. J.
Synlett 1990, 10-19. (c) Stephenson, G. R.; Finch, H.; Owen, D. A.;
Swanson, S. Tetrahedron 1993, 49, 5649-5662. (d) Heck, J.; Lange, G.;
Reimelt, O. Angew. Chem., Int. Ed. 1998, 37, 520-522.
(6) (a) Takemoto, Y.; Yoshikawa, N.; Iwata, C. J. Chem. Soc., Chem.
Commun. 1995, 631-632. (b) Takemoto, Y.; Baba, Y.; Yoshikawa, N.;
Iwata, C.; Tanaka, T.; Ibuka, T. Chem. Commun. 1998, 1911-1912. The
similar 1,2-migration reaction of Fe(CO)3 group has been reported by the
French group: Braun, A.; Toupet, L.; Lellouche, J.-P. J. Org. Chem. 1996,
61, 1914-1915.
‡ Osaka University.
§ Osaka University of Pharmaceutical Sciences.
(1) (a) Macrolide Antibiotics: Chemistry, Biology, Practice; Omura, S.,
Ed.; Academic Press: Orlando, FL, 1984. (b) Rychnovsky, S. D. Chem.
ReV. 1995, 95, 2021-2040.
(2) (a) Paterson, I.; Mansuri, M. M. Tetrahedron 1985, 41, 3569-3624.
(b) Oishi, T.; Nakata, T. Synthesis 1990, 635-645. (c) Smith, A. B.; Boldi,
A. M. J. Am. Chem. Soc. 1997, 119, 6925-6926. (d) Richardson, T. I.;
Rychnovsky, S. D. J. Am. Chem. Soc. 1997, 119, 12360-12361. (e) Evans,
D. A.; Kim. A. S.; Metternich, R.; Novack, V. J. J. Am. Chem. Soc. 1998,
120, 5921-5942.
(3) Reviews: (a) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke,
R. G. Principles and Applications of Organotransition Metal Chemistry;
University Science Books: Mill Valley, CA, 1987. (b) Gre´e, R. Synthesis
1989, 341-355. (c) Transition Metals in Total Synthesis; Harrington, P. J.,
Ed.; John Wiley & Sons: New York, 1990. (d) Pearson, A. J. Iron
Compounds in Organic Synthesis; Academic Press: London, 1994. (e) Iwata,
C.; Takemoto, Y. Chem. Commun. 1996, 2497-2504.
10.1021/ja991889q CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/21/1999

9144 J. Am. Chem. Soc., Vol. 121, No. 39, 1999
Takemoto et al.
Scheme 1. Utility of an Iron-Tricarbonyl Group as a
Mobile Chiral Auxiliary
Scheme 2
hydrolysis with aqueous 10% HCl in methanol to give the
desired cyanohydrin complexes 2 as a 1:1 mixture of diaster-
eomers in a quantitative yield. The obtained cyanohydrins 2
were converted to the esters 3a-c and 4a-c in 78-97% yields
by reaction with acetic anhydride, 3,5-dinitrobenzoyl (3,5-DNB)
chloride, and 2,4,6-trichlorobenzoyl (2,4,6-TCB) chloride, re-
spectively. Although the 3,5-DNB esters 3b and 4b were an
inseparable mixture, the acetates 3a, 4a and 2,4,6-TCB esters
3c, 4c were separated by silica gel column chromatography.
Then, the diastereomerically pure 3,5-DNB esters 3b and 4b
were synthesized from the cyanohydrin complexes ψ-exo-2 and
ψ-endo-2, which were obtained in a diastereomerically pure
form by recrystallization from hexane/benzene and subsequent
silica gel column chromatography, respectively. The relative
stereochemistries (ψ-exo and ψ-endo) of 3a-c and 4a-c were
estimated by comparison with their Rf values on thin-layer
chromatography of each diastereomer according to Clinton and
Lillya’s report.8 The O-diethylphosphoryl cyanohydrin com-
plexes 5 were synthesized as a 2/3 diastereomixture by reaction
of 1 with diethyl phosphorocyanidate in the presence of LiCN.9
The obtained products 5 were unstable toward silica gel column
chromatography and, therefore, were used for the next reaction
without purification.
has the following advantages: (i) the starting complexes are
readily available in an enantiomerically pure form;3 (ii) since
the Fe(CO)3 moiety possesses excellent stereodirecting ability,
the intermolecular addition of nucleophiles to carbocations
adjacent to the Fe(CO)3 group and/or (pentadienyl)iron(1+)
cations generally occurs with high stereoselectivity; (iii) distinct
from cyclic metal complexes, the introduction of desired
nucleophiles into acyclic complexes can be conducted iteratively
with no limitation of ring size (multifunctionalization); and (iv)
the Fe(CO)3 moiety is easily removed under mild oxidative
conditions in the final stage of the synthesis. In this paper, we
report that both enantiomers can be obtained by switching the
reaction conditions of 1,5-nucleophilic substitution of acyclic
O-phosphoryl cyanohydrin complexes with perfect stereoselec-
tivity; furthermore, several diastereomers bearing contiguous
stereogenic centers can be synthesized via the iterative 1,5-
substitution with concurrent 1,2-migration of the Fe(CO)3 group.
With the requisite cyanohydrin derivatives 2-5 in hand, we
turned our attention to their reactivity with heteroatomic
nucleophiles in the presence of several acidic catalysts.10 At
first, the cyanohydrin complexes 2 were treated with HBF4 in
acetic anhydride at room temperature, but the migrated product
6 (Nu ) OAc) was obtained in very poor yield along with 1
and the corresponding acetates 3a and 4a (eq 2).
Results
Preparation of Starting Complexes 2-5 and Their Reac-
tivity to the 1,5-Nucleophilic Substitution with Concurrent
1,2-Migration of the Fe(CO)3 Group. To examine the 1,5-
nucleophilic substitutions accompanied with 1,2-migration of
the Fe(CO)3 group (eq 1), the (O-protected 2-hydroxy-η4-3,5-
heptadienenitrile)Fe(CO)3 complexes 3a-c, 4a-c, and 5 with
various protecting groups were prepared from hexadienal Fe-
(CO)3 complex 17 (Scheme 2). Treatment of 1 with trimethylsilyl
We next investigated the substitution reactions of 3a-c and
4a-c with methanol under various acidic conditions to clarify
(7) Franck-Neumann, M.; Martina, D.; Heitz, M. P. Tetrahedron Lett.
1982, 23, 3493-3496.
(8) Clinton, N. A.; Lillya, C. P. J. Am. Chem. Soc. 1970, 92, 3058-
3064.
(9) (a) Harusawa, S.; Yoneda, R.; Kurihara, T.; Hamada, Y.; Shioiri, T.
Tetrahedron Lett. 1984, 25, 427-430. (b) Harusawa, S.; Nakamura, S.;
Yagi, S.; Kurihara, T.; Hamada, Y.; Shioiri, T. Synth. Commun. 1984, 14,
1365-1371.
(10) (a) Gre´e, R.; Laabassi, M.; Mosset, P.; Carrie´, R. Tetrahedron Lett.
1985, 26, 2317-2318. (b) Hachem, A.; Teniou, A.; Gre´e, R. Bull. Soc.
Chim. Belg. 1991, 100, 625-626. (c) Gre´e, D.; Gre´e, R.; Lowinger, T. B.;
Martelli, J.; Negri, J. T.; Paquette, L. A. J. Am. Chem. Soc. 1992, 114,
8841-8846. (d) Donaldson, W. A.; Tao, C. J. Org. Chem. 1993, 58, 2134-
2143. (e) Hachem, A.; Toupet, L.; Gre´e, R. Tetrahedron Lett. 1995, 36,
1849-1852. (f) Gre´e, D. M.; Martelli, J. T.; Gre´e, R. L.; Toupet, L. J. J.
Org. Chem. 1995, 60, 2316-2317. (g) Gre´e, D. M.; Kermarrec, C. J. M.;
Martelli, J. T.; Gre´e, R. L.; Lellouche, J.-P.; Toupet, L. J. J. Org. Chem.
1996, 61, 1918-1919. (h) Pearson, A. J.; Alimardanov, A.; Pinkerton, A.
A.; Fouchard, D. M.; Kirschbaum, K. Tetrahedron Lett. 1998, 39, 5919-
5922.
cyanide in the presence of zinc chloride was followed by acidic

Functionalization of Acyclic Diene Ligands
J. Am. Chem. Soc., Vol. 121, No. 39, 1999 9145
Table 1. Nucleophilic Substitution of the Cyanohydrin Derivatives
3-5 with MeOH in the Presence of Acidic Catalysts
sub-
entry strate
product
ratio de of
Figure 1. Chemical shift values and NOE experiment of 7A.
reaction conditions
(yield, %) 6A/7Aa 6Aa
1
2
3
4
5
6
7
8
3a Dowex 50W, reflux, 48 h 6A (23)
>98:<2 <50
>98
>98:<2 >98
>98:<2 >98
>98:<2 >98
>98:<2 >98
4a Dowex 50W, reflux, 48 h
3b Dowex 50W, 60 °C, 6 h
0
-
6A (65)
4b Dowex 50W, 60 °C, 23 h 6A (45)
3c Dowex 50W, 60 °C, 5 h 6A (71)
4c Dowex 50W, 60 °C, 10 h 6A (53)
5
5
HBF4, room temp, 6 h
Nafion NR-50, 60 °C, 24 h 6A (61)
6A/7A (53) 40:60 >98
tuted diene Fe(CO)3 complexes (I) are observed around 0.5 and
1.0 ppm, respectively (Figure 1).10d,11 In contract, those of the
anti- and syn-protons Hc and Hd of (1E,3Z)-1,4-disubstituted
diene Fe(CO)3 complexes (II) are observed around 1.5 and 2.5
ppm, respectively. Indeed, the signals of the C2 protons of 6A
and 7A appear at 0.42 ppm for 6A and 1.56 ppm for 7A, and
those of the C5 protons appear at 1.17 ppm for 6A and 2.60
ppm for 7A. In addition, the nuclear Overhauser effect (NOE)
enhancement between C2-H and C6-H and also between
C4-H and C5-H confirmed that 6A adopts (2E,4E)-geometry
and 7A adopts (2E,4Z)-geometry (Figure 1). The relative
stereochemistry of C6 in 6A and 7A was elucidated from the
reported examples10 and the reaction mechanism described
below (Scheme 5). Furthermore, the elucidation was unambigu-
ously confirmed by chemical transformation of the related
compound 6E into the compound 24.
Stereoselective Synthesis of 6-Substituted (2E,4E)- and
(2E,4Z)-(η4-2-5-hepta-2,4-dienenitrile)Fe(CO)3 Complexes
6A-E and 7A-E. Expecting a stereoselective 1,5-nucleophilic
substitution with various nucleophiles other than methanol, we
investigated the reactivity of the phosphates 5, substitution of
which occurs at room temperature. Attempts to introduce other
nucleophiles were unsuccessful under similar conditions. For
example, treatment of 5 with thiophenol in the presence of
Nafion NR-50 or HBF4 in ether at room temperature resulted
in formation of the demetalated 1,5-substituted (2E,4Z)-adduct.
We were unable to improve this reaction with Brønsted acids,
but these results did indicate that it would be possible to achieve
regioselective 1,5-nucleophilic substitution of 5 with other soft
nucleophiles, if demetalation of the product is suppressed. We
next directed our attention to Lewis acids as an acidic catalyst
for the 1,5-nucleophilic substitution of 5. After many experi-
ments with various solvents and Lewis acids, we found that
the reaction of 5 with 2.5-10 equiv of nucleophile in the
presence of 1.1 equiv of triphenylcarbenium perchlorate (Tr-
ClO4) furnished the corresponding (2E,4E)-adducts 6A-E in
moderate yields (Table 2). A variety of heteroatomic nucleo-
philes such as ethanol, thiophenol, and TMSN3 could be used
in this reaction, and only 6-substituted (2E,4E)-adducts 6A-E
were produced in all cases, irrespective of the nucleophiles
employed (entries 1-5). Although neither TrBF4 nor LiClO4
gave the desired product 6E, resulting in the formation of 7E
and its demetalated product (see Table 3), silver perchlorate
(AgClO4) could be employed in CH2Cl2 instead of TrClO4 (entry
6). The reaction should be performed with a stoichiometric
amount of TrClO4 or AgClO4 at room temperature to furnish
>98:<2 >98
a Determined by 500-MHz H NMR analysis.
1
the difference in reactivity between the diastereomers 3 and 4
in the nucleophilic substitution and to find a suitable leaving
group and acidic catalyst which would give the maximum
chemical yield (Table 1). While a variety of acidic catalysts
could be used to generate the (η5-pentadienyl)Fe(CO)3 cation
in these reactions, we preferred to use acidic ion-exchange resins
such as Dowex 50W and Nafion NR-50 due to the ease of
workup procedure. Treatment of the ψ-exo acetate 3a with
Dowex 50W in refluxing methanol afforded the desired (2E,4E)-
adduct 6A in 23% yield. The diastereoselectivity at C6 of 6A
decreased slowly with increasing reaction time (after 48 h, de
< 50%) (entry 1). On the other hand, the ψ-endo acetate 4a
did not undergo the 1,5-nucleophilic substitution under the same
conditions, and only the starting material 4a was recovered,
along with the aldehyde 1 (entry 2). From these results, the
acetate is revealed to be unsuitable as a leaving group for the
1,5-nucleophilic substitution. In contrast to these results, both
diastereomers of the 3,5-DNB and 2,4,6-TCB esters 3b,c and
4b,c, possessing a more reactive leaving group, gave rise to
6A in moderate yield under milder reaction conditions (entries
3-6). The C6-diastereomer of 6A could not be detected by 500-
MHz 1H NMR analysis. It should be also noted that both isomers
3b,c and 4b,c gave the same product 6A irrespective of the
C1-chirality of the starting materials, even though the reaction
of 4b,c required prolonged reaction time to consume the starting
material completely and gave 6A in a lower chemical yield than
3b,c. Furthermore, a similar reaction of the phosphates 5 in the
presence of HBF4 proceeded smoothly even at room tempera-
ture, but a mixture of the (2E,4E)-adduct 6A and (2E,4Z)-adduct
7A was obtained in 53% combined yield with a 6A/7A ratio of
40:60 (entry 7). In this case, both diastereoselectivities at C6
of 6A and 7A were still high (>98% de). On the other hand,
the above reaction was performed at 60 °C in the presence of
Nafion NR-50, resulting in the single production of 6A in good
yield (entry 8). Based on these results, we speculate that 7A
would be isomerized to the energetically more stable isomer
6A by heating (>60 °C) the reaction mixture, while both 6A
and 7A are initially produced. This speculation was proven by
the acid-catalyzed isomerization experiment of 7A to 6A in
refluxing methanol (eq 3). The olefin geometry of 6A and 7A
was determined by the chemical shift values (δ) and NOE
experiment of the C2 and C5 olefinic protons. In general, the
signals of the anti-protons Ha and Hb of (1E,3E)-1,4-disubsti-
(11) (a) Maglio, G.; Musco, A.; Palumbo, R. J. Organomet. Chem. 1971,
32, 127-136. (b) Adams, C. M.; Cerioni, G.; Hafner, A.; Kalchhauser, H.;
von Philipsborn, W.; Prewo, R.; Schwenk, A. HelV. Chim. Acta 1988, 71,
1116-1142. (c) Enders, D.; Jandeleit, B.; von Berg, S. J. Organomet. Chem.
1997, 533, 219-236.

9146 J. Am. Chem. Soc., Vol. 121, No. 39, 1999
Takemoto et al.
Table 2. Nucleophilic Substitution of the O-Diethylphosphoryl
Cyanohydrins 5 with Various Nucleophiles in the Presence of
TrClO4 and AgClO4
Scheme 3
product
de of major
a
entry MClO4
NuH
solvent time (yield, %) product (6/7)e
1
2
3
4
5
6
7
8
TrClO4 MeOH THF
4 h
4 h
4 h
6A (49) >95 (>98:<2)
6B (56) >95 (>98:<2)
6C (39) >95 (>98:<2)
6D (25) >95 (>98:<2)
6E (56) >95 (>98:<2)
6E (43) >95 (>98:<2)
7E (47) >95 (<2:>98)
TrClO4 EtOH
TrClO4 BnOH
TrClO4 PhSHb
THF
THF
CH2Cl2 4 h
4 h
AgClO4 TMSN3 CH2Cl2 3 h
TrClO4 TMSN3 THF
b
c
b
TrClO4 TMSN3 THF
4 h
d
b
AgClO4 TMSN3 CH2Cl2 10 min 7E (60) >95 (<2:>98)
a The reactions were carried out with MClO4 (1.1 equiv) and
nucleophile (10 equiv) at room temperature. b 2.5 equiv of nucleophile
was added. c 0.1 equiv of TrClO4 was used. d At 0 °C. e Determined
by the reaction of 5 with TMSN3 (Table 3, entries 1-4).
Similarly, several ethers 7A,B were synthesized by treatment
of 5 with 10 equiv of the corresponding alcohols in the presence
of 1.1 equiv of LiClO4 in ether at room temperature, but the
(2E,4E)-adducts 6A,B always contaminated the reaction mixture
as a minor product (entries 5 and 6). Therefore, reaction with
a catalytic amount of BF3‚etherate in THF at 0 °C was the
method of choice for the synthesis of 7A-C, leading to the
exclusive formation of the (2E,4Z)-isomers in comparable yields
(entries 7-9). Similarly, reaction of 5 with 10 equiv of PhSH
under the same reaction conditions afforded the corresponding
sulfide 7D stereoselectively in 54% yield (entry 10).
1
by 500-MHz H NMR analysis.
Table 3. Nucleophilic Substitution of the O-Diethylphosphoryl
Cyanohydrins 5 with Various Nucleophiles in the Presence of Lewis
Acid Catalyst
nucleophile
(NuH)
product
entry Lewis acid
(yield, %) ratio 6/7c de of 7c
The stereochemistry of 6E was unambiguously confirmed by
chemical transformation of 6E into 24 and X-ray crystal-
lographic analysis of 28, which had been derived from 6E. The
relative configuration of the remaining adducts 6B-D and
7B-E was elucidated by comparison of their spectra data with
those of 6A, 6E, and 7A.
We have succeeded in developing a method for synthesizing
both (2E,4E)- and (2E,4Z)-adducts 6A-E and 7A-E in a
stereoselective manner. This method would provide us an
efficient tool for constructing both central chiralities of the C6
carbon adjacent to the (diene)Fe(CO)3 group.
Construction of Contiguous Chiral Centers Using Iterative
1,2-Migration of Fe(CO)3 Group and Determination of Their
Stereochemistry. There are numerous biologically important
1,2-amino alcohols with a 1,2-syn- or 1,2-anti-configuration,
such as sphingosine,13 statin,14 and so on. We assumed that both
diastereomers of these compounds could be synthesized from
the same chiral starting material by using iterative manipulation
of the 1,5-nucleophilic substitution developed above (Scheme
3).
a
1
2
3
4
5
6
7
8
9
LiClO4
TrBF4
HClO4
TMSN3
TMSN3
TMSN3
TMSN3
MeOH
EtOH
MeOH
EtOH
BnOH
PhSH
7E (60)
7E (22)
7E (32)
7E (58)
7A (51)
7B (53)
7A (52)
7B (54)
7C (42)
7D (54)
<2:>98
10:90
10:90
<2:>98
16:84
>95
>95
>95
>95
>95
>95
>95
>95
>95
>95
b
b
BF3‚Et2Oc
a
LiClO4
LiClO4
a
17:83
BF3‚Et2Oc
BF3‚Et2Oc
BF3‚Et2Oc
BF3‚Et2Oc
<2:>98
<2:>98
<2:>98
<2:>98
10
a LiClO4 (1.1 equiv) and nucleophile (10 equiv) were kept in diethyl
ether at room temperature. b Lewis acid (1.1 equiv) and nucleophile
(2.5 equiv) were kept in THF at room temperature. c BF3‚etherate (0.1
equiv) and nucleophile (10 equiv) were kept in THF at 0 °C.
c Determined by 500-MHz H NMR analysis.
1
the (2E,4E)-adducts exclusively. If not, 7E was obtained as a
major product (entries 7 and 8). In addition, subjection of the
obtained (2E,4Z)-adduct 7A to a stoichiometric amount of
TrClO4 (1.1 equiv) in THF in the presence of 10 equiv of MeOH
led to the exclusive formation of 6A in 81% yield (eq 4). The
At first, we examined the possibility of iterative manipulation
of this 1,5-substitution with the obtained azide 6E. The requisite
cyanophosphate 9 was easily prepared from 6E in two steps.
The reduction of 6E with diisobutylaluminum hydride (DIBAL-
H) gave the aldehyde 8 in 88% yield, which was efficiently
converted to the desired cyanophosphate 9 by the same
procedure described above. We undertook the second 1,5-
isomerization of 7A into 6A also proceeded with a catalytic
amount of TrClO4 (0.1 equiv), giving 6A in 66% yield as a
major product (6A/7A ) 93:7). Based on these results, TrClO4
and AgClO4 are unique promoters of this reaction and seem to
play an important role12 in the catalytic isomerization of 7 to 6,
the mechanism of which is not clear at this stage.
(12) (a) Mahler, J. E.; Pettit, R. J. Am. Chem. Soc. 1963, 85, 3955-
3959. (b) Mahler, J. E.; Gibson, D. H.; Pettit, R. J. Am. Chem. Soc. 1963,
85, 3959-3963. (c) Pearson, A. J.; Ray, T. Tetrahedron 1985, 41, 5765-
5770.
(13) A review of recent synthetic studies: Koskinen, P. M.; Koskinen,
A. M. P. Synthesis 1998, 1075-1091.
(14) A review of recent synthetic studies of statins: Nachr. Chem. Tech.
Lab. 1988, 36, 756-758.
In contrast to TrClO4, other Lewis acids such as LiClO4 and
TrBF4 afforded the 6-substituted (2E,4Z)-adducts 7E exclusively

Functionalization of Acyclic Diene Ligands
J. Am. Chem. Soc., Vol. 121, No. 39, 1999 9147
nucleophilic substitution of 9 under the reaction conditions of
method A. The crude cyanophosphate 9 was subjected to 1.1
equiv of TrClO4 and 10 equiv of methanol in THF at room
temperature to afford the desired 6,7-disubstituted (2E,4E)-
adduct anti-10 in 52% yield from the aldehyde 8. We could
Scheme 4a
1
not detect other diastereomers by 500-MHz H NMR. In a
similar manner, the treatment of 9 with a catalytic amount of
BF3‚etherate in methanol at 0 °C furnished the 6,7-disubstituted
(2E,4Z)-adduct syn-11 in 53% yield in two steps as the single
isomer. Thus, it is revealed that, by the iterative manipulation,
(1) the second nucleophiles were introduced regio- and stereo-
selectively with the 1,2-migration of the Fe(CO)3 group without
influence of the neighboring stereogenic functional group, i.e.,
the azide group at C7, and (2) both diastereomers with 1,2-
anti- and 1,2-syn-configuration could be synthesized simply by
switching the reaction conditions (methods A and B).
Having succeeded in the iterative use of 6E, we next
investigated the possibility of the (2E,4Z)-adduct 7A for the
iterative manipulation. The cyanophosphate 12 was prepared
from 7A by the same procedure as that used for 6E. However,
in contrast to 9, 1,2-migration of 12 to syn-13 did not occur by
the reaction of 12 with methanol in the presence of TrClO4 or
BF3‚etherate, resulting in a complex mixture. These results
indicate that 7A-E bearing 6,7-syn-configuration cannot be used
for further iterative manipulation; that is, synthesis of (2E,4Z)-
isomers such as 7 and 11 means the termination of this iterative
manipulation.
To determine the relative stereochemistry of 10 and 11 and
also to extend this iterative method to the asymmetric synthesis
of (2R,3S)-2-amino-5,7-tetradecadien-3-ol (25),15 the iterative
manipulation of the 1,5-nucleophilic substitution was applied
to the chiral starting material (+)-6E (Scheme 4). The reaction
of dialdehyde Fe(CO)3 complex 1416 with 1.8 equiv of dimeth-
ylzinc and 1.8 equiv of titanium(IV) isopropoxide in the
presence of (1S,2S)-N,N′-bis(trifluoromethanesulfonyl)-1,2-cy-
clohexyldiamine 15 (3 mol %) as a chiral ligand in toluene at
0 °C gave rise to monomethylated complex 16 in 71% yield
with 96% ee.17,18 After acetylation of 16, an azide group was
introduced stereoselectively by treatment of 17 with TMSN3
and Sc(OTf)3 in methylene chloride at room temperature to
afford the nitrile (+)-6E in 92% yield with no racemization.
Under these conditions, the aldehyde group of 17 was converted
to a nitrile group simultaneously. This reaction is an uncommon
but not unobserved occurrence.19 With the target chiral azide
complex 6E in hand, we undertook the same manipulation
developed above [DIBAL-H reduction, phosphorylcyanation,
1,2-migration of the Fe(CO)3 group with MeOH and TrClO4]
with (+)-6E to obtain the anti-adduct (+)-10 in a comparable
yield. To next introduce a hydride as the third nucleophile
together with 1,2-migration of the Fe(CO)3 group, we first
attempted the trialkylsilane reduction20 of the O-phosphoryl
cyanohydrin derived from (+)-18 under various Lewis acidic
conditions. The reaction, however, did not proceed cleanly
regardless of the Lewis acids used, giving the desired product
in less than 19% yield along with unidentified products. To
a Conditions: (a) Me2Zn, Ti(Oi-Pr)4, chiral ligand (15), -20 to 0
°C, toluene, 71%; (b) Ac2O, pyridine, CH2Cl2, 80%; (c) TMSN3,
Sc(OTf)3, CH2Cl2, 92%; (d) DIBAL-H, CH2Cl2, -78 °C, 88%; (e)
(EtO)2P(O)CN, LiCN, THF; TrClO4, MeOH (10 equiv), THF, 52%;
(f) DIBAL-H, CH2Cl2, -78 °C, 77%; (g) (EtO)2P(O)CN, LiCN, THF;
TrClO4, EtSH (10 equiv), THF, 61%; (h) H2 (5 atm),10% Pd/C,
(Boc)2O, MeOH, 85%; (i) DIBAL-H, CH2Cl2, -78 °C, 78%; (j)
C5H11PPh3Br, n-BuLi, toluene, -78 tp 0 °C, 73%; (k) H2 (3 atm), 10%
Pd/C, MeOH, 81%; (l) Me3NO, benzene, 60 °C, 87%; (m) p-TsOH,
MeOH, 82%; (n) MeI, Ag2O, MeCN, reflux, 54%.
avoid this step, we next tried the two-step sequence, that is,
introduction of the sulfide group (18 f 19) and hydrogenolysis
of the C-S bond (19 f 20). The introduction of an ethylsulfanyl
group into the O-phosphoryl cyanohydrin derived from (+)-18
using TrClO4 and ethanethiol (method A) successfully afforded
the desired (2E,4E)-adduct 19 as the single isomer in 61% yield
(the relative stereochemistry of 19 was confirmed by X-ray
crystallography of the racemic N-Boc derivative 28; see
Supporting Information). The hydrogenolysis of the C-S bond
and concurrent reduction of the azide group of 19 were
conducted by medium-pressure hydrogenation with 10% pal-
ladium-on-charcoal in the presence of di-tert-butyl dicarbonate,
giving the 1,2-amino alcohol derivative 20 in good yield. The
right-side chain of the nitrile 20 was elongated by a three-step
sequence: DIBAL-H reduction (21, 78% yield), Wittig reaction
with C5H10dPPh3 (22, 73% yield), and subsequent hydrogena-
tion over 10% palladium-on-charcoal (23, 81% yield). Finally,
demetalation of 23 with trimethylamine oxide21 gave rise to the
N-Boc-O-methyl derivative (-)-24 of (2R,3S)-2-amino-5,7-
(15) Glanita, N. K.; Scheuer, P. J. J. Org. Chem. 1989, 54, 366-369.
(16) Roush, W. R.; Park, J. C. Tetrahedron Lett. 1990, 31, 4707-4710.
(17) (a) Takemoto, Y.; Baba, Y.; Noguchi, I.; Iwata, C. Tetrahedron
Lett. 1990, 31, 4707-4710. (b) Takemoto, Y.; Baba, Y.; Honda, A.; Nakao,
S.; Noguchi, I.; Iwata, C.; Tanaka, T.; Ibuka, T. Tetrahedron 1998, 54,
15567-15580.
(18) Takhashi, H.; Kawakita, T.; Ohno, M.; Yoshikawa, M.; Kobayashi,
S. Tetrahedron 1992, 48, 5691-5700.
(19) Nishikawa, K.; Watanabe, A. Chem. Lett. 1984, 773-774.
(20) Benvegnu, T.; Schio, L.; Le Floc’h, Y.; Gre´e, R. Synlett 1994, 505-
506.
(21) Shvo, Y.; Hazum, E. J. Chem. Soc., Chem. Commun. 1974, 366-
377.

9148 J. Am. Chem. Soc., Vol. 121, No. 39, 1999
Takemoto et al.
Scheme 5
most important in this 1,5-nucleophilic substitution. The se-
quential bond rotation of the C3-C4 bond of the S-shaped cation
complex A gave the more stable U-shaped (η5-pentadienyl)-
iron(1+) cation B. This conversion from A to B relieves the
electronic repulsion between the nitrile group and the C2-
carbocation. Such electronic repulsion10d and configurational
preference play a key role in determining the regio- and
stereochemical outcomes of the 1,5-nucleophilic substitution
with 1,2-migration of the Fe(CO)3 group. Once the U-shaped
cation B is generated in the presence of BF3‚etherate (method
B), the nucleophilic attack of the heteroatomic nucleophiles such
as alcohols, thiophenol, and trimethylsilyl azide at the C6
position occurs from the anti direction to the Fe(CO)3 moiety
of B, resulting in the exclusive formation of (2E,4Z)-adducts
7A-E. Unlike the azide and thiol, if alcohols are employed as
a nucleophile at a higher temperature or with a stoichiometric
amount of the Lewis acid, the (2E,4Z)-adducts 7A-C are
equilibrated with the corresponding (2E,4E)-adducts 6A-C via
cation complexes B and C, affording the more stable (2E,4E)-
adducts predominantly or exclusively, depending on the reaction
temperature and acidic catalyst. Similarly, alcohols attack from
the anti direction to the Fe(CO)3 moiety of C, giving the
(2E,4E)-adducts 6A-C with high diastereoselectivity. Further-
more, we found that triphenylcarbenium perchlorate promotes
the isomerization of 7A to 6A in the presence of methanol at
room temperature (eq 4). Interestingly, this isomerization
proceeded effectively with either a catalytic or stoichiometric
amount of TrClO4. The mechanism of the isomerization
promoted by TrClO4 is not clear, but judging from the facts
that (1) this reaction occurs with a catalytic amount of TrClO4
(or AgClO4) and (2) Lewis acids such as HClO4, LiClO4, and
TrBF4 do not promote this reaction, their oxidation ability and
perchlorate counteranion should play a key role in this isomer-
ization. It is reasonable to speculate that the isomerization might
proceed via a cation radical intermediate (eq 5). In other words,
tetradecadien-3-ol 25 in 87% yield. Alternatively, (+)-24 was
prepared from the authentic sample 26, which had been
synthesized as a synthetic intermediate of the natural product
2522 by deprotection of the acetonide of 26 and subsequent
methylation of the hydroxy group of 27. These two compounds
1
24 were identical to each other with respect to H NMR, IR,
mass, and [R]D, except for the opposite sign of the specific
rotation. Based on these results, all substituents in 10 and 19
are revealed to possess the (6R,7R)-6,7-anti- and (6R,7R,8R)-
6,7-anti-6,8-syn-configurations, which furthermore demonstrates
that all nucleophiles would be introduced from the opposite side
of the Fe(CO)3 group in this iterative manipulation using method
A.
Discussion
The formation of (2E,4E)- and (2E,4Z)-1,5-substituted prod-
ucts 6 and 7 is reasonably explained by the mechanism via
U-shaped (η5-pentadienyl)iron(1+) cation complexes (Scheme
5).23 The first step is a formation of unstable S-shaped cation
complex A, together with loss of the leaving group such as
diethyl phosphate. It is well known that ψ-exo alcohol deriva-
tives are more reactive to an acidic catalyst than ψ-endo ones,
because the leaving group of the former can occupy the anti-
periplanar position to the Fe(CO)3 group more easily than that
of the latter.10,23,24 From the investigation of the leaving groups
[AcO, DNBO, TCBO, (EtO)2P(O)O] of the O-protected cyano-
hydrin Fe(CO)3 complexes 3-5 in Table 1, we also observed
moderately to quite different reactivity between the ψ-exo and
ψ-endo isomers in terms of reaction time and chemical yield.
Although only 3a gave the desired product 6A in a case of the
acetate, the difference in reactivity between the diastereoisomers
3 and 4 becomes smaller as the ability of the leaving group
becomes stronger. It is presumed that, due to the small steric
bulkiness of the nitrile group, the ψ-endo complexes 4a-c can
adopt the anti-periplanar alignment of the leaving group to the
Fe(CO)3 group as easily as the ψ-exo complexes 3a-c.
However, it should be difficult to generate a cationic species
on the C2-carbon bearing the nitrile group. Therefore, the ability
of the leaving group to form the cation complex A would be
7A was more easily oxidized by TrClO4 than 6A, resulting in
the cation-radical complex G, which was converted into 6A
via the C4-C5 bond rotation and recombination of the methoxy
group with inversion of the configuration.
By adding a stoichiometric amount of TrClO4 in the presence
of appropriate nucleophiles, several (2E,4E)-adducts 6A-E
could be synthesized from 5 in one step. The highly stereose-
lective synthesis of 6A-E in this reaction would be strongly
dependent on the ability of TrClO4 to isomerize 7 to 6.
In the second nucleophilic substitution of 6E, a similar
reaction via η5-(pentadienyl)cation complexes D and E occurs
to afford the 6,7-disubstituted (2E,4E)- and (2E,4Z)-adducts 10
and 11, dependent on the reaction conditions (method A and
method B), respectively (Scheme 6). On the other hand, the
same treatment of 7A by methods A and B gave none of the
desired products, resulting in a complex mixture. Perhaps the
failure of the second substitution of 7A would be attributed to
instability of the η5-(pentadienyl)cation complex F due to the
severe steric hindrance between the C2-H and substituents of
C7.
(22) Mori, K.; Matsuda, H. Liebigs Ann. Chem. 1992, 131-137.
(23) (a) Gresham, D. G.; Kowalski, D. J.; Lillya, C. P. J. Organomet.
Chem. 1978, 144, 71-79. (b) Bayoud, R. S.; Biehl, E. R.; Reeves, P. C. J.
Organomet. Chem. 1978, 150, 75-83. (c) Donaldson, W. A. J. Organomet.
Chem. 1990, 395, 187-193. (d) Quirosa-Guillou, C.; Lellouche, J.-P. J.
Org. Chem. 1994, 59, 4693-4697. (e) Donaldson, W. A. Aldrichimica Acta
1997, 30, 17-24.
(24) (a) Uemura, M.; Minami, T.; Yamashita, Y.; Hiyoshi, K.; Hayashi,
Y. Tetrahedron Lett. 1987, 28, 641-644. (b) Roush, W. R.; Wada, C. K.
J. Am. Chem. Soc. 1994, 116, 2151-2152. (c) Roush, W. R.; Wada, C. K.
Tetrahedron Lett. 1994, 35, 7347-7350.

Functionalization of Acyclic Diene Ligands
J. Am. Chem. Soc., Vol. 121, No. 39, 1999 9149
4.9, 7.9 Hz); 13C NMR (75.5 MHz, CDCl3) δ 19.0, 56.9, 59.2, 62.9,
79.5, 86.8, 118.7, 210.6; IR (KBr) 3408, 2048, 1975 cm-1; MS (EI)
m/z (relative intensity) 236 (M+ - CN, 7.2), 208 (29), 180 (73), 152
(100). Anal. Calcd for C10H9FeNO4: C, 45.66; H, 3.45; N, 5.23.
Found: C, 45.49; H, 3.45; N, 5.34. exo-2: yellow crystals, mp 101 °C
(hexane/benzene); 1H NMR (CDCl3) δ 0.97 (dd, 1H, J ) 7.9, 8.5 Hz),
1.37 (dq, 1H, J ) 9.1, 6.1 Hz), 1.46 (d, 3H, J ) 6.1 Hz), 2.41 (d, 1H,
J ) 6.7 Hz), 4.25 (dd, 1H, J ) 6.7, 8.7 Hz), 5.13 (dd, 1H, J ) 4.9, 9.2
Hz), 5.28 (dd, 1H, J ) 4.9, 7.9 Hz); 13C NMR (75.5 MHz, CDCl3) δ
19.1, 55.1, 59.6, 63.7, 81.4, 87.5, 118.9, 210.2; IR (KBr) 3394, 2050,
1980 cm-1; MS (EI) m/z (relative intensity) 236 (M+ - CN, 5.2), 208
(29), 180 (71), 152 (100). Anal. Calcd for C10H9FeNO4: C, 45.66; H,
3.45; N, 5.23. Found: C, 45.73; H, 3.52; N, 5.25.
Scheme 6
(1RS,2RS,5SR,2E,4E)-Tricarbonyliron[(η4-2-5)-1-cyanohexa-3,5-
dienyl] Acetate (3a) and (1RS,2SR,5RS,2E,4E)-Tricarbonyliron[(η4-
2-5)-1-cyanohexa-3,5-dienyl] Acetate (4a). To a stirred solution of
crude 2 (120 mg, 0.458 mmol) in dry CH2Cl2 (4.8 mL) were added
Ac2O (64.8 µL, 0.687 mmol) and dry pyridine (44.5 µL, 0.550 mmol)
at room temperature under a nitrogen atmosphere. After 2 h, a saturated
NaHCO3 solution was added to the reaction mixture, and the resulting
mixture was extracted with CH2Cl2. The extract was washed with brine,
dried over MgSO4, and then concentrated in vacuo. The residue was
purified by column chromatography (SiO2, hexane/AcOEt ) 10:1) to
give 4a (62.8 mg, 45%) and 3a (62.9 mg, 45%). 4a: yellow crystals,
Conclusion
The reactions outlined herein demonstrate that the iron-
mediated 1,5-nucleophilic substitution can be an effective
method for constructing contiguous stereogenic centers in
acyclic ligands. In addition, this is the first example in which
the iterative 1,2-migration of a metal has been utilized in the
multiple functionalization of acyclic compounds. The ability to
construct both central chiralities (R and S) at each chiral center
with excellent stereoselectivity by simply switching the reaction
conditions (method A and method B) enhances the utility of
this method.
1
mp 92-94 °C (hexane); H NMR (CDCl3) δ 0.92 (dd, 1H, J ) 7.3,
7.3 Hz), 1.32 (dq, 1H, J ) 8.5, 6.1 Hz), 1.46 (d, 3H, J ) 6.1 Hz), 2.17
(s, 3H), 5.09 (d, 1H, J ) 7.3 Hz), 5.14 (dd, 1H, J ) 5.5, 8.5 Hz), 5.31
(dd, 1H, J ) 5.5, 7.3 Hz); 13C NMR (67.8 MHz, CDCl3) δ 19.1, 20.2,
52.3, 59.4, 62.8, 79.8, 87.0, 115.9, 168.7, 210.2; IR (KBr) 2052, 1984,
1977, 1755 cm-1; MS (EI) m/z (relative intensity) 249 (M+ - 2CO,
18), 221 (55), 80 (100). Anal. Calcd for C12H11FeNO5: C, 47.25; H,
3.63; N, 4.59. Found: C, 47.26; H, 3.59; N, 4.54. 3a: yellow crystals,
mp 96-98 °C (hexane/AcOEt); 1H NMR (CDCl3) δ 0.90 (dd, 1H, J )
8.5, 8.5 Hz), 1.39 (dq, 1H, J ) 7.3, 6.1 Hz), 1.46 (d, 3H, J ) 6.1 Hz),
2.14 (s, 3H), 5.10 (dd, 1H, J ) 4.9, 8.5 Hz), 5.17 (d, 1H, J ) 8.5 Hz),
5.34 (dd, 1H, J ) 4.9, 7.3 Hz); 13C NMR (75.5 MHz, CDCl3) δ 19.0,
20.4, 51.3, 59.7, 63.3, 81.8, 87.5, 116.0, 168.9, 210.0; IR (KBr) 2054,
1983, 1753 cm-1; MS (EI) m/z (relative intensity) 221 (M+ - 3CO,
16), 80 (100). Anal. Calcd for C11H11FeNO4: C, 47.25; H, 3.63; N,
4.59. Found: C, 47.21; H, 3.64; N, 4.58. (1RS,2SR,5RS,2E,4E)-
Tricarbonyliron[(η4-2-5)-1-cyanohexa-2,4-dienyl] 3,5-Dinitroben-
zoate (4b). To a stirred solution of endo-2 (65.0 mg, 0.247 mmol) in
dry CH2Cl2 (4 mL) were added 3,5-dinitrobenzoyl chloride (71.2 mg,
0.309 mmol) and dry pyridine (30.0 µL, 0.371 mmol) at room
temperature under a nitrogen atmosphere. After 2 h, a saturated NaHCO3
solution was added to the reaction mixture, and the resulting mixture
was extracted with AcOEt. The extract was washed with brine, dried
over MgSO4, and then concentrated in vacuo. The residue was purified
by column chromatography (SiO2, hexane/AcOEt ) 5:1) to give 4b
(109.4 mg, 97%) as yellow crystals: mp 113 °C (petroleum ether/
Experimental Section
General. Melting points are uncorrected. IR spectra were obtained
using a Horiba FT-210 spectrometer. H NMR spectra were obtained
1
using JEOL JNM-GX-500 (500 MHz) and JEOL JNM-LA-500 (500
MHz) spectrometers. 13C NMR spectra were obtained using JEOL JNM-
EX-270 (67.8 MHz) and JEOL JNM-AL-300 (75.5 MHz) spectrom-
eters. Optical rotations were measured with a JASCO DIP-360
polarimeter. Mass spectra (MS) were measured with a Shimadzu
GCMS-QP-1000 spectrometer. High-resolution mass spectra (HRMS)
were measured with JEOL JMS-D300 and JEOL JMS-600 spectrom-
eters. Chemical ionization mass spectra (CIMS) were measured with a
JEOL JMS-D300 spectrometer. Column chromatography was carried
out using Merck Kieselgel 60. Toluene and THF were distilled from
sodium benzophenone ketyl radical under argon. Dichloromethane was
freshly distilled from calcium hydride. Dry ether and acetonitrile were
obtained from Kanto Chemicals. (2RS,3SR,6RS,3E,5E)-Tricarbonyl-
iron[(η4-3-6)-2-hydroxyhepta-3,5-dienenitrile] (endo-2) and (2RS,-
3RS,6SR,3E,5E)-Tricarbonyliron[(η4-3-6)-2-hydroxyhepta-3,5-di-
enenitrile] (exo-2). To a stirred solution of 1 (550 mg, 2.33 mmol) in
dry CH2Cl2 (15 mL) were added TMSCN (0.49 mL, 3.50 mmol) and
ZnCl2 (635 mg, 0.466 mmol) at 0 °C under a nitrogen atmosphere.
After 1 h, a saturated NaHCO3 solution was added to the reaction
mixture, and the resulting mixture was extracted with CH2Cl2. The
extract was washed with brine, dried over MgSO4, and then concentrated
in vacuo. A 10% HCl solution (50 µL) was added to a solution of the
residue in MeOH (15 mL), and the mixture was stirred for 15 min.
Ice-water was added, and the resulting mixture was extracted with
CH2Cl2. The extract was washed with brine, dried over MgSO4, and
then concentrated in vacuo to give crude 2 (610 mg, 100%, 2 setps) as
a diastereomeric mixture. The crude mixture was purified by recrys-
tallization from a mixture of benzene and hexane, giving exo-2 as
yellow crystals (240 mg, 39%). The diastereomerically pure endo-2
(195 mg, 32%) was obtained by column chromatography (SiO2, hexane/
AcOEt ) 7:1) of the mother liquid along with exo-2 (100 mg, 16%).
endo-2: yellow crystals, mp 95-96 °C (hexane/AcOEt); 1H NMR
(CDCl3) δ 0.97 (dd, 1H, J ) 6.7, 7.9 Hz), 1.28 (dq, 1H, J ) 9.1, 6.1
Hz), 1.46 (d, 3H, J ) 6.1 Hz), 2.45 (d, 1H, J ) 5.5 Hz), 4.33 (dd, 1H,
J ) 5.5, 6.7 Hz), 5.14 (dd, 1H, J ) 4.9, 9.2 Hz), 5.31 (dd, 1H, J )
1
toluene); H NMR (CDCl3) δ 1.09 (dd, 1H, J ) 7.9, 7.9 Hz), 1.26-
1.30 (m, 1H), 1.50 (m, 3H), 5.24 (m, 1H), 5.29 (d, 1H, J ) 7.9 Hz),
5.45 (dd, 1H, J ) 4.9, 7.9 Hz), 9.23 (d, 2H, J ) 2.4 Hz), 9.32 (dd, 2H,
J ) 2.4, 2.4 Hz); 13C NMR (75.5 MHz, CDCl3) δ 19.1, 50.9, 60.6,
65.4, 80.1, 87.8, 115.0, 123.4, 129.7, 131.6, 148.8, 160.7, 210.0; IR
(KBr) 2052, 1986, 1975, 1747, 1549, 1346 cm-1; MS (EI) m/z (relative
intensity) 430 (M+ + 1 - CO, 0.6), 402 (0.4), 374 (12), 79 (100).
Anal. Calcd for C17H11FeN3O9: C, 44.67; H, 2.43; N, 9.19. Found: C,
44.57; H, 2.59; N, 9.14.
(1RS,2RS,5SR,2E,4E)-Tricarbonyliron[(η4-2-5)-1-cyanohexa-3,5-
dienyl] 3,5-Dinitrobenzoate (3b). The same treatment of exo-2 (71.2
mg, 0.271 mmol) as described for the synthesis of 4b gave the crude
mixture, which was purified by column chromatography (SiO2, hexane/
AcOEt ) 4:1) to give 3b (111.3 mg, 90%) as yellow crystals: mp 142
1
°C (hexane/AcOEt); H NMR (CDCl3) δ 1.05 (m, 1H), 1.27 (m, 1H),
1.51 (m, 3H), 5.16-5.19 (m, 1H), 5.46-5.49 (m, 2H), 9.17 (d, 2H,
J ) 1.8 Hz), 9.30 (dd, 2H, J ) 1.8, 1.8 Hz); 13C NMR (75.5 MHz,
CDCl3) δ 19.1, 49.7, 60.5, 65.9, 81.8, 88.1, 115.1, 123.3, 129.7, 131.8,
148.8, 161.0, 209.4; IR (KBr) 2054, 1986, 1975, 1745, 1549, 1346
cm-1; MS (EI) m/z (relative intensity) 430 (M+ + 1 - CO, 0.6), 374

9150 J. Am. Chem. Soc., Vol. 121, No. 39, 1999
Takemoto et al.
(3), 79 (100). Anal. Calcd for C17H11FeN3O9: C, 44.67; H, 2.43; N,
9.19. Found: C, 44.56; H, 2.68; N, 9.15.
Entry 7. The reaction of 5 (77.8 mg, 0.195 mmol) according to the
typical procedure, except a 54% solution of HBF4 in ether (0.14 mL,
0.923 mmol) was used in the place of Dowex 50W, gave a 40:60
mixture of 6A and 7A (28.4 mg, 53%).
(1RS,2RS,5SR,2E,4E)-Tricarbonyliron[(η4-2-5)-1-cyanohexa-3,5-
dienyl] 2,4,6-Trichlorobenzoate (3c) and (1RS,2SR,5RS,2E,4E)-
Tricarbonyliron[(η4-2-5)-1-cyanohexa-3,5-dienyl] 2,4,6-Trichlo-
robenzoate (4c). To a stirred solution of crude 2 (230 mg, 0.878 mmol)
in dry CH2Cl2 (9.0 mL) were added 2,4,6-trichlorobenzoyl chloride
(0.18 mL, 1.18 mmol) and dry pyridine (0.10 mL, 1.13 mmol) at room
temperature under a nitrogen atmosphere. After 2 h, a saturated NaHCO3
solution was added to the reaction mixture, and the resulting mixture
was extracted with CH2Cl2. The extract was washed with brine, dried
over MgSO4, and then concentrated in vacuo. The residue was purified
by column chromatography (SiO2, hexane/AcOEt ) 10:1) to give 4c
(156 mg, 38%) and 3c (164 mg, 40%). 3c: yellow oil; 1H NMR (CDCl3)
δ 0.97 (dd, 1H, J ) 8.1, 8.7 Hz), 1.37 (dq, 1H, J ) 6.0, 9.0 Hz), 1.48
(d, 3H, J ) 6.0 Hz), 5.14 (dd, 1H, J ) 6.3, 9.0 Hz), 5.31 (d, 1H, J )
8.7 Hz), 5.41 (dd, 1H, J ) 6.3, 8.1 Hz), 9.30 (m, 2H); 13C NMR (75.5
MHz, CDCl3) δ 19.1, 50.1, 60.1, 65.5, 82.0, 88.2, 115.2, 128.2, 130.0,
132.9, 137.2, 162.3, 210.5; IR (KBr) 2056, 1988, 1755 cm-1; MS (EI)
m/z (relative intensity) 422 (M+ + 1 - CO, 1.6), 413 (M+ - 2CO,
2.7), 385 (M+ - 3CO, 62), 106 (100); HRMS calcd for C17H10Cl3-
FeNaNO5 491.8872 (FAB, M + Na), found 491.8877. 4c: yellow oil;
1H NMR (CDCl3) δ 0.88 (dd, 1H, J ) 8.6, 8.6 Hz), 1.37 (dq, 1H, J )
6.9, 6.7 Hz), 1.41 (d, 3H, J ) 6.7 Hz), 5.08 (dd, 1H, J ) 6.9, 6.9 Hz),
5.29 (d, 1H, J ) 8.6 Hz), 5.34 (dd, 1H, J ) 6.9, 8.6 Hz), 7.31 (s, 2H);
13C NMR (67.8 MHz, CDCl3) δ 19.1, 50.1, 60.1, 65.4, 82.0, 88.2, 115.2,
128.2, 130.0, 133.0, 137.2, 168.9, 210.0; IR (KBr) 2056, 1986, 1755
cm-1; MS (EI) m/z (relative intensity) 413 (M+ - 2CO, 1.5), 385 (M+
- 3CO, 31), 106 (100); HRMS calcd for C17H10Cl3FeNaNO5 491.8872
(FAB, M + Na), found 491.8854.
Entry 8. The reaction of 5 (21.7 mg, 0.0544 mmol) according to
the typical procedure, except Nafion NR-50 was used in the place of
Dowex 50W, gave 6A (9.1 mg, 61%) as yellow crystals.
1
6A: mp 58 °C (hexane); H NMR (CDCl3) δ 0.42 (d, 1H, J ) 7.3
Hz), 1.17 (dd, 1H, J ) 6.1, 8.5 Hz), 1.33 (d, 3H, J ) 6.1 Hz), 3.24
(dq, 1H, J ) 6.1, 6.1 Hz), 3.30 (s, 3H), 5.46 (dd, 1H, J ) 4.9, 8.5 Hz),
5.90 (dd, 1H, J ) 4.9, 7.3 Hz); 13C NMR (75.5 MHz, CDCl3) δ 21.9,
24.0, 56.0, 67.1, 77.2, 81.5, 86.4, 121.3, 203.4; IR (KBr) 2220, 2063,
1990 cm-1; MS (CI) m/z (relative intensity) 278.0 (M+ + 1, 100). Anal.
Calcd for C11H11FeNO4: C, 47.69; H, 4.00; N, 5.06. Found: C, 47.80;
H, 4.04; N, 5.10.
Isomerization of 7A to 6A. Equation 3. A mixture of 7A (16.2
mg, 0.0585 mmol), Dowex 50W (22 mg), and dry MeOH (1.5 mL)
was stirred at 60 °C under a nitrogen atmosphere. After 5 h, Dowex
50W (11 mg) was added to the reaction mixture, and the resulting
mixture was stirred at 60 °C for 2 h. The reaction mixture was filtered
to remove the acidic catalyst, the filtrate was concentrated in vacuo,
and the residue was purified by column chromatography (SiO2, hexane/
AcOEt ) 7:1) to give 6A (8.8 mg, 54%).
Equation 4. Stoichiometric Reaction. To a stirred solution of 7A
(20.0 mg, 0.0722 mmol) in dry THF (0.75 mL) were added MeOH
(0.03 mL, 0.752 mmol) and TrClO4 (28.2 mg, 0.0827 mmol) at room
temperature under a nitrogen atmosphere. After 4 h, a saturated NaHCO3
solution was added to the reaction mixture, and the resulting mixture
was extracted with AcOEt. The extract was washed with brine, dried
over MgSO4, and then concentrated in vacuo. The residue was purified
by column chromatography (SiO2, hexane/AcOEt ) 4:1) to give 6A
(16.2 mg, 81%). Catalytic Reaction. To a stirred solution of 7A (20.0
mg, 0.0722 mmol) in dry THF (0.75 mL) were added MeOH (0.03
mL, 0.752 mmol) and TrClO4 (2.6 mg, 7.52 µmol) at room temperature
under a nitrogen atmosphere. After 51 h, a saturated NaHCO3 solution
was added to the reaction mixture, and the resulting mixture was
extracted with AcOEt. The extract was washed with brine, dried over
MgSO4, and then concentrated in vacuo. The residue was purified
by column chromatography (SiO2, hexane/AcOEt ) 4:1) to give
6A/7A ) 93:7 (13.1 mg, 66%).
(2RS,5SR,2E,4E)-Tricarbonyliron[(η4-2-4)-1-cyanohexa-2,4-di-
ethyl] Diethyl Phosphate (5). To a stirred solution of 1 (201 mg, 0.851
mmol) in dry THF (8.5 mL) were added diethyl phosphorocyanidate
(DEPC) (0.14 mL, 0.935 mmol) and LiCN (2.7 mg, 85.1 µmol) at room
temperature under a nitrogen atmosphere. After 15 min, a saturated
NaHCO3 solution was added to the reaction mixture, and the resulting
mixture was extracted with AcOEt. The extract was washed with brine,
dried over MgSO4, and then concentrated in vacuo to give crude 5
(340 mg, 100%), which was used without further purification. 5: a
yellow oil; 1H NMR (CDCl3) δ 0.89 (m, 1/3H), 0.97 (m, 2/3H), 1.25-
1.39 (m, 1H), 1.35-1.29 (m, 6H), 1.46 (d, 3H, J ) 6.7 Hz), 4.10-
4.24 (m, 4H), 4.69 (dd, 2/3H, J ) 8.5, 8.5 Hz), 4.97 (dd, 1/3H, J )
6.1, 8.5 Hz), 5.11-5.15 (m, 1H), 5.33 (dd, 1/3H, J ) 4.9, 7.3 Hz),
5.39 (dd, 2/3H, J ) 4.9, 7.3 Hz); 13C NMR (75.5 MHz, CDCl3) δ
15.9, 16.0, 19.0, 19.1, 52.05, 52.10, 53.5, 53.6, 59.2, 59.9, 64.8, 67.3,
78.8, 81.8, 86.8, 88.0, 115.99, 116.07, 210.3; IR (KBr) 2219, 2051,
1974 cm-1; MS (EI) m/z (relative intensity) 260 (M+ - Fe(CO)3, 19),
161 (100).
General Procedure for Nucleophilic Substitution of the Cyano
Esters 3a-d, 4a-d, and 5 (Table 1). A mixture of the cyano esters,
Dowex 50W (26 mg), and dry MeOH (3 mL) was refluxed or stirred
at 60 °C for the appropriate time under a nitrogen atmosphere. After
the reaction mixture was filtered to remove the acidic catalyst, the
filtrate was concentrated in vacuo, and the residue was purified by
column chromatography (SiO2, hexane/AcOEt ) 7:1) to give 6A.
(2RS,5SR,6SR,2E,4E)-Tricarbonyliron[(η4-2-5)-6-methoxyhepta-
2,4-dienenitrile] (6A). Entry 1. The reaction of 3a (38.1 mg, 0.125
mmol) and Dowex 50W (10 mg) according to the typical procedure
gave 6A (8.0 mg, 23%).
General Procedure for Nucleophilic Substitution of 5 with
Perchlorate Salts (Table 2). The perchlorate salts TrClO4 or AgClO4
(1.1 equiv) and appropriate nucleophiles (2.5-10 equiv) were succes-
sively added to a stirred solution of 5 in dry THF or CH2Cl2 at 0 °C
under a nitrogen atmosphere, and the mixture was allowed to warm
slowly to room temperature. After being quenched with a saturated
NaHCO3 solution, the resulting mixture was extracted with AcOEt.
The extract was washed with water and brine, dried over MgSO4, and
then concentrated in vacuo to give the crude mixture.
(2RS,5SR,6SR,2E,4E)-Tricarbonyliron[(η4-2-5)-6-methoxyhepta-
2,4-dienenitrile] (6A). Entry 1. The reaction of 5 (91.7 mg, 0.230
mmol) with methanol according to the typical procedure and purification
of the crude mixture by column chromatography (SiO2, hexane/AcO-
Et ) 7:1) gave 6A (31.2 mg, 49%).
(2RS,5SR,6SR,2E,4E)-Tricarbonyliron[(η4-2-5)-6-ethoxyhepta-
2,4-dienenitrile] (6B). Entry 2. The reaction of 5 (73.2 mg, 0.183
mmol) with EtOH according to the typical procedure and purification
by column chromatography (SiO2, hexane/AcOEt ) 4:1) gave 6B (29.9
1
mg, 56%) as yellow crystals: mp 60 °C (hexane); H NMR (CDCl3)
Entry 3. The reaction of 3b (25.7 mg, 0.0562 mmol) and Dowex
50W (13 mg) according to the typical procedure gave 6A (10.1 mg,
65%).
Entry 4. The reaction of 4b (22.6 mg, 0.0494 mmol) and Dowex
50W (13 mg) according to the typical procedure gave 6A (6.2 mg,
45%).
Entry 5. The reaction of 3c (21.7 mg, 0.0461 mmol) and Dowex
50W (12 mg) according to the typical procedure gave 6A (9.1 mg,
71%).
Entry 6. The reaction of 4c (21.1 mg, 0.0448 mmol) and Dowex
50W (11 mg) according to the typical procedure gave 6A (6.6 mg,
53%).
δ 0.41 (d, 1H, J ) 7.3 Hz), 1.17 (t, 3H, J ) 7.1 Hz), 1.21 (m, 1H),
1.33 (d, 3H, J ) 6.2 Hz), 3.34 (dq, 1H, J ) 6.1, 6.2 Hz), 3.46 (q, 2H,
J ) 7.1 Hz), 5.48 (dd, 1H, J ) 5.0, 8.8 Hz), 5.58 (dd, 1H, J ) 5.0, 7.3
Hz); 13C NMR (75.5 MHz, CDCl3) δ 15.2, 22.4, 24.1, 63.9, 67.7, 75.5,
81.4, 86.5, 121.4, 206.0; IR (KBr) 2220, 2062, 1992 cm-1; MS (CI)
m/z (relative intensity) 292.0 (M+, 100). Anal. Calcd for C12H13-
FeNO4: C, 49.52; H, 4.50; N, 4.82. Found: C, 49.59; H, 4.40; N, 4.80.
(2RS,5SR,6SR,2E,4E)-Tricarbonyliron[(η4-2-5)-6-benzyloxyhepta-
2,4-dienenitrile] (6C). Entry 3. The reaction of 5 (59.2 mg, 0.148
mmol) with BnOH according to the typical procedure and purification
by column chromatography (SiO2, hexane/AcOEt ) 4:1) gave 6C (20.5
mg, 39%) as a yellow oil: 1H NMR (CDCl3) δ 0.30 (d, 1H, J ) 7.6

Functionalization of Acyclic Diene Ligands
J. Am. Chem. Soc., Vol. 121, No. 39, 1999 9151
Hz), 1.33 (m, 1H), 1.37 (d, 3H, J ) 5.9 Hz), 3.70 (dq, 1H, J ) 5.6, 5.9
Hz), 4.39 (d, 1H, J ) 12.0 Hz), 4.63 (d, 1H, J ) 12.0 Hz), 5.45 (dd,
1H, J ) 5.1, 8.9 Hz), 5.55 (dd, 1H, J ) 5.0, 7.6 Hz), 7.23-7.36 (m.
5H); 13C NMR (75.5 MHz, CDCl3) δ 22.2, 23.4, 70.4, 70.6, 74.0, 80.7,
85.0, 121.6, 127.6, 127.7, 128.4, 137.9, 206.3; IR (KBr) 2218, 2062,
1990 cm-1; MS (EI) m/z (relative intensity) 325 (M+ - CO, 3.5), 269
(M+ - 3CO, 100); HRMS calcd for C17H16FeNO4 354.0429 (FAB,
M + H), found 354.0421.
to the typical procedure and purification of the crude mixture by column
chromatography gave a 90:10 mixture of 7E and 6E (10.7 mg, 32%).
Entry 4. The reaction of 5 (43.7 mg, 0.109 mmol) with TMSN3
(0.14 mL, 1.09 mmol) and BF3‚Et2O (2.3 µL, 10.9 µmol) according to
the typical procedure and purification of the crude mixture by column
chromatography gave 7E (18.3 mg, 58%) as yellow crystals: mp 73-
74 °C (hexane/AcOEt); 1H NMR (CDCl3) δ 1.37 (d, 3H, J ) 6.3 Hz),
1.49 (d, 1H, J ) 7.3 Hz), 2.72 (dd, 1H, J ) 7.5, 7.5 Hz), 2.83 (dq, 1H,
J ) 7.5, 6.3 Hz), 5.40 (dd, 1H, J ) 6.4, 7.5 Hz), 5.85 (dd, 1H, J )
6.4, 7.3 Hz); 13C NMR (75.5 MHz, CDCl3) δ 21.7, 25.5, 57.8, 61.6,
(2RS,5SR,6SR,2E,4E)-Tricarbonyliron[(η4-2-5)-6-phenylthiohepta-
2,4-dienenitrile] (6D). Entry 4. The reaction of 5 (65.2 mg, 0.163
mmol) with PhSH (0.042 mL, 0.408 mmol) and TrClO4 (61.2 mg, 0.179
mmol) in dry CH2Cl2 (1.6 mL) according to the typical procedure and
purification by preparative TLC (hexane/CH2Cl2) 1:1 × 3) gave 6D
85.0, 93.2, 121.0, 205.5; IR (KBr) 2220, 2100, 2067, 2003, 1996 cm-1
;
MS (CI) m/z (relative intensity) 289.0 (M+ + 1, 100). Anal. Calcd for
C10H8FeN4O3: C, 41.70; H, 2.80; N, 19.45. Found: C, 41.74 H, 2.93;
N, 19.46.
1
(14.4 mg, 25%) as yellow crystals: mp 124 °C (hexane); H NMR
(2RS,5RS,6RS,2E,4Z)-Tricarbonyliron[(η4-2-5)-6-methoxyhepta-
2,4-dienenitrile] (7A). Entry 5. The reaction of 5 (163 mg, 0.408
mmol) with methanol (0.17 mL, 4.08 mmol) and LiClO4 (47.9 mg,
0.448 mmol) according to the typical procedure and purification of
the crude mixture by column chromatography (SiO2, hexane/AcOEt )
4:1) gave an 84:16 mixture of 7A and 6A (56.4 mg, 51%).
Entry 7. The reaction of 5 (197 mg, 0.494 mmol) with methanol
(0.20 mL, 4.94 mmol) and BF3‚Et2O (6.3 µL, 49 µmol) according to
the typical procedure and purification of the crude mixture by column
chromatography (SiO2, hexane/AcOEt ) 4:1) gave 7A (70.9 mg, 52%)
(CDCl3) δ 0.43 (d, 1H, J ) 7.9 Hz), 1.22-1.26 (m, 1H), 1.48 (d, 3H,
J ) 7.3 Hz), 2.90 (dq, 1H, J ) 3.7, 7.3 Hz), 4.63 (dd, 1H, J ) 4.9, 9.2
Hz), 5.36 (dd, 1H, J ) 4.9, 7.9 Hz), 7.28-7.45 (m, 5H); 13C NMR
(75.5 MHz, CDCl3) δ 23.1, 24.4, 48.9, 69.1, 81.3, 86.6, 121.1, 128.8,
129.2, 132.9, 135.2, 205.1; IR (KBr) 2220, 2062, 1996 cm-1; MS (EI)
m/z (relative intensity) 355 (M+, 0.7), 327 (14), 299 (8), 271 (71), 161
(100). Anal. Calcd for C16H13FeNO3S: C, 54.11; H, 3.69; N, 3.94; S,
9.03. Found: C, 54.09; H, 3.74; N, 3.93; S, 8.98.
(2RS,5SR,6SR,2E,4E)-Tricarbonyliron[(η4-2-5)-6-azidohepta-
2,4-dienenitrile] (6E). Entry 5. The reaction of 5 (62.0 mg, 0.155
mmol) with TMSN3 (206 µL, 1.55 mmol) and TrClO4 (57.8 mg, 0.170
mmol) in THF according to the typical procedure and purification by
column chromatography (SiO2, hexane/AcOEt ) 7:1) gave 6E (25.1
mg, 56%).
Entry 6. The reaction of 5 (57.1 mg, 0.143 mmol) with TMSN3 (48
µL, 0.358 mmol) and AgClO4 (32.6 mg, 0.157 mmol) in CH2Cl2 at
room temperature for 3 h according to the typical procedure and
purification by column chromatography (SiO2, hexane/AcOEt ) 7:1)
gave 6E (17.9 mg, 43%).
Entry 7. The reaction of 5 (60.4 mg, 0.151 mmol) with TMSN3 (50
µL, 0.378 mmol) and TrClO4 (5.2 mg, 0.015 mmol) in THF according
to the typical procedure and purification by column chromatography
(SiO2, hexane/AcOEt ) 7:1) gave 7E (20.4 mg, 47%).
1
as yellow crystals: mp 46 °C (hexane/AcOEt); H NMR (CDCl3) δ
1.35 (d, 3H, J ) 5.8 Hz), 1.56 (d, 1H, J ) 7.9 Hz), 2.60 (dd, 1H, J )
8.1, 9.7 Hz), 2.80 (dq, 1H, J ) 9.7, 5.8 Hz), 3.23 (s, 3H), 5.38 (dd,
1H, J ) 5.3, 8.1 Hz), 5.85 (dd, 1H, J ) 5.3, 7.9 Hz); 13C NMR (75.5
MHz, CDCl3) δ 22.3, 24.7, 55.3, 63.2, 76.4, 86.5, 92.0, 121.4, 203.4;
IR (KBr) 2220, 2064, 1998 cm-1; MS (CI) m/z (relative intensity) 278.0
(M+ + 1, 71), 246.0 (100). Anal. Calcd for C11H11FeNO4: C, 47.69;
H, 4.00; N, 5.06. Found: C, 47.83; H, 4.00; N, 5.11.
(2RS,5RS,6RS,2E,4Z)-Tricarbonyliron[(η4-2-5)-6-ethoxyhepta-
2,4-dienenitrile] (7B). Entry 6. The reaction of 5 (83.6 mg, 0.209
mmol) with ethanol (0.12 mL, 2.09 mmol) and LiClO4 (24.5 mg, 0.223
mmol) according to the typical procedure and purification of the crude
mixture by column chromatography (SiO2, hexane/AcOEt ) 5:1) gave
an 83:17 mixture of 7B and 6B (32.1 mg, 53%).
Entry 8. The reaction of 5 (72.2 mg, 0.181 mmol) with EtOH (0.11
mL, 1.81 mmol) and BF3‚Et2O (2.7 µL, 18.1 µmol) at 0 °C according
to the typical procedure and purification of the crude mixture by column
chromatography (SiO2, hexane/AcOEt ) 4:1) gave 7B (28.4 mg, 54%)
as yellow crystals: mp 46-47 °C (hexane); 1H NMR (CDCl3) δ 1.12
(t, 3H, J ) 6.7 Hz), 1.35 (d, 3H, J ) 6.1 Hz), 1.60 (d, 1H, J ) 7.9,
Hz), 2.60 (dd, 1H, J ) 8.5, 9.2 Hz), 2.81 (dq, 1H, J ) 9.1, 6.1 Hz),
3.11 (dq, 1H, J ) 13.4, 6.7 Hz), 3.53 (dq, 1H, J ) 13.4, 6.7 Hz), 5.36
(dd, 1H, J ) 4.9, 8.5 Hz), 5.84 (dd, 1H, J ) 4.9, 7.9 Hz); 13C NMR
(67.8 MHz, CDCl3) δ 15.2, 22.7, 24.5, 63.1, 63.8, 74.5, 86.3, 92.1,
121.5, 206.7; IR (KBr) 2206, 2065, 1992 cm-1; MS (CI) m/z (relative
intensity) 292.0 (M+, 25), 69.0 (100). Anal. Calcd for C12H13FeNO4:
C, 49.52; H, 4.50; N, 4.82. Found: C, 49.52; H, 4.52; N, 4.83.
(2RS,5RS,6RS,2E,4Z)-Tricarbonyliron[(η4-2-5)-6-benzyloxyhepta-
2,4-dienenitrile] (7C). Entry 9. The reaction of 5 (80.0 mg, 0.200
mmol) with BnOH (0.21 mL, 2.00 mmol) and BF3‚Et2O (2.5 µL, 20.0
µmol) at 0 °C according to the typical procedure and purification of
the crude mixture by column chromatography (SiO2, hexane/AcOEt )
4:1) gave 7C (29.6 mg, 42%) as a yellow oil: 1H NMR (CDCl3) δ
1.39 (d, 1H, J ) 6.0, Hz), 1.40 (d, 3H, J ) 6.0 Hz), 2.65 (dd, 1H, J )
7.7, 9.2 Hz), 2.87 (dq, 1H, J ) 9.2, 6.0 Hz), 4.23 (d, 1H, J ) 12.0
Hz), 4.40 (d, 1H, J ) 12.0 Hz), 5.38 (dd, 1H, J ) 6.2, 7.7 Hz), 5.84
(dd, 1H, J ) 6.0, 6.2 Hz), 7.23-7.36 (m. 5H); 13C NMR (75.5 MHz,
CDCl3) δ 22.6, 24.5, 63.5, 69.5, 73.7, 86.4, 92.1, 121.4, 127.7, 127.9,
128.5, 137.6, 207.3; IR (KBr) 2220, 2067, 1998 cm-1; MS (EI) m/z
(relative intensity) 325 (M+ - CO, 0.6), 297 (3.3), 269 (100). Anal.
Calcd for C17H15FeNO4: C, 57.82; H, 4.30; N, 4.00. Found: C, 57.92;
H, 4.26; N, 4.08.
Entry 8. The reaction of 5 (159 mg, 0.398 mmol) with TMSN3 (134
µL, 1.01 mmol) and AgClO4 (91.8 mg, 0.443 mmol) in CH2Cl2 at 0
°C for 10 min according to the typical procedure and purification by
column chromatography (SiO2, hexane/AcOEt ) 4:1) gave 7E (69.1
1
mg, 60%) as yellow crystals: mp 48 °C (hexane/AcOEt); H NMR
(CDCl3) δ 0.53 (d, 1H, J ) 8.1 Hz), 1.12 (dd, 1H, J ) 7.5, 8.6 Hz),
1.43 (d, 3H, J ) 7.0 Hz), 3.33 (dq, 1H, J ) 7.5, 7.0 Hz), 5.43 (dd, 1H,
J ) 5.2, 8.6 Hz), 5.65 (dd, 1H, J ) 5.2, 8.1 Hz); 13C NMR (67.8 MHz,
CDCl3) δ 21.7, 24.9, 60.1, 63.8, 82.9, 86.6, 120.8, 205.4. IR (KBr)
2220, 2100, 2067, 2003, 1986 cm-1; MS (EI) m/z (relative intensity)
289 (M+, 53), 261 (14), 108 (100). Anal. Calcd for C10H8FeN4O3: C,
41.70; H, 2.80; N, 19.45. Found: C, 41.77 H, 2.87; N, 19.45.
General Procedure for Nucleophilic Substitution of 5 to 7A-E
(Table 3). The appropriate nucleophile (10 equiv) and Lewis acid (1.1
or 0.1 equiv) were successively added to a stirred solution of 5 in dry
ether or THF (0.10 M solution) at 0 °C under a nitrogen atmosphere,
and the resulting mixture was allowed to warm slowly to room
temperature. After 16 h, a saturated NaHCO3 solution was added to
the reaction mixture, and the resulting mixture was extracted with
AcOEt. The extract was washed with brine, dried over MgSO4, and
then concentrated in vacuo to give the crude mixture.
(2RS,5RS,6RS,2E,4Z)-Tricarbonyliron[(η4-2-5)-6-azidohepta-
2,4-dienylnitrile] (7E). Entry 1. The reaction of 5 (51.9 mg, 0.130
mmol) with TMSN3 (0.18 mL, 1.30 mmol) and LiClO4 (15.5 mg, 0.143
mmol) according to the typical procedure and purification of the crude
mixture by column chromatography (SiO2, hexane/AcOEt ) 4:1) gave
7E (22.4 mg, 60%).
Entry 2. The reaction of 5 (40.1 mg, 0.100 mmol) with TMSN3 (33
µL, 0.251 mmol) and TrBF4 (36.3 mg, 0.110 mmol) according to the
typical procedure and purification of the crude mixture by column
chromatography gave a 90:10 mixture of 7E and 6E (6.2 mg, 22%).
(2RS,5RS,6RS,2E,4Z)-Tricarbonyliron[(η4-2-5)-6-phenylthiohepta-
2,4-dienenitrile] (7D). Entry 10. The reaction of 5 (62.6 mg, 0.157
mmol) with PhSH (0.16 mL, 1.57 mmol) and BF3‚Et2O (2.0 µL, 15.7
µmol) at 0 °C according to the typical procedure and purification of
the crude mixture by column chromatography (SiO2, hexane/AcOEt )
Entry 3. The reaction of 5 (46.5 mg, 0.117 mmol) with TMSN3 (39
µL, 0.291 mmol) and HClO4 (1 M in ether solution, 0.05 mL) according

9152 J. Am. Chem. Soc., Vol. 121, No. 39, 1999
Takemoto et al.
8:1) gave 7D (30.3 mg, 54%) as yellow crystals: mp 108 °C (hexane);
1H NMR (CDCl3) δ 1.23 (d, 1H, J ) 7.0 Hz), 1.48 (d, 3H, J ) 6.2
Hz), 2.58 (dq, 1H, J ) 8.8, 6.2 Hz), 2.78 (dd, 1H, J ) 7.1, 8.8 Hz),
4.72 (dd, 1H, J ) 6.4, 7.1 Hz), 5.31 (dd, 1H, J ) 6.4, 7.0 Hz), 7.50
(m, 5H);13C NMR (75.5 MHz, CDCl3) δ 22.3, 24.8, 46.4, 66.8, 84.2,
91.0, 121.3, 128.7, 129.0, 133.9, 135.0, 207.5; IR (KBr) 2219, 2063,
2007, 1984 cm-1; MS (CI) m/z (relative intensity) 356.0 (M+ + 1,
73), 108.0 (100); HRMS calcd for C16H13FeNO3S 354.9966, found
354.9969.
(2RS,5SR,6SR,2E,4E)-Tricarbonyliron[(η4-2-5)-6-azidohepta-
2,4-dienal] (8). To a stirred solution of 6E (2.70 g, 9.37 mmol) in dry
CH2Cl2 (50 mL) was added DIBAL-H (1.01 M in toluene, 12.1 mL,
12.19 mmol) at -78 °C under a nitrogen atmosphere. After 5 min, a
saturated potassium sodium tartrate solution (15 mL) was added to the
reaction mixture at -78 °C, and the resulting mixture was stirred at
room temperature. The mixture was extracted with AcOEt, and the
extract was washed with brine, dried over MgSO4, and then concentrated
in vacuo. The residue was purified by column chromatography (SiO2,
hexane/AcOEt ) 5:1) to give 8 (2.40 g, 88%) as a yellow oil: 1H
NMR (CDCl3) δ 1.39 (m, 2H), 1.44 (d, 3H, J ) 6.8 Hz), 3.35 (dq, 1H,
J ) 7.7, 6.8 Hz), 5.48 (dd, 1H, J ) 6.6, 6.8 Hz), 5.89 (dd, 1H, J )
6.4, 6.6 Hz), 9.37 (d, 1H, J ) 3.4 Hz); 13C NMR (67.8 MHz, CDCl3)
δ 21.5, 55.0, 60.4, 64.0, 82.9, 86.4, 195.5, 207.2; IR (KBr) 2118, 2065,
2017, 1691 cm-1; MS (EI) m/z (relative intensity) 291 (M+, 100). Anal.
Calcd for C10H9FeN3O4: C, 41.27; H, 3.12; N, 14.44. Found: C, 41.16;
H, 3.07; N, 14.62.
a solution of 14 (5.0 g, 20.0 mmol) in dry toluene (90 mL) were
successively added to the reaction mixture. The resulting mixture was
allowed to warm slowly to 0 °C and stirried at 0 °C for 1 h. After
being quenched with a 2 M aqueous HCl solution (80 mL), the mixture
was extracted with AcOEt. The extract was washed with brine, dried
over MgSO4, and concentrated in vacuo. The crude residue was purified
by column chromatography (SiO2, CHCl3/acetone ) 20:1 to 10:1) to
give 14 (0.59 g, 12%), a diastereomer of 16 (0.37 g, 7%), and 16 (3.82
g, 71%). 16: yellow crystals; mp 72-73 °C (hexane/benzene); [R]25
D
+163.5 (c ) 1.03, CHCl3); 1H NMR (CDCl3) δ 1.34 (dd, 1H, J ) 4.3,
8.1 Hz), 1.42 (d, 3H, J ) 6.0 Hz), 1.51-1.54 (m, 1H), 1.64 (d, 1H,
J ) 4.3 Hz), 3.78 (m, 1H), 5.55 (dd, 1H, J ) 4.7, 9.0 Hz), 5.84 (dd,
1H, J ) 4.7, 8.1 Hz), 9.32 (d, 1H, J ) 4.3 Hz); 13C NMR (67.8 MHz,
CDCl3) δ 25.7, 54.9, 68.8, 69.6, 82.4, 86.6, 196.2, 207.2; IR (KBr)
3398, 2059, 1988, 1673 cm-1; MS (EI) m/z (relative intensity) 238
(M+ - CO, 8.5), 210 (19), 182 (32), 81 (100). Anal. Calcd for C10-
H10FeO5: C, 45.15; H, 3.79. Found: C, 45.17; H,3.77. The diastereomer
of 16: a yellow oil; [R]26D +30.8 (c ) 1.31, CHCl3); 1H NMR (CDCl3)
δ 1.23 (dd, 1H, J ) 4.3, 8.5 Hz), 1.41 (d, 3H, J ) 6.0 Hz), 1.47 (d,
1H, J ) 3.4 Hz), 1.62 (dd, 1H, J ) 6.0, 8.6 Hz), 3.97-4.01 (m, 1H),
5.49 (dd, 1H, J ) 5.1, 8.6 Hz), 5.84 (dd, 1H, J ) 5.1, 8.5 Hz), 9.32 (d,
1H, J ) 4.3 Hz); 13C NMR (67.8 MHz, CDCl3) δ 26.5, 54.5, 68.4,
72.5, 81.1, 85.0, 196.0, 208.4; IR (KBr) 3453, 2973, 2057, 1996, 1678
cm-1; MS (EI) m/z (relative intensity) 266 (M+, 5.4), 238 (7.2), 210
(16), 182 (21), 81 (100); HRMS calcd for C10H10FeO5 265.9877, found
265.9890.
(2S,5R,6R,2E,4E)-Tricarbonyliron[(η4-2-5)-6-acetoxyhepta-2,4-
dienal] (17). To a stirred solution of 14 (3.47 g, 13.04 mmol) in a
mixture of pyridine (6 mL) and CH2Cl2 (6 mL) were added (dimeth-
ylamino)pyridine (79.7 mg, 0.652 mmol) and Ac2O (1.48 mL, 15.65
mmol) at 0 °C under a nitrogen atmosphere. After the resulting mixture
was stirred at room temperature for 2.5 h, solvents were evaporated.
The residue was purified by column chromatography (SiO2, hexane/
AcOEt ) 5:1 to 3:1) to give 17 (3.21 g, 80%) as yellow crystals: mp
54-55 °C (hexane); [R]25D +170 (c ) 1.84, CHCl3); 1H NMR (CDCl3)
δ 1.36 (dd, 1H, J ) 4.3, 8.5 Hz), 1.40-1.44 (m, 1H), 1.43 (d, 3H,
J ) 6.1 Hz), 2.05 (s, 3H), 4.81 (dq, 1H, J ) 8.5, 6.1 Hz), 5.68 (dd,
1H, J ) 4.9, 8.5 Hz), 5.82 (dd, 1H, J ) 4.9, 8.5 Hz), 9.34 (d, 1H, J )
4.3 Hz); 13C NMR (67.8 MHz, CDCl3) δ 21.3, 22.1, 55.1, 64.0, 71.9,
(2RS,5RS,6RS,7SR,2E,4Z)-Tricarbonyliron[(η4-2-5)-7-azido-6-
methoxyocta-2,4-dienenitrile] (syn-11). To a stirred solution of 8 (33.2
mg, 0.114 mmol) in dry THF (1.2 mL) were added DEPC (0.021 mL,
0.137 mmol) and LiCN (1.9 mg, 0.0570 mmol) at room temperature
under a nitrogen atmosphere. After 15 min, a saturated NaHCO3 solution
was added to the reaction mixture, and the resulting mixture was
extracted with AcOEt. The extract was washed with brine, dried over
MgSO4, and then concentrated in vacuo to give the crude 9 as a yellow
oil. To a stirred solution of 9 (51.2 mg, 0.114 mmol) in dry MeOH
(1.2 mL) was added BF3‚Et2O (1.4 µL, 11.4 µmol) at 0 °C under a
nitrogen atmosphere. After 2 h, a saturated NaHCO3 solution was added
to the reaction mixture, and the resulting mixture was extracted with
AcOEt. The extract was washed with brine, dried over MgSO4, and
then concentrated in vacuo. The residue was purified by column
chromatography (SiO2, hexane/AcOEt ) 4:1) to give 11 (20.0 mg, 53%)
as a yellow oil: 1H NMR (CDCl3) δ 1.32 (d, 1H, J ) 6.8 Hz), 1.35 (d,
3H, J ) 6.8 Hz), 2.49 (dd, 1H, J ) 3.4, 9.4 Hz), 2.74 (dd, 1H, J )
8.5, 9.4 Hz), 3.17 (s, 3H), 3.67 (dq, 1H, J ) 3.4, 6.8 Hz), 5.45 (dd,
1H, J ) 5.1, 6.8 Hz), 5.88 (dd, 1H, J ) 5.1, 8.5 Hz); 13C NMR (67.8
MHz, CDCl3) δ 15.5, 24.8, 56.7, 57.3, 59.5, 82.3, 86.1, 92.5, 121.2;
IR (KBr) 2220, 2116, 2065, 1998 cm-1; MS (EI) m/z (relative intensity)
276 (M+ - 2CO, 33), 250 (M+ - 3CO, 100); HRMS calcd for C12H12-
FeN4O4 332.0206, found 332.0188.
(2RS,5SR,6SR,7SR,2E,4E)-Tricarbonyliron[(η4-2-5)-7-azido-6-
methoxyocta-2,4-dienenitrile] (anti-10). To a stirred solution of 9 (509
mg, 1.12 mmol) in dry THF (12 mL) were added MeOH (0.45 mL,
11.2 mmol) and TrClO4 (419 mg, 1.31 mmol) at room temperature
under a nitrogen atmosphere. After 2 h, a saturated NaHCO3 solution
was added to the reaction mixture, and the resulting mixture was
extracted with AcOEt. The extract was washed with brine, dried over
MgSO4, and then concentrated in vacuo. The residue was purified by
column chromatography (SiO2, hexane/AcOEt ) 4:1) to give 10 (191
mg, 52%) as a yellow oil: 1H NMR (CDCl3) δ 0.42 (d, 1H, J ) 7.1
H), 1.02 (dd, 1H, J ) 4.1, 4.2 Hz), 1.26 (d, 3H, J ) 5.7 Hz), 3.29 (dd,
1H, J ) 4.1, 5.3 Hz), 3.40 (s, 3H), 3.70 (dq, 1H, J ) 5.3, 5.7 Hz),
5.58 (dd, 1H, J ) 4.2, 5.4 Hz), 5.63 (dd, 1H, J ) 5.4, 7.1 Hz); 13C
NMR (67.8 MHz, CDCl3) δ 14.1, 24.1, 57.6, 59.1, 60.2, 81.4, 83.3,
86.2, 121.2, 207.2; IR (KBr) 2218, 2109, 2056, 2011 cm-1; MS (CI)
m/z (relative intensity) 333.0 (M+ + 1, 100); HRMS calcd for C12H13-
FeN4O4 333.0286 (FAB, M + H), found 333.0288.
82.7, 87.4, 170.4, 195.7, 209.2; IR (KBr) 2062, 1986, 1731, 1681 cm-1
;
MS (EI) m/z (relative intensity) 280 (M+ - CO, 6.4), 224 (100). Anal.
Calcd for C12H12FeO6: C, 46.78; H, 3.93. Found: C, 47.07; H, 3.96.
(2S,5R,6R,2E,4E)-Tricarbonyliron[(η4-2-5)-6-azidohepta-2,4-di-
enenitrile] (+)-6E. To a stirred solution of 17 (3.21 g, 10.42 mmol)
in dry CH2Cl2 (22 mL) were added TMSN3 (2.9 mL, 20.84 mmol) and
Sc(OTf)3 (512.8 mg, 1.042 mmol) at 0 °C under a nitrogen atmosphere.
The resulting mixture was stirred at 0 °C for 1.5 h and at room
temperature for 20 min. After water (20 mL) was added to the reaction
mixture, the resulting mixture was extracted with AcOEt. The extract
was washed with brine, dried over MgSO4, and then concentrated in
vacuo. The residue was purified by column chromatography (SiO2,
hexane/AcOEt ) 5:1) to give (+)-6F (2.76 g, 92%): [R]26 +91.7
D
(c ) 0.84, CHCl3).
(2S,5R,6R,2E,4E)-Tricarbonyliron[(η4-2-5)-6-azidohepta-2,4-di-
enal] (+)-8. The chiral nitrile (+)-6E was treated by the same procedure
as described for the racemic 6E to give (+)-8 (4.60 g, 88%) as a yellow
oil: [R]25 +183.6 (c ) 1.13, CHCl3).
D
(2S,5R,6R,7R,2E,4E)-Tricarbonyliron[(η4-2-5)-7-azido-6-meth-
oxyocta-2,4-dienylnitrile] ((+)-10). The chiral aldehyde (+)-8 was
treated by the same procedure as described for the racemic 8 to give
(+)-10 (1.04 g, 52%) as a yellow oil. [R]25D +61.6 (c ) 0.95, CHCl3).
(2S,5R,6R,7R,2E,4E)-Tricarbonyliron[(η4-2-5)-7-azido-6-meth-
oxyocta-2,4-dienal] ((+)-18). The same treatment of (+)-10 (286 mg,
0.861 mmol) as described for 8 gave an oily residue, which was purified
by column chromatography (SiO2, hexane/AcOEt ) 4:1) to give (+)-
18 (221 mg, 77%) as a yellow oil: [R]25D +108 (c ) 0.75, CHCl3); 1H
NMR (CDCl3) δ 1.26-1.35 (m, 2H), 1.30 (d, 3H, J ) 6.8 Hz), 3.29
(dd, 1H, J ) 2.6, 5.1 Hz), 3.42 (s, 3H), 3.68 (dq, 1H, J ) 2.6, 6.8 Hz),
5.62 (dd, 1H, J ) 5.1, 8.6 Hz), 5.88 (dd, 1H, J ) 5.1, 8.2 Hz), 9.34 (d,
1H, J ) 4.0 Hz); 13C NMR (67.8 MHz, CDCl3) δ 13.8, 54.7, 57.6,
59.5, 60.3, 81.8, 83.9, 86.3, 195.9, 208.3; IR (KBr) 2106, 2060, 1990,
(2S,5R,6R,2E,4E)-Tricarbonyliron[(η4-2-5)-6-hydroxyhepta-2,4-
dienal] (16). A solution of 15 (227 mg, 0.600 mmol) and Ti(Oi-Pr)4
(10.7 mL, 36.0 mmol) in dry toluene (50 mL) was stirred at 50 °C for
30 min under a nitrogen atmosphere. After the mixture was cooled to
-78 °C, a 1.0 M solution of Me2Zn (36 mL, 36 mmol) in hexane and

Functionalization of Acyclic Diene Ligands
J. Am. Chem. Soc., Vol. 121, No. 39, 1999 9153
1687 cm-1; MS (EI) m/z (relative intensity) 335 (M+, 62), 306 (100).
Anal. Calcd for C12H13FeN3O5: C, 43.01; H, 3.91; N, 12.54. Found:
C, 43.31; H, 4.04; N, 12.60.
(s, 3H), 3.83 (m, 1H), 4.73 (br, 1H), 5.03 (dd, 1H, J ) 5.1, 8.6 Hz),
5.16 (dd, 1H, J ) 5.1, 8.6 Hz), 5.36-5.37 (m, 2H); 13C NMR (67.8
MHz, CDCl3) δ 14.0, 14.7, 22.4, 22.7, 28.4, 31.4, 34.6, 47.8, 56.7,
57.7, 58.4, 79.2, 82.9, 84.4, 84.7, 130.1, 132.2, 155.2, 212.0; IR (KBr)
3448, 2038, 1971, 1708, 1646 cm-1; MS (EI) m/z (relative intensity)
422 (M+ + 1 - 2CO, 3.2), 394 (26), 348 (18), 320 (100); HRMS
calcd for C21H35FeNO4 (M+ - 2CO) 421.1915, found 421.1915.
(2R,3S,5R,8S,5E,7E)-Tricarbonyliron[(η4-5-7)-2-(tert-butoxycar-
bonylamino)-3-methoxytetradodeca-5,7-diene] ((+)-23). A mixture
of (-)-22 (18.3 mg, 0.0383 mmol), 10% Pd/C (4.1 mg), and dry MeOH
(1 mL) was vigorously stirred at room temperature under a medium-
pressured hydrogen atmosphere (3 atm) for 12 h. The reaction mixture
was filtered off through a pad of Celite, and the filtrate was concentrated
in vacuo. The residue was purified by column chromatography (SiO2,
hexane/AcOEt ) 8:1) to give (+)-23 (14.9 mg, 81%) as a yellow oil:
[R]24D +27.1 (c ) 0.81, CHCl3); 1H NMR (CDCl3) δ 0.89 (t, 3H, J )
6.8 Hz), 1.07 (d, 3H, J ) 6.6 Hz), 1.25-1.35 (m, 10H), 1.45 (s, 9H),
1.60-1.96 (m, 4H), 3.17 (m, 1H), 3.37 (s, 3H), 3.81 (m, 1H), 4.77 (br,
1H), 5.01 (m, 2H); 13C NMR (67.8 MHz, CDCl3) δ 14.1, 14.5, 22.6,
28.4, 29.0, 31.6, 32.1, 34.3, 34.5, 47.7, 56.8, 58.1, 64.8, 79.2, 84.0,
84.6, 84.7, 156.2, 212.3. IR (KBr): 3450, 2038, 1965, 1716 cm-1; MS
(EI) m/z (relative intensity) 424 (M+ + 1 - 2CO, 0.6), 396 (33), 350
(12), 322 (100); HRMS calcd for C21H37FeNO (M+ - 2CO) 423.2071,
found 423.2076.
(2S,5R,6R,17R,8R,2E,4E)-Tricarbonyliron[(η4-2-5)-8-azido-6-
ethylthio-7-methoxynona-2,4-dienenitrile] ((+)-19). The same treat-
ment of (+)-18 (114 mg, 0.34 mmol) with DEPC (0.078 mL, 0.512
mmol) and LiCN (5.6 mg, 0.171 mmol) as described for syn-11 gave
the crude cyanophosphate, which was subjected to EtSH (0.25 mL,
3.40 mmol) and TrClO4 (128 mg, 0.374 mmol). Similar workup of the
reaction mixture and purification by column chromatography (SiO2,
hexane/AcOEt ) 6:1) afforded (+)-19 (83.4 mg, 61%) as yellow
crystals: mp 42 °C (petroleum ether/benzene); [R]25D +71.0 (c ) 1.14,
1
CHCl3); H NMR (CDCl3) δ 0.53 (d, 1H, J ) 7.9 Hz), 1.28 (t, 3H,
J ) 7.3 Hz), 1.44 (d, 3H, J ) 6.7 Hz), 1.61 (dd, 1H, J ) 9.2, 9.2 Hz),
2.63 (dq, 1H, J ) 4.9, 7.9 Hz), 2.70 (dq, 1H, J ) 4.9, 7.9 Hz), 2.82
(dd, 1H, J ) 3.1, 9.2 Hz), 3.14 (dd, 1H, J ) 3.1, 7.9 Hz), 3.48 (s, 3H),
3.96 (dq, 1H, J ) 7.9, 6.7 Hz), 5.48 (dd, 1H, J ) 4.9, 9.2 Hz), 5.57
(dd, 1H, J ) 4.9, 7.2 Hz); 13C NMR (67.8 MHz, CDCl3) δ 14.5, 15.8,
24.6, 26.5, 44.9, 58.0, 60.0, 63.6, 81.6, 86.9, 88.4, 121.1, 207.2; IR
(KBr) 2218, 2109, 2056, 2011 cm-1; MS (EI) m/z (relative intensity)
350 (M+ - 2CO, 37), 322 (47), 191 (100); HRMS calcd for C13H18-
FeN4O2S (M+ - 2CO) 350.0499, found 350.0495.
(2S,5R,7S,8R,2E,4E)-Tricarbonyliron[(η4-2-5)-8-(tert-butoxycar-
bonylamino)-7-methoxynona-2,4-dienenitrile] ((+)-20). A mixture
of (+)-19 (20.0 mg, 0.0492 mmol), 10% Pd/C (12.5 mg), Boc2O (33.9
µL, 0.148 mmol), and dry MeOH (1 mL) was vigorously stirred at
room temperature under a medium-pressured hydrogen atmosphere (5
atm) for 24 h. The reaction mixture was filtered off throuth a pad of
Celite, and the filtrate was concentrated in vacuo. The residue was
purified by column chromatography (SiO2, hexane/AcOEt ) 4:1) to
(2R,3S,5E,7E)-2-(tert-Butoxycarbonylamino)-3-methoxytetra-
dodeca-5,7-diene ((-)-24). A mixture of (+)-23 (7.8 mg, 0.0163
mmol), anhydrous Me3NO (9.8 mg, 0.130 mmol), and dry benzene
(0.8 mL) was stirred at 60 °C for 1 h under a nitrogen atmosphere.
The reaction mixture was filtered through a pad of Celite, and the filtrate
was concentrated in vacuo. The residue was purified by column
chromatography (SiO2, hexane/AcOEt ) 8:1) to give (-)-24 (4.8 mg,
give (+)-20 (17.6 mg, 85%) as yellow crystals: mp 143 °C (hexane/
1
87%) as a pale yellow oil: [R]26 -5.8 (c ) 0.21, CHCl3); H NMR
1
benzene); [R]25 +98.0 (c ) 0.98, CHCl3); H NMR (CDCl3) δ 0.49
D
D
(CDCl3) δ 0.88 (t, 3H, J ) 6.8 Hz), 1.06 (d, 3H, J ) 6.4 Hz), 1.26-
1.30 (m, 8H), 1.45 (s, 9H), 2.03-2.10 (m, 3H), 2.40 (ddd, 1H, J )
7.3, 7.3, 7.3 Hz), 3.26 (m, 1H), 3.39 (s, 3H), 3.75 (m, 1H), 4.80 (br,
1H), 5.50 (ddd, 1H, J ) 7.3, 7.3, 14.6 Hz), 5.59 (ddd, 1H, J ) 7.2,
7.2, 14.6 Hz), 5.97 (dd, 1H, J ) 10.3, 14.6 Hz), 6.06 (dd, 1H, J )
10.3, 14.6 Hz); 13C NMR (67.8 MHz, CDCl3) δ 14.1, 14.3, 22.6, 28.4,
28.9, 29.3, 31.7, 32.6, 33.9, 48.3, 58.2, 79.1, 83.1, 126.6, 129.9, 133.1,
133.7, 155.3; IR (KBr): 3375, 1713, 1660 cm-1; MS (EI) m/z (relative
intensity) 340 (M+ + 1, 0.9), 309 (2.1), 267 (7), 253 (100), 239 (10);
HRMS calcd for C20H38NO3 340.2852 (FAB, M + H), found 340.2849.
(2R,3S,5E,7E)-2-(tert-Butoxycarbonylamino)-3-methoxytetra-
dodeca-5,7-diene ((+)-24). To a stirred solution of (+)-26 (30.0 mg,
0.0821 mmol) in dry MeOH (0.5 mL) was added p-TsOH‚H2O (1.6
mg, 0.0821 mmol) at room temperature under a nitrogen atmosphere.
After 13 h, the solvent was concentrated in vacuo. The residue was
purified by column chromatography (SiO2, hexane/AcOEt ) 6:1 to 2:1)
to give the recovered starting material 26 (3.8 mg, 13%) and 27 (18.9
(d, 1H, J ) 7.1 Hz), 1.09 (d, 3H, J ) 6.8 Hz), 1.44 (s, 10H), 1.60
(ddd, 1H, J ) 5.8, 8.7, 14.3 Hz), 1.96 (ddd, 1H, J ) 5.5, 5.7, 14.3
Hz), 3.29 (m, 1H), 3.37 (s, 3H), 3.75 (m, 1H), 4.59 (br, 1H), 5.25 (dd,
1H, J ) 4.5, 5.5 Hz), 5.57 (dd, 1H, J ) 5.5, 7.1 Hz); 13C NMR (67.8
MHz, CDCl3) δ 15.3, 24.1, 28.3, 34.3, 47.7, 58.5, 60.1, 79.5, 81.6,
84.5, 88.9, 121.3, 155.2, 207.7; IR (KBr) 3356, 2220, 2060, 1994, 1701
cm-1; MS (EI) m/z (relative intensity) 365 (M+ + 1 - 2CO, 1.3), 337
(M+ + 1 - 3CO, 23), 59 (100). Anal. Calcd for C18H24FeN2O6: C,
51.45; H, 5.76; N, 6.67. Found: C, 51.71; H, 5.80; N, 6.66.
(2S,5R,7S,8R,2E,4E)-Tricarbonyliron[(η4-2-5)-8-(tert-butoxycar-
bonylamino)-7-methoxynona-2,4-dienal] ((+)-21). The same treat-
ment of (+)-20 (51.5 mg, 0.121 mmol) with DIBAL-H (1.0 M in
toluene, 0.303 mL, 0.303 mmol) as described for 8 gave the crude
mixture, which was purified by column chromatography (SiO2, hexane/
AcOEt ) 4:1) to give (+)-21 (40.5 mg, 78%) as yellow crystals: mp
118 °C (hexane); [R]25D +137.9 (c ) 0.98, CHCl3); 1H NMR (CDCl3)
δ 1.10 (d, 3H, J ) 6.0 Hz), 1.44 (s, 11H), 1.66-1.69 (m, 1H), 1.99-
2.04 (m, 1H), 3.23 (m, 1H), 3.40 (s, 3H), 3.81 (m, 1H), 4.66 (br, 1H),
5.31 (dd, 1H, J ) 4.7, 8.6 Hz), 5.81 (dd, 1H, J ) 4.7, 8.6 Hz), 9.31 (d,
1H, J ) 3.4 Hz); 13C NMR (67.8 MHz, CDCl3) δ 15.0, 28.4, 34.5,
47.9, 54.7, 58.5, 60.4, 79.4, 81.7, 84.6, 88.8, 155.2, 195.9, 208.9; IR
(KBr) 3348, 2055, 1988, 1687 cm-1; MS (EI) m/z (relative intensity)
339 (M+ - 3CO, 67), 59 (100). Anal. Calcd for C18H25FeNO7: C,
51.08; H, 5.95; N, 3.31. Found: C, 51.01; H, 5.89; N, 3.36.
mg, 71%) as colorless crystals. 27: mp 91-92 °C (hexane); [R]25
D
1
-15.4 (c ) 0.95, CHCl3); H NMR (CDCl3) δ 0.88 (t, 3H, J ) 6.7
Hz), 1.11 (d, 3H, J ) 6.77 Hz), 1.25-1.41 (m, 8H), 1.44 (s, 9H), 2.05
(dd, 1H, J ) 7.3, 14.0 Hz), 2.10 (m, 4H), 3.69 (m, 2H), 4.76 (br, 1H),
5.55 (ddd, 1H, J ) 7.3, 7.3, 14.6 Hz), 5.62 (ddd, 1H, J ) 7.3, 7.3,
14.6 Hz), 6.01 (dd, 1H, J ) 10.4, 14.6 Hz), 6.10 (dd, 1H, J ) 10.4,
14.6 Hz); 13C NMR (67.8 MHz, CDCl3) δ 14.2, 14.7, 22.7, 28.5, 29.0,
29.3, 31.8, 32.7, 37.2, 50.3, 73.7, 79.4, 126.7, 129.6, 133.8, 134.1, 155.6;
IR (KBr) 3351, 1682 cm-1; MS (FAB) 326 (M + H); HRMS calcd for
C19H36NO3 326.2695 (FAB, M + H), found 326.2708.
(2R,3S,5R,8S,5E,7E,9Z)-Tricarbonyliron[(η4-5-8)-2-(tert-butoxy-
carbonylamino)-3-methoxytetradodeca-5,7,9-triene] ((-)-22). A 1.5
M solution of n-BuLi in hexane (0.022 mL, 0.0325 mmol) was added
to a stirred suspension of C5H11PPh3Br (13.4 mg, 0.0325 mmol) in dry
toluene (0.25 mL) at 0 °C under a nitrogen atmosphere. After 5 min,
a solution of (+)-21 (5.5 mg, 0.0130 mmol) in dry toluene (0.5 mL)
was added to the mixture at -78 °C, and the resulting mixture was
stirred at -78 °C for 30 min and at 0 °C for 30 min. After being
quenched with water at 0 °C, the resulting mixture was extracted with
AcOEt. The extract was washed with brine, dried over MgSO4, and
then concentrated in vacuo. The residue was purified by column
chromatography (SiO2, hexane/AcOEt ) 7:1) to give (-)-22 (4.5 mg,
To a solution of (-)-27 (24.4 mg, 0.0750 mmol) in dry MeCN (1
mL) were added MeI (0.047 mL, 0.750 mmol) and Ag2O (40.0 mg,
0.188 mmol), and the resulting mixture was refluxed for 6 h under a
nitrogen atmosphere. The reaction mixture was filtered through a pad
of Celite, and the filtrate was concentrated in vacuo. The residue was
purified by column chromatography (SiO2, hexane/AcOEt ) 8:1) to
give (+)-24 (11.1 mg, 44%), along with the recovered starting material
27 (4.3 mg, 18%). (+)-24: pale yellow oil; [R]24 +4.2 (c ) 0.12,
D
CHCl3).
73%) as a yellow oil: [R]25 -296 (c ) 1.02, CHCl3); 1H NMR
D
Acknowledgment. This work was supported by the Grant-
in-Aid for Scientific Research on Priority Area of Reactive
(CDCl3) δ 0.92 (t, 3H, J ) 6.8 Hz), 1.09 (d, 3H, J ) 6.4 Hz), 1.25-
1.39 (m, 5H), 1.45 (s, 10H), 1.98-2.12 (m, 4H), 3.23 (m, 1H), 3.39

9154 J. Am. Chem. Soc., Vol. 121, No. 39, 1999
Takemoto et al.
Organometallics No.05236101 from the Ministry of Education,
Science, Sports and Culture, Japan.
28 (PDF). An X-ray crystallographic file, in CIF format, is also
available. This material is available free of charge via the
Internet at http://pubs.acs.org.
Supporting Information Available: 1H NMR spectra of
6A, 6D, 6E, 7A, 7D, 7E, 10, 11, 19, (-)-24, and (+)-24, and
X-ray structural information of the racemic N-Boc derivative
JA991889Q