Migratory insertion of isonitriles into titanacyclobutane complexes. A novel stereocontrolled synthesis of substituted cyclobutanimines

Article abstract of DOI:10.1021/om0110080

Migratory insertion of isonitriles into titanacyclobutane complexes was investigated. A stereocontrolled synthesis of substituted cyclobutanimines was also studied. Using the sterically crowded permethyltitanocene system, the intermediate iminoacyl complex is isolable and can be diverted by carbonylation to yield five-membered-ring enamidolate complexes.

Full text of DOI:10.1021/om0110080

Organometallics 2002, 21, 1011-1013
1011
Migr a tor y In ser tion of Ison itr iles in to Tita n a cyclobu ta n e
Com p lexes. A Novel Ster eocon tr olled Syn th esis of
Su bstitu ted Cyclobu ta n im in es
Grace Greidanus-Strom,† Charles A. G. Carter,‡ and J effrey M. Stryker*
Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2 Canada
Received November 21, 2001
Summary: Isonitrile migratory insertion into substituted
titanacyclobutane complexes provides for the stereocon-
trolled synthesis of synthetically valuable organic cy-
clobutanimines. Using the sterically crowded permeth-
yltitanocene system, the intermediate iminoacyl complex
is isolable and can be diverted by carbonylation to yield
five-membered-ring enamidolate complexes.
raising the possibility for greater control of post-inser-
tion reactivity. The synthesis of iminoacyl complexes by
isonitrile insertion in group 4 metal complexes is well-
precedented,5,6 including isolated examples of insertions
into the titanacyclobutane structural class.7 In this
communication, isonitrile insertion and subsequent
transformations in two series of titanacyclobutane
complexes are reported, culminating in a general syn-
thesis of stereochemically defined organic cyclobutan-
imines.
Exploratory reactions were conducted in the per-
methyltitanocene series. The addition of 1 equiv of
either tert-butyl isocyanide or cyclohexyl isocyanide to
3-isopropylbis(pentamethylcyclopentadienyl)titanacyclobu-
tane (1)1a at low temperature yields the iminoacyl
complexes 2a and 2b, respectively, in high yield (Scheme
1).8 Both complexes were isolated as thermally stable,
analytically pure brownish green cubes after recrystal-
lization from cold hexane. Although both iminoacyl
moieties are assigned as η1-coordinated on the basis of
infrared spectroscopy,9 the νCN band for the tert-butyl
complex 2a appears at 1588 cm-1, more than 20 cm-1
higher in energy than the corresponding band for the
The development of titanacyclobutane formation by
radical alkylation of (η3-allyl)titanium complexes has
raised considerable potential for generating new organic
methodology based on this reactivity pattern.1 The
conversion of titanacyclobutane complexes to organic
products can, in principle, be accomplished in a number
of ways, exploiting the polarized titanium-carbon bonds
to elaborate a range of stereochemically defined, highly
functionalized products. The most direct titanacyclobu-
tane transformations involve the migratory insertion of
unsaturated small molecules: we recently reported that
carbonylation of titanacyclobutanes can be controlled to
provide organic cyclobutanones2 and cyclopentenediolate
complexes,3,4 respectively, by single and double inser-
tions of carbon monoxide. The titanium cyclopentene-
diolate intermediates can be further converted to vari-
ous functionalized cyclopentanone derivatives.3
(5) Reviews: (a) Durfee, L. D.; Rothwell, I. P. Chem. Rev. 1988, 88,
1059. (b) Carnahan, E. M.; Protasiewicz, J . D.; Lippard, S. J . Acc. Chem.
Res. 1993, 26, 90.
Isonitrile migratory insertion, complementary to the
carbonylation reaction, potentially provides for the
direct introduction of nitrogen functionality into the
derived organic products.5 Although isoelectronic with
carbon monoxide, isonitriles can be modulated both
sterically and electronically via the nitrogen substituent,
(6) Recent and leading references for group
4 metal isonitrile
insertions: (a) Santamar´ıa, C.; Beckhaus, R.; Haase, D.; Koch, R.; Saak,
W.; Strauss, I. Organometallics 2001, 20, 1354. (b) Antin˜olo, A.;
Carrillo-Hermosilla, F.; Corrochano, A.; Ferna´ndez-Baeza, J .; Lara-
Sanchez, A.; Ribeiro, M. R.; Lanfranchi, M.; Otero, A.; Pellinghelli, M.
A.; Portela, M. F.; Santos, J . V. Organometallics 2000, 19, 2837. (c)
Bashall, A.; Collier, P. E.; Gade, L. H.; McPartlin, M.; Mountford, P.;
Pugh, S. M.; Radojevic, S.; Schubart, M.; Scowen, I. J .; Tro¨sch, D. J .
M. Organometallics 2000, 19, 4784. (d) Kuroda, S.; Sato, Y.; Mori, M.
J . Organomet. Chem. 2000, 611, 304. (e) Segerer, U.; Blaurock, S.;
Sieler, J .; Hey-Hawkens, E. J . Organomet. Chem. 2000, 608, 21. (f)
Thorn, M. G.; Fanwick, P. E.; Rothwell, I. P. Organometallics 1999,
18, 4442. (g) Cadierno, V.; Zablocka, M.; Donnadieu, B.; Igau, A.;
Majoral, J .-P.; Skowronska, A. J . Am. Chem. Soc. 1999, 121, 11086.
(h) Tomaszewski, R.; Arif, A. M.; Ernst, R. D. J . Chem. Soc., Dalton
Trans. 1999, 1883. (i) Ahlers, W.; Erker, G.; Fro¨hlich, R. J . Organomet.
Chem. 1998, 571, 83. (j) Andre´s, R.; Galakhov, M.; Go´mez-Sal, M. P.;
Mart´ın, A.; Mena, M.; Santamar´ıa, C. Chem. Eur. J . 1998, 4, 1206.
(k) Scott, M. J .; Lippard, S. J . Organometallics 1997, 16, 5857. (l)
Rietveld, M. H. P.; Hagen, H.; van de Water, L.; Grove, D. M.;
Kooijman, H.; Veldman, N.; Spek, A. L.; van Koten, G. Organometallics
1997, 16, 168. (m) Giannini, L.; Caselli, A.; Solari, E.; Floriani, C.;
Chiesi-Villa, A.; Rizzoli, C.; Re, N.; Sgamellotti, A. J . Am. Chem. Soc.
1997, 119, 9709.
(7) Two reports of insertion into R-methylenetitanacyclobutane
complexes have appeared: (a) See ref 4c. (b) Beckhaus, R.; Wagner,
T.; Zimmermann, C.; Herdweck, E. J . Organomet. Chem. 1993, 460,
181.
(8) Complete experimental, spectroscopic, and analytical data are
included as Supporting Information.
(9) See ref 5a and the following: (a) Carmona, E.; Palma, P.;
Paneque, M.; Poveda, M. L. Organometallics 1990, 9, 583. (b) Boch-
mann, M.; Wilson, L. M.; Hursthouse, M. B.; Short, R. Organometallics
1987, 6, 2556.
* To whom correspondence should be addressed. E-mail:
jeff.stryker@ualberta.ca.
† Previously published under the name Grace Greidanus. Current
address: Department of Chemistry, The King’s University College,
Edmonton, Alberta T6B 2H3, Canada.
‡ Current address: NOVA Research and Technology Centre, NOVA
Chemicals Corp., 2928 16th Street N.E., Calgary, Alberta T2E 7K7,
Canada.
(1) (a) Casty, G. L.; Stryker, J . M. J . Am. Chem. Soc. 1995, 117,
7814. (b) Ogoshi, S.; Stryker, J . M. J . Am. Chem. Soc. 1998, 120, 3514.
(c) Carter, C. A. G.; McDonald, R.; Stryker, J . M. Organometallics 1999,
18, 820. (d) Greidanus, G.; McDonald, R.; Stryker, J . M. Organome-
tallics 2001, 20, 2492.
(2) Carter, C. A. G.; Greidanus, G.; Chen, J .-X.; Stryker, J . M. J .
Am. Chem. Soc. 2001, 123, 8872.
(3) Carter, C. A. G.; Casty, G. L.; Stryker, J . M. Synlett 2001, 1046
(Special Issue).
(4) Enediolate formation by reductive double carbonylation of met-
allacyclobutane complexes is well-known: (a) Brown-Wensley, K. A.;
Buchwald, S. L.; Cannizzo, L.; Clawson, L.; Ho, S.; Meinhardt, D.;
Stille, J . R.; Straus, D.; Grubbs, R. H. Pure Appl. Chem. 1983, 55, 1733.
(b) Petersen, J . L.; Egan, J . W., J r. Organometallics 1987, 6, 2007. (c)
Dennehy, R. D.; Whitby, R. J . J . Chem. Soc., Chem. Commun. 1990,
1060. (d) Beckhaus, R.; Wilbrandt, D.; Flatau, S.; Bohmer, W.-H. J .
Organomet. Chem. 1992, 423, 211. (e) Tjaden, E.; Stryker, J . M. J .
Am. Chem. Soc. 1993, 115, 2083.
10.1021/om0110080 CCC: $22.00 © 2002 American Chemical Society
Publication on Web 02/16/2002

1012 Organometallics, Vol. 21, No. 6, 2002
Communications
Sch em e 1a
At low temperature, both iminoacyl complexes 2a and
2b evidence similar reactivities. Carbonylation proceeds
cleanly in both cases, affording titanium cyclopentena-
midolates 6a and 6b in high yield as exclusive products
(Scheme 1).8 Although each complex is obtained in
crystalline form, neither provides consistent combustion
analysis. High-resolution mass spectrometry, however,
was used to confirm the elemental composition; spec-
troscopic analysis was consistent both with the assigned
structures and with known examples of this structural
class.15 The insertion of a second isonitrile equivalent
into iminoacyl complexes 2a and 2b proved to be
illuminating, if ultimately less successful. While the
reactions of titanacyclobutane complex 1 and cyclohexyl
iminoacyl complex 2b with excess cyclohexyl isocyanide
return only intractable mixtures, the corresponding
reactions in the tert-butyl isocyanide series indeed
produce an enediamidate complex by double isonitrile
insertion (eq 1).15,16 In the event, however, the perm-
a
Conditions: (i) RNtC, toluene, -78 °C f room temper-
ature, 1 h, yield 92% (2a ), 90% (2b); (ii) 65 °C, toluene, 23 h,
quantitative; (iii) C2H4 (10 psi), 65 °C, toluene, 12 h, yield 90%
(4), 94% (5); (iv) CO (60 psig), toluene, -78 °C f room
temperature, 10 h, yield 93% (6a ), 85% (6b).
cyclohexyl complex 2b (νCN 1567 cm-1). In the structur-
ally similar complexes reported by Beckhaus, iminoacyl
complexes derived from both tert-butyl isocyanide and
cyclohexyl isocyanide show nearly identical infrared
absorptions (1564 and 1567 cm-1, respectively), with the
coordination mode of the cyclohexyl derivative in the
solid state definitively determined to be η1 by X-ray
crystallography.7b The large difference in infrared ab-
sorptions observed for complexes 2a and 2b is un-
usual: iminoacyl infrared absorptions are generally
insensitive to the identity of the alkyl substituent.9
Consistent with this difference in imine functionality,
thermolysis of the two complexes results in dramatically
different reactivities. Thus, heating the cyclohexyl iso-
cyanide adduct 2b to 65 °C induces reductive cycliza-
tion,10 affording the strained cyclobutanimine 58,11 as
the exclusive organic product, isolated in 72% yield.
Under these conditions, the titanium fragment largely
decomposes to intractable materials.12 In the presence
of ethylene, however, the reaction is considerably cleaner,
producing the cyclobutanimine in higher yield and
returning the titanium exclusively as the known eth-
ylene adduct Cp*2Ti(C2H4)13 (Cp* ) η5-C5Me5). In
contrast, thermolysis of the tert-butyl isocyanide adduct
2a , in either the presence or absence of added ethylene,
leads to exclusive deinsertion of the isonitrile, returning
titanacyclobutane complex 1 quantitatively. No tert-
ethyltitanocene complex undergoes an unprecedented
fragmentation, ejecting one pentamethylcyclopentadi-
enyl ligand and one tert-butyl fragment, producing the
half-sandwich enediamidate complex 78 bearing an
ancillary cyanide ligand!17 This product is obtained as
a 1:1 mixture of diastereomers; the structure was
confirmed by X-ray crystallography (Figure 1) of the syn
isomer obtained by recrystallization from cold hexane.18
While the sterically crowded coordination sphere clearly
plays a role in this unique transformation, the mecha-
nism remains entirely obscure.
The synthesis of substituted cyclobutanimines can be
generalized using the bis(2-(dimethylamino)indenyl)-
titanium template, which tolerates the synthesis of
stereochemically pure disubstituted titanacyclobutane
complexes by free radical alkylation.1d Thus, addition
of 2,6-dimethylphenyl isocyanide19 (3 equiv) to titana-
cyclobutane complexes 8 at low temperature leads to
clean production of 2,3-disubstituted cyclobutanimines
1
butyl isocyanide is observed in the H NMR spectrum
of the crude product, suggesting that the deinsertion
may proceed by a complex decomposition mechanism.
Migratory deinsertion of isonitriles from iminoacyl
complexes is comparatively rare.14
(14) The conversion of aldimines to isonitriles by migratory dein-
sertion of an intermediate iminoacyl complex has been recently
reported using trans-[Mo(N2)2(dppe)2]: Seino, H.; Arita, C.; Nonokawa,
D.; Nakamura, G.; Harada, Y.; Mizobe, Y.; Hidai, M. Organometallics
1999, 18, 4165.
(15) Enamidolate and enediamide complexes of the (ArO)2Ti frag-
ment: Chamberlain, L. R.; Durfee, L. D.; Fanwick, P. E.; Kobriger, L.
M.; Latesky, S. L.; McMullen, A. K.; Steffey, B. D.; Rothwell, I. P.;
Folting, K.; Huffman, J . C. J . Am. Chem. Soc. 1987, 109, 6068.
(16) Enediamide complexes of zirconocene and hafnocene systems:
Kloppenburg, L.; Petersen, J . L. Organometallics 1997, 16, 3548 and
references therein.
(10) (a) Probert, G. D.; Witby, R. J .; Coote, S. J . Tetrahedron Lett.
1995, 36, 4113. (b) Davis, J . M.; Witby, R. J .; J axa-Chamiec, A.
Tetrahedron Lett. 1994, 35, 1445 and references therein.
(11) Cyclobutanimines are known but are relatively rare: (a)
Logothetis, A. L. J . Am. Chem. Soc. 1965, 87, 749. (b) Newcomb, M.;
Williams, W. G. Tetrahedron Lett. 1984, 25, 2723. (c) Betz, J .;
Heushmann, M. Tetrahedron Lett. 1995, 36, 4043. (d) Stevens, C.;
DeKimpe, N. J . Org. Chem. 1996, 61, 2174. (e) Bisel, P.; Breitling, E.;
Frahm, A. W. Eur. J . Org. Chem. 1998, 729.
(12) A minor portion (5% isolated yield) of the titanium is recovered
from this reaction as the known double “tuck-in” complex, (η3:η4-1,2,3-
trimethyl-4,5-dimethylenecyclopentadienyl)titanium: Pattiasina, J . W.;
Hissink, C. E.; de Boer, J . L.; Meetsma, A.; Teuben, J . H.; Spek, A. J .
Am. Chem. Soc. 1985, 107, 7758.
(17) We have as yet been unable to determine the fate of the organic
fragment(s) produced during this reaction.
(18) Crystal data for complex 7 (C27H45N3Ti, -60 °C): monoclinic,
P21/c (No. 14), a ) 16.4949(4) Å, b ) 9.4610(3) Å, c ) 17.5737(9) Å, â
) 94.381(3)°, V ) 2734.5(2) Å3, Z ) 4, Fcalcd ) 1.116 g cm-3, µ ) 2.761
mm-1, R1 ) 0.0524, wR2 ) 0.1374 (Fo > -3σ(Fo2). Details of the
2
structure determination are included as Supporting Information.
(19) The use of alkyl isocyanides in this reaction leads to low
selectivity in the insertion reaction and poor recovery of the titanium
fragment.
(13) Cohen, S. A.; Auburn, P. R.; Bercaw, J . E. J . Am. Chem. Soc.
1983, 105, 1136.

Communications
Organometallics, Vol. 21, No. 6, 2002 1013
Ta ble 1. Cyclobu ta n im in e Syn th esis by Ison itr ile
In ser tion in to Com p lex 8a
isonitrile yield
R′ complex (%) product
yield
(%)
E:Z
ratio
complex
R
8a
8b
8c
8d
CH3 Bn
CH3 iPr
10
10
10
10
quant
84
83
9a
9b
9c
9d
quant
90
quant
86
6:1
>99:<1
6:1
Ph
Ph
Bn
iPr
78
10:1
a
Conditions: 3 equiv of 2,6-dimethylphenyl isocyanide, -35 °C
f room temperature, THF, 3 h.
F igu r e 1. ORTEP drawing of complex 7. Selected bond
distances (Å) and angles (deg): Ti-N2, 1.915(2); Ti-N3,
1.922(3), Ti-C1, 2.177(4); Ti-C2, 2.361(3); Ti-C3, 2.361-
(3); N1-C1, 1.141(4); N2-C2, 1.384(4); N3-C3, 1.381(4);
C2-C3, 1.389(4), Ti-C1-N1, 177.3(3); N2-Ti-N3, 91.4-
(1); Ti-N2-C2, 89.2(2); Ti-N2-C10, 145.8(2); C2-N2-
C10, 124.2(3).
substituent21 and the titanocene ancillary ligands. The
efficient synthesis of strained, functionalized, and highly
substituted four-membered rings by migratory cycliza-
tion is particularly noteworthy; current efforts are
underway to extend and generalize this interesting
reactivity pattern.
9 and, importantly, recovery of the titanium as the bis-
(isonitrile) complex 10 in high yield (Table 1).8 The latter
is separated from the cyclobutanimine by crystallization
from pentane at low temperature; isolation of the
cyclobutanimine is accomplished after exposure to air
and filtration of any insoluble titanium-derived resi-
dues.20 In this system, however, we have been unable
to isolate (or intercept) the putative iminoacyl interme-
diates, even upon reaction at low temperature in the
presence of 1 equiv of isonitrile.
Ackn owledgm en t. Financial support from the Natu-
ral Sciences and Engineering Research Council of
Canada and the University of Alberta is gratefully
acknowledged. We thank Dr. Robert McDonald (Faculty
Service Officer, University of Alberta, Department of
Chemistry X-ray Crystallography Laboratory) for the
X-ray structure determination.
Isonitrile insertion into titanacyclobutane complexes
thus provides a rich and potentially exploitable reactiv-
ity manifold, sensitive to both the nature of the isonitrile
Su p p or tin g In for m a tion Ava ila ble: Text giving experi-
mental procedures and complete spectroscopic and analytical
data for all new compounds and tables giving details of the
crystal structure determination of complex 7. This material
is available free of charge via the Internet at http://pubs.acs.org.
(20) The cyclobutanimines are recovered in reasonable purity,
containing only minor amounts (e5%) of unidentified impurities by
spectroscopic analysis. Further purification, however, is precluded by
competitive hydrolysis during column chromatography.
(21) The variability of isonitrile reactivity as a function of substitu-
ent has been noted in other contexts. See, for example, refs 15 and 17
and: Kloppenburg, L.; Petersen, J . L. Polyhedron 1995, 14, 69.
OM0110080