Regio- and stereochemical control in bis-functionalization-Cyclization: Use of alleneyne precursors for carbocyclic and heterocyclic synthesis [2]

Full text of DOI:10.1021/ja011281t

8416
J. Am. Chem. Soc. 2001, 123, 8416-8417
Scheme 1. Cyclizations Mediated by Bifunctional Reagents
Regio- and Stereochemical Control in
Bis-functionalization-Cyclization: Use of Alleneyne
Precursors for Carbocyclic and Heterocyclic
Synthesis
Seunghoon Shin and T. V. RajanBabu*
Department of Chemistry
The Ohio State UniVersity
Columbus, Ohio 43210
Scheme 2. Silylstannylation/Cyclization of Allenyne
ReceiVed May 25, 2001
Catalytic synthesis of carbocyclic and heterocyclic compounds
from acyclic olefinic and acetylenic precursors is a subject of
great topical interest. A wide variety of substrates including
eneynes, eneallenes, dienes, and diynes have been subjected to
metal-catalyzed intramolecular cyclizations.1 Many of these
reactions are characterized by operationally simple procedures,
high catalytic turnover and selectivity, and in several cases,
exceptional functional group tolerance of the reagents. More
recently, the value of such reactions have been enhanced further
by the use of bifunctional (X-Y) reagents such as R3Si-SiR′3,
R3Si-SnR′3, R3Si-BR′2, R3Sn-BR′2, as well as the more
traditional trialkylsilicon- and trialkyltin- hydrides.2 These reagents
are incorporated into the reaction leading to highly functionalized
end products (Scheme 1).
Last year we reported the cyclization of 1,6-diynes aided by
trialkylsilyltrialkylstannanes (R3Si-SnR′3)3 in the presence of Pd-
(0) to give novel, helically chiral 1,2-dialkylidenecyclopentanes
with an uncommon (ZZ)-geometry at the double bonds (eq 1).4
This highly stereoselective reaction proceeds in good yields with
no special care taken to avoid moisture and air, and is compatible
with common functional groups such as ethers, esters, amides,
carbonyl groups, and even tertiary amines. While the full synthetic
potential of the product dienes remains to be explored, preliminary
studies show that they undergo a number of selective transforma-
tions including proto-destannylation, Sn-halogen exchange, Stille
coupling, and epoxidation of the vinylstannane.5 Nevertheless,
one limitation of this and all other related X-Y-mediated
cyclizations that has become apparent is the lack of regioselec-
tivity in some unsymmetrical substrates as illustrated in eq 2. The
of an alleneyne would give a highly substituted alkylidenecyclo-
pentane which maybe further elaborated through vinylsilane and
vinylstannane chemistry (Scheme 1). We were encouraged by a
timely study by Kang et al.7 who reported that symmetric diallenes
underwent Pd-catalyzed, stereoselective cyclization in the presence
of Bu3SnSnBu3 and Me3SiSnBu3. In the meantime, our expecta-
tions on the allenyne cyclization have been borne out, and in this
paper we report our initial findings on a highly chemo-, regio-,
and stereoselective silylstannylation/cyclization reaction of these
substrates.
The alleneyne 3, in the presence of Ph3Sn-SiMe2But (1.1
equiv), Pd2(dba)3‚CHCl3 (5 mol % in Pd) and P(C6F5)3 (10 mol
%) in C6D6 undergoes an exceptionally clean reaction (>95%
yield of product by NMR) at room temperature to give the
cyclic product 5a in 80% isolated yield (Scheme 2). The lower
isolated yield of the product is a measure of the instability of
this relatively sensitive material which was isolated by column
chromatography on silica gel using hexane containing 5% Et3N.8
The structure and configuration of 5a were unambiguously
(2) For recent review articles, see: (a) Suginome, M.; Ito, Y. Chem. ReV.
2000, 100, 3221. (b) Smith, N. D.; Mancuso, J.; Lautens, M. Chem. ReV.
2000, 100, 3257. For more recent representative publications that deal with
R3SiH and R3SnH, see: (c) Ojima, I.; Lee, S.-Y. J. Am. Chem. Soc. 2000,
122, 2385 and references therein. (d) Kisanga, P.; Widenhoefer, R. A. J. Am.
Chem. Soc. 2000, 122, 10017. (e) Lautens, M.; Mancuso, J. Org. Lett. 2000,
2, 671. (f) R3Si-BR2: Onozawa, S.; Hatanaka, Y.; Tanaka, M. J. Chem. Soc.,
Chem. Commun. 1997, 1229. Suginome, M.; Matsuda, T.; Ito, Y. Organometl-
lics 1998, 5233. (g) R3SnBR2: Onozawa, S.; Hatanaka, Y.; Choi, N.; Tanaka,
M. Organometallics 1997, 16, 5389. (h) R3SiSiR3/R3SnSnR3/R3SiSnR3: Obora,
Y.; Tsuji, Y.; Kakehi, T.; Kobayashi, M.; Shinkai, Y.; Ebihara, M.; Kawamura,
T. J. Chem. Soc., Perkin Trans. 1 1995, 599. [SiSn]-mediated cyclization of
eneynes: (i) Mori, M.; Hirose, T.; Wakamatsu, H.; Imakuni, N.; Sato, Y.
Organometallics 2001, 20, 1907. See also, Radetich, B. Ph.D. Thesis, The
Ohio State University, 2000.
(3) (a) Chenard, B. L.; Laganis, E. D.; Davidson, F.; RajanBabu, T. V. J.
Org. Chem. 1985, 50, 3666. (b) Mitchell, T. N.; Killing, H.; Dicke, R.;
Wickenkamp, R. J. Chem. Soc., Chem. Commun. 1985, 354.
proline-derived diyne gave essentially a 1:1 mixture of regioiso-
meric products. We wondered whether by exploiting the different
reactivities of allenes and acetylenes in Pd-catalyzed X-Y
additions we could circumvent this problem.6 Thus, cyclization
(4) Gre´au, S.; Radetich, B.; RajanBabu, T. V. J. Am. Chem. Soc. 2000,
122, 8579.
(5) Unpublished results of Warren, S.; Shin, S.
(6) (a) Addition of R3Si-SnR′3 and R3Sn-SnR′3 to allenes has been
explored by Mitchell. See: Mitchell, T. N.; Schneider, U. J. Organomet. Chem.
1991, 407, 319. (b) Additions of (OR)2B-B(OR)2 to allenes have also been
reported: Ishiyama, T.; Kitano, T.; Miyaura, N. Tetrahedron Lett. 1998, 39,
2357. (c) For a review of Pd-catalyzed reactions of allenes see: Zimmer, R.;
Dinesh, C. U.; Nandanan, E.; Khan, F. A. Chem. ReV. 2000, 100, 3067.
(7) Kang, S.-K.; Baik, T.-G.; Kulak, A. N.; Ha, Y.-H.; Lim, Y.; Park, J. J.
Am. Chem. Soc. 2000, 122, 11529.
(1) For pertinent reviews see: Tamao, K.; Kobayashi, K.; Ito, Y. Synlett
1992, 539. (b) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49. (c)
Negishi, E.-i.; Cope´ret, C.; Ma, S.; Liou, S.-Y.; Liu, F. Chem. ReV. 1996, 96,
365. (d) Ojima, I.; Tzamarioudaki, M.; Li, Z.; Donovan, R. J. Chem. ReV.
1996, 96, 635. (e) Grubbs, R. H.; Chang, S. Tetrahedron, 1998, 54, 4413. (f)
Trost, B. M.; Krische, M. J. Synlett 1998, 1. (f) Sato, F.; Urabe, H.; Okamoto,
S. Chem. ReV. 2000, 100, 2835. (g) Brummond, K. M.; Kent, J. L. Tetrahedron,
2000, 56, 3263.
(8) See Supporting Information for details.
10.1021/ja011281t CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/02/2001

Communications to the Editor
J. Am. Chem. Soc., Vol. 123, No. 34, 2001 8417
Table 1. Cyclization of Alleneynes Mediated by R3SiSnR′3 and
R3SnSnR3
Scheme 3. Possible Mechanism of Silylstannylation/
Cycliation of an Allenyne
Table 1 shows the generality of the cyclization reaction.
Reaction of Ph3Sn-SiMe2But with N-tosylalleneyne 6 gives the
cyclic product 7 in >90% yield at room temperature whereas the
oxygenated derivative 8 gives the product 9 as a single diaste-
reomer.8 The less reactive trimethylsilyltributyl stannane takes 5
h at 80 °C to complete the cyclization of 8 to give the product
10. At room temperature in the presence of (PhCN)2PdCl2 and
(C6F5)3P, 8 gives a mixture (1:3) of the allylstannane 11 and the
cyclic product 10.
The silyltin reagents are generally superior to other bis-
functionalization reagents in this type of cyclizations. For
comparison, reactions of 3 and 8 with Me3Sn-SnMe3 and a
boron-tin reagent Me3Sn-B[-N(Me)CH2CH2(Me)N-] were
attempted. Judged by “in situ” NMR analysis, the distannylation
reaction proceed to give a good yield of 13, albeit at a higher
temperatures (entry 8).8 Allenyne 8 gave a mixture of cyclic and
acyclic products. The borostannylation is a relatively poor
reaction, giving a similar adduct (<50% crude yield). Isolation
of the Sn-Sn and Sn-B compounds presents significant prob-
lems, and upon chromatography severe losses are encountered.
A unified mechanism that accounts for the observed results is
shown in Scheme 3. Bidentate coordination of the Pd2+ on the
allene and acetylene (15) would lead to the more stable anti π-allyl
Pd-complex 16, which upon reductive elimination with formation
of the less congested allylstannane and regeneration of Pd(0)
would give the primary product 4b. A more energetically
demanding insertion of the acetylene into this π-allyl Pd complex
takes place at a higher temperature, leading to the cyclic product
5b via 17.10 In support of such a mechanism we have observed
that isolated 4b can be converted into 5b using Pd(0) and (C6F5)3P
at elevated temperatures.11
a A: 5 mol % Pd2(dba)3‚CHCl3 with 10 mol % P(C6F5)3; B: 5 mol
% Pd(PhCN)2Cl2 with 10 mol % P(C6F5)3. b Isolated yields (yields
determined by NMR in brackets). c Isolated material contained 8% 5b.
established by NMR spectroscopy and elemental analysis. The
identity of the SnC-H and the geometry of the double bond are
2
clear from the coupling pattern (δ 6.40; s, JSn-H ) 74 Hz) and
nOe difference spectrum.8 Among the large number of mono-
phosphine ligands that were screened for the reaction only P(3,5-
Me2-C6H3)3 and (C6F5)3P gave any appreciable reaction after 12
h at room temperature (39 and 61%, respectively). The source of
Pd, while not as critically important, showed a definite trend in
reactivity when used in conjunction with (C6F5)3P: (PhCN)2PdCl2
≈ [Pd(allyl)Cl]2/AgOTf>, Pd2(dba)3‚CHCl3. PdCl2. When the
reaction was repeated with a less reactive silylstannane, Bu3-
SnSiMe3, we were able to isolate an uncyclized adduct 4b in
excellent yield (81% isolated along with 8% 5b) and stereochem-
ical purity (Scheme 2).9 On prolonged heating (45 °C, 48 h) the
intermediate allylstannane 4b is quantitatively converted into the
cyclic product 5b. Isolation of this key intermediate is indicative
of the higher reactivity of the allene moiety (vis-a`-vis the
acetylene) and has clear mechanistic implications (vide infra).
Presumably the corresponding allyltriphenylstannane 4a is too
reactive to accumulate in solution to any appreciable degree.
Acknowledgment. We acknowledge the financial assistance by the
U.S. National Science Foundation (CHE-9706766 and CHE 0079948).
Supporting Information Available: Spectroscopic and other analyti-
cal data for full characterization of all new compounds and NMR spectra
(1H, 13C, COSY and nOe’s) (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
JA011281T
(10) (a) For a metal-catalyzed carbocyclization by intramolecular reactions
of allylsilanes and allylstannanes with alkynes, see: Ferna´ndez-Rivas, C.;
Me´ndez, M.; Echavarren, A. M. J. Am. Chem. Soc. 2000, 122, 1221. This
reaction in which the trialkyltin moiety is lost is mechanistically different
from latter stages of the silylstannylation/cyclization. (b) For intermolecular
versions see: Shirakawa, E.; Yoshida, H.; Nakao, Y.; Hiyama, T. Org. Lett.
2000, 2, 2209 and references therein. A less likely alternate mechanism
proceeding through an oxidative cyclization to form an intermediate palla-
dacycle with Pd(IV) cannot be ruled out at this time.
(9) The regioselectivity of addition of the silylstannanes under our modified
reaction conditions appear to be different and, gratifyingly, better than
originally reported by Mitchell et al.6a who used (Ph3P)4Pd at 85 °C to effect
the silylstannylation of allenes. For example, we find that addition of Me2-
ButSiSnPh3 and Me3SiSnBu3 to an N-allenyl-2-(tert-butyldimethylsiloxym-
ethyl)oxazolidinone at room temperature leads to a single diastereomer in high
yield. See Supporting Information for details.
(11) The Pd(0)-catalyzed isomerization of â-silyl-substituted allylstannanes
observed by Mitchell6a could also involve a π-allyl-Pd intermediate.