Phosphine-mediated stereoselective reductive cyclopropanation of α-substituted allenoates with aromatic aldehydes

Article abstract of DOI:10.1021/ol902747c

[Chemical equation presented] A novel phosphine-mediated reductive cyclopropanation between α-substituted allenoates 2 and aldehydes 1 is described. It represents a new member of the allene-based annulations, which provides facile and efficient access to highly functionalized cyclopropanes 3 from simple and readily available starting materials. It also unveils an unprecedented reactivity pattern of allenoates with aldehydes.

Full text of DOI:10.1021/ol902747c

ORGANIC
LETTERS
2010
Vol. 12, No. 3
544-547
Phosphine-Mediated Stereoselective
Reductive Cyclopropanation of
r-Substituted Allenoates with Aromatic
Aldehydes
Silong Xu, Lili Zhou, Renqin Ma, Haibin Song, and Zhengjie He*
The State Key Laboratory of Elemento-Organic Chemistry and Department of
Chemistry, Nankai UniVersity, 94 Weijin Road, Tianjin 300071, P.R. China
zhengjiehe@nankai.edu.cn
Received November 29, 2009
ABSTRACT
A novel phosphine-mediated reductive cyclopropanation between r-substituted allenoates 2 and aldehydes 1 is described. It represents a new
member of the allene-based annulations, which provides facile and efficient access to highly functionalized cyclopropanes 3 from simple and
readily available starting materials. It also unveils an unprecedented reactivity pattern of allenoates with aldehydes.
The development of efficient methods to construct the
cyclopropane motif is of great importance in synthetic
organic chemistry since this molecular architecture is
present in a large number of naturally occurring and
medicinally relevant substances.1 Moreover, the rigid
structure and strain-driven reactivity make cyclopropyl
derivatives attractive as versatile intermediates in organic
synthesis.2 Over the past decades, vast efforts from
chemists have been engaged by this area. As a result, many
effective methodologies enabling the generation of diverse
three-membered carbocycles with high chemo- and ste-
reoselectivity have been developed,3 which could be
simply classified as the Simmons-Smith process,4
metal-carbenoid reaction,5 Michael-initiated ring closure
(MIRC) reaction,6 and recently emerging organocatalytic
cyclopropanation.7 Even so, complementary new ap-
proaches with high synthetic efficiency to build this all-
carbon triangular structure from simple and readily
available starting materials remain highly desirable.
(4) Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. ReV. 1993, 93, 1307.
(5) For representative examples, see: (a) Denmark, S. E.; O’Connor,
S. P.; Wilson, S. R. Angew. Chem., Int. Ed. 1998, 37, 1149. (b) Charette,
A. B.; Molinaro, C.; Brochu, C. J. Am. Chem. Soc. 2001, 123, 12168. (c)
Xu, Z.-H.; Zhu, S.-N.; Sun, X.-L.; Tang, Y.; Dai, L.-X. Chem. Commun.
2007, 1960. (d) Thompson, J. L.; Davies, H. M. L. J. Am. Chem. Soc. 2007,
129, 6090. (e) Ruppel, J. V.; Gauthier, T. J.; Snyder, N. L.; Perman, J. A.;
Zhang, X. P. Org. Lett. 2009, 11, 2273.
(6) (a) Hudlicky, T.; Radesca, L.; Luna, H.; Anderson, F. E. J. Org.
Chem. 1986, 51, 4746. (b) Caine, D. Tetrahedron 2001, 57, 2643. (c) Corey,
E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1965, 87, 1353. (d) Bestmann,
H. J.; Seng, F. Angew. Chem., Int. Ed. 1962, 1, 116. (e) Hu, W.-H.;
Timmons, J.; Doyle, M. P. Org. Lett. 2002, 4, 901. (f) Huang, L.-Y.; Chen,
Y.; Gao, G.-Y.; Zhang, X. P. J. Org. Chem. 2003, 68, 8179.
(1) (a) Faust, D. Angew. Chem., Int. Ed. 2001, 40, 2251. (b) Wessjohann,
L. A.; Brandt, W.; Thiemann, T. Chem. ReV. 2003, 103, 1625. (c)
Donaldson, W. A. Tetrahedron 2001, 57, 8589.
(2) (a) Reissig, H.-U.; Zimmer, R. Chem. ReV. 2003, 103, 1151. (b) De
Pol, S.; Zorn, C.; Klein, C. D.; Zerbe, O.; Reiser, O. Angew. Chem., Int.
Ed. 2004, 43, 511. (c) Wong, H. N. C.; Hon, M.-Y.; Tse, C.-W.; Yip, Y.-
C.; Tanko, J.; Hudlicky, T. Chem. ReV. 1989, 89, 165–198.
(3) For leading reviews, see: (a) Lebel, H.; Marcoux, J.-F.; Molinaro,
C.; Charette, A. B. Chem. ReV. 2003, 103, 977. (b) Li, A.-H.; Dai, L.-X.;
Aggarwal, V. K. Chem. ReV. 1997, 97, 2341. (c) Aggarwal, V. K.; Winn,
C. L. Acc. Chem. Res. 2004, 37, 611. (d) Pellissier, H. Tetrahedron 2008,
64, 7041–7095.
(7) (a) Papageorgiou, C. D.; Cubillo de Dios, M. A.; Ley, S. V.; Gaunt,
M. J. Angew. Chem., Int. Ed. 2004, 43, 4641. (b) Kunz, R. K.; MacMillan,
D. W. C. J. Am. Chem. Soc. 2005, 127, 3240. (c) Johansson, C. C. C.;
Bremeyer, N.; Ley, S. V.; Owen, D. R.; Smith, S. C.; Gaunt, M. J. Angew.
Chem., Int. Ed. 2006, 45, 6024. (d) Xie, H.; Zu, L.; Li, H.; Wang, J.; Wang,
W. J. Am. Chem. Soc. 2007, 129, 10886. (e) Ibrahem, I.; Zhao, G.-L.; Rios,
R.; Vesely, J.; Sunden, H.; Dziedzic, P.; Cordova, A. Chem.sEur. J. 2008,
14, 7867. (f) Lv, J.; Zhang, J.; Lin, Z.; Wang, Y. Chem.sEur. J. 2009, 15,
972, and references cited therein.
10.1021/ol902747c  2010 American Chemical Society
Published on Web 01/12/2010

During the past decade, phosphine-triggered annulation
reactions employing electron-deficient allenes have emerged
as a facile protocol for the construction of a variety of
carbocycles and heterocycles.8 For example, the extensively
studied Lu’s [3 + 2] cycloadditions of allenoates with
activated olefins or imines provide convenient and practical
access to various five-membered carbocycles and nitrogen
heterocycles;9 using R-substituted allenoates as a reactant,
both [4 + 2] annulation with activated olefins or imines and
[3 + 3] annulation with aziridines have been realized by
Kwon, providing facile entries into highly functionalized
cyclohexenes and tetrahydropyridines.8j,k,10 Up to date, these
allene-based annulations with various electrophiles constitute
a valuable platform to build five-, six-, and seven-membered
ring systems. Some of them have also been successfully
utilized in the syntheses of natural or biologically important
substances.11 In this context, herein we wish to report a
phosphine-mediated reductive cyclopropanation of R-sub-
stituted allenoates with aldehydes as the first example of the
allene-based synthesis of the smallest carbocycle.
we attempted to investigate the possible reactions between
R-substituted allenoates and aldehydes under the influence
of a nucleophilic phosphine.14 Gratifyingly, this attempt led
to the discovery of a new allene-based annulation.
Initially, we examined the reaction of diethyl 2-vinylide-
nesuccinate (2a, 0.75 mmol) and 2-chlorobenzaldehyde (1a,
0.5 mmol) with PPh3 (0.75 mmol) (eq 1). To our delight,
the reaction proceeded smoothly in dichloromethane (5 mL)
at room temperature, affording vinyl cyclopropane 3a in 75%
yield and excellent diastereoselectivity (trans/cis ) 10:1, Z
alkene isomer only). Identification of the product 3a, in
combination with isolation of the byproduct triphenylphos-
phine oxide in comparable yield, clearly implied that a
stoichiometric phosphine-mediated reductive cyclopropana-
tion between allenoate 2a and aldehyde 1a occurred. To our
knowledge, this reaction unveiled an unprecedented reactivity
pattern of allenoates with aldehydes, as well as a new
synthesis for highly functionalized cyclopropanes.
Regarding those with activated olefins or imines, the
reactivities of electron-poor allenes with aldehydes under the
mediation of a nucleophilic phosphine were much less
explored. The pioneering works by Kwon revealed interesting
and distinctive reactivity patterns between nonsubstituted
allenoates and aldehydes, leading to efficient syntheses of
oxygen-containing heterocycles like 1,3-dioxanes, pyrones,
and dihydropyrones.12 Very recently, two new phosphine-
mediated reactivity modes of γ-substituted allenoates with
aldehydes were reported by our group: typically, γ-methyl
allenoates underwent a phosphane-catalyzed [3 + 2] annu-
lation with aromatic aldehydes to form tetrahydrofurans,8l
and γ-benzyl allenoates gave rise to a stoichiometric phos-
phine-mediated olefination with both aliphatic and aromatic
aldehydes to yield 1,3-dienes with high stereoselectivity.13
Intrigued by these exciting findings together with those
specific reactivity patterns like [4 + 2] annulations of
R-substituted allenoates with activated olefins or imines,8j,10
Further survey on reaction conditions was carried out by
using the reaction of 2a and 1a as a probe (Table 1). Among
Table 1. Survey on Conditions for the Reductive
Cyclopropanation of the Allenoate 2a with Aldehyde 1aa
entry
PR3
solvent
CH2Cl2
time (h) yield (%)b
drc
1
2
3
4
5
6
7
8
P(OMe)3
P(NMe2)3 CH2Cl2
120
120
21
24
21
14
47
22
8
21
23
13
13
41
6
0
0
N/A
N/A
10:1
3:1
3:1
3:1
10:1
10:1
10:1
10:1
10:1
10:1
N/A
10:1
10:1
(8) For leading reviews, see: (a) Ye, L.-W.; Zhou, J.; Tang, Y. Chem.
Soc. ReV. 2008, 37, 1140. (b) Lu, X.; Zhang, C.; Xu, Z. Acc. Chem. Soc.
2001, 34, 535. (c) Methot, J. L.; Roush, W. R. AdV. Synth. Catal. 2004,
346, 1035. (d) Ma, S. Chem. ReV. 2005, 105, 2829. (e) Cowen, B. J.; Miller,
S. J. Chem. Soc. ReV. 2009, 38, 3102. For most recent examples, see: (f)
Cowen, B. J.; Miller, S. J. J. Am. Chem. Soc. 2007, 129, 10988. (g) Fang,
Y.-Q.; Jacobsen, E. N. J. Am. Chem. Soc. 2008, 130, 5660. (h) Voituriez,
A.; Panossian, A.; Fleury-Bregeot, N.; Retailleau, P.; Marinetti, A. J. Am.
Chem. Soc. 2008, 130, 14030. (i) Zhang, B.; He, Z.; Xu, S.; Wu, G.; He,
Z. Tetrahedron 2008, 64, 9471. (j) Tran, Y. S.; Kwon, O. J. Am. Chem.
Soc. 2007, 129, 12632. (k) Guo, H.; Xu, Q.; Kwon, O. J. Am. Chem. Soc.
2009, 131, 6318. (l) Xu, S.; Zhou, L.; Ma, R.; Song, H.; He, Z. Chem.sEur.
J. 2009, 15, 8698. (m) Meng, X.; Huang, Y.; Chen, R. Org. Lett. 2009, 11,
137. (n) Liang, Y.; Liu, S.; Yu, Z.-X. Synlett 2009, 905, and references
cited therein. (o) Sampath, M.; Loh, T.-P. Chem. Commun. 2009, 1568.
(9) Zhang, C.; Lu, X. J. Org. Chem. 1995, 60, 2906.
PPh3
Ph2PMe
PhPMe2
PBu3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
toluene
DMSO
1,4-dioxane
DMF
75
62
50
68
46
72
85
65
96
68
0
9
10
11
12
13
14d
15e
CH3CN
ethanol
DMF
73
99
DMF
a Typical conditions: under N2 atmosphere and at room temperature, to a
stirred solution of aldehyde 1a (0.5 mmol) and phosphorus reagent (0.75 mmol)
in solvent (2 mL) was added a solution of allenoate 2a (0.75 mmol) in solvent
(3 mL). b Combined yield of isolated diastereomers (based on 1a). c Calculated
by the major (trans,Z)-3a versus the sum of other isolated diastereomers. d PPh3
and 2a were used in 1.2 equiv. e PPh3 and 2a were used in 2.0 equiv.
(10) Zhu, X.-F.; Lan, J.; Kwon, O. J. Am. Chem. Soc. 2003, 125, 4716
.
(11) (a) Du, Y.; Lu, X. J. Org. Chem. 2003, 68, 6463. (b) Wang, J.-C.;
Krische, M. J. Angew. Chem., Int. Ed. 2003, 42, 5855. (c) Tran, Y. S.;
Kwon, O. Org. Lett. 2005, 7, 4289. (d) Pham, T. Q.; Pyne, S. G.; Skelton,
B. W.; White, A. H. J. Org. Chem. 2005, 70, 6369–6377.
(12) (a) Zhu, X.-F.; Henry, C. E.; Wang, J.; Dudding, T.; Kwon, O.
Org. Lett. 2005, 7, 1387. (b) Zhu, X.-F.; Schaffner, A.-P.; Li, R. C.; Kwon,
O. Org. Lett. 2005, 7, 2977. (c) Dudding, T.; Kwon, O.; Mercier, E. Org.
Lett. 2006, 8, 3643. (d) Creech, G. S.; Kwon, O. Org. Lett. 2008, 10, 429–
432.
a series of nucleophilic phosphorus reagents screened,
trimethyl phosphite and hexamethyl phosphorus triamide
(13) Xu, S.; Zhou, L.; Zeng, S.; Ma, R.; Wang, Z.; He, Z. Org. Lett.
2009, 11, 3498–3501.
Org. Lett., Vol. 12, No. 3, 2010
545

could not mediate the reaction (entries 1, 2), and phosphines
with relatively stronger nucleophilicity such as Ph2PMe,
PhPMe2, and Bu3P also readily produced the cyclopropane
3a in comparable yield, but only in modest diastereoselec-
tivity (entries 4-6). With 1.5 equiv of Ph3P used, screening
of common solvents revealed that DMF was the best,
affording 3a in 96% yield and high diastereoselectivity (entry
11). Other solvents also gave moderate to good yields (entries
7-10, 12) except that ethanol completely inhibited the
cyclopropanation (entry 13).15 Lowering the amounts of the
allenoate and PPh3 to 1.2 equiv resulted in substantial
decrease in the yield (entry 14), while increasing the amounts
to 2.0 equiv led to almost quantitative yield (entry 15). Thus,
the cyclopropanation was best run in DMF at room temper-
ature with 1.5 or 2.0 equiv of both allenoate and PPh3.
Under the optimized conditions, the generality of this
cyclopropanation was further explored (Table 2). A variety
Heteroaromatic aldehydes like pyridyl- and furylaldehydes
also worked well (entries 14-17). Relatively electron-rich
benzaldehydes were less reactive and afforded only moderate
yields but high diastereoselectivity (entries 18-20). Con-
versely, alkyl aldehydes like propylaldehyde and butyralde-
hyde were totally ineffective in this cyclopropanation.
Several structurally similar R-substituted allenoates were
also investigated. Ethyl 2-(cyanomethyl) buta-2,3-dienoate
(R ) CN, 2b) possessed reactivity similar to that of 2a and
readily underwent the cyclopropanation with representative
aromatic aldehydes at a lowered temperature (-20 °C),
giving the corresponding cyclopropanes 3 in moderate yields
(Table 2, entries 21-25). However, following the optimal
conditions, neither R-methyl allenoate (R ) H, 2c) nor
R-benzyl allenoate (R ) Ph, 2d) afforded any expected
cyclopropanation products with 1a. Assumingly, a strongly
electron-withdrawing group R in 2 is required to effect this
cyclopropanation.
In all cases of the cyclopropanation, the overall diaste-
reoselectivity remained on a modest to high level. The
diastereomeric ratio of the major (trans,Z)-3 versus the sum
of other isomers fell in the range of 2.5:1 to >20:1 (Table
2). The structures and relative stereochemistry of the
Table 2. Synthesis of Highly Functionalized Cyclopropanes 3
from Allenoates 2 and Aldehydes 1a
1
cyclopropanes 3 were well identified by H and 13C NMR
spectra and in some cases also by NOESY spectra and X-ray
crystallographic analyses16 (for details, see Supporting In-
formation).
entry
Ar
2-ClC6H4
4-ClC6H4
2-FC6H4
4-FC6H4
2,4-Cl2C6H3
4-IC6H4
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2-CF3C6H4
4-CF3C6H4
2-CNC6H4
R
time (h) yield (%)b
drc
1
2
3
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
23
46
16
41
12
45
14
6
3a, 96
3b, 71
3c, 84
3d, 57
3e, 97
3f, 78
3g, 99
3h, 98
3i, 82
3j, 93
3k, 98
3l, 91
3m, 88
3n, 78
3o, 99
3p, 86
3q, 71
3r, 50
3s, 35
3t, 31
3u, 53
3v, 51
3w, 68
3x, 63
3y, 57
10:1
10:1
9:1
>20:1
5:1
>20:1
3:1
5:1
Interestingly, the introduction of a methyl group into the
allenoate 2a at the γ-carbon dramatically changed its
reactivity pattern: under similar conditions for the cyclopro-
panation, the resulting R,γ-disubstituted allenoate 2e pre-
dominantly underwent a phosphine-catalyzed [3 + 2]
annulation with aldehydes, producing tetrahydrofurans 4 in
good yields (eq 2). This result is well consistent with our
findings in the prior study on γ-substituted allenoates and
aldehydes.8l
4d
5e
6d
7
8e
9
5
4:1
10
11
12
13
14
15
16
17
19
11
17
13
22
12
3
>20:1
>20:1
3:1
5:1
8:1
3-CH3O-2-NO2C6H3 CO2Et
2-pyridyl
3-pyridyl
4-pyridyl
2-furyl
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CN
6:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
2.5:1
>20:1
>20:1
71
60
60
69
24
7
18d C6H5
19d 4-CH3C6H4
20d 2-CH3OC6H4
To better elucidate the cyclopropanation mechanism,
deuterium-labeling and 31P NMR monitoring experiments
were run. A deuterated allenoate 2a-d2 (80% D) was
subjected to the reaction with 2,4-dichlorobenzaldehyde (1e)
under anhydrous conditions (eq 3). Four deuterated isomeric
cyclopropanes 3e-d2 were obtained in 98% combined yield
with 72-75% deuterium at the γ-carbon. This result clearly
indicated that the γ-hydrogen of the allenoate did not
21f
22f
23f
24f
25f
4-CF3C6H4
4-NO2C6H4
3-CH3O-2-NO2C6H3 CN
2,4-Cl2C6H3
2-pyridyl
CN
12
22
13
CN
CN
a For a typical procedure, see Supporting Information. b Combined yield
of isolated diastereomers of 3 (based on aldehyde 1). c Calculated by the
major (trans,Z)-3 versus the sum of other diastereomers on the basis of the
isolated yields or H NMR assay. d Allenoate 2 and PPh3 were both used
1
in 2.0 equiv. e Reaction temperature: -10 °C. f Run at -20 °C.
(14) A phosphine-mediated olefination of salicylic aldehydes with
R-methyl allenoate was reported: He, Z.; Tang, X.; He, Z. Phosphorus Sulfur
Silicon Relat. Elem. 2008, 183, 1518–1525.
(15) Our speculation about the failure of the cyclopropanation in ethanol
is that ethanol inhibited the transformation from 8 to 9 according to the
proposed mechanism (Scheme 1).
of aldehydes were examined with the allenoate 2a. Aromatic
aldehydes with halogen or electron-withdrawing groups
readily gave the desired cyclopropanes 3 in fair to excellent
yields and modest to high diastereoselectivity (entries 1-13).
(16) The ORTEP presentations and CIF files of (trans,E)-3i and
(trans,Z)-3v (CCDC 752167; 752168) are available in the Supporting
Information.
546
Org. Lett., Vol. 12, No. 3, 2010

significantly participate in any intramolecular hydrogen
exchanges. In contrast, with 1.5 equiv of D2O added, the
nondeuterated 2a reacted with 4-chlorobenzaldehyde (1b),
solely giving deuterated (trans,Z)-3b in 65% yield with
10-27% D incorporations at the ꢀ-, ꢀ′-, and γ-carbons (eq
4). This result implied that in the presence of D2O H/D
exchanges took place at the aforementioned carbons during
the reaction. Furthermore, monitoring the reaction between
2a and 1a under the mediation of PPh3 by 31 P NMR revealed
the formation of two phosphorus-containing intermediate
corresponding signals at δ 20.73 and 16.47 ppm with a
relative intensity ratio of ca. 3:1. These 31P NMR chemical
shifts strongly implied that the intermediates were tetravalent
phosphorus species,17 which disappeared over 24 h at the
completeness of the reaction (for details, see Supporting
Information).
formation of a more stable phosphorus ylide 8.18 It is
believed that a conjugative and electron-withdrawing group
R, e.g., CO2Et or CN, in 2 facilitates the transformations
from 6 to 8. By this means, the nature of the R group
critically affects this cyclopropanation, as observed in this
study. Theoretically, the ylide 8 contains a pair of isomers
(E)-8 and (Z)-8 owing to the variation of the alkene
configuration. The observation of two 31P signals at δ 20.73
and 16.47 ppm in 31P NMR tracking experiment provides
strong evidence on the existence of 8.19 Subsequently, the
ylide 8 reversibly converts into an oxaphospholane 9 which
undergoes C-P bond cleavage followed by intramolecular
SN2 displacement to bring about the cyclopropane 3 and
phosphine oxide.20 Accordingly, the trans stereoselectivity
of the cyclopropane 3 can be well rationalized with regard
to the SN2 ring closure step.
In conclusion, a novel phosphine-mediated reductive
cyclopropanation of R-substituted allenoates with aldehydes
was demonstrated. This cyclopropanation represents a new
allene-based annulation which provides facile access to
highly functionalized cyclopropanes 3 from simple and
readily available starting materials. It also unveils an
unprecedented reactivity mode between allenoates and al-
dehydes under the mediation of nucleophilic phosphines. In
the reaction, the phosphine acts as both a nucleophilic trigger
to generate the reactive zwitterions 5 and a deoxygenating
agent. Recently, dual-functional phosphine of strong nucleo-
philicity and deoxygenating ability has gained renewed
interest in new organic transformations.21 Following this new
cyclopropanation mode, future efforts in our laboratory will
focus on developing a general methodology to construct
diversely functionalized cyclopropanes from readily available
activated olefins or alkynes, aldehydes, and phosphines.
On the basis of these results and previous studies by Kwon
and others,8n,12 a plausible mechanism for this reductive
cyclopropanation is presented in Scheme 1, in which the
Scheme 1. Plausible Mechanism for the Cyclopropanation
Acknowledgment. Financial support from National Natu-
ral Science Foundation of China (Grant nos. 20872063;
20672057) is gratefully acknowledged.
Supporting Information Available: Experimental details
and spectral data for all new compounds 3 and 4, as well as
the X-ray crystallographical data for representative com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL902747C
(18) Phosphorus has the ability to stabilize the ylide-like structure which
is commonly proposed as a key intermediate in nucleophilic phosphine
catalysis. For typical examples, see: (a) Ref 8b. (b) Evans, C. A.; Miller,
S. J. J. Am. Chem. Soc. 2003, 125, 12394.
(19) Those 31P NMR data provided diagnostic information to distinguish
8 from 9. The 1-2λ5-oxaphospholane ring system like 9 is expected to
exhibit a 31P NMR resonance signal in the δ -40 to -60 ppm range. See:
Adam, W.; Harrer, H. M.; Treiber, A. J. Am. Chem. Soc. 1994, 116, 7581–
7587.
phosphine fulfills two roles: a nucleophile and a deoxygen-
ating agent. Initially, PPh3 undertakes a nucleophilic attack
at the allenoate 2, producing a resonance-stabilized zwitte-
rionic intermediate 5. Addition of 5 to an aldehyde generates
an alkoxyphosphonium zwitterion 6, which undergoes proton
transfer followed by double bond migration, leading to the
(20) Similar mechanisms are commonly proposed in other phosphorus
ylide-involved cyclopropanation reactions. For leading reports, see: (a)
Denney, D. B.; Vill, J. J.; Boskin, M. J. J. Am. Chem. Soc. 1962, 84, 3944.
(b) Schweizer, E. E.; Creasy, W. S. J. Org. Chem. 1971, 36, 2379. (c)
Avery, T. D.; Fallon, G.; Greatrex, B. W.; Pyke, S. M.; Taylor, D. K.;
Tiekink, E. R. T. J. Org. Chem. 2001, 66, 7955.
(17) Hudson, H. R.; Dillon, K. B.; Walker, B. J. 31P NMR Data of Four
Coordinate Phosphonium Salts and Betaines. In Handbook of Phosphorus-
31 Nuclear Magnetic Resonance Data; Tebby, J. C., Ed.; CRC Press: Boca
Raton, FL, 1991; pp 181-226.
(21) For representative examples, see: (a) Ref 13. (b) Low, K. H.;
Magomedov, N. A. Org. Lett. 2005, 7, 2003. (c) McDougal, N. T.; Schaus,
S. E. Angew. Chem., Int. Ed. 2006, 45, 3117.
Org. Lett., Vol. 12, No. 3, 2010
547