Communications
At the outset, we explored the reaction of phenylacety-
We next turned our attention to the cyclopropenation
lene (5a) with 2,4-dimethyl-3-pentyl a-diazopropionate (6a)
in dichloromethane at room temperature using dirhodium(II)
carboxylate catalysts 1a–c (1 mol%) that incorporate N-
phthaloyl-(S)-amino acids as bridging ligands (Table 1,
reaction of 5a with a-diazobutanoates bearing more reactive
ꢁ
ꢁ
C H bonds at the b position than the methyl C H bonds of a-
diazopropionate (Table 2). The reaction with 2,4-dimethyl-3-
pentyl a-diazobutanoate (6b) using [Rh2(S-tbpttl)4] (1 f)
Table 1: Enantioselective cyclopropenation of phenylacetylene (5a) with
2,4-dimethtyl-3-pentyl a-diazopropionate (6a) catalyzed by chiral RhII
carboxylates.[a]
Table 2: Enantioselective cyclopropenation of phenylacetylene (5a) with
a-alkyl-a-diazoesters 6 catalyzed by chiral RhII carboxylates.
Entry
6
R1
R2
RhII t [h] 7/8[a]
7
Yield ee
Entry
RhII
T [8C]
t [h]
Yield [%][b]
ee [%][c]
[%][b] [%][c]
1
2
3
4
5
6
7
8
[Rh2(S-pttl)4] (1a)
[Rh2(S-ptv)4] (1b)
[Rh2(S-pta)4] (1c)
[Rh2(S-tfpttl)4] (1d)
[Rh2(S-tcpttl)4] (1e)
[Rh2(S-tbpttl)4] (1 f)
[Rh2(S-tbpttl)4] (1 f)
[Rh2(S-tbpttl)4] (1 f)
23
23
23
23
23
0.2
0.2
0.2
0.2
0.2
0.2
4
86
78
91
80
89
94
89
90
46
36
38
35
72
85
94
95
1
2
3
4
5
6
7
8
6b Me
6b Me
6b Me
6b Me
6c Me
6d Me
6e Me
6 f Et
iPr2CH 1 f 11
87:13 7b 78
54:46 7b 48
29:71 7b 26
77:23 7b 58
95
53
42
85
96
50
51
99
99
98
99
98
iPr2CH 1a
iPr2CH 1d
iPr2CH 1e
7
0.3
7
tBu
iPr
Et
1 f
1 f
1 f
6
3
0.5
48:52 7c
40
23
31:69 7d 25
ꢁ40
27:73 7e
22
93
ꢁ60
5
iPr2CH 1 f 12
iPr2CH 1 f 22
iPr2CH 1 f 22
>99:1 7 f
9
6g nPr
6h iBu
6i n-C7H15
92:8 7g[d] 84
84:16 7h 71
[a] All reactions were carried out as follows: RhII catalyst (1 mol%) was
added to a solution of 5a (1.0 mmol, 5 equiv) and 6a (0.20 mmol) in
CH2Cl2 (0.1m). [b] Yield of isolated product. [c] Determined by HPLC on
a chiral stationary phase using a Daicel Chiralpak IC column.
10
11
12
iPr2CH 1 f
4
94:6 7i
94:6 7j
85
88
6j Ph(CH2)3 iPr2CH 1 f 24
1
[a] Determined by H NMR spectroscopy of the crude reaction mixture.
[b] Yield of isolated product. [c] Determined by HPLC on a chiral
stationary phase using a Daicel Chiralpak IC column. [d] The preferred
entries 1–3). Although all of these catalysts provided the
corresponding cyclopropene product 7a in good to high yields
with no signs of alkene product 8a,[16] the highest level of
enantioselectivity was only 46% ee when [Rh2(S-pttl)4] (1a)
was used (Table 1, entry 1). Notably, syringe-pump tech-
niques for slow addition of the diazo compound 6a were not
necessary to prevent the formation of dimeric products such
as carbenes dimers[17] and azines.[12b,c] Focusing on [Rh2(S-
pttl)4]-type catalysts, we then evaluated the performance of
[Rh2(S-tfpttl)4] (1d)[18] and [Rh2(S-tcpttl)4] (1e),[19,20] which
are fluorinated and chlorinated analogues of 1a and therefore
could bring about an electron deficiency on the rhodium(II)
center. Although 1d gave poor enantioselectivity (35% ee;
Table 1, entry 4), catalysis with 1e provided cyclopropene
derivative 7a in 89% yield with 72% ee (Table 1, entry 5). At
this stage, we envisaged that switching to larger halogen
atoms could lead to further enhancement of the enantiose-
lectivity. Thus, [Rh2(S-tbpttl)4] (1 f) was prepared from [Rh2-
(OAc)4] by a ligand exchange reaction[21,22] with N-tetrabro-
mophthaloyl-(S)-tert-leucine.[23] Pleasingly, the cyclopropena-
tion under catalysis with 1 f produced 7a in 94% yield with
85% ee (Table 1, entry 6). A survey of solvents with 1 f
revealed that dichloromethane was the optimal solvent for
this transformation.[24,25] Enantioselectivity was further
enhanced up to 95% ee using 1 f without compromising
product yield when the reaction was conducted at ꢁ608C
(Table 1, entry 8). The preferred absolute configuration of 7a
21
absolute configuration of 7g [½aꢂD ¼ꢁ78.0 (c=1.08, EtOH) for 99% ee]
was established as R by its conversion to the known (1R,2S)-ethyl 1-butyl-
23
2-phenylcyclopropane-1-carboxylate [½aꢂD ¼ꢁ81.8 (c=1.18, CHCl3);
29
Ref. [14], ½aꢂD ¼+67 (c=0.93, CHCl3) for the 1S,2R enantiomer] (see
the Supporting Information).
provided cyclopropene product 7b in 78% yield with
95% ee, along with (Z)-alkene 8b (7b/8b = 87:13; Table 2,
entry 1). In stark contrast, catalysis with [Rh2(S-pttl)4] (1a),
[Rh2(S-tfpttl)4] (1d), or [Rh2(S-tcpttl)4] (1e) was accompa-
nied with a significant decrease in enantioselectivity as well as
the formation of substantial amounts of (Z)-alkene 8b
(Table 2, entries 2–4). The effect of the ester moiety was
examined using 1 f as the catalyst. Although the use of tert-
butyl ester 6c gave a similar high enantioselectivity (96% ee;
Table 2, entry 5), reactions with ethyl and isopropyl esters 6d
and 6e resulted in only modest enantioselection (50–51% ee;
Table 2, entries 6 and 7). In these reactions, poor product
yields (22–40%) were obtained owing to the formation of a
large amount of (Z)-alkenes 8c–e (Table 2, entries 5–7).
These findings clearly demonstrate that the combined use of
[Rh2(S-tbpttl)4] (1 f) and 2,4-dimethyl-3-pentyl ester
moiety[27] is crucial for high levels of both enantio- and
chemoselectivities. By using this optimal combination, we
explored the reaction with a range of a-alkyl-a-diazoesters.
Switching the R1 substituent from a methyl group to ethyl,
propyl, or isobutyl groups gave cyclopropenes 7 f–h with good
to high chemoselectivities (7/8 from 84:16 to > 99:1) and
exceptionally high enantioselectivities (98–99% ee; Table 2,
entries 8–10). Although a-alkyl-a-diazoesters 6i and 6j are
21
[½aꢂD ¼ꢁ125 (c = 1.09, EtOH) for 95% ee] was established as
R by its conversion to the known (1S,5R)-5-methyl-3-
24
oxabicyclo[3.1.0]hexan-2-one
EtOH); Ref. [26], ½aꢂD ¼ꢁ53.3 (c = 1.0, EtOH) for the
(1S,5R)-enantiomer] (see the Supporting Information).
[½aꢂD ¼ꢁ49.6
(c = 1.02,
26
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 6803 –6808