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ratio from 1:1 to 1:2 caused the enantiomeric excess of the
ketones with aromatic R4 groups, both L1 and L2 ligands gave
the desired products in high yields with excellent enantio- and
diastereoselectivity (d.r. > 20:1) (Table 2, entries 1–7). How-
ever, placing aliphatic R2 substituents on the olefin moiety or
R3 substituents on the alkyne moiety of the ketone resulted in
dramatic decreases in enantio- and diastereoselectivity. For
examples, the bicyclic products 3da with R3 = nBu (L1;
Table 2, entry 8) and 3ea with R2 = nBu (Table 2, entry 9)
were obtained under the catalysis of [L1(AuCl)2]/AgOTf in
55% and 75% ee, respectively. These results indicate that
there is a steric demand to obtain excellent enantioselectivity.
Gratifyingly, a cyclohexenyl group was tolerated as R3, and
was bulky enough to afford excellent yield and enantioselec-
tivity (Table 2, entry 11; see entry 12). The attempt to
improve ee values of 3da and 3ea by using an [L2(AuCl)2]/
AgOTf complex as the catalyst failed, thus providing the
desired products with even lower ee values (L2, Table 2,
entries 8 and 9). The reactions of cyclic ketone 1h with
nitrones 2a–f (Table 2, entries 13–18) proceed smoothly to
give the corresponding bicyclic products in good yields and
greater than 92% ee with the use of either L1 or L2 as ligand.
The (R)-C1-tunephos complex gave a higher enantioselectiv-
ity than (R)-MeO-dtmb-biphep for the reaction of 1h with N-
benzyl nitrone 2g at room temperature (Table 2, entry 19).
The absolute configuration of the products were confirmed by
single-crystal X-ray diffraction analysis of representative
compounds 3ae and 3he (Figure 1).[10]
product to decrease from 95% to 76% (Table 1, entries 2–4).
There is an obvious solvent effect on the reactivity and
diastereoselectivity rather than enantioselectivity. No reac-
tion occurred in toluene or ether, despite chloroform giving
3aa in excellent enantiomeric excess but with a relatively
lower diasteroselectivity (Table 1, entry 6). Moreover, the
excellent enantioselectivity was maintained when AgPF6
(Table 1, entry 7), AgBF4 (Table 1, entry 8), or AgSbF6
(Table 1, entry 9) were employed as silver additives. Replace-
ment of C1-tunephos with C2- or C3-tunephos led to lower
enantioselectivities (Table 1, entries 10 and 11). To our
delight, introduction bulky substituents onto the phosphine
aryl rings (R)-MeO-dtbm-biphep also dramatically increased
the enantioselectivity in comparison to (R)-MeO-biphep, thus
providing 3aa in 94% yield with 99% ee at 08C. In contrast,
the gold(I) complexes of (S)-binap (binap = 2,2’-bis(diphe-
nylphosphanyl)-1,1’-binaphthyl) and (R)-tolyl-binap induced
29% and 38% ee, respectively, but with the enantiomer ent-
3aa as the major isomer for the latter case (Table 1, entries 13
and 14).
Under the optimized reaction conditions, various (1-
alkynyl)-2-alken-1-ones and nitrones were examined to study
the scope and limitations of this enantioselective gold(I)-
catalyzed tandem reaction (Table 2). In general, for those
Table 2: Reaction scope.[a]
Entry Product
R
Yield [%] (%ee)
L1 L2
1
2
3
4
5
3ab R4 =1-furanyl
3ac R4 =4-NO2C6H4
3ad R4 =4-MeOC6H4
3ae R4 =4-BrC6H4
3af R4 =styryl
90 (96) 97 (96)
93 (95) 93 (97)
98 (95) 95 (95)
85 (94) 95 (95)
97 (97) 88 (97)
Figure 1. X-ray crystal structures of compounds 3ae (left) and 3he.
Ellipsoids are drawn at the 30% probability level.[10]
6
7
8
9
3ba R2/R3 =Ph/4-MeC6H4
99 (92) 99 (95)
3ca R2/R3 =Ph/4-MeOC6H4 72 (96) 99 (95)
3da R2/R3 =Ph/n-C4H9
3ea R2/R3 =n-C4H9/Ph
77 (55) 59 (32)
92 (75) 84 (64)
The structure of gold complexes 4 (Figure 2) and 5
(Figure 3) were also determined by single-crystal X-ray
diffraction analysis.[10] The dihedral angels of complexes 4
10
11
12
3 fa R3 =Ph
92 (93) 94 (98)
99 (92) 87 (94)
92 (28) 62 (4)
3ga R3 =1-cyclohexenyl
3ia R3 =1-hexenyl
À
and 5 were 63.3 and 77.78, respectively. Interestingly, the Au
Au bond lengths of complexes 4 and 5 were 2.994 and 5.316 ꢀ,
À
respectively, which indicates the presence of Au Au inter-
actions in complex 4 but not complex 5.[11] This Au Au
À
13
14
15
16
17
18
19[b]
3ha R4/R5 =Ph/Ph
90 (97) 75 (97)
84 (98) 63 (97)
interaction lends the structure of complex 4 a degree of
rigidity. This difference may account for the observation that
complex 4 gives better results than complex 5 for substrates
with flexible alkyl groups (Table 2, entries 8 and 9).
3hb R4/R5 =1-furanyl/Ph
3hc R4/R5 =4-NO2C6H4/Ph 84 (98) 82 (97)
3hd R4/R5 =4-MeOC6H4/Ph 74 (92) 55 (97)
3he R4/R5 =4-BrC6H4/Ph
3hf R4/R5 =styryl/Ph
3hg R4/R5 =Ph/Bn
94 (95) 78 (97)
74 (96) 51 (94)
61 (84) 59 (57)
Furthermore, catalyst loading could be reduced to
0.2 mol% with a larger reaction scale (5 mmol) without loss
of any selectivity and efficiency, providing 3aa in quantitative
yield with 93% ee [Eq. (1)]. To our delight, enantioenriched
[a] L1: the reaction temperature is À108C for entries 1-11, À308C for
entries 12–18; L2: 08C for entries 1–18. [b] Room temperature.
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 6669 –6672
Liu, Feng
