C O M M U N I C A T I O N S
Table 2. Regiodivergent Epoxide Opening of Unbiased Substrates
(See Supporting Information for Details)
Table 3. Regiodivergent Epoxide Opening for the Synthesis of
Derivatives of 1,2- and 1,3-Diols (See Supporting Information)
entry
substrate
catalyst
product
yield/%
10/11a
10/erb
11/erb
1
2
3
4
9a
9a
9b
9b
3
10a/11a
10a/11a
10b/11b
10b/11b
85
81
77
74
54:46 10:90 96:4
52:48 91:9 3:97
66:34 19:81 99:1
80:20 65:35 10:90
ent-3
3
ent-3
a Determined by 1H NMR analysis of the purified products. For
Cp2TiCl2: 9a, 72:28; 9b, 90:10. b Absolute configuration not determined.
Measured from products and separated lactones.
entry
substrate
catalyst
product
yield/%
7/8a
7/erb
8/erb
1
2
3
4
5
6
7
8
6a
6a
6b
6b
6c
6c
6d
6d
3
7a/8a
77
88
73
76
82
86
89
88
86:14 99:1
18:82 35:65
82:18 99:1
12:88 45:55
84:16 0.5:99.5 34:66
4:96 40:60 0.5:99.5
83:17 0.5:99.5 70:30
12:88 50:50 0.5:99.5
66:34
99:1
53:47
99:1
In summary, we have devised the first regiodivergent opening
of unbiased epoxides that provides the ring-opened products in high
enantiomeric excess from racemic and exceptionally high enantio-
meric purity from enantioenriched substrates in a double asymmetric
process. It constitutes a more general case of the very important
enantioselective openings of meso-epoxides.
ent-3 7a/8a
7b/8b
ent-3 7b/8b
7c/8cc
ent-3 7c/8cc
7d/8dc
ent-3 7d/8dc
3
3
3
a Determined by 1H NMR analysis of the crude mixture; 7/8 with
Cp2TiCl2 was about 40:60 in all cases (see Supporting Information).
b (R)/(S) from configuration of substrates. c Zn used instead of Mn; 7 and
8 not separated.
Acknowledgment. We thank the DFG (Ga 619/5-1) and the
Alexander von Humboldt-Stiftung for financial support.
Supporting Information Available: Experimental details and
compound characterization. This material is available free of charge
Scheme 3. Regiodivergent Epoxide Opening for the Synthesis of
Derivatives of 1,2- and 1,3-Diols
References
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and the minor pathway of the minor complex. This double
asymmetric process results in major products with much higher
enantiomeric purity than the substrate, exactly as found for 2. Table
2 summarizes further examples of the reaction.
Our reaction is general and ester substitution is not necessary
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intermediates for the synthesis of γ- and δ-lactones.10 By treatment
of 8b with TsOH, (R)-4-dodecanolide,11 a defensive secretion of
beetles, was obtained (92%) with the highest enantiomeric purity
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of cheddar,12 was obtained (96%). Reactions with glycidol ethers
were also carried out (Scheme 3).
In these substrates chelation of titanium constitutes an additional
potential control element for the regioselectivity of ring opening.
This has been demonstrated to be very important in the reactions
of the “Sharpless” epoxides.2b The products of ring opening,
derivatives of 1,2- and 1,3-diols are important intermediates for
the synthesis of complex molecules. Our results are summarized
in Table 3.
For simple alkylethers (entries 1-2), the possible chelation does
not affect the reagent controlled course of the reaction. Thus
derivatives of both 1,2- and 1,3-diols become available in high
enantiomeric purity from racemic substrates similar to the reactions
of 1. However, with two chelating groups in one substituent a
partially substrate controlled reaction results, displaying matched
and mismatched cases of selectivity of ring opening (entries 3-4).
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