Fragmentation Reactions of Quaternized γ-Amino Alcohols – Diastereoselective Synthesis of Highly Functionalized Oxetanes and Unsaturated Aldehydes and Ketones with a (Z)-CC Double Bond
✍ Scribed by Detlef Mölm; Ulrich Flörke; Nikolaus Risch
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 248 KB
- Volume
- 1998
- Category
- Article
- ISSN
- 1434-193X
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✦ Synopsis
Quaternized γ-amino alcohols 5 derived from ternary bond in a Grob-type fragmentation and highly functionalized oxetanes 7 by intramolecular substitution. iminium salts 2 are stereospecifically converted into both unsaturated aldehydes/ketones 6 with a (Z)-CϪC double Scheme 1
Typical methods used for the preparation of the synthetically very useful unsaturated carbonyl compounds include the base-induced fragmentation of monotosylated 1,3-diols [1] [2] [3] [4] [5] [6] , flash thermolysis of γ-hydroxyammonium compounds [7] and the selective CϪC bond cleavage of quaternized β-amino aldehydes and β-amino ketones [8] . In most cases, the generated CϪC double bond is an exomethylene group. Only a few examples are known in which fragmentation reactions lead specifically to unsaturated compounds with either (E)-or (Z)-CϪC double bonds [9] [10] [11] .
We now wish to report a method for obtaining not only aldehydes and ketones 6 with a (Z)-CϪC double bond by a Grob-type fragmentation but also highly functionalized oxetanes by the intramolecular substitution of readily available quaternized γ-amino alcohols 5.
Functionalized oxetanes have attracted much interest, since they can undergo preparatively valuable ring-opening reactions [12] [13] [14] [15] [16] .
figuration of 4bЈЈ was determined by a single-crystal X-ray structure analysis (Figure 1). Using these data we assigned
Results and Discussion
the relative configuration of 4Ј and 4ЈЈ to all entries a؊h [20] [21] [22] (Table 1). The efficient CϪC bond formation of enamines 1 with preformed ternary iminium salts 2 is the basis of our syn-
The excellent diastereoselectivities for formation of the tertiary amino alcohols 4d؊h are remarkable. The sub-thetic strategy. This type of Mannich reaction is easy to perform and guarantees good yields, an excellent anti dia-sequent quaternization of 4 to the ammonium iodides 5 by refluxing with methyl iodide transforms the amino group stereoselectivity and a great diversity of β-amino ketones 3 [17] . This high diastereoselectivity is essential for the ensu-into a suitable leaving group which is necessary for the reactions that follow [8] . ing fragmentation and intramolecular substitution reaction, respectively.
In the course of our previous research on bond cleavage reactions of 1-azaadamantane derivatives, quaternized β-The reduction of 3 was carried out with NaBH 4 and yielded the amino alcohols 4 (R ϭ H) [18] [19] . The addition amino ketones and β-amino aldehydes, NaH in THF was found to be very effective for inducing fragmentation reac-of Grignard reagents gave 4 (R ϭ Me, Et, Bzl, Ph and naphthyl) [20] [21] [22] . The diastereoselectivities of these reac-tions [8] [23] . Under similar reaction conditions we observed, that the isomers 5Ј and 5ЈЈ react in a different manner. 5Ј tions are shown in Table 1.
The mixture of isomers of 4b was separated chromato-was converted exclusively to the expected compounds 6 by CϪC bond cleavage. However, 5ЈЈ was transformed to the graphically into the diastereoisomers 4bЈ and 4bЈЈ. The con-