Hydroxyalkylierungen von Cystein über das Enolat von (2R,5R)-2(tert-Butyl)-1-aza-3-oxa-7-thiabicyclo[3.3.0]octan-4-on und unter Selbstreproduktion des Ciralitätszentrums
✍ Scribed by Dieter Seebach; Theodor Weber
- Publisher
- John Wiley and Sons
- Year
- 1984
- Tongue
- German
- Weight
- 777 KB
- Volume
- 67
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
Abstract
Hydroxyalkylations of Cysteine through the Enolate of (2__R__,5__R__)‐2(tert‐Butyl)‐1‐aza‐3‐oxa‐7‐thiabicyclo[3.3.0]octan‐4‐one with Self‐Reproduction of the Center of Chirality
The heterobicyclic compound 1 specified in the title is readily prepared as a single stereoisomer from (R)‐cysteine, formaldehyde, and pivalaldhyde. While it is not possible to generate the enolate 10 from 1 qunatitatively – due to β‐elimination of thiolate (→6) – an in‐situ addition to aromatic aldehydes such as benzaldehydes (→13–16), pyrrol‐, furan‐, and thiophen‐2‐carbaldehydes (→17–19), pyridine‐3‐carbaldehyde (→21), as well as to other non‐enolizable aldehydes like cinnamaldehyde (→22), can be achieved in yields of ca. 50%. The adducts (8 and 9) of lithium diisopropylamide or t‐butoxide to these aldehydes are acting, probably as bases for deprotonation and as in‐situ sources of the electrophilic aldehyde species (cf. 11, 12). ‐ Of the four possible diastereoisomeric products, one is usually formed with >90% selectivity (Table). It is assumed that the preferred stereochemical course of the reaction corresponds to that observed previously with the analogous proline‐derived enolate (See 23,24). A chemical correlation with l‐α‐methyl‐β‐phenylserine (25) proves the relative configuration of the benzaldehyde adduct 13. All hydroxyalkylated products (13–19, 21, 22) are obtained as crystalline, diastereoisomerically pure compounds and are fully characterized. – The benzaldehyde derivative 13 was used to exemplify the various possible transformations of these products to monocyclic or acyclic amino‐acid derivatives such as the oxazolidionenes 26 and 29 (cleavage of the ring containing the S‐atom), the thiazolidines 28, 31, and 32 (cleavage of the cyclic N,O‐acetal) and the α‐branched cysteine 27 and the phenylserines 25 and 30 (cleavage of both rings to give open‐chain aminoacids).