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Preparation and reactions of silyl nitronates derived from 2,2,2‐trifluoronitroethane. Diastereoselective synthesis of trifluoromethyl‐substituted aminoethanols and ‐propanols
Author(s) -
Marti Roger E.,
Heinzer Josef,
Seebach Dieter
Publication year - 1995
Publication title -
liebigs annalen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0947-3440
DOI - 10.1002/jlac.1995199507162
Subject(s) - chemistry , silylation , nitronate , trifluoromethyl , raney nickel , medicinal chemistry , diastereomer , deprotonation , nitro , isomerization , trimethylsilyl , protonation , organic chemistry , stereochemistry , catalysis , ion , alkyl
Silyl nitronates of 2,2,2‐trifluoronitroethane and of 1,1,1‐trifluoro‐2‐nitropropane [SiMe 3 , SiMe 2 ( t Bu), SiMe 2 CMe 2 ‐CHME 2 ] were prepared and their reactions studied. – The TBDMS nitronate of the nitroethane is present at the ( E ) and (Z) isomer (2.3:1 at room temperature; E A = 9.3 kcal mol −1 for their isomerization). BU 4 NF‐catalyzed silyl nitro aldol additions to aldehydes show reasonable selectivities for the formation of the syn diastereoisomers of 5–13 (a. 4:1; with the non‐fluorinated analogs anti isomers prevailing!). The anti epimers (5–9, 12, 13, 17–20) in the trifluoromethyl series can be prepared by diastereoselective protonation of the corresponding O‐silyl lithium nitronates (ca. 9:1, Scheme 3). Careful reduction of the NO 2 groups (H 2 /Raney nickel) gives trifluoroamino alcohol derivatives (22–30, Scheme 4). –The trimethylsilyl nitronates are also used for 1,3‐dipolar cycloadditions (to 1‐hexene, styrene, methyl vinyl ketone, and acrylates) to give N ‐(silyloxy)isoxazolidines (2–40; Scheme 5). The configuration of the major products (2,3‐ cis , 3,5‐ trans ) was derived from NMR measurements, X‐ray structure determinations, and thermal equilibration studies. The major course of reactions was thus derived to be an exo approach of the dipolarophiles to the ( Z )‐silyl nitronates (Scheme 8).– Some conversions of the N ‐(silyloxy)isoxazolidines (treatment with acid, base, and Raney nickel) are also described (products 42–51).