Propanoyl-iron complexes

Asymmetric aldol reactions are also possible with chiral propanoyl-iron complexes, as shown in Scheme 62. ° Good to excellent stereoselectivities for anti aldol products (140) are obtained when the lithium enolate of the propanoyl-iron complex is treated with 3 equiv. of EtaAlCl at -40 °C, followed by an aldehyde at -100 °C. Interestingly the same reaction using CuCN instead of Et2AlCl provides exclusively syn aldol products (141). 

The lithium enolate 2a (M = Li ) prepared from the iron propanoyl complex 1 reacts with symmetrical ketones to produce the diastercomers 3 and 4 with moderate selectivity for diastereomer 3. The yields of the aldol adducts are poor deprotonation of the substrate ketone is reported to be the dominant reaction pathway45. However, transmetalation of the lithium enolate 2a by treatment with one equivalent of copper cyanide at —40 C generates the copper enolate 2b (M = Cu ) which reacts with symmetrical ketones at — 78 °C to selectively produce diastereomer 3 in good yield. Diastereomeric ratios in excess of 92 8 are reported with efficient stereoselection requiring the addition of exactly one equivalent of copper cyanide at the transmetalation step45. Small amounts of triphcnylphosphane, a common trace impurity remaining from the preparation of these iron-acyl complexes, appear to suppress formation of the copper enolate. Thus, the starting iron complex must be carefully purified. 

In continuation of their research on N-hydroxypeptides Akiyama s group obtained the anilide hexapeptide with a 6-aminohexanoyl-3-(hydroxyamino)propanoyl sequence (225). This linear tri-N-hydroxy-amide bears a structural resemblance to the natural siderophores fer-rioxamines. Cyclic voltametry and UV spectrometry were used for the study of its iron complex. The key substrate was obtained by the addition of benzyloxyamine to / -nitrophenyl acrylate. 

Treatment of tricarbonylh4-1-(ethoxycarbonyl)-l//-azepine]iron(0) (30) with acetic anhydride and tetrafluoroboric acid at 0 C (Method A) yields the 3-acetyl derivative 31.226 The acetyl derivative is also formed, but in lower yield, by the action of acetic anhydride and tin(IV) chloride (Method B) on complex 30. The 3-propanoyl derivative (20% mp 95-96 C) can be prepared similarly, whereas formylation to give aldehyde 32 is successful under Vilsmeier conditions. 

Iron-acyl enolates such as 1, 2, and 3 react readily with electrophiles such as alkyl halides and carbonyl compounds (see Houben-Weyl, Vol. 13/9a p418). The reactions of these enolatc species with alkyl halides and similar electrophiles are discussed in Section D.1.1.1.3.4.1.3. To date, only the simple enolates prepared by a-deprotonation of acetyl and propanoyl complexes have been reacted with ketones or aldehydes. 

Aldol Additions of Enolatcs of Chiral Iron-Propanoyl Complexes... 

Reaction of the lithium enolate 2 with prochiral aldehydes at low temperature proceeds with little selectivity, producing all four possible diastereomers 3, 4, 5, and 6 in similar amounts50. Transmetalation of the lithium enolate by treatment with three equivalents of diethylaluminum chloride or with one equivalent of copper cyanide generates the corresponding cthylaluminum and copper enolates which react at — 100°C with prochiral aldehydes to produce selectively diastereomers 1 and 2, respectively50. The reactivity of tin enolates of iron- propanoyl complexes has not been described. 

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