Iron derivatives stereochemistry

Our knowledge of the stereochemistry of porphyrins and related tetrapyrrole macrocycles has expanded rapidly since the first reported x-ray structure determination in 1959 The structures of metallotetrapyrrole complexes are of interest because of the common occurrence of this type of macrocycle in biological systems. As is well known, foremost among these are the heme proteins (iron derivatives), the various photosynthetic pigments (magnesium complexes), the vitamin Bn coenzyme (cobalt corrinoids), and coenzyme F430 (nickel corphinoids) of the methanogenic bacteria. 

Treatment of a-alkoxy-substituted iron acyl complexes 20 with bromine in the presence of an alcohol produces free acetals 22 with loss of stereochemistry at the center derived from the a-carbon of the starting complexl2,49. Electron donation from the alkoxy group allows formation of the oxonium intermediate 21, which is captured by the alcohol to generate the product acetal. 

One advantage of this method is the predictable stereochemistry of the alkylation reaction, since the electrophile adds exclusively irons to the substituent in the 2-position. Because of the large variety of usable electrophiles, the bis-lactimether method provides a powerful and versatile tool for preparing a large array of a-amino acids ( glycine derivatives) and a,a-di-substituted amino acids in optically active form. 

Reactions of acyclic derivatives with carbon electrophiles have also been examined.33,34 An illustrative reaction involving methylation of the unsubstituted complex [MnCr 4-butadiene)(CO)3], (19), is shown in Scheme 16. Again, the reaction is presumed to occur via a methylmanganese species (20) and after methyl migration the unsaturated metal center is stabilized by formation of a Mn—H—C bridge (isomers 21a and 21b). Deprotonation of equilibrating (21a and 21b) yields the [Mn(l-methylbutadiene)(CO>3]-complex (22), which has exclusively trans stereochemistry.34 This sequence represents alkylation of the terminal carbon of butadiene and complements the iron carbonyl chemistry, where terminal acylation has been achieved as described above. Unpublished results indicate that a second methylation of (22) occurs... 

Sulfur dioxide readily inserts into metal-carbon tr bonds (136, 137). The reaction is stereospecific with respect to the configuration at the a-carbon atom of the alkyl group (138) and proceeds with inversion of configuration at the a-carbon atom (139-142). The stereospecificity of the S02 insertion with respect to the metal center was demonstrated with diastereoisomeric pairs of enantiomers of Fe compounds (143-146). Also, the stereochemistry of the S02 insertion at the iron atom was studied by starting with the optically active iron alkyl derivative 26a (see Scheme 18). Retention of configuration was concluded from the similarity in the... 

Reaction of FeCo2(CO)9S with a series of phosphines (31, 133) and isocyanides (126) yielded mono-, di-, and trisubstituted derivatives, Eqs. (77) and (78). 57Fe-Mossbauer spectra of the phosphine-substituted derivatives indicated that substitution at cobalt occurs prior to substitution at iron (31). Unfortunately, no crystallographic evidence has been obtained for any of these derivatives, and the precise stereochemistry has not been resolved, even with the aid of l3C-NMR spectra (9). The problem is compounded with the isocyanide ligands since several isomers of the trisubstituted derivatives are formed. 

The carbonyls are in general volatile compounds with an extensive chemistry which presents many problems as regards valence and stereochemistry. Some are reactive and form a variety of derivatives, as shown in Chart 22.1 for the iron compounds, while others are relatively inert, as for example, Cr(CO)6 etc. and Re2(CO)iQ. This rhenium compound, although converted to the carbonyl halides by gaseous halogens, is stable to alkalis and to concentrated mineral acids. A few carbonyls may be prepared by the direct action of CO on the metal, either at atmospheric pressure (Ni(C0)4) or under pressure at elevated temperatures (Fe(CO)s, Co4(CO)i2)- Others are prepared from halides or, in the case of Os and Re, from the highest oxide. The polynuclear carbonyls are prepared photo-synthetically, by heating the simple carbonyls, or by other indirect methods. 

A final example of the use of tartrate-derived crotylboronates in natural product synthesis is illustrated in the formal total synthesis of ikarugamicin (Scheme II-11) [179]. Here, Roush and Wada used the asymmetric crotylboration of meso-(t/" -2,4-hexadien-1,6-dial)iron tricarbonyl 266 with (S,S)-(E)-219 to set three stereocenters in their synthesis of the a,s-indacene unit of ikarugamycin. This key reaction provided 267 in 90% yield and >98% ee. Homoallylic alcohol 267 was converted to the allylic acetate 268, which underwent stereoselective ethylation with EtsAl with retention of stereochemistry. The resulting adduct 269 was subsequently elaborated to as -indacene unit 271 through a 15-step synthetic sequence, including the intramolecular Diels-Alder reaction of 270. 

The Dewar-benzene iron carbonyl derivative [97], like perfluorobicyclo[2,2,0]hexa-2,5-diene itself, undergoes Diels-Alder addition to give [98a and b], with the chemical shifts shown. (53) [98a] is also formed, although in low yield, by the reaction of the preformed Diels-Alder adduct [99] with Na[(7r-C5H5)Fe(CO)2], confirming the stereochemistry of the addition. 

While copper and iron Lewis acids are the most prominent late transition metal Diels-Alder catalysts, there are reports on the use of other chiral complexes derived from ruthenium [97,98],rhodium [99],andzinc [100] in enantioselective cycloaddition reactions, with variable levels of success. As a comparison study, the reactions of a zinc(II)-bis(oxazoline) catalyst 41 and zinc(II)-pyridylbis(ox-azoline) catalyst 42 were evaluated side-by-side with their copper(II) counterparts (Scheme 34) [101]. The study concluded that zinc(II) Lewis acids catalyzed a few cycloadditions selectively, but, in contrast to the [Cu(f-Bubox)](SbFg)2 complex 31b (Sect. 3.2.1), enantioselectivity was not maintained over a range of temperatures or substitution patterns on the dienophile. An X-ray crystal structure of [Zn(Ph-box)] (01)2 revealed a tetrahedral metal center the absolute stereochemistry of the adduct was consistent with the reaction from that geometry and opposite that obtained with Cu(II) complex 31. 

Bond.— Side chain dehydrogenation is reviewed by Lederer. Unlike the dehydrogenations of the steroid nucleus, introduction of the Irons A -double bond of ergosterol and related steroids does not require the presence of a or A -double bond. However, the suggested formation of ergosta-5,7,22,24(28)-tetraen-3) -ol is supported by incorporation studies. The stereochemistry of this process is species-dependent. In protozoa Ochromonas tetrahymena) the (22R)- and (23S)-hydrogens of cholesterol are lost, i.e. the hydrogens at these positions derived from [2R- H,3R]- and [3R,5R-... 

The only main Group III metal, other than boron, that has been utilized in the aldol reaction is aluminum, the enolates of which behave rather capriciously in terms of stereochemistry. The A1—C bond is relatively weak. However, aldol reactions with aluminum enolates derived from chiral acyl-iron complexes proceed with high asymmetric induction. 

It should be noted that all these plakortides have a close structural similarity with plakortin and, therefore, their lower level of antimalarial activity can be utilized to gain useful information about the structure-activity relationships within this class of simple cycloperoxide derivatives. The main differences among these compounds are ascribable to the stereochemistry. Indeed, while in the structure of plakortin the most hindered chains attached to the 1,2-dioxane ring are in cis orientation, in the other analogues a irons orientation is present. Most likely, these latter molecules experience a more problematic approach of the cycloperoxide group to its target. However, the chemical structure of the side chains must be also important, as indicated by the marked difference of activity between plakortides K (53) and L (54) and between plakortides O (55) and P (56). 

The C n.m.r. spectra of santonin (259) and some of its derivatives indicate that the data obtained can be used to determine the stereochemistry of the lactone fusion and the configuration of the methyl group at C-ll. Further work on the chemistry of santonin, santonene, and related compounds has been reported and pyrosantonin has been shown to have structure (260). Pyrolysis of santonin also produces a smaller amount of 1-nordesmotroposantonin (261). Reaction of santonin (259) with nonacarbonyldi-iron at 40 °C produces the two... 

In the past 15 years, a number of reviews have appeared. Two general reviews appeared in the mid 70s Both of these reviews attempted to comprehensively survey the topic of porphyrin stereochemistry up to the time of publication. These two reviews are appropriately consulted for complete information of all work completed to that time. In addition, there have been a number of more specialized reviews pertaining to tetrapyrrole macrocyclic structure. An excellent article by Glusker has detailed the structural work on vitamin B12 derivatives. An early classic review examined the stereochemistry of hemes (iron porphyrinates) and their relationship to the function of the hemoproteins A review of trends in metalloporphyrin stereochemistry as a function of electronic state and position in the periodic table was written by the author in 1977 There are also two subsequent reviews in which the senior author has participated a 1983 article (with Martin Gouterman) that attempted to reach an understanding of control of spin state in metalloporphyrins and a 1981 article (with Christopher A. Reed) that catalogues spin-state/stereochemical relationships of the iron porphyrinates and the implications of these structures for the hemoproteins. Articles by Hoffinan and Ibers have discussed the use of oxidized porphyrins and phthalocyanine derivatives as molecular metals. It is not the intention of the present review to attempt to supplant any of these earlier reviews but rather to extend them when appropriate, new information is available. Further, we will review some additional topics that have not been considered previously. 

It is well known that derivatives of a-amino acids, especially the esters, can undergo cyclodimerization to form piperazine-2,5-diones. The stereochemistry of such self-condensation of rf/-aminoacid esters has been investigated [86JCS(P1)1557]. Piperazinediones with a cis orientation of substituents were preferentially formed at the initial stages but increasing amounts of the Irons product were formed later. The results have been interpreted as reflecting the difference in the rates of cyclization of the two diastereomeric dipeptide esters. 

---