Steroids boronates

Lead tetraacetate reacts with ketones to form a-acetoxyketones. Reported yields are seldom high, however. The reaction has been successfully applied to keto steroids. Boron trifluoride can be used to catalyze these oxidations. It is presumed to function by catalysis of enolization, and it is assumed that the enol is the reactive species. ... 

Boron Bromide. Approximately 30% of BBr produced in the United States is consumed in the manufacture of proprietory pharmaceuticals (qv) (7). BBr is used in the manufacture of isotopicaHy enriched crystalline boron, as a Etiedel-Crafts catalyst in various polymerization, alkylation, and acylation reactions, and in semiconductor doping and etching. Examples of use of BBr as a catalyst include copolymerization of butadiene with olefins (112) polymerization of ethylene and propylene (113), and A/-vinylcarbazole (114) in hydroboration reactions and in tritium labeling of steroids and aryl rings (5). 

The preparation of 16a,17a-methylene steroids (4) is best carried out by treatment of (2) with perchloric acid or boron trifluoride etherate. °° ° In this process the pyrazoline is introduced as a solid at room temperature into a solution of acetone containing a catalytic amount of the acid. The reaction requires 5 to 30 minutes for completion. 

Spiro-pyrazoline derivatives (18) are obtained smoothly from 16-methy-lene-17-ketones (17). ° The sole products formed from (18) by pyrolysis or cleavage in the presence of boron trifluoride etherate, are the 16-spiro-cyclopropyl steroids (19). ... 

Boron trifluoride etherate in benzene converts A -20-acetoximinosteroids to the 17-ketones in somewhat lower yield, but the reaction of A -20-oximino steroids with this catalyst in the presence of acetic anhydride does not give the expected product two different compounds have been isolated and identified. ... 

If ethoxyacetylene is allowed to react in an anhydrous system with aliphatic ketones in the presence of boron trifluoride etherate, the unsaturated acid is obtained directly. This variation apparently has not yet been tried on steroids. 

The diazoketohe synthesis for the preparation of 21-methyl-20-keto steroids has been discussed earlier. 21-Oxygenated derivatives can also be prepared by this route simply by reacting the diazoketone with an appropriate acid-nucleophile combination. For example, reaction of a diazoketone with acetic acid leads to the 21-acetate and boron trifluoride in the presence of methanol affords the 21-methyl ether. 

In the course of synthetic efforts aimed at obtaining 6j5-fluoro steroids, Kirk and Petrow treated a 3)5-acetoxy-6-raethyl-5a,6a-epoxide with boron trifluoride etherate and unexpectedly obtained a fluorine-free acetoxy ketone." Later transformations established that the product was the A-homo-B-norsteroid (104). 

Note It is reported that the use of chlorobenzene as solvent is essential when the reagent is to be used to detect aromatic amines [1]. In the case of steroids, penicillins, diuretics and alkaloids the reaction should be accelerated and intensified by spraying afterwards with dimethylsulfoxide (DMSO) or dimethylformamide (DMF), indeed this step makes it possible to detect some substances when this would not otherwise be possible [5,9-11] this latter treatment can, like heating, cause color changes [5,9]. Penicillins and diuretics only exhibit weak reactions if not treated afterwards with DMF [10, 11]. Steroids alone also yield colored derivatives with DMSO [9]. Tlreatment afterwards with diluted sulfuric acid (c = 2 mol/L) also leads to an improvement in detection sensitivity in the case of a range of alkaloids. In the case of pyrrolizidine alkaloids it is possible to use o-chloranil as an alternative detection reagent however, in this case it is recommended that the plate be treated afterwards with a solution of 2 g 4-(dimethyl-amino)-benzaldehyde and 2 ml boron trifluoride etherate in 100 ml anhydrous ethanol because otherwise the colors initially produced with o-chloranil rapidly fade [12]. 

Treatment of a pentacyclic la, I I -(2-oxethano) thioketal steroid with excess Et3SiH/TFA causes reduction of the carbon-carbon double bonds as well as the 17-carbonyl group to give a single reaction product (Eq. 213).368 Other work utilizes trifluoroacetic acid, triethylsilane, and anisole in the presence of a catalytic amount of boron trifluoride etherate to reduce the acetyl carbonyl of a 3-acetyl-2-azetidinone derivative with a dr of 8 1 (Eq. 214).395... 

The tetracyclic alcohol 179 is produced by the action of boron trifluoride etherate or tin(IV) chloride on the oxirane 178 (equation 85)95. A similar cyclization of the oxirane 180 yields DL-<5-amyrin (181) (equation 86)96. In the SnCLt-catalysed ring-closure of the tetraene 182 to the all-fraws-tetracycle 183 (equation 87) seven asymmetric centres are created, yet only two of sixty-four possible racemates are formed97. It has been proposed that multiple ring-closures of this kind form the basis of the biosynthesis of steroids and tetra-and pentacyclic triterpenoids, the Stork-Eschenmoser hypothesis 98,99. Such biomimetic polyene cyclizations, e.g. the formation of lanosterol from squalene (equation 88), have been reviewed69,70. 

Mercaptoles of ketones are best prepared by treatment of ketones with ethanedithiol or 1,3-propanedithiol in the presence of anhydrous zinc chloride or boron trifluoride etherate. Many desulfurizations have been carried out with these cyclic mercaptoles, especially in steroids. Yields of the hydrocarbons range from 50 to 95% [797]. 

The cleavage of an oxirane ring with boron trifluoride-diethyl ether complex has been broadly investigated in the field of steroid chemistry. Both 5a,6a- and 5j6,6j6-epoxycholestane (10) rearranged when treated with boron trifluoride-diethyl ether complex in benzene.35-36... 

Kenbest and Wrigley748 noted, the reaction of epoxy steroids wiiU boron trifluoride to be markedly solvent-dependent, since the use of... 

Several instructive illustrations taken from the field of natural products will serve to conclude the present discussion of acid-catalyzed epoxide isomerization. Much has been said about the occurrence of simple i,2-hydride transfers in boron trifhioiide-catajyzed epoxy steroid rearrangements. Although initiated by a mineral acid rather than a Lewis acid, an instance of traneatmular hydride transfer has boon reported far a 9/3,110-epoxy steroid,1824 as shown in Eq. (484). Such migrations can in principle occur elsewhere. 

In the steroid field, Henbest and Wrigley18 - have examined a number of epoxides with reference to boron trifluoride, which is a much stronger Lewis add than magnesium bromide and hence requires much milder operating temperatures. In all instances studied, hydride shifts look place in preference to ring contraction. The product stereochemistry indicated unequivocally a Walden inversion at the site of... 

This section includes oxidations of alkanes and cycloalkanes, alkenes and cycloalkenes, dienes, alkynes, aromatic fluorocarbons, alcohols, phenols, ethers, aldehydes, ketones and carbohydrates, carboxylic acids, nitrogen compounds, and organoelement compounds, such as boron, phosphorus, sulfur, selenium, and iodine compounds, and steroids. 

Fig. 1 The major classes of steroid hormones progestagens, mineralocorticoids, glucocorticoids, androgens, and estrogens. Enzymes, their cellular location, substrates, and products in human steroidogenesis. Boron WF, Boulpaep EL (2003) Medical Physiology a cellular and molecular approach, p 1300, Elsevier/Saunders (reprinted with permission from Elsevier/Saunders)...

In a route towards new estrogens which bind to the /1-unit of the K+-channel located on the surface of the endothelium, L.F. Tietze et al. described the synthesis of a novel enantiopure B-Nor-steroid, applying multiple Pd-catalyzed transformations [141] (Scheme 38). A combination of a Suzuki-Miyaura and a Heck reaction using a 2-bromobenzylchloride derivative and a boronic ester, derived from the enantiopure Hajos-Wiechert ketone [142-... 

The situation is similar with cyclic boronates, which are prepared by the following procedure. Steroid (10 pmol) and the respective substituted boric acid (10 jumol) are dissolved in ethyl acetate (1 ml) and the mixture is allowed to stand for 5 min at room temperature. Under these conditions, 17,20-diols, 20,21-diols and 17,20,21-triols are converted completely into boronates. Cyclic boronate was mainly produced from 17,21-dihydroxy-20-ketone, but side-products also appeared, the formation of which could be suppressed by adding a 10% excess of the reagent [387—389]. Different substituents on the boron atom, such as methyl, n-butyl, tert.-butyl, cyclohexyl and phenyl, are interesting from the viewpoint of GC—MS application. They are further suitable for converting isolated hydroxyl groups into TMS or acetyl derivatives. 

A 16a-bromo-ketone (233) reacts with 1,2-diaminoethane to give the dihyd-ropyrazine (234) the required oxidation step probably uses atmospheric oxygen.202 Some further steroidal tetrazoles and bis-tetrazoles have been prepared from ketones by the action of hydrazoic acid-boron trifluoride.203... 

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