Ketones steroidal, selectivity

Reduction of steroid ketones. Steroid 3-ketones can be reduced selectively by potassium tri-sec-butylborohydride in the presence of 17- and 20-keto groups to the 3-axial alcohol (3a-OH for 5a-steroids 3/f-OH for 5/J-steroids). 

In acidic media the protonated form of the ketone (19a) is considered to bond to the catalyst by accepting electrons into the formally vacant -orbital of the carbonium ion form (19b. In this case the metal-carbon bond forms most readily in the unhindered equatorial direction, so that the hydroxyl group is forced to become axial. Final hydrogenolysis of the metal-carbon bond affords the axial alcohol. Exceptions occur where the equatorial direction is exceptionally hindered, e.g. in steroidal y-ketones where selective axial bonding of the catalyst results in preponderance of the 7j - equatorial) alcohol [12,22 ]. 

LiAKOBujaH. A selective reducing agent for converting RCOCl to aldehydes and reducing steroid ketones. See aluminium hydride. 

Dimethylamino-l,3-dioxolane/cat. HOAc, CH2CI2, 83% yield. 2-Di-methylamino-l,3-dioxolane protects a reactive ketone under mild conditions it reacts selectively with a C3-keto steroid in the presence of a A -3-keto steroid. C12- and C2o-keto steroids do not react. 

With some ketones there is a sufficient difference in the rate of loss of various a-hydrogens at the enolization step and a steric preference for the incoming deuterium during ketonization to facilitate selective exchange of certain a-hydrogens. Typical examples are the steroids. 

The enolization of 5a-3-ketones appears to be cleanly directed to C-2, whereas that of 5j5-3-ketones is less selective. Remote substituents can have a significant effect on the kinetic and thermodynamic enol acetylation of 5j3-steroids. ... 

In practice the 3-ketone in both 5a- and 5i -steroids is the least hindered and most reactive carbonyl group, whereas the 11-ketone is the most hindered and least reactive. The 6-ketone is less reactive than the 3-ketone but it can be selectively protected in the presence of a 17- or 20-ketone. The 7-ketone is more reactive than a 12-ketone. 

Steroidal A -dienamines are formed with a high degree of selectivity in the presence of 17- or 20-ketones. Preparation of morpholine and pyrrolidine enamines is achieved by azeotropic removal of water with or without a catalyst. Pyrrolidine enamines are also formed efficiently by addition of the base to the hot solution of the ketone in methanol followed by immediate cooling. ... 

The selective formation of the 3-monosemicarbazones of polyketonic steroids can be achieved only in the presence of 21-acetoxy-20-ketones by the use of nonbuffered conditions. Partial hydrolysis of 3,20-bissemicar-bazones can be achieved with acetic anhydride in pyridine "" to yield the 3-semicarbazone. Kinetic studies on the rates of formation of Girard hydra-zones showed that the A" -3-ketone is less reactive than the saturated 3- and 6-ketones, as reactive as the 7- and 17-ketones and more reactive than the 20- and 12-ketones. ... 

Many selective epoxidations are possible with polyunsaturated steroids. In general, oc, -unsaturated ketones are not attacked by peracid, although linear dienones react slowly at the y,5-double bond. Aw-Chloroperbenzoic acid is the reagent of choice for this reaction.When two isolated double bonds are present in the steroid nucleus, e.g. (27) and (30), the most highly substituted double bond reacts preferentially with the peracid. Selective epoxidation of the nuclear double bond of stigmasterol can likewise be achieved.However, one exception to this general rule has been reported [See (33) (34)]. ... 

Double bonds in a,/3-unsaturated keto steroids can be selectively oxidized with alkaline hydrogen peroxide to yield epoxy ketones. In contrast to the electrophilic addition mechanism of peracids, the mechanism of alkaline epoxidation involves nucleophilic attack of hydroperoxide ion on the con-... 

The reaction can be performed under a variety of conditions. Origin-aiiyi2o,i26,234 acetylene and potassium in liquid ammonia were used. Subsequently, this was simplified by the use of potassium r-amylate in r-amyl alcohol and later this system was found to react selectively at C-17 in the presence of an A-ring a,j5-unsaturated ketone. A closer investigation of these reaction conditions revealed the formation of a small amount (2-3 %) of the disubstituted acetylene this can be avoided by reacting the 17-keto steroid with acetylenedimagnesium bromide in ether-tetrahydrofuran (see chapter 10.)... 

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