11-Steroid Aldehydes

That an aminal is a necessary intermediate was first questioned by Herr and Heyl (2). They found that by using a slight excess of amine the yield of the enamine from two of the steroidal aldehydes studied was 84%. Also, the -fluorocnamines discussed earlier are formed in 60-90% yield from equimolar amounts of the 8-fluoroaldehyde and secondary cyclic amine (27). However, neither of these studies was specifically designed to show whether or not aminals were intermediates. 

Alkynylation of aldehydes.3 The reaction of alkynylmetals with chiral aldehydes shows no or slight diastereoselectivity, but in the presence of TiCl4, alkyn-yltributyltin reagents react with the steroid aldehyde 1 with about 9 1 diastereoselectivity. TiCl4-catalyzed reaction of 1 with allyltrimethylsilane or allyltributyltin also shows similar and comparable diastereoselectivity. 

Stannylalkynes in the presence of TiC34 react with a steroidal aldehyde in a highly Cram selective maimer. The use of lithium derivatives gives 1 1 mixtures of two diastereomers (equation 23). ... 

The ozonolysis reaction was used to prepare the steroidal aldehyde, 3-ketobisnor-4-cholen-22-al from 4,22-stigmastadien-3-one. Methylene chloride was used as the solvent. When aldehydes are prepared by ozonolysis, exactly the right amount of ozone must be added. An infrared method makes it possible to follow quantitatively the rate of disappearance of double bonds and locate the end point exactly. 

Wittig cleavage of the product (Scheme 134, Table 8, entry 24) [100] The resin was suspended in benzene (5 mL) and a steroidal aldehyde (see Scheme 134) (1.2 mmol) and benzoic acid (10 mg, 0.08 pm) were added. The product is now in the solution phase The resin was filtered off and washed with THF (50 mL) and CH2CI2 (50 mL). The combined filtrate and washings were concentrated in vacuo... 

Iodine monobromide [1, 501-502, after citation of ref. 1]. The reagent effects mono-bromination of steroid aldehydes in high yield.2 The diastereoisomeric product in... 

The reaction of (S)-l with the steroidal aldehyde 2 catalyzed by TiCl4 gives the. vyn-product 3 as a single steroisomcr with control at three contiguous centers. 

The compound has been produced from a steroidal aldehyde by total synthesis, using a triflic acid-catalyzed 2 -discriminated and P-selective glucosylation in addition to an a-selective thermal rhamnosylation (101). 

Stereoselective Wittig reaction. The reagent has been used in a novel synthesis of 25-hydroxycholesterol (5). Thus the /-steroid aldehyde 2 reacts with 1 to form 3. Two features of the reaction are noteworthy. The 20-methyl group does not epimerize and the A -double bond of the major product has the E-con-... 

A highly efficient KR of bishomoallylic alcohols has been performed by Loh et al. [114]. Alcohols 199 underwent In(OTf)3-catalysed 3,5-oxonium-ene-type cycliza-tion with steroidal aldehyde 200. Besides the produced oxocyclohexane 201, the unreacted (S)-alcohols 199 were isolated in >99% ee. Among various Lewis acids investigated, In(OTf)3 proved the best. However, as only one enantiomer of the chiral source is readily available, the use of this interesting method has limitations. 

The ylide (35), prepared from base treatment of the methylenetriphenyl-phosphorane-isobutene oxide adduct, has been shown to react with steroidal aldehydes to give the (E)-homoallylic alcohol stereoselectively [equation (6)], especially at low temperatures. 

However, two examples of aldehydes that did not foUow this general rule were described in the early studies. The first example of an ODPM reaction in a P,y-unsaturated aldehyde was observed by Schaffner et al." in the direct and triplet-sensitized irradiation of the steroidal aldehyde 12 that gives the alkene 13 resulting from decarbonylation, and two other compounds, 14 and 15, derived from the ODPM rearrangement and the 1,3-formyl migration, respectively (Scheme 1). 

Some of the aldehydes that were reactive toward oxa-di-ii-methane reaction are given in Scheme 9. Direct irradiation of the steroidal aldehyde 50 was reported to give the ODPM product 51 in 30% yield, along with two other products. Armesto recently reported the photoreaction of a number of aldehydes, including 52 and 54 that rearranged to the corresponding ODPM products 53 and 55, respectively, on sensitized irradiation. > ... 

Alkynyltributyltin compounds react with steroidal aldehydes. In the presence of TiCU the reaction gives 9 1 diastereoselec-tivity (eq 17). Reactions of alkynylmetals with chiral aldehydes... 

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

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