Enone Cyanide addition

Other routes you might have suggested include cyanide addition to enones, e.g. (3i), alkane... 

A further improvement in the cuprate-based methodology for producing PGs utilizes a one-pot procedure (203). The CO-chain precursor (67) was first functionalized with zirconocene chloride hydride ia THF. The vinyl zirconium iatermediate was transmetalated direcdy by treatment with two equivalents of / -butyUithium or methyUithium at —30 to —70° C. Sequential addition of copper cyanide and methyUithium eUcited the /V situ generation of the higher order cyanocuprate which was then reacted with the protected enone to give the PG. 

Addition (Sections 14.2, 19.13) Addition of a reactant to the ends of a conjugated tt system. Conjugated dienes yield 1,4 adducts when treated with electrophiles such as MCI. Conjugated enones yield 1,4 adducts when treated with nucleophiles such as cyanide ion. 

Conjugate addition, 34-5, 51-2,53, 132, 133 Conjugate hydroxymethylation, 59-60 Copper(n) bromide, 54 Copper([) chloride, 120 Copper(n) chloride, 120 Copper(i) cyanide, 7,52, 53 Copper(i) iodide, 54 Corey s internal quench, 104 Cyanohydrin trimethylsilyl ether, 137 Cycloaddition. 34,112 Cydobutane-l,2-dione, 135 Cyclohept-2-dione, 135 Cyclohex-2-enone, 52,123 Cyclohcxa-1,3-diene, 26 Cyclohexane carboxaldehyde, 22-3,69 73,78... 

Cyanide ion acts as a carbon nucleophile in the conjugate addition reaction. An alcoholic solution of potassium or sodium cyanide is suitable for simple enones. 

Except for the well-documented conjugate additions of diethylaluminum cyanide,92 triethylaluminum-hydrogen cyanide and Lewis acid-tertiary alkyl isonitriles,93 examples of Lewis acid catalyzed conjugate additions of acyl anion equivalents are scant Notable examples are additions of copper aldimines (233),94, 94b prepared from (232), and silyl ketene acetals (234)940 to a,(3-enones which afford 1,4-ketoal-dehydes (235) and 2,5-diketo esters (236), respectively (Scheme 37). The acetal (234) is considered a glyoxylate ester anion equivalent. 

Interestingly, the trans enones 91 and 92 (R=H or CHj) have their ring A essentially conformationally rigid. Consequently, the addition of cyanide ion from the a face, occurring via a chair-like transition state (93 - 94) should be preferred over that on the B face which can take place only via a boat-like transition state (93->95). Agami, Fadlallah and Levisalles (35) have recently observed that in strictly kinetically controlled conditions, only the axial cyano isomer resulting from an attack on the a face was observed with the trans enones 91 and 92. 

Contrary to this bicyclic series, the equilibration of the a- and the b-cyano isomers derived from the steroid enones 92 (R=H or CH3) does not occur. It has also been impossible to produce the B-cyano isomer from the hydrocyanation reaction. This result was explained by the fact that in the steroid series, there is a strong steric interaction between the cyano group and the C-ll methylene group of ring C in the boat-like conformation 95 (cf 98). Consequently, addition to the B-face never occurs in these compounds. This was confirmed by the fact that 1a-cyanocholestanone (derived from 92, [KH3) readily incorporates labeled cyanide (13C=N) under the experimental conditions of the hydrocyanation reaction. 

The very first conjugate addition reaction in this chapter depended on the conditions of the reaction. Treating an enone with cyanide and an acid catalyst at low temperature gives a cyanohydrin by direct attack at C-O, while heating the reaction mixture leads to conjugate addition. What is going on ... 

Trimethylsilyl cyanide is a useful reagent for the preparation of /8-amino alcohols,2 a-amino nitriles,3 and a-trimethylsiloxyacrylo-nitriles4 from the corresponding ketones, imines, and ketenes. The reagent adds rapidly to the carbonyl of aldehydes at 25°C,2 and the resulting adducts have proven useful precursors for the preparation of carbonyl anion synthons.5 Enones give exclusively the products derived from 1,2-addition.2... 

In recent years, Ireland and his colleagues have made a major contribution to the total synthesis of tetra- and penta-cyclic triterpenoids. The details of some of this work have been published in a series of papers.55-58 The tetracyclic ketone (75) was conceived as a key intermediate in the synthesis of shionone (76). Three routes to (75) were undertaken.55 The most efficient involved a triethylaluminium-catalysed conjugate addition of cyanide to the enone (77) (see Vol. 5, p. 135). The second... 

What is the controlling factor in the stereochemical outcome of the conjugate addition of cyanide to enone 1 ... 

Phase transfer, also called crown ether cataly, is also useful to promote the 1,4-addition of the cyanide anion to a conjugated enone. 

Ordinary carbon nucleophiles such as cyanide or Grignard reagents or organolithium compounds fit the patterns we have described already. They usually give the more stable product by 5 2 or 5 2 reactions depending on the starting material. If we use copper compounds, there is a tendency— no more than that—to favour the 5 2 reaction. You will recall that copper(l) was the metal we used to ensure conjugate addition to enones (Chapter 10) and its use in Sn2 reactions is obviously related. 

Termite soldiers produce a large number of different chemical defense agents. Several of these molecules are unusual bioactive terpenoids such as the secotrinervitanes that have been isolated and their structure elucidated. In the laboratory of T. Kato, the total synthesis of (+)-3a-acetoxy-7,16-secotrinervita-7,11-dien-15P-ol was accomplished. The Nagata hydrocyanation was used to introduce a carbon at the P-position of a macrocyclic enone intermediate. The substrate was treated with excess diethylaluminum cyanide in dry toluene and the addition resulted in the formation of a 1 1 mixture of diastereomers, which could be readily separated by column chromatography. The cyano group was later converted to the corresponding methyl ester. 

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