Raney nickel desulphurisation

Addition of (159, R = Et) to methyl 3,P-dimethylacrylate followed by Raney nickel desulphurisation also provides a convenient route to m-chrysanthemic acids 127>. 

The 5-methyl group of (5) can be deprotonated with strong base. The resulting anion (6) undergoes nucleophilic addition to prochiral ketones, generating the two diastereomers (7) and (8) in unequal quantities. Separation of these on a silica column followed by Raney nickel desulphurisation gives both tertiary alcohols (9) and (10) with variable e.e. 

The nocardicin nucleus 3-aminonocardicinic acid (3-ANA) (7) has not been found in nature, but can be prepared by deacylation of nocardicin C using microbial amidases 10). The first chemical method leading to (7) involved acid treatment of the bisthiourea derivative (8) of nocardicin C 11). A more recent method 12) makes use of the reaction of the oxime grouping of nocardicin A with di-/-butyl dicarbonate. This results in (9) which on treatment with trifluoroacetic acid gives (7). Further confirmation of the structure and stereochemistry of the nocardicins was the identification of the acylamino-derivative (10) derived from 3-ANA, with a compound obtained by partial synthesis from penicillin G 11). Another semi-synthetic approach (75) to the nocardicins from penicillin is by way of the thiazoline (11), the final step being Raney nickel desulphurisation of (12). 

The synthesis of 3,4-substituted anisoles [for example, R = R = (CH2)4] has been effected in the manner shown by the reaction of propynylmagnesium bromide with a sulphur-containing a,p-unsaturated ketone derivative to afford an intermediate carbinol. Cyclisation of this with boron trifluoride-etherate in the presence of methanol occurred with loss of methylthiol and desulphurisation by means of Raney nickel gave the final product (ref.86). The same sulphur-containing intermediates have been used with aryl esters to derive 4-methoxy acetophenone (ref. 87,88). Carbonyl derivatives of phenols are considered in detail in Chapter 7. 

Desulphurisation of the dithioketal shown with W2 Raney nickel afforded... 

Pyrimidone nucleosides (147) are traditionally synthesised by desulphurisation of 2-thiopyrimidine (148) nucleosides using Raney Nickel based methods. The yield from these reactions, is however, poor. An improved synthesis of these compounds utilises meta-chloroperbenzoic acid to desulphurise the starting material. The nucleosides were protected for DNA assembly and oligodeoxynucleotides were synthesised. 

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