Patent GB-1251522-A (GB)
IPC: C07F9/653
Filed: 1968-11-26
Abstract: 1,251,522. Unsaturated carbocyclic ketones. SYNTEX CORP. 26 Nov., 1968 [4 Dec., 1967; 25 July, 1968; 4 Nov., 1968], No. 56058/68. Headings C2C, C2P and C2U. α,#-Unsaturated carbocyclic ketones are prepared by reacting under anhydrous conditions in an inert organic solvent an enol lactone having at least 5 members in the heterocyclic ring thereof with about an equimolar amount of a carbanion generated by reaction of a phosphonate of one of the formulµ CH 3 -PO(OR) 2  and R<SP>1</SP>-CH 2 -PO(OR) 2  (wherein R and R<SP>1</SP> are each substituted or unsubstituted aliphatic, carbocyclic or carbocyclic-aliphatic radicals or R<SP>1</SP> may also be a heterocyclic-substituted aliphatic radical) and a base selected from organo alkali metal compounds, alkali metal hydrides and alkali metal amides in about equimolar amounts under anhydrous conditions in an inert organic solvent at temperatures between about - 150 and - 20 C., whereby the ring oxygen atom of the enol lactone is replaced by a = CH- or = CR<SP>1</SP>- group. Enol lactones are defined as unsaturated lactones having α,#-ethylenic unsaturation with respect to the ring oxygen atom. Novel products have the formulµ (wherein R<SP>3</SP> and R<SP>4</SP> are C 1-6  alkyl; R<SP>5</SP> is H or CH 3 ; R<SP>7</SP> is =O or alkylenedioxy of at most 6 carbon atoms or α-H (#-R<SP>8</SP>) in which R<SP>8</SP> is OH or an ester or acid-labile ether thereof; and R<SP>1</SP> is t-butyl), those of the formulµ (III<SP>1</SP>) and (IV<SP>!</SP>) being prepared from products of the inventive process of the Formula (II<SP>1</SP>) by treatment with an aqueous organic acid to give (III<SP>1</SP>) and catalytic hydrogenation to give (IV<SP>!</SP>). In the inventive process keto and hydroxy groups are preferably protected and subsequently regenerated. Steroids are among the products prepared. Phosphonates of the above formulae are prepared from disubstituted phosphites and appropriate organic halides or sulphonates in the presence of a base. Dimethyl 3-carboxypropylphosphonate is prepared by hydrolysing dimethyl 4,4 - dimethoxybutylphosphonate to give the corresponding aldehyde and then oxidizing this. The compound of the formula (wherein Ac is H and R<SP>4</SP> is CH 3 ) may be prepared by catalytic hydrogenation followed by deketalization of the compound of the formula to give the compound followed by cyclization of this. Compounds of the formulµ are prepared by cyclization of compounds (IV<SP>1</SP>) above. The compound of the Formula (LXIII) (R<SP>4</SP> = CH 3 ; R<SP>7</SP> = oxo) is prepared as follows where R<SP>4</SP> and R<SP>7</SP> are as above except that in (LX) and (LXI) R<SP>7</SP> is ethylenedioxy. The compound of the Formula (LXV) (R<SP>'</SP> = C 2 H 5 ; R<SP>7</SP> = oxo) is prepared as follows where R<SP>7</SP> in the starting material is ethylenedioxy. The compound of the Formula (LXVII) (R<SP>4</SP> = CH: 3 ; R<SP>7</SP> = oxo) is. prepared as follows (where R<SP>7</SP> in the starting material is ethylenedioxy). Similarly compounds of the formula are prepared from compounds of the formula (LXVIII) or those of the formula (LXX) and compounds of the Formula (LXXIII) are prepared as follows where R<SP>4</SP> is C 1-6  alkyl and R<SP>7</SP> is oxo in the final product and its precursor and ethylenedioxy in the starting material. The tosylate of 2.hydroxymethyl-3.(m.meth. oxyphenyl)-propane is prepared from the free ol. The corresponding 2-halo-methyl compounds are also prepared from the free ol. The compound of the formula is prepared from the correspondingly sub stituted thiane and ethylene-glycol and is converted to its toxylate. The compound of the formula (where R<SP>4</SP> is C 2 H 5  and Ac is benzoyl) is prepared by oxidation of the corresponding aldehyde, prepared in turn from its dimethyl acetal.