
TY  - JOUR
A1  - Collins, DJ 
A1  - Fallon, GD 
A1  - Skene, CE 
T1  - The Structure and Function of Estrogens. XI. Synthesis of (&#177;)-7(8&#8594;11&#945;)<I>abeo</I>-Estradiol and Its 9,11-Didehydro Derivative
JF  - Australian Journal of Chemistry
JO  - Aust. J. Chem.
Y1  - 1992
VL  - 45
IS  - 1
SP  - 71
EP  - 97
KW  - 
UR  - https://doi.org/10.1071/CH9920071 
N2  - Two approaches to the synthesis of (±)-7(8&#8594;11&#945;)abeo-estra-1,3,5(10)-triene-3,17 &#946;- diol (2a) from (±)-1 &#946;-t-butoxy-7a &#946;-methy1-2,3,3a  &#945;,6,7,7a-hexahydro-1H-inden-5(4H)-one (11) were studied. A pathway involving 6-alkylation of (11) with 2-(3&#8242;-methoxyphenyl)ethyl halides or sulfonate esters was unsuccessful, but conjugate addition of 3-methoxybenzyl nucleophiles with (±)-1&#946;-t-butoxy-7a &#946;-methyl-6-methylene-2,3,3a,6,7,7a-hexahydro-1H-inden-5(4H)-one (18), prepared from (11), led to ( ±)-1&#946;-t-butoxy-6 &#945;-[2&#8242;-(3&#8243;-methoxyphenyl)ethy1]-7a  &#946; &#945;,6,7,7a-hexahydro-1H-inden-5(4H-one (10a). Acid-catalysed cyclization of (10a) afforded (±)-17&#946;-t-butoxy-3-methoxy-7(8 &#8594;11)abeo-estra-l,3,5(10),9(11)-tetraene (29) which upon lithium/ammonia reduction in the presence of diphenylmethane gave ( ±)-17  &#946;- t-butoxy-3-methoxy-7(8 &#8594;11&#945;)abeo-estra,1,3,5(10)- triene (31). Deprotection of (31) and (29) afforded (±)-7(8 &#8594;11 &#945;)abeo-estra-1,3,5(10)-triene-3,17  &#946;- diol (2a) and (±)-7(8 &#8594;1l)abeo-estra-1,3,5(10),9(11)-tetraene-3,17&#946;-diol (32), respectively. Alternatively, reaction of (±)-1&#946;-t-butoxy-7a &#946;-methyl-6-methylene-2,3,3a &#945;,6,7,7a-hexahydro-1H-inden-5(4H)-one (18) with 3-methoxybenzyl phenyl sulfoxide (23a) gave (1RS,3&#8242;SR,2RS,-3a&#8242;SR,7a&#8242;SR)-3&#8242;-t-butoxy-2-(3&#8243;-methoxyphenyl)-3a&#8242;-methyl-2&#8242;,3&#8242;,3a&#8242;,4&#8242;7&#8242;,7a&#8242;-hexahydrospiro- [cyclopropane-1,5&#8242;-[5H]inden ]-6&#8242;(1&#8242;H)-one (26), reductive cleavage of which with lithium/ammonia afforded (10a). The relative stereochemistries of (31) and of the spiro cyclopropyl ketone intermediate (26) were established unambiguously by X-ray crystallography. 
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