Organic Chemistry of Drug Synthesis. Volume 7

gonane, with hydrogen peroxide, results in selective reaction at the 5,10
double bond to give the epoxide 78. The proximity of the acetal
oxygens at the 3 position accounts for the regiochemistry of the product;
attack from the more open a-side accounts for the stereochemistry.
Condensation of 78 with the Grignard reagent from the methyl acetal
of p-bromobenzaldehyde in the presence of cuprous salts leads to
conjugate addition to the 11 position with concomitant shift of the
double bond to the 5,9 position ( 79 ). Construction of the side chain
at the 17 position starts with the addition of the ylide from the tri-
methylsulfonium iodide to the carbonyl group give the oxirane 80.
Reaction of the product with sodium methoxide opens the epoxide ring
to give the ether–alcohol 81. Alkylation of the hydroxyl group at 17
with methyl iodide and base affords the bis(methyl ether) 82. Exposure
of that intermediate to acid leads to hydrolysis of the acetal protecting
groups on the ketone at 3 as well as the aromatic aldehyde; the tertiary
alcohol on the AB ring junction dehydrates under those conditions,
restoring the double bond ( 83 ). Reaction of this last intermediate with
hydroxylamine leads to formation of the aldoxime in a 95 : 5 (E)/(Z) ratio.

O

(CH 3 ) 2 N CH 3

76

H 2 O 2

O

CH 3 O

CH 3 O

78

O

Br OCH

3

OCH 3

Mg,Cu2+

O

CH 3 O

CH 3 O

77

O

CH 3 O

CH 3 O OH

CH 3 O

CH 3 O

79

O

CH 3 O

CH 3 O OH

CH 3 O

CH 3 O

80

(CH 3 ) 3 SO+

tBuOK

OH

CH 3 O

CH 3 O OH

CH 3 O

CH 3 O

81

CH 3 ONa

OCH 3

OCH 3

CH 3 O

CH 3 O OH

CH 3 O

CH 3 O

OCH 3

CH 3 I

CH 3 ONa

82

TsA

O=HC OCH 3

OCH 3

O

83

OCH 3

OCH 3

O

84

HON

NH 2 OH

2. POLYCYCLIC COMPOUNDS: STEROIDS 33