Asymmetric Total Synthesis of (+)‐Estrone

Abstract

4] Under the conditions chosen (vide inJra), the thermodynamically more stable of the two enolate anions of the D ring component adds, in extremely regioselective manner, to (12). The (CH,),Si ligand ensures that the reaction also produces rac-(lO) in extremely high stereoselectivity. m-Cresol methyl ether (3-melhylanisole) is brominated analogously to 3ethylanisole: D. J. Nelson, E. A Uschak, J. Org. Chem. 42, 3308 (1977).[5][6] A. Ottolenghi, M. Friedkin, A . Zrlkha, Can. J. Chem 41. 2977 (1963.[7] rac-/8), R =C2Hr. was synthesized by R. W . Kzersread, R. P. Linsfead, B. C. L Weedon, J. Chem. SOC. 1952,3613; we adopted to procedure of J. M. Stewart, G. K. Pagenkopf, J. Org. Chem. 34, 7 (1969), but used (61, R=CH,. Concerning nucleophilic ring opening of cyclopropane derivatives activated by electron acceptors, see S. Danishefsky, Acc. Chem. Res. 12, 66 (1979).[8] The diastereomer of rac-(5) having 2-configurated 9.10-double bond traverses mainly that transition structure in which the dienophilic vinyl group approaches the o-quinonoid dienic moiety from the @-side, from the ex0 orientation: this affords rac-(3). A competition reaction, of admittedly subordinate proportions, proceeds via that transition structure in which the vinyl group approaches the diene unit from the a-side, from the endo orientation- this gives rac-(14). rac-(3) and roc-(14) are separated only for identification. mc-(2) and rac-(l5) are separated only for identification. The mixture rac-(2) + rac-(15) is reduced by potassium in liquid ammonia in the presence of aniline and then oxidized by chromic acid to give rac-(l), The mixture rac-(2) + roc-(IS) is reduced by potassium in liquid ammonia in the presence of aniline and then treated with diisobutylaluminum hydride rac-(16); R = H: J.-C. Hilscher, DBP 2409991 (1976); Schering; Chem. Abstr. 84, 59862v (1976). The mixture rac-(2) + rac-(l5) is converted by Birch reduction into rac-(17) [by analogy with the procedure of W. S. Johnson, W. A. Vredenburgh, J. E. Pike. J. Am. Chem. SOC. 82, 3409 (1960)l.Since mc-(l0) undergoes at least 61% conversion into [roc-(2) + rac-(l5)], the overall yield of this mixture is 22% for m-cresol methyl ether and 12% for (E)-l.4-dibromo-2-butene or dimethyl malonate.

Applications of Continuous-Flow Photochemistry in Organic Synthesis, Material Science, and Water Treatment

“…131 Deriving from these earliest approaches, photochemistry continuously evolved. 132 In the late 20th century, fundamental applications emerged: among them the synthesis of cubane, 133 lycopodine, 134 estrone, 135 and ginkgolide B. 136 It did not take long before the usefulness of photochemistry was implemented in the chemical industry.…”

“…Deriving from these earliest approaches, photochemistry continuously evolved . In the late 20th century, fundamental applications emerged: among them the synthesis of cubane, lycopodine, estrone, and ginkgolide B …”

Photochemical Approaches to Complex Chemotypes: Applications in Natural Product Synthesis

“…Here, photochemically triggered formation of dienol 380 from precursor 379 allowed for [4 + 2] cycloaddition to afford alcohol 381 , which could subsequently be converted to estrone ( 3 ) via already known transformations (Scheme ). − Other early examples where the photoenolization/[4 + 2] cycloaddition sequence had been employed include the formal total synthesis of podophyllotoxin ( 385 , Scheme ) and the synthesis of 6-methylpretetramid ( 389 , Scheme ). , …”

“…Trommsdorff found in the early 19th century that crystals of the sesquiterpene santonin reacted upon exposure to sunlight, which may be considered the birth of photochemistry. , From the mid-20th century, myriad examples have been reported where photochemistry has been exploited for remarkable rearrangements and construction of complex molecular scaffolds. , Figure depicts some of the outstanding and now classic examples of natural product synthesis where photochemical reactions have been applied in key steps. These include the synthesis of α-cedrene ( 1 ), ingenol ( 2 ), estrone ( 3 ), − and ginkgolide B ( 4 ), among others.…”

The Diels–Alder Reaction in Steroid Synthesis

“…The importance of Kametani's contribution -and the value of the benzocyclobutene ring opening-IMDA sequence in aromatic steroid synthesis -can be measured by the large number of subsequent syntheses that implement variations upon it. Since this inaugural publication, a wide array of steroids and steroid analogues, in both enantiopure [55][56][57][58][59][60][61] and racemic [62][63][64] forms, have been accessed by this approach. Ibrahim-Ouali and Santelli have prepared thiasteroids, 65,66 oxasteroids, 67 azasteroids, 68,69 selenasteroids, 70 tellurasteroids, 71 and analogues in this manner.…”