THE SYNTHESIS OF CONDENSED RING COMPOUNDS. II. THE REACTION OF 1,3,4-HEXATRIENE WITH 1,4-NAPHTHOQUINONE²

Abstract

Although most of the known naturally occurring steroids are nonbenzenoid, the total synthesis of this type has not yet been accomplished. It should be possible to build up a large variety of such compounds by means of successive Diels-Alder diene additions. The Diels-Alder reaction has the great advantage that it always proceed^stereoselectively to give polycyclic compounds with cis configuration at the ring junctions, and furthermore two successive additions lead exclusively to one of the possible cis,cis isomers (1). Dane and collaborators (2) have employed this reaction for the synthesis of steroids containing one benzene ring, and Cook and Lawrence (3), Meggy and Robinson (4), Butz (5), Goldberg, and Müller (6), and others have reported applications of the reaction which might be extended to the synthesis of steroids.We have explored some of the possibilities making use of compounds which contain an open chain of six carbon atoms as the basis of the synthesis. From these, the angular tetracyclic skeleton of the steroids might be built up by successive diene additions according to the schemes in diagrams A, B, and C, in which the broken lines represent new carbon-tocarbon links. 1,3,5-Hexatriene, 1,3-hexadien-5-yne, 1,5-hexadien-3-yne, and their derivatives would be examples of six-carbon chains potentially capable of adding successively two molecules of dienophile.3 We have found that both 1,3,5-hexatriene and 2,5-dimethyl-l, 5-hexadien-3-yne form adducts of interest in this connection. This paper will present only the results obtained with hexatriene and a single dienophile, 1,4-naphthoquinone.

New synthesis of 2-alkylpyrrolidines and 2-alkylpiperidines

“…To obtain an authentic sample of this cis amide 29a, a mixture of 11.3 g (0.10 mol) of the cis amine 30a18 (Aldrich Chemical Co.) and 12 g of Ac20 was stirred for 1 h and then treated with 20 ml of aqueous 6 KOH and extracted with Et20. The ethereal extract was washed with aqueous 3 M HC1, dried, concentrated, and distilled to separate 4.07 g (26%) of the cis amide 29a as a colorless liquid: bp 83-86 °C (3.5 mm), n25D 1.4772 [lit.13a bp 62-63 °C (0.15 mm), n2SD 1.4785]; ir (CCD 1645 cm""1 (amide C=0); NMR (CC14) ó 4.1-4.7 (2 H, m, CHN), 1.97 (3 H, s, CH3CO), 1.4-1.9 (6 H, m, CH2), and 1.22 (6 H, d, =7 = 6.5 Hz, CH3); mass spectrum m/e (rel intensity) 155 (M+, 24), 140 (18), 112 (14), 98 (100), 70 (21), 43 (32), and 42 (17).…”

“…This material was partially purified by preparative TLC (silica gel coating with a PhH-Et20 eluent, 1:10 v/v) to separate 691 mg of the benzoate 11 as a yellow liquid, n2BD 1.5079. Distillation under reduced pressure in a short-path still afforded 645 mg (60%) of the benzoate 11 as a yellow liquid: n2BD 1.5080; ir (CC14), 1742 cm"1 (C=0); uv max (95% EtOH) 225 nm (e 14 200), 273 (860), and 280 (710); NMR (CC14) 7.1-8.1 (5 H, m, aryl CH), 2.0-3.7 (2 H, m, CHN and part of AB system for CH2N), 2.67 (1 H, d,J = 9.5 Hz, part of AB system for CH2N), 1.0-2.5 (11 H, m, CH2 with CH3 singlets at 1.15 and 1.22 and a CH3 doublet, J -7 Hz, at 1.20); mass spectrum m/e (rel intensity) 122 (26), 105 (40), 96 (21), 77 (38), 69 (24), 55 (100), 51 (27), and 41 (32). Our efforts to obtain an analytically pure sample of this benzoate 11 were thwarted by the partial decomposition that occurred during each attempt to distill the material.…”

Kinetics of the Gas Phase Reactions of (+)-trans-2,3-Divinyloxirane

“…Resolrrtiotz of 2-Acetoxy-5-vit~yltetral~ydrofurat~ (11) A solution of 11 (65.4 g, 420 mmol) (17) in dry T H F (50 ml) was added over a period of 1 h to a suspension of di-3-pinanylborane (7) (160 mmol) in ether and diglyme at -15 to -20'. The reaction mixture was stirred for 4 h at 0" and then water (6 ml) was added to destroy the excess borohydride.…”

The Diels-Alder Diene Synthesis.

“…«-Naphthoquinone itself (290) adds nearly all dienes easily. For example, it adds butadiene to give 1,1a,4,4a-tetrahydro-9,10anthraquinone (136), 2,3-dimethylbutadiene to give 2,3-dimethyl-1,1 a,4,4atetrahydro-9,10-anthraquinone (223), cyclopentadiene to give 1,4-endomethylene-1,1a, 4,4a-tetrahydro-9,10-anthraquinone (153), and 1,3,5-hexatriene (99) to give what is believed to be 1-vinyl-1,1a,4,4a-tetrahydro-9,10-anthraquinone. Atmospheric oxidation of the hexatriene adduct gives 1-vinyl-9,10anthraquinone.…”

“…The adduct with «-naphthoquinone may be oxidized by air to «-vinyl-9,10anthraquinone. Butz (98,99) opines that the structures given for the adducts with 4-hydroxytoluquinone acetate and wTith 1-formylcyclopentene are the "most probable" structures (II and III), but says that the structure assigned to III is tentative. It is certain, however, that angular groups exist in the compounds represented by II and III.…”