Ring fusion

Repeat Problem 3 35 for the stereoisomenc steroid skeleton having a cis ring fusion between the first two nngs... 

In contrast to the above, the reaction of a heterocyclic thione with an a-halogenoketone (Scheme 3) has been widely exploited as a route to [5,6] ring-fused systems with a heteroatom at a ring fusion point. 

In general, the methods of synthesis and reactions of oxiranes and thiiranes fused to ordinary or large rings are not particularly affected by the ring fusion. The reader is referred to Chapters 5.05 and 5.06, and reviews cited there, many of which include fused-ring examples. 

When ring fusions and/or bridges are present in addition to spiro linkages, the fused or bridged units are first named individually (by any of the available methods) and the names are then cited (in square brackets and in alphabetical order) with the prefix spiro- or dispiro-, etc. Points of spiro attachment are indicated between the names of the components, with primes as necessary (examples 64-66). This method is also applicable to structures like (62) and (63) but is more cumbersome. 

There is significant bond alternation, however. The bond at the ring fusion is quite long 11.539 A). A molecular mechanics calculation on this molecule that included an SCF-MO treatment of the planar conjugated system found the molecule to be slightly destabilized (4kcal/mol) relative to a polyene reference. " ... 

When the C/D ring fusion is cis, the 17a-hydroxy compound is the main product from NaBH4 reductions of l7-keto-13a-androst-5-en-3)9-oE or 14/ -H compounds. The absence of a 10-methyl also affects the course of the reaction when rings A and B are cw-fused. A 19-nor-5/ -H 3-ketone is reduced to the 3/ -isomer, as is a 10a-H-5a-H-19-nor-3-keto compound. ... 

In general, epoxidation of steroids with trans-anti-trans ring fusions leads to exclusive formation of the a-oxirane. Steroid Reactions lists examples of exclusive a-epoxide formation from 2-, 4-, 6-, 7-, 8(9)-, 14-, 16- and 17(20)-unsaturated steroids. Further examples of a-epoxidation of steroid 1-enes, 3-enes, 8-enes, 9(ll)-enes, 8(14)-enes and 16-enes have been reported. The preferred attack by the reagent on the a-side of the steroid nucleus can be attributed to shielding of the -side of the molecules by the two angular methyl groups. 

The first objective was the conversion of L-tryptophan into a derivative that could be converted to pyrroloindoline 3, possessing a cis ring fusion and a syn relationship of the carboxyl and hydroxyl groups. This was achieved by the conversions shown in Scheme 1. A critical step was e. Of many variants tried, the use of the trityl group on the NH2 of tryptophan and the t-butyl group on the carboxyl resulted in stereospecific oxidative cyclization to afford 3 of the desired cis-syn stereochemistry in good yield. 

There are several instances of heterocyclic ring annellation, including 4,5-furoxano and 4,5-furazano ring fusion (17 and 18),... 

Ring fusion seems to occur in the quinoxaline derivative (28), which has been stated to exist in red and blue-black forms. Other derivatives of type 28 are reported. Attempts to prepare 5,6-furo-xanobenzofuroxan by pyrolysis of the azide (29) met with no success. An early example in the literature of such a linear fused structure was shortly afterward revised to the angularly fused type (17). 

Armulated thiophenes of types 195 and 197 (A benzo, naphtho) were studied concerning keto-enol tautomerism. The ring fusion has a remarkable influence upon these equilibria. Whereas for the c-fused thiophenes 197 only keto tautomers were present, for h-fused derivatives 195 also the enol forms 196 were found (the equilibria are solvent dependent) (82JOC705). 

Thiazolo[5,4-/]quinoline 23 was prepared in 1949 starting from 6-aminobenzo-thiazole using Skraup reaction conditions glycerol, sodium 3-nitrobenzenesulfo-nate, and 78% sulfuric acid and heating at 110°C for 12 hours. Angular ring fusion... 

The steroids as a class represent a structurally complex problem for the synthetic chemist. Even a relatively simple compound such as estrone possesses three ring fusions, two of which can lead to isomers and four chiral centers (identified below by ). Only one of the sixteen possible isomers possesses the desired activity in satisfactory potency. 

In this experiment, advantage is made of the fact that lithium-ammonia reduction usually proceeds to give trans-fused Decalins 4). Thus, hydrogenation of A -octal one-2 over palladium catalyst gives essentially cw-2-decalone as the product, whereas the lithium-ammonia reduction of the octalone gives the trans ring fusion. 

In intramoleculdf Diels-Alder reacdons, two rings are formed in one step The reacdon has been used to synthesize a number of interesting ring systems" The intramolecular cyckzadon of fE -l-nitrodeca-l,6,8-triene at 80 C affords an endo cycioaddnct with the irons ring fusion preferendally, as shown in Eq 8 18 In contrasr, fZ -nitroalkenes produce a nearly I T mixture of cis- and rrruii -hised cycioaddncts ... 

Steroid, 1079-1089 adrenocortical, 1083 anabolic. 1083 androgens, 1082 biosynthesis of, 1084-1089 cis A-B ring fusion in, 1081 conformation of, 1081... 

It is important to note here that both of the 5-exo radical cyclizations (133—>132—>131, Scheme 27) must proceed in a cis fashion the transition state leading to a strained mms-fused bicy-clo[3.3.0]octane does not permit efficient overlap between the singly occupied molecular orbital (SOMO) of the radical and the lowest unoccupied molecular orbital (LUMO) of the alkene. The relative orientation of the two side chains in the monocyclic radical precursor 134 is thus very significant because it dictates the relationship between the two outer rings (i. e. syn or anti) in the tricyclic product. The cis-anti-cis ring fusion stereochemistry of hirsutene would arise naturally from a cyclization precursor with trans-disposed side chain appendages (see 134). 

The oxazolo[3,4-a]azepinones 4, in which 5 7 ring fusion imparts considerable planarity and hence antiaromatic character on the ring system, undergo spontaneous dimerization.153 The mode of dimerization appears to depend on the nature and position of substituents. The unsubstituted system and the 9-chloro derivative 4 (R1 = Cl R2 = H) produce the exo.anti-dimers, e.g. 5, upon spray-vacuum pyrolysis at 300 C, whereas the 7-/ert-butyl, 7-bromo, 7-methyl, and 7,9-dichloro (4, R1 = R2 = Cl) compounds yield the exo,syn-dimcrs, e.g. 6. 

This intramolecular Michael addition, when followed by an aldol condensation provides a useful route to tram-octahydroindenes methylated in the ring fusion positions. 

Ring extension, to dihydro-1,4-thiazine. 35 to djhydro-1,4-thiazine, 36 Ring fusion, of some 2-methylthiazolium,... 

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