Polycyclic ketones, selectivity

McDonald and coworkers studied a series of tandem endo-selective and stereospecific oxacyclization of polyepoxides by reaction with Lewis acid [92-95]. Polyepoxides, such as 50, can be obtained from the epoxidation of triene 49 with ketone 26 (Scheme 8). This cascade cyclization of polyepoxides provides an efficient method to synthesize substituted polycyclic ether structures, which are present in a number of biologically active marine natural products. 

Dehydrogenation. The oldest and still important synthetic use of quinones is in the removal of hydrogen, especially for aromatizahon. This method has often been applied to the preparation of polycyclic aromatic compounds. Quinones are used extensively in the dehydrogenation of steroidal ketones. Such reactions are marked by high yield and selectivity. Generally, the results when using nonsteroidal ketones are disappointing. 

The selectivities observed in the steroid field result from sieric interactions. In fact, empirical rules have been elaborated from studies on polycyclic jU-unsatured ketones and three types of polycyclic systems have been recognized as leading to different selectivities ... 

Wiesner discovered that the photoreaction of an allene to an a/J-unsaturated ketone always shows the regioselectivity illustrated in the example (487 — 488) above. The general reaction shows another interesting feature in polycyclic a/l-unsaturated ketones, the allene often adds highly selectively to one face of the double bond.402 In the case of the ketone (489), the product (490) appeared from models to be more crowded than the alternative (491) also, the lower face of the double bond in 489 appeared to be the more hindered face. On both counts, the alternative product (491) ought to have been formed and was not. 

Finally, there are many substrates in which a cyclohexanone is incorporated in a rigid bi-or polycyclic framework which imposes particular constraints on an approaching reagent. A particularly well-studied example is bicyclo[2.2.1]hcptan-2-one (norcamphor) which is attacked from the exo direction even by the least-hindered hydride reagents. A systematic discussion of these ketones is not practicable within this volume, but it is probably a fair generalization to say that one of the trialkylborohydride reagents will be capable of attacking the less-hindered face of most such substrates with excellent selectivity. 

Table 10. Polycyclic 2-Cyclohcxcnols by Stereoselective Reduction of the Corresponding Ketones with Lithium Aluminum Hydride or Sodium Borohydride (Selective Axial Attack)...

Oxidation. This complex is made by passing gaseous fluorine into aqueous acetonitrile. It converts secondary alcohols to ketones (note that unsaturated alcohols are selectively oxidized to epoxy alcohols) and eventually to lactones. Phenols and polycyclic arenes are rapidly oxidized to give quinones. ... 

Similarly the bicyclic cyclopropyl ketone 134 is readily converted to the tricyclo[5.3.0.0 - ]decane 135 under similar conditions via a domino ring opening/Michael/aldol reaction sequence as shown in the Scheme 4.27 [45]. The selective attack of the iodide ion at the 6-position of 136 leading to the intermediate 137 may be due to the effective overlap between cleaved bond and the % orbital of the carbonyl group. This novel domino reaction producing polycyclic cyclobutanes was exploited for the synthesis of natural products like ( )-anthoplalone and ( )-lepidozene by the same workers [45]. 

A group of polycyclic polyether natural products are of special interest owing to their fascinating structure and biological activities. One of the proposed biosynthetic origins of these molecules features an epoxide-opening cascade pathway. Shi asymmetric epoxidation of un-activated alkenes has been frequently employed in the preparation of polyepoxide intermediates. McDonald and co-workers studied a series of tandem e 7o-selective and stereospecific oxacyclization of polyepoxides mediated by Lewis acid. Polyepoxides, such as 64, can be obtained from the epoxidation of triene 63 with ketone 2. Furthermore, a cascade cyclization, initiated by a Lewis acid-promoted epoxide opening of 64, furnished the desired polyether 65. 

The selective oxidative phenolic orf/io-coupling reaction of simple methyl-substituted phenols turned out to be challenging [12]. When 2,4-dime thy Iphenol (1) is treated by conventional or electro-organic methods, not only the desired biphenol (2) is formed but rather a plethora of polycyclic architectures (Scheme 2) is observed. The major product is Pummerer s ketone (3) and related compounds with a wide structural diversity [13-16]. Application of a boron tether ameliorated the situation tremendously, and biphenol (2) was obtained as the major product [17, 18]. This templated anodic oxidation of 1 represents a multistep process but is suitable for the electro-organic synthesis of (2) on larger scale (see entry Electrosynthesis Using Template-Directed Methods ) [19]. 

Carbonylation procedures were explored and applied in phthalide synthesis as well. In 1986, Negishi and co-workers studied the palladium-catalyzed cyclization of o-iodoatyl alkenyl ketones. By using Pd(dba)2 as the catalyst, bicyclic and polycyclic quinones could be produced in high yields. Interestingly, phthalides were formed when using Pd(OAc)2/PPh3 as the catalyst system (Scheme 2.159). Afterwards, the group carried out systematic studies on this topic. Lactones and lactams were produced selectively from various substrates. 

The selective abstraction of y hydrogen is a purely geometric phenomenon, due to the fact that in normal conformations of the alkyl chain it is the y hydrogen that is nearest to the oxygen atom. The overriding importance of geometry in these reactions is exemplified by the fact that variations in the photochemical reactivity in a series of straight-chain and polycyclic alkyl ketones could be attributed almost entirely to variations in AS for the reactions. ... 

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