Bicyclo heptane synthesis

The Baeyer-Villiger reaction has found considerable application in the synthesis of prostaglandins. One common pattern involves the use of bicyclo[2.2.1]heptan-2-one derivatives, which are generally obtained by Diels-Alder reactions. For example, compound 10 is known as the Corey lactone and has played a prominent role in the synthesis of prostaglandins.237 This compound was originally prepared by a Baeyer-Villiger oxidation of 7-(methoxymethyl)bicyclo[2.2.1]hept-5-en-2-one.238... 

In the synthesis of Travoprost, an antiglaucoma agent, a bicyclo[2.2.1]heptan-2-one is converted to a lactone.240 The commercial process uses peroxyacetic acid as the oxidant and gives a 40% yield. The regioselectivity in this case is only 3 1 but the unwanted isomer can be removed by selective hydrolysis. 

Scheme 1.19. Cationic domino ring-enlargement/annulation process for the synthesis of bicyclo[3.2.0]heptanes.

Scheme 2.122. Synthesis of bicyclo[2.2.1]heptanes 2-536 and frans-bicyclo[3.3.0]octanes 2-541.

Other examples of the synthesis of cyclobutanes with abstraction of an allylic hydrogen are the photochemical formation of tricyclo[4.1.0.03,7]heptan-5-ones (e.g., 5) from norborn-5-en-2-ones33 and of bicyclo[4.2.0]octenes (e.g., 7) from doubly unsaturated ketones.34... 

Bicyclo[3.2.0]heptan-6-ones 10 were obtained by transformation of 2-methoxycyclohex-2-enones 8 to l-methoxybicyclo[4.1.0]heptan-2-ols 9 and subsequent rearrangement (Table 13).155 161 For the synthesis of the requisite precursors, a sequence of reduction and cyclopropanation 8 - 9, eventually followed by oxidation and an addition to the carbonyl group 9 — 11 — 12, proved most effective. 

Another example of a synthesis problem makes use of the cycloaddition reactions discussed in this chapter. Consider the synthesis of bicyclo[2.2.1]heptane, 9, from compounds with fewer carbons. 

Photocyclization of 1,3-cycloheptadienes is a particularly efficient process, since ring fission is not possible. The photocyclization of 1,3-cycloheptadienes in conjunction with a recently developed synthesis of substituted 1,3-cycloheptadienes (159) constitutes an important synthetic entry to the bicyclo[3.2.0]heptane series. Irradiation of 1,3-cycloheptadiene (Formula 361) gives the bicyclic photoisomer (Formula... 

Synthetic applications of the reaction are somewhat limited as the highly reactive biradicals and radical pairs tend to undergo reactions that compete with C—C bond formation. As in previous cases, the reaction may have synthetic value for the synthesis of strained structures involving small rings. For example, the preparation of the simplest [2]-ladderane 55 by photodecarbonylation of bicyclo[3.2.0]heptan-3-one 54 gave the bicyclic structure in 5% yield with a ring-opened 1,5-heptadiene being the dominant product (Scheme 2.14) [41]. 

Two other examples of the synthesis of bicyclic compounds whose skeleton consists only of carbon atoms are shown in Sch. 24, each of them is instructive in its own way. Upon irradiation of the cyclohexane derivative 65, not the expected product from a hydrogen abstraction from the allylic position, but the bicyclo[3.3.1]heptane 67 was obtained by cyclization of the less stable biradical 66-B [57]. The reason for this is the exclusive hydrogen back-transfer of the more stable biradical and it underlines the importance of this process in regioselectivity phenomena of the Norrish-Yang reaction. 

Both macropolycyclizations (59 + 64 - 65) and (59 + 66 -> 67) proceed in an equally facile manner to that described for the synthesis of the original [14]cyclacene derivative 63. Neither reaction of 64 or 66 with the 2 1 adduct 59 requires high pressure to effect the final ring closure. These facts reinforce the suggestion that the bicyclic bisdienes 64 and 66 with a bicyclo[2.2.1]heptane framework constitute a good stereoelectronic match for the reactive termini present in 59. The resonances... 

Further papers of interest in the bicyclo[3,l,l]heptane series report acid-catalysed addition to phenols,301 dehalogenation of 7,7-dimethylnorpinane-2-spiro-l -(2, 2 -dibromocyclopropane),297 and a synthesis of 2-pinanol.334... 

An alternative synthesis of ( )-sesquifenchene (53) has been described27 in which stereoselective methylation of an appropriate bicyclo[2,2,l]heptane derivative (52) is the key step (Scheme 11). Isoepicampherenol (54), a sesquiterpenoid whose... 

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