Ring Transformation of the Derivatized Cyclobutenone

Varied Reactivity in Ring Opening and Ring Closure

The intrinsic reactivity of small rings is ascribable to ring strain relief in nature, and in squaric acid chemistry it is accomplished by conversion of rather stable cyclobutene-1,2-dione to the more reactive 4-hydroxy-2-cyclobutenone [55,56] as described in the previous section. At the same time, this conversion step fulfills the regiospecific introduction of substituents required for the targeted heterocyclic structure. Thereby, the set-up four-membered ring is now subjected to directed synthesis through variable ring transformation reactions.

These involve tandem ring opening and ring closure steps, which are concerted or non-concerted. The typical concerted process is 4n-electrocyclic ring opening of cyclobutene to 1,3-butadiene. This was discussed in terms of torquoselectivity by Houk [57-64]. According to his theory, n-donor sub-stituents (R = O-, OH, NH2) prefer outward rotation while n-acceptor sub-stituents (R = BMe2, CHO) should rotate inwardly on the thermal process (Fig. 2). Recent discovery has extended this concept; a silyl substituent accelerates and promotes inward rotation despite the resulting steric congestion, and a stannyl substituent does similarly [65,66].

Fig.2 Torquoselectivity in 4n electrocyclic ring opening (thermal conditions) [57-64]

4-Hydroxy-2-cyclobutenone adheres to the above prediction [55-64]. In this case, it is important that the inwardly-directed substituent (i.e., OH is an outward-directing group) is capable of participating within the molecule. Moreover, a highly reactive vinylogous ketene function occurs instead of butadiene formation to assist efficient ring-closure through intramolecular interaction. When an unsaturated bond is located at the 4-position, the consecutive process is thermally allowed 6n-electrocyclization (Fig. 3).

Fig. 3 Sequence of 4n-6n electrocyclic ring opening and ring closure [19-23]

This strategy is very powerful and fruitful for the directed synthesis of both carbo- and heterocycles, and successful examples have cumulatively been reported until now [19-23]. The major contribution has come from the Moore and Liebeskind groups. Among many efforts devoted in this area, the recent typical example [polysubstituted naphthoquinone, Echinochrome A (30)] constitutes a characteristic feature for the method of directed synthesis including 26 ^ 27 and 28 ^ 29 as key steps [67]. Ferro-cenyl quinone and 5-O-methylembelin were also synthesized according to this methodology [68,69] (Scheme 5).

In the case of monosubstituted cyclobutenone 31, the adduct with lithiovinylsuofone 32 was reported to undergo an extraordinarily facile tandem 4n-6n electrocyclic process (33 ^ 34) at - 78 °C to give cyclohexenone 36 [70]. The photochemical process may oblige the opposite direction on a hy-droxyl group to be oriented inwardly; actually cyanohydrin 37 was reported to give butenolide 39 as a result of an intramolecular addition reaction of (Z)-hydroxyvinylketene 38 [71] (Scheme 6).

Fig.2 Torquoselectivity in 4n electrocyclic ring opening (thermal conditions) [57-64]

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