Carbocyclic compounds, reaction with

The growing importance of cyclopropane derivatives (A. de Meijere, 1979), as synthetic intermediates originates in the unique, olefin-like properties of this carbocycle. Cyclopropane derivatives with one or two activating groups are easily opened (see. p. 69f.). Some of these reactions are highly regio- and stereoselective (E. Wenkert, 1970 A, B E. J. Corey, 1956 A, B, 1975 see p. 70). Many appropriately substituted cyclopropane derivatives yield 1,4-difunctional compounds under mild nucleophilic or reductive reaction conditions. Such compounds are especially useful in syntheses of cyclopentenone derivatives and of heterocycles (see also sections 1.13.3 and 4.6.4). 

Since diazaquinones are among the most powerful dienophiles, they undergo [4+2] cycloaddition (Diels-Alder) reactions with a great variety of dienes to give various heterocyclic systems accessible with difficulty by other methods. Diazaquinone reacts with butadiene and substituted butadienes, carbocyclic and heterocyclic dienes, 1-vinylcycloalkenes, polyaromatic compounds and vinylaromatic compounds to afford bicyclic and polycyclic bridgehead diaza systems, including diazasteroids (Scheme 56). 

At higher temperatures the mixture of 10 and methyl vinyl ketone yields the 1,4-carbocyclic compound as described previously. Methyl isopropenyl ketone (5), ethyl acetylacrylate (d), 2-cyclohexenone (21), and 1-acetyl-1-cyclohexene (22) also undergo this type of cyclization reaction with enamines at higher temperatures. This cycloalkylation reaction occurs with enamines made of strongly basic amines such as pyrrolidine, but the less reactive morpholine enamine combines with methyl vinyl ketone to give only a simple alkylated product (7). Chlorovinyl ketones yield pyrans when allowed to react with the enamines of either alicyclic ketones or aldehydes (23). 

A regio- and diastereoselective Pd-catalyzed domino silastannylation/allyl addition of allenes 6/1-236 containing a carbonyl moiety with Bu3Sn-SiMe3 6/1-237 is described by Kang and coworkers [117]. The reaction allows the synthesis of hetero-and carbocyclic compounds with a ring size of five and six. It can be assumed that... 

This chapter deals with thermal ring-closure reactions of dienes and polyenes resulting in carbocyclic compounds the formation of heterocycles is mentioned only occasionally. The account is highly selective, concentrating on recent work, since two comprehensive general reviews have appeared1,2. Other pertinent reviews are cited at appropriate places in the text. 

Reactions of Titanium Carbene Complexes with Carbon—Carbon Double Bonds Table 14.1. Preparation of carbocyclic compounds from alkenyl thioacetals. 

Cycloadditions and cyclization reactions are among the most important synthetic applications of donor-substituted allenes, since they result in the formation of a variety of carbocyclic and heterocyclic compounds. Early investigations of Diels-Alder reactions with alkoxyallenes demonstrated that harsh reaction conditions, e.g. high pressure, high temperature or Lewis acid promotion, are often required to afford the corresponding heterocycles in only poor to moderate yield [12b, 92-94]. Although a,/3-unsaturated carbonyl compounds have not been used extensively as heterodienes, considerable success has been achieved with activated enone 146 (Eq. 8.27) or with the electron-deficient tosylimine 148 (Eq. 8.28). Both dienes reacted under... 

Whereas alkylation of activated methylene systems by classical methods produces a mixture of mono- and dialkylated products, with the latter frequently predominating, phase-transfer catalytic procedures permit better control and it is possible to obtain only the monoalkylated derivatives. Extended reaction times or more vigorous conditions with an excess of the alkylating agent lead to dialkylated products or, with dihaloalkanes, carbocyclic compounds as the technique mimics dilute concentration conditions, e.g. the resonance stabilized cyclopentadienyl anion, generated under solidiliquid two-phase conditions, or under liquiddiquid conditions, reacts with 1,2-dihaloethanes to form spiro[2,4]hepta-4,6-diene (70-85%) [1-3]. Reaction with dichloromethane produces bis(cyclopenta-2,4-dien-l-yl)methane (60%) [4],... 

Friedrichsen and co-workers (135), along with Padwa, has utilized the carbonyl ylide cycloaddition to generate reactive furan moieties that can be further used in inter- or intramolecular Diels-Alder reactions to prepare aza- and carbocyclic compounds. Friedrichsen conducted a number of synthetic and theoretical studies on the reactivity, regioselectivity, and stereoselectivity of substituted furan formation and subsequent Diels-Alder reaction (Scheme 4.69). 

In the majority of dehydration reactions, heterocyclic compounds are formed, rather than carbocyclic compounds. Many possibilities for formation of carbocyclic compounds exist, but these are important only if (a) the heterocyclic or acyclic tautomers cannot undergo further elimination reactions, or (b) the conditions of reaction greatly favor the formation of an acyclic tautomer capable of affording only the carbocyclic compound. Both five- and six-membered carbocyclic compounds have been isolated, with reductic acid being the compound most frequently reported. Ring closure occurs by an inter-molecular, aldol reaction that involves the carbonyl group and an enolic structure. Many examples of these aldol reactions that lead to formation of carbocyclic rings have been studied.47 As both elimination and addition of a proton are involved, the reaction occurs in both acidic and basic solutions. As examples of the facility of this reaction, pyruvic acid condenses spontaneously to a dibasic acid at room temperature in dilute solution, and such 8-diketones as 29 readily cyclize to form cyclohexenones, presumably by way of 30, either in acid or base. 

The stable tautomer of indole-2-thiol is the thione, thiooxindole, and this compound and simple derivatives are conveniently prepared from the corresponding oxindoles by reaction with phosphorus pentasulfide (69CPB550). Like the pyrrole analogs, these compounds are quite oxygen sensitive. Spande has reviewed other aspects of the synthesis of sulfur-substituted indoles, including methods for the synthesis of compounds with carbocyclic sulfur substituents (79HC(25-3)199). 

In the fused compounds (241) and (242) the furan ring fails to react as a diene and Diels-Alder reaction with dienophiles occurs on the terminal carbocyclic rings. However, (243) and (244) afford monoadducts with dimethyl fumarate by addition to the furan rings (70JA972). The rates of reaction (Table 2) of a number of dehydroannuleno[c]furans with maleic anhydride, which yield fully conjugated dehydroannulenes of the exo type (247), have been correlated with the aromaticity or antiaromaticity of the products (76JA6052). It was assumed that the transition state for the reactions resembled products to some extent, and the relative rates therefore are a measure of the resonance energy of the products. The reaction of the open-chain compound (250), which yields the adduct (251), was taken as a model. Hence the dehydro[4 + 2]annulenes from (246) and (249) are stabilized compared to (251), and the dehydro[4 ]annulenes from (245) and (248) are destabilized (Scheme 84). 

The reaction products of the treatment of a, 3-unsaturated ketones with malononitrile in most cases are the expected derivatives of 2-amino-3-cyanopyridine. But an alternate direction with the formation of carbocyclic compounds 120 was described [128]. It is clear from structure 120 that two molecules of unsaturated ketone 5 and 1 equiv of malononitrile 107 are involved in the reaction (Scheme 3.37). 

Intramolecular olefinic C-H/olefin coupling with the aid of Ru(CO)3(PPh3)2, which is also effective for the reaction of aromatic ketones with olefins, yields the carbocyclic compounds in excellent yield (Eq. 42) [67]. This type of cy-clization reaction can be extended to an asymmetric version when the [RhCl(coe)2]2/PPFOMe catalyst system is employed [68]. 

Treatment of the bromo compound (38) with Hunig s base caused intramolecular attack of a substituent on the carbocyclic ring, with formation of the cyclopropane ring in compound (39) <81JA5621) and this was used in another approach to CC-1065 (155) (see Section 7.21.12). A similar reaction was achieved by treatment of a related mesylate with dbu <83CC1198>. 

Details have been published of the pyridine-type molecule approach for the construction of carbocyclic compounds,11 in particular ( )-D-homo-oestrone. Treatment of (39) with toluene-p-sulphonic acid in hot benzene for one minute gave12 compound (40) of the elusive A8(9)-structure further reaction led to the expected oestrapentaene (41) from which by suitable reduction procedures 8aH-, 9 8H,14j3H-, 8aH,14 3H-, and 9/3H-oestrone methyl ethers were obtained. The well known compound (42) on electrocatalytic reduction13 (palladinized platinium... 

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