Carvones cycloaddition

A total synthesis of functionalized 8,14-seco steroids with five- and six-membered D rings has been developed (467). The synthesis is based on the transformation of (S)-carvone into a steroidal AB ring moiety with a side chain at C(9), which allows the creation of a nitrile oxide at this position. The nitrile oxides are coupled with cyclic enones or enol derivatives of 1,3-diketones, and reductive cleavage of the obtained cycloadducts give the desired products. The formation of a twelve-membered ring compound has been reported in the cycloaddition of one of the nitrile oxides with cyclopentenone and as the result of an intramolecular ene reaction, followed by retro-aldol reaction. 

The photocyclization of carvone, 36, to carvonecamphor, 37, is a good example of intramolecular cycloaddition of an enone to an isolated double bond422 ... 

The photochemical cycloaddition of two different alkenes leads to multiply substituted cyclobutanes, and allows for a general access to this class of compounds. More specifically, ever since Ciamician observed the light-induced isomerization of carvone (1 —> 2) (Scheme 6.1) in 1908 [1], the inter- and intramolecular reaction between an a,(3-unsaturated carbonyl compound and an alkene has become the most intensively studied and most widely used class of [2 + 2]-photocycloaddition reactions [2-9]. 

The first such reaction published in 1908 by Ciamician and Silber was the light induced carvone —> carvonecamphor isomerization, corresponding to type b [1]. Between 1930 and 1960 some examples of photodimerizations (type c) of steroidal cyclohexenones and 3-alkylcyclohexenones were reported [2-5]. In 1964, Eaton and Cole accomplished the synthesis of cubane, wherein the key step is again a type b) photocycloisomerization [6]. The first examples of type a) reactions were the cyclopent-2-enone + cyclopentene photocycloaddition (Eaton, 1962) and then the photoaddition of cyclohex-2-enone to a variety of alkenes (Corey, 1964) [7,8]. Very soon thereafter the first reviews on photocycloaddition of a,(3-unsaturated ketones to alkenes appeared [9,10]. Finally, one early example of a type d) isomerization was communicated in 1981 [11]. This chapter will focus mainly on intermolecular enone + alkene cycloadditions, i.e., type a), reactions and also comprise some recent developments in the intramolecular, i.e., type b) cycloisomerizations. 

The photochemical [2 + 2] cycloaddition reaction of alkenes, the light-induced cycloaddition of two carbon-carbon ir-bonds to produce a cyclobutane, is a potentially highly useful reaction in organic synthesis since two new carbon-carbon bonds are formed and a maximum of four new stereocenters are introduced in the process. Ciamician reported the first example in 1908 when he observed the formation of carvone camphor (2) on prolonged exposure of carvone (1) to Italian sunlight (equation 1). ... 

Phase-transfer addition (c/. Vol. 6, p. 31) of dibromocarbene to carvone and reduction to a monobromo-ketone by tributyltin hydride, or to a dibromo-alcohol with lithium aluminium hydride, is reported/ 1,3-Dipolar cycloaddition of acetonitrile oxide occurs exclusively at the exocyclic double bond in limonene to give (155 R = Me, X = Hi), whereas isoxazoline formation with carvone yields (155 R = Me, X —O) and the isomeric product from attack at the C-6 double bond benzonitrile oxide, however, only yields (155 R = Ph, X = 0 or NOH). A re-investigation of aqueous chlorination of a -terpineol indicates that the diequator-ial chlorohydrin (156) and the corresponding diaxial chlorohydrin are the major... 

A reinvestigation of previous results6 from the [4+2] cycloaddition of dienes 2 to (—)-carvone (12) has been undertaken. These new results are in accordance with model studies4-5 and a good anti diastereoselectivity is obtained1. 

The first example of a photoinduced cnone cycloaddition was the conversion of carvone to carvone camphor by Ciamician in 19081. 

Schonberg proposed in his book [4] that the 2+2 cycloaddition first reported by Ciamician for the case of carvone [38] should be named in honor of that scientist. Note that a non photochemical reaction, the Ciamician-Dennstedt ring enlargement of pyrroles (1881), does bear his name... 

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