Synthesis intermolecular cycloisomerization

In a recent report, Shi et al. developed a valuable tool for the synthesis of 2,6-trans substituted morpholines by addition of water and alcohol to epoxy alkynes [109]. The procedure involved a domino three-membered ring opening, 6-exo-cycloisomerization, and subsequent intra-or intermolecular nucleophilic addition or a double-bond sequence. 

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. 

An intermolecular diene cycloisomerization was the key step in a synthesis of the putative structure of fistulosin 11.248, an anti-fungal compound from Welsh onion roots (Scheme 11.82)." The substrate 11.246 could be prepared by Mitsunobu alkylation of a sulfonamide 11.243, followed by migration of the double bond with a ruthenium catalyst. The cycloisomerization was achieved using a species generated from the Grubbs second-generation catalyst and the silyl enol ether of acetaldehyde. When the target structure 11.248 was finally reached, the spectroscopic data showed that the reported structure of the natural product was incorrect. 

The development of new procedures for the creation of C-C bonds is of major importance in organic synthesis. In this respect, gold catalysis has emerged as a very efficient synthetic tool, allowing the generally easy and efficient formation of such bonds by addition of various carbone nucleophiles onto alkynes, allenes, and alkenes. These transformations, which can be performed in an intra- or intermolecular manner, are extremely varied. It should however be noted that tlie cycloisomerization of ene-ynes, diene-ynes, or ene-allenes remains the most frequently encountered. A very short selection of such transformations is presented in Scheme 16.16 [15g,k, 20]. 

Hydroalkoxylation. The cycloisomerization of unactivated unsaturated alcohols has been achieved using Al(OTf)3 (eq Reaction with unsaturated oximes also led to 1,2-oxaza heterocycles with five-, six-, and seven-membered rings. This catalyst provided a straightforward route to cyclic ethers with a Markovnikov-type regioselectivity. Notably, these conditions were used for efficient synthesis of olfactory-active rose oxide derivatives. Mechanistic studies showed that Al(OTf)3 coordinates to the oxygen atom of the alcohol, leading to strong acidification of the hydroxyl proton. Intermolecular hydroalkoxylation with methanol has also been reported. ... 

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