Cycloalkenones synthesis

Posner and coworkers have published a series of papers in which they described a successful application of the Michael reaction between a variety of carbanionic reagents and chiral cycloalkenone sulphoxides 557 to the synthesis of chiral organic compounds (for reviews see References 257, 649, 650). In several cases products of very high optical purity can be obtained. Subsequent removal of the sulphinyl group, serving as a chiral adjuvant, leads to optically active 3-substituted cycloalkenones 558 (equation 356 Table 27). 

Minuti L., Taticchi A., Costantini L. High Pressnre Diels-Alder Reactions of Cycloalkenones in Organic Synthesis Recent Res. Dev. Org. Chem. 1999 3 105-116 Keywords ketones, regiochemistry, stereoselectivity, reactivity... 

Jasmonates are important odorant compounds. For the synthesis of new substances of this type, Giersch and Forris developed a domino Claisen/ene/retro-ene process which allows the acid-catalyzed transformation of sorbyl alcohol 4-285 and the cyclic acetals 4-286 into the cycloalkenone 4-292 with the proposed intermediates 4-287 to 4-291 (Scheme 4.61) [97]. A similar domino process had been described by Srikrishna and coworkers [98]. Acyclic acetals gave only the Claisen rearrangement products. 

A different approach towards titanium-mediated allene synthesis was used by Hayashi et al. [55], who recently reported rhodium-catalyzed enantioselective 1,6-addition reactions of aryltitanate reagents to 3-alkynyl-2-cycloalkenones 180 (Scheme 2.57). In the presence of chlorotrimethylsilane and (R)-segphos as chiral ligand, alle-nic silyl enol ethers 181 were obtained with good to excellent enantioselectivities and these can be converted further into allenic enol esters or triflates. In contrast to the corresponding copper-mediated 1,6-addition reactions (Section 2.2.2), these transformations probably proceed via alkenylrhodium species (formed by insertion of the C-C triple bond into a rhodium-aryl bond) and subsequent isomerization towards the thermodynamically more stable oxa-jt-allylrhodium intermediates [55],... 

The photoinduced-addition of alcohols to cycloalkenones has been investigated by Fraser-Reid and co-workers,4 by Paquette,5 and was used as the key step in the synthesis of the prostaglandin endoperoxide analogue (15S)-hydroxy-9a,11a-epoxymethanoprosta-(52,13E)-dienoic acid,6 and for the recent synthesis of 2, 3 -dideoxy-3 -hydroxymethyl-5 -carbanucleosides.7 No work (other than our own) has been reported on the photoinduced-addition of alcohols to 5-substituted furan-2(5H)-ones. 

Tandem 1,4-addition to cycloalkenones constitutes an extremely versatile and elegant methodology for the synthesis of 2,3-disubstituted cycloalkanones, as is evident from its application in areas such as prostaglandin synthesis. Noyori et al. have reported the use of organozinc reagents in copper-catalyzed tandem additions [64]. The zinc enolate resulting from the catalytic enantioselective 1,4-addition of Et2Zn to cyclohexenone reacts readily with an aldehyde in a subsequent aldol condensation. 

F. Fringuelli, A. Taticchi, E. Wenkert, Diels—Alder Reactions of Cycloalkenones in Organic Synthesis. A Review Org. Prep. Proced. Int. 1990, 22, 131—165. 

Ito, Y, Fujii, S., and Saegusa, T. 1976. Reaction of l-silyloxybicyclo[n.l.OJalkanes with Fe Clj. A facile synthesis of 2-cycloalkenones via ring enlargement of cyclic ketones. J Org Chem 41, 2073-2074. 

A synthetic route to Q, /i-disubstituted cycloalkenones via a four step one-pot synthesis employed (4a) for RCM and then oxidative rearrangement giving products in low to moderate overall yields as a way to access estrogen receptor ligand tetrahydrofluorenones (equation 29)3 Crimmins reported an asymmetric aldol-oleftn metathesis approach to the synthesis of functionalized cyclopentenes exploiting the acyclic stereocontrol of the aldol reaction with efficient (2a) catalyzed RCM (equation 30)3 ... 

The osmylation of l-[Af-methylphenylsulfoximinomethyl]-l-hydroxy-2-cyclopentenols and -2-cyclohexenols, obtained in turn from the corresponding 2-cycloalkenones by the addition of lithiated, V,.S -dimethyl-5-phenylsulfoximine, occurs from the same side as the sulfoximino functionality with complete Ik topicity. Subsequent thermal elimination of the sulfoximine group allows the synthesis of optically pure 2,3-dihydroxycycloalkanones. This method can, therefore, be regarded as proceeding via an auxiliary-controlled osmylation92-93. 

Which of these two pathways is operative is unclear at this time, but it is clear that the vinyl substituent on the cycloalkenone plays an important role in the selectivity. Pattenden, in a synthesis of epipre-... 

The same type of process using osmylation instead of the Simmons-Smith reaction leads to a synthesis of enantiomerically pure 2,3-dihydroxycycloalkanones from 2-cycloalkenones. Addition of (S)-(141) to 3,S,S-trimethyl-2-cyclohexenone (162) produces a mixture of diastereomers (163a) and (163b), which are easily separable by silica gel chromatography. Treatment of the individual diastereomers with tri-ethylamine N-oxide and 0s04 (5 mol %) afford crude triols. In each case, a single diastereomeric product is produced. The subsequent thermolysis of the diastereomeric triols gives enantiomeric 2,3-dihydroxy-3,5,5-trimethyl-2-cyclohexanones(164 Scheme 37). 

Conjugate addition to enones. In the presence of l equivalent of TiCl4,1 undergoes 1,4-addition to cycloalkenones. An example is formulated for a recent synthesis of methyl jasmonate (2) in equation (1). 

Treatment of diethyltrichloromethylphosphonate with butyllithium followed by an aldehyde or cycloalkenone leads to a-chlorovinylphosphonates (89). Pyranosic 3,4-enuloses exhibit anomalous behaviour when treated with the enolate of dimethyl(methoxycarbonyl)-methylphosphonate, leading to phos-phorylated products. The synthesis of a-(alkyl)methylene-Y-iodo-Y-butyrolac-tones has been accomplished in high yields, but with poor selectivity, from the reaction of a-phosphono-y-iodo-Y-butyrolactones and aldehydes. ... 

---