Bicyclic ketones, synthesis

The Baeyer-Villiger oxidation is a synthetically very useful reaction it is for example often used in the synthesis of natural products. The Corey lactone 11 is a key intermediate in the total synthesis of the physiologically active prostaglandins. It can be prepared from the lactone 10, which in turn is obtained from the bicyclic ketone 9 by reaction with m-chloroperbenzoic acid (MCPBA) " ... 

Bicyclic ketone 13 is a pivotal intermediate in Corey s approach to the prostaglandins. Buried within 13 is the five-membered ring of PGF2a, albeit in an undeveloped form. It would appear that a particularly direct approach to the synthesis of 13 would involve a [4+2] cycloaddition reaction between substituted cyclopentadiene 15 and ketene. Unfortunately, however, ketene itself is not a suit-... 

An expedient and stereoselective synthesis of bicyclic ketone 30 exemplifies the utility and elegance of Corey s new catalytic system (see Scheme 8). Reaction of the (R)-tryptophan-derived oxazaboro-lidine 42 (5 mol %), 5-(benzyloxymethyl)-l,3-cyclopentadiene 26, and 2-bromoacrolein (43) at -78 °C in methylene chloride gives, after eight hours, diastereomeric adducts 44 in a yield of 83 % (95 5 exo.endo diastereoselectivity 96 4 enantioselectivity for the exo isomer). After reaction, the /V-tosyltryptophan can be recovered for reuse. The basic premise is that oxazaborolidine 42 induces the Diels-Alder reaction between intermediates 26 and 43 to proceed through a transition state geometry that maximizes attractive donor-acceptor interactions. Coordination of the dienophile at the face of boron that is cis to the 3-indolylmethyl substituent is thus favored.19d f Treatment of the 95 5 mixture of exo/endo diastereo-mers with 5 mol % aqueous AgNC>3 selectively converts the minor, but more reactive, endo aldehyde diastereomer into water-soluble... 

Bicyclic ketone (33) was needed for a chrysanthemic acid synthesis. tarbene disconnection next to the ketone group (Chapter T30) reveals y. (5-unsaturated acid (35) as an intermediate, available by a Claisen-Cope rearrangement. 

Section B of the Scheme 9.1 shows several procedures for the synthesis of ketones. Entry 6 is the synthesis of a symmetrical ketone by carbonylation. Entry 7 illustrates the synthesis of an unsymmetrical ketone by the thexylborane method and also demonstrates the use of a functionalized olefin. Entries 8 to 10 illustrate synthesis of ketones by the cyanide-TFAA method. Entry 11 shows the synthesis of a bicyclic ketone involving intramolecular hydroboration of 1,5-cyclooctadiene. Entry 12 is another ring closure, generating a potential steroid precursor. 

Scheme 3.46. Domino radical ring-opening/cyclization procedure in the synthesis of bicyclic ketone 3-174.

The bicyclic ketone (555) was treated with cyclopentenyllithium (354) at —78 °C to form the intermediate (555), which underwent a rapid Cope rearrangement to the intermediate (356). By treatment of (356) with methyl iodide, compound (357) was obtained. The ketone (357) would serve as an intermediate in the synthesis of ophiobolin A (358) 124). 

Pirrung [153] has described the synthesis of ( )-pongomol 66 via the rhodium(II)-mediated reaction of the diazacyclohexane dione 67, to afford the fused bicyclic ketone 68 (Scheme 19.8). Moreover, this group [154] also detailed a similar approach in their synthesis of ( )-isoeuparin 69 (Scheme 19.9). Pirrung and Lee [155] expanded their rhodium(II)-mediated dihydrofuran cycloaddition strategy, for the conversion of the... 

The Fischer indolization of bicycloketones of the morphane series often has been used for the synthesis of the corresponding azocinoindoles (89TL3841, 90TL2449, 92LA461). Thus, bicyclic ketone 44, under Fischer conditions, has been transformed into azocinoindole 45 in moderate yields (94JOC3939 Scheme 11). 

The use of chiral auxiliary groups on the amide function permits the synthesis of chiral bicyclic ketones, e.g. 15, with enantioselectivity maximized with two chiral groups on the amide function.15... 

BICYCLIC KETONES FOR TROPINONE SYNTHESIS 2a,4a-DIMETHYL-8-OXABICYCLO[3.2.1]OCT-6-EN-3-ONE... 

Bicyclic and cyclic ketones are also useful intermediates and a series of preparations are given in BICYCLIC KETONES FOR TROPINONE SYNTHESIS 2a,4a-DIMETHYL-8-OXABI-CYCLO[3.2.1 ]OCT -6-EN-3-ONE CYCLOPENTENONES... 

Triclavulone 3, recently isolated from Ciavularia vulgaris, is one of the most complex of the family of about forty structurally-related fatty acid-derived marine prostanoids described from this species. Hisanaka Ito and Kazuo Iguchi of the Tokyo University of Pharmacy and Life Science recently reported (J. Am. Chem. Soc. 2004,126,4520) the total synthesis of 3, starting with the preparation of the enantiomerically-enriched bicyclic ketone 1. 

Cyciopentanones. I hc cyclization of 4-pentenals to cyclopentanones catalyzed by Wilkinson s catalyst (4, 560) has been improved considerably by modification of the phosphine ligands.1 Catalysts containing tri-p-tolylphosphine. tri-p-anisylphos-phine, and lris(p-dimethylaminopheny )phosphine are particularly useful. Simple cyclopentanones can he prepared in high yields. The reaction also provides a route to spirocyclic and bicyclic ketones (equations I and II). Unfortunately this method is not applicable to synthesis of larger rings. 

Intramolecular cyclopropanation of diazoketones to furnish [3.1.0] and [4.1.0] bicyclic systems are the most common and effective reactions in this category. Two recent examples are shown in equations 48 and 49. The bicyclic ketone 34 has been used in the synthesis of polycyclic cyclobutane derivatives77, whereas ketone 35 is the key intermediate in the total synthesis of ( )-cyclolaurene78. When the olefinic double bond is attached to, or is part of, a ring system, the cyclopropanation process also works well. Copper oxide catalysed decomposition of diazoketone 36 produces the strained tricyclic ketone 37 in 86% yield (equation 50)79. In another case, in which the cyclopropanation of diazoketone 38 gave stereospecifically the cyclopropyl ketone 39, copper sulphate catalysis was used. The cyclopropyl ketone 39 is the key intermediate in the total synthesis of ( )-albene 40 (equation 51). ... 

Photoisomerization of eucarvol (Formula 371) followed by chromic acid oxidation of the photoalcohol (Formula 372) gives the bicyclic ketone (Formula 373) in good yield (164). This approach to the synthesis... 

Corey, Mitra, and Uda (92) in their synthesis of caryophylene have found that the tricyclic hydroxy-mesylate 330 was converted under basic conditions into the bicyclic ketone 331 having the double-bond with the desired E geometry. 

An example is the synthesis of (+)-desepoxy-4,5-didehydromethylenomycin (2) from the bicyclic ketone 1. 

Route I The bicyclic ketone structure of camphor proposed by Bredt in 1893 was confirmed by total synthesis (58,59)as follows ... 

The retrosynthetic approach to welwitindolinone A isonitrile (6) used by the Wood group is shown in Scheme 33. After recognition of the possibility of deriving the vinyl isonitrile fragment from a ketone, the disconnection of 6 to 140 was proposed. A literature report of a samarium (II) iodide-mediated reductive coupling of acrylates with isocyanates to give amides, which could be expected to lead to a new spirooxindole synthesis, prompted the disconnection of 140 to 141. This compound was to be obtained from the readily available cyclohexadiene derivative 143, by way of bicyclic ketone 142. 

In the synthesis of Reiswigin A, MaGee and coworkers used 42 to deprotonate the bicyclic ketone 44 to generate silylenol ether 45 in 85% ee in the absence of HMPA (Scheme 29)67. 

Bonne, J. R., Reduction of Cyclic and Bicyclic Ketones by Complex Metal Hydrides, 11, 53. Bosnich, B., Asymmetric Synthesis Mediated by Transition Metal Complexes, 12, 119. 

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