Syntheses from bicyclic ketones

Syntheses from Bicyclic Ketones. In many syntheses of steroid compounds of the type AB D, in addition to tricyclic C14, ketones bicyclic ketones with keto groups in positions Cn, and C14, according to the steroid nomenclature, have been used as intermediates. 

Even shorter (six stages) is the method of synthesizing (27) in which a five-carbon fragment containing the angular methyl group is introduced directly [269]. The action of o -bromo-ce-methylsuccinic ester and zinc on 

The Reformatskii reaction between the ketone (149) and ce-bromopro-pionic ester, dehydration, hydrogenation, and allylation led to a mixture of isomers of the ester (146). An enantiomer of one of these isomers was converted into one of the enantiomers of the cis-acid (27) by oxidation to (147), cyclization to (148), and hydrogenolysis of the 11-oxo group [271-274]. 

The yields in the various stages were very low, and this variant of the synthesis of (27) is therefore of no preparative importance and is used only for the correlation of the configurations between the series of allenolic and bisdehydrodoisynolic acids. 

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Trost et al. reported an efficient method for synthesis of plumericin (67), allamcin (68), and antileukemic allamandin (69), applying a biomimetic strategy. The requisite key intermediates were synthesized using the concept of spiro-annulation and stereocontrolled geminal alkylation. Their strategy required 9, 13, and 14 steps from bicyclic ketone (70) for synthesis of allamcin, plumericin, and allamandin, respectively. The bicyclic ketone was synthesized from cycloocta-1,3-diene in three steps. The synthetic route is outlined in Scheme 97.3 [101]. 

The use of Vogel s "naked sugar approach to the synthesis of myo-inositol derivative (80) from bicyclic ketone (79) and the use of the latter in the preparation of glycoside (81) has been reported. ... 

The main intermediates of total syntheses of the type considered have been tricyclic C14 ketones containing the aromatic system of naphthalene (rings A and B) or benzene (ring A) (Schemes 1-12). Several methods of synthesis have started from bicyclic ketones (Schemes 13 and 14) and also from ABC diacids obtained by cyclization or by the diene synthesis (Schemes 15 and 16). 

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) " ... 

A highly versatile method for the synthesis of a variety of 6-membered monocyclic and fused bicyclic peroxylactols 440 from activated ketones 438 (EWG = electron-withdrawing... 

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. 

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

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. 

The synthesis of bicyclic cyclopentanols (46) via photoreductive cyclization of 5,8-unsaturated ketones (45) has been realized by Belotti et al. using hexamethylphosporic triamide (HMPA) or triethylamine (TEA) as electron donor [46]. The photocyclization proceeded remarkably efficient when HMPA was used as donor and solvent (Sch. 24). Furthermore, only one stereoisomer was obtained carrying methyl and hydroxy groups in trans-configuration. In contrast, the yields for cyclization dropped significantly when TEA in a polar solvent such as acetonitrile was used. As an example, the yield for 46 (n= 1) decreased from 81% in HMPA to 50% in TEA/ MeCN. 

The synthesis of dihydrofuran derivatives such as 177 has been performed to explore scope and limitations of the Lewis acid promoted hydroxyalkylation of siloxycyclopropanes. Table 6 shows that aromatic as well as aliphatic ketones can efficiently be incorporated. Enolization of ketones does not occur and a 1-methyl group at the cyclopropane is no obstacle for the reaction, which now binds the carbonyl compound to a quartemary center with surprisingly high efficiency (entry 5). Albeit there are some restrictions with regard to the substitution pattern of the cyclopropanes, bicyclic siloxycyclopropanes also give good yields (e.g. entry 6 and Eq. 76). Further examples of the tetrahydrofuran synthesis from intermediate y-lactols with... 

Examples of such three-carbon synthons are 2-nitro-2-propen-l-yl acetates and piva-lates, which have been developed by Seebach and coworkers57,58 as reagents for [3 + 3] cyclizations with cyclic and acyclic ketone enamines. After workup these reactions give 4-nitrocyclohexanones. With enamines from prolinol methyl ether and cyclic ketones, enantiomerically pure compounds were obtained58. An example of such a [3 + 3] cyclization is the synthesis of bicyclic nitroketone 99 from nitroallylic ester 97 and enamine 98 (equation 18). 

An example of the utilization of a bridged bicyclic ketone for preparation of an acyclic moiety is the stereoselective synthesis of the C-21 to C-27 segment of rifamycin-S, a member of the ansamycin family of antibiotics (Scheme 18). Rao et alP used ketone (61), derived from furan, to prepare lactone (62). Exhaustive reduction of (62) provided the segment (63), which contains five chiral centers of lifamycin-S. 

Following on from Money s important work on the use of a monocyclic precursor for the synthesis of bicyclic and tricyclic sesquiterpenoids, Noyori et al. have now gone one step further and shown that the dibromo-ketone (101) (prepared... 

The methyl-substituted BCR is useful for the construction of some iridoid cyclopentanoids. Keto alcohol (137), a crucial intermediate for a synthesis of ( )-chrysomelidial (138), can be prepared from the cycloadduct (108) of cyclopentenone and the methyl-TMM synthon (equation 145)7 This expedient approach to the keto cohol, four steps and 83% overall yield from the bifunctional reagent (107), is a considerable improvement over a previous 14-step sequence using conventional methodologies. Although the initial bicyclic ketone (108) is a 1 1 epimeric mixture, base-catalyzed equilibration of the products from ozonolysis results in only one epimer, having the required stereochemistry. This... 

The synthesis of bicyclo[3.2.2]non-6-en-3-one (192) and the spiro-substituted derivatives (195) can be achieved via similar methodology. Thus, thermolysis of the enol silyl ether (190), which is readily derived from the ketone (189), gives the bicyclic substance (191). Mild acid hydrolysis of (191) affords (192 Scheme 27). In a similar fashion the exo-ketones (193) have been converted, via the enol silyl ethers (194), into the tricyclic keto alkenes (195). ... 

Hua has used the products of Pauson-Khand cycloadditions for syntheses of optically active pental-enene and racemic pentalenolactone E methyl ester. The racemic ketone in the first case was converted to the necessary optically active intermediate by kinetic resolution via 1,4-addition of an optically active allyl sulfoxide anion. These represented the first synthesis of natural products containing the angularly fused triquinane skeleton from bicyclic Pauson-Khand products (equation 53 and Scheme 20). ... 

Intramolecular heterocyclization in polyacrylonitrile 86UK62. a-Isocyano acetates, synthesis of N-heterocycles from 85YGK764. Isonitrosotosyl malonates in synthesis of N-heterocycles 80H(14)1581. Lactams, regioselective formation from bridged bicyclic ketones 81T1283. Malononitrile derivatives, synthesis of N-heterocycles condensed from ... 

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