Cis-fused bicyclic

Fused cyclic ethers can be derived from appropriately substituted sugars. An example is given with the stereoselective 5-exo radical cyclization of allylic 2-bromo-2-deoxysugars, in the presence of 1,1,2,2-tetraphenyldisilane as the radical mediator and AIBN in refluxing ethyl acetate. The corresponding cis-fused bicyclic sugars have been prepared in moderate to good yields (Reaction 7.28) [39]. 

A masked allylic boron unit can be revealed through a transition-metal-catalyzed borylation reaction. For example, a one-pot borylation/allylation tandem process based on the borylation of various ketone-containing allylic acetates has been developed. The intramolecular allylboration step is very slow in DMSO, which is the usual solvent for these borylations of allylic acetates (see Eq. 33). The use of a non-coordinating solvent like toluene is more suitable for the overall process provided that an arsine or phosphine ligand is added to stabilize the active Pd(0) species during the borylation reaction. With cyclic ketones such as 136, the intramolecular allylation provides cis-fused bicyclic products in agreement with the involvement of the usual chairlike transition structure, 137 (Eq. 102). 

However, this intramolecular cycloadditiou methodology has found more widespread use in the preparation of cis-fused heterobicychc rather than carbobicyclic products, by insertion of a heteroatom into the hydrocarbon tail of the alkenyl nitrone. Particular attention has been given to the synthesis of THF adducts (326, X = 0) (202,317,354,358-365), and to a lesser extent the N (82,361,366-368) S (202,203,369), or silyloxy analogues (54,55,370). Aurich and Biesemeier (359) prepared ether dipoles (327), which slowly cyclized at ambient temperature to afford the cis-fused bicyclic adducts 328 (Scheme 1.70). Reductive cleavage of the... 

A number of intramolecular cycloadditions of alkene-tethered nitrile oxides, where the double bond forms part of a ring, have been used for the synthesis of fused carbocyclic structures (18,74,266-271). The cycloadditions afford the cis-fused bicyclic products, and this stereochemical outcome does not depend on the substituents on the alkene or on the carbon chain. When cyclic olefins were used, the configuration of the products found could be rationalized in terms of the transition states described in Scheme 6.49 (18,74,266-271). In the transition state leading to the cis-fused heterocycle, the dipole is more easily aligned with the dipolarophile if the nitrile oxide adds to the face of the cycloolefin in which the tethering chain resides. In the trans transition state, considerable nonbonded interactions and strain would have to be overcome in order to achieve good parallel alignment of the dipole and dipolarophile (74,266). 

A more dramatic example is the synthesis of cA-chrysanthemic acid 11, the basis of most modern insecticides, from dimedone 8, whose synthesis we discussed in chapter 21. Methylation between the two carbonyl groups gives 9, with the complete skeleton of 11—a little reorganisation of the atoms is needed. Treatment with bromine and base gives the inevitably cis-fused bicyclic dione 10 and a further three simple steps produce chrysanthemic acid.3... 

Mn(OAc)3-mediated reaction of acetylacetone with 1,5-cyclooctadiene (137) leads to the formation of a cis-fused bicyclic compound (138), through the addition of a acetylacetonyl radical to 1,5-cyclooctadiene and subsequent intramolecular radical cyclization (eq. 4.48). 

This is the key to cis-fused bicyclic rings—everything happens on the outside (on the cover of the book). Nucleophiles add to carbonyl groups from the outside, enolates react with alkyl halides or Michael acceptors on the outside, and alkenes react with peroxyacids on the outside, Notice that this means the same side as the substituents at the ring junction. The rings are folded away from these substituents that are on the outside. 

The diastereoselectivity of the cycloadditions of 4-substituted 3//-l,2,4-triazole-3,5(4//)-diones to cis-fused bicyclic compounds A-I has been examined. 

The reaction of cyclohexene with AT-(phenylseleno)phthalimide in the presence of (S,S)-hydrobenzoin in methylene chloride afforded two diastereomeric oxyselenides (38 and the (li , 2R) diastereomer) in a 1 1 ratio. Compound 38 was separated and converted into the olefin 39 via selenoxide elimination. The second PhSeOTf promoted oxyselenenylation reaction gave only the cis fused bicyclic dioxane 40. Oxidation and subsequent elimination provided the olefin 41. This is the key intermediate for the syntheses of the cyclitols 42 and 43, that were obtained from a series of classical reactions as indicated in the Scheme. Oxyselenenylation reactions have also been employed to promote glycosylation reactions [43]. 

An asymmetric, thermal [2 + 2] cycloaddition of ketemmmium salts derived from rrm -2.5-dimethylpyirolidme has been employed in the synthesis of prostaglandins. An intramolecular [2 + 2] cycloaddition affords a cis-fused bicyclic system which is then further transformed into a common prostaglandin intermediate (eq 12). 

The rearrangement is also useful for furan aimulation, through enlargement of the starting carbocycle [82]. Thus addition of SnCU to either diastereomer of the allylic acetal produces the cw-fused cycloheptatetrahydrofuran in 48-76 % yield (Eq. 49). Acetals derived from frara-diols rearrange to the same cis-fused bicyclics in higher yield. 

Another TiCU-mediated electrophilic annulation using acetal stannane (48) has also been developed recently. As an example, the silyl enol ether of 2-methylcyclohexanone has been shown to form the cis-fused bicyclic alcohol (49) in reasonable yield with this tin reagent (equation 42). ... 

Epoxidation is stcreospecific and ds—both new C-O bonds have to be on the same face of the old alkene. But Chapter 20 introduced you to several electrophilic additions to alkcnes that were stereospecific and tmns, many of them proceeding through a bromonium ion. If stereospecific trans addition occurs on a cis-fused bicyclic alkene, the electrophile will first add to the outside of the fold, and the nucleophile will then be forced to add from the inside. A telling example occurs when the 4/5 fused unsaturated ketone below is treated with h/-bromoacetamide in water. 

Removal of the tether was realized in two ways. Oxidative cleavage of an activated C-Si bond has been shown to proceed with retention of configuration [11]. Thus treating 19 and 20 with 1 equiv of TBAF and a 30% solution of H2O2 in DMF at 55 °C for 2 h afforded the diastereoisomeric diols 21 and 22, respectively, both in 80% yield. Alternatively hydrodesilylation could be achieved using 2 equiv of TBAF in DMF at 60 °C for 4 h. In the case of the cis-fused, bicyclic Diels-Alder adduct 19, the basic conditions of... 

Actually it is true that under the catalysis of a Pd(0) species, i.e., Pd(dba)2, the czs-cyclohexyl carboxylate-allene 101 afforded the bicyclic trienes 102 and 103 via the oxidative addition of the allylic carboxylate moiety forming a 7i-allylic Pd intermediate, which underwent intramolecular carbopalladation and P-H elimination to afford the cis fused bicyclic products 102 and 103 (Scheme 47)... 

Inside/outside selectivity may allow the distinction between two otherwise similar functional groups. The cis-fused bicyclic diester below may look at first rather symmetrical but ester hydrolysis leaves one of the two esters alone while the other is converted to an acid. 

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