Bicyclic aldehyde

Epoxidation of norbornene was found some time prior to this work not to stop at the monoepoxide step. Instead, this intermediate goes on to rearrange to the bicyclic aldehyde, 31, ... 

We should also expect stereoelectronic control when the hydroxyl group is replaced by another nucleophile in the reaction with cyclic oxonium ions. A recent report (110) shows that hydride transfer to cyclic oxonium ion is subject to stereoelectronic control. Tricyclic spiroketal 140 (Fig. 19) undergoes an acid-catalyzed oxidation-reduction reaction to give the equatorial bicyclic aldehyde 147 stereospecifically. Similarly, spiroketals 148 and M9 gave the corresponding equatorial bicyclic ketone 150. 

In the Woodward synthesis of prostaglandin (621, intermediate 172 formed in situ from the corresponding amine was smoothly transformed into bicyclic aldehyde 173. Seebach and co-workers (63) have also observed several stereospecific rearrangements using the same reaction. For example, diazotization of amine 174 gave specifically the cis-cyclopentane 175 which was then epimerized into the more stable trans-cyclopentane 176. 

Hydrolysis of dioxetane 223, or of ketal 10, led to an inseparable mixture of expected product 225, as well as bicyclic isomer 226. The mixture was 1 2 (225 226), and underwent standard acylation reactions to give, for example, 179 on treatment with Ac20/pyridine/CH2Cl2. Carbonates such as 181 were available from 225 upon treatment with various chloroformates in pyridine/CH2Cl2. In other words, the alcohol 225 could be funneled away from the mixture by reaction with electrophiles, providing the desired tricyclic products. The bicyclic aldehyde 10 was isomerized to obtain tricyclic ketal 228 under dehydrating conditions in the presence of an alcohol. 

A stereospecific total synthesis of prostaglandins E3 and F3, containing an additional double bond in this side chain, starts from the optically active phosphonium salt 161. In this synthesis the ( )-13-double bond and the 15-hydroxy function are generated simultaneously by condensation of the chiral bicyclic aldehyde 163 with the P-oxido ylide 162 obtained by treatment of 161 with methyllithium. The corresponding phosphonium salt S) +)-161, already possessing the (Z)-configurated A17-double bond of prostaglandins, was prepared from (S)(—)-tartaric acid 1351 (Scheme 29). 

Indium-mediated allylation of m/<9-2-acetoxybicyclo[2.2.1]heptan-7-one shows poor diastereoselectivity.129 On the contrary, indium-mediated allylation of the bicyclic aldehyde has been performed with different solvent systems, and the homoallylic alcohols 10 and 11 are formed in excellent yields with high diastereoselectivity. The highest diastereoselectivity has been observed in DMSO in 94% yield (Scheme 16).130 Indium-mediated propargylation of the same aldehyde gives two diastereomers in 94% yield in a ratio of 60 40 (Equation (9)).130... 

Enamines have been made from a bicyclic aldehyde (5)126 from bicyclic ketones (6)i27,i28, (7)129, (8)129 and (9)129, from cyclic ketones fused to a benzene ring, such as a-tetralone130-134 and jS-tetralone131,135,136, from ketones with a seven-membered ring133,137,138 fused to the benzene ring, or with a five-membered ketonic ring130,139-143 fused to the benzene ring. 

Marine organisms have continued to provide unusual diterpenoid skeleta. 14-Bromo-obtus-l-ene-13,ll-diol (144) has been obtained from the sea hare Aplysia dactylomola. The irieols A—G (145)—(151) are a group of dibromo-diterpenoids which have been obtained from the marine red alga Laurencia irieii. Their structures were established by n.m.r. spectroscopy and by degradation to a bicyclic aldehyde. 

Acetals Various lanthanide chlorides are efficient catalysts for acetalization of aldehydes by methanol. Lanthanum chloride and cerium chloride are satisfactory for aliphatic aldehydes, but erbium chloride and ytterbium chloride are generally superior, particularly for aromatic and bicyclic aldehydes. Addition of trimethyl orthoformate as a water scavenger allows use of the commerically available hydrated forms of the salts. Acetals can be obtained in 80-100% yield from reactions conducted for 10 minutes at 25°. 

The unusual 6-azabicyclo[3.2.1]oct-3-ene core of the alkaloid (+)-peduncularine was assembled using the [3+2] annulation of an allylic silane with chlorosulfonyl isocyanate by K.A. Woerpel and co-workers. In the endgame of the total synthesis, the bicyclic aldehyde was masked as the acetal, and an efficient Fischer indole synthesis was performed using phenylhydrazine hydrochloride along with 4% H2SO4. Several subsequent steps led to the natural product. 

In the laboratory of FI. Flagiwara, the first total synthesis of the polyketide natural product (-)-solanapyrone E was achieved. The installation of the pyrone moiety required the addition of the b/s(trimethylsilyl) enol ether of methyl acetoacetate to a bicyclic aldehyde precursor in the presence of titanium tetrachloride. The resulting -hydroxy- -ketoester was oxidized with the Jones reagent to afford the corresponding -diketoester in good yield. 

Enamines have been made from a bicyclic aldehyde from bicyclic ketones... 

Connolly, T. J., Durst, T., Photochemically Generated Bicyclic o Quinodimethanes Photoenolization of Bicyclic Aldehydes and Ketones, Tetrahedron 1997, 53, 15969 15982. 

Use of polymer-bound chlorite 11 was shown to be more efficient for the oxidation of secondary alcohols to the corresponding ketone [23c]. The method was applied to a series of complex synthetic intermediates and gave excellent results. Immobilized chlorite was shown to be also a very efficient co-oxidant in the conversion of primary alcohols into the corresponding carboxylic acid [24]. This method is particularly attractive due to the ease of purification, the excellent yields and purity obtained also on more complex structures. What makes these techniques particularly interesting is that they have found applications in the synthesis of complex molecules. It was the method of choice for the synthesis of intermediate 13, the core of azadirachtin, in studies towards the synthesis of this natural product by the Nicolaou group [25]. This bicyclic aldehyde was obtained very cleanly using this method (Scheme 4.2). 

A transannular 6-endo reaction takes place in the boron trifluoride-diethyl ether complex induced cyclization of a bicyclic aldehyde. After the Markovnikov-orientated ring-closure step, a tertiary cation is generated, which is stabilized by //-proton loss and tetracycle 18, bearing a cyclopropyl unit, is formed in 67% yield24. In this case an ene reaction is impossible. 

The group of Biichi, who also determined the structure and absolute configuration of several aflatoxins (20-22), achieved the first total synthesis of racemic aflatoxin Bi (1) in 1966 (34, 35). They started from phloroacetophenone (17), which was converted in two steps into its monomethyl ether 18 (see Scheme 2.2). Selective monobenzylation, followed by Wittig condensation and selenium dioxide oxidation gave the bicyclic aldehyde 19 in good yield. 

In 2009, Nicolaou and co-workers reported an organocatalytic total synthesis of demethyl calamenene (168), a potent cytotoxic agent, which is a beautiful application of SOMO-activated catalysis (Scheme 17.29) [68]. The key step involved an asymmetric intramolecular Friedel-Crafts reaction of aldehyde 166 to achieve the bicyclic aldehyde 167 using imidazolidinone 122 as a SOMO-activated catalyst (56% yield, 90% ee). 

The decarbonylation of a bicyclic aldehyde prepared by a Diels-Alder reaction was conducted with the Madsen catalyst (Scheme 8.13) [9]. 

According to PMO method T.S. of first step and also second step has 6-electrons, 0-node and therefore aromatic. Thus, both the steps are thermally allowed. T.S. of fourth step has 4-electrons, 0-node and is therefore antiaromatic indicating this step is photochemically allowed. First step is a (rt a+a s-i-a a) thermal rearrangement of exo-epoxide to bicyclic aldehyde through aromatic transition state as shown below ... 

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