Bicyclic diols

The Wharton fragmentation was used as a key step in an approach toward the total synthesis of xenicanes by H. Pfander et al. ° Two optically active substituted frans-cyclononenes were synthesized starting from (-)-Hajos-Parrish ketone. First, the bicyclic 1,3-diol was protected regioselectively on the less sterically hindered hydroxyl group with p-toluenesulfonyl chloride in quantitative yield. Next, the monosulfonate ester was exposed to dimsylsodium in DMSO, which is a strong base, to initiate the desired heterolytic fragmentation. 

The same group also published a similar procedure using unsaturated bicyclic diols 7-124 to yield the tricyclic ene-acetals 7-125, using PhI(OAc)2 as oxidizing agent The products can be further transformed by treatment with Pb(OAc)4, and this led to the tricyclic bisacetat 7-126 in remarkably good yield (Scheme 7.33) [56]. 

Yttrocene complexes catalyze the cascade cyclization/hydrosilylation of trienes to form saturated silylated bicyclic compounds.For example, reaction of the 4-silyloxy-4-vinyl-l,6-hexadiene 69 and phenylsilane catalyzed by Gp 2YMe(THF) at room temperature for 1 h followed by oxidation of crude 70a gave [3.3.0]bicyclic diol 70b in 73% yield over two steps as a single diastereomer (Scheme 18). Selective conversion of 69 to 70a presumably requires initial 1,2-hydrometallation of one of the less-hindered G=G bonds to form alkylyttrium alkene complex II (Scheme 18). Selective S-exo carbometallation of II in preference to -exo carbometallation would form cyclopentyl-methylyttrium complex III (Scheme 18). Gyclization of III via a chairlike transition state would form the strained /r< /75 -fused alkylyttrium complex IIIl, which could undergo silylation to form 70a. 

P. Stoss (Dottikon, Switzerland) and R. Hemmer (Senden, Germany), in their article on the 1,4 3,6-dianhydrohexitols, provide the perspective of the industrial chemist and bring up to date a subject that was treated by Wiggins in Volume 5 of this series and by Soltzberg in the tabular material contributed in Volume 25. These anhydrides are of considerable theoretical interest, but much of the rapidly burgeoning related research is recorded in the patent literature because of the wide practical potential manifested by these bicyclic diols. 

Treatment of 106 with silylated enediols 105 in the presence of TMSOTf gives the corresponding annulated bicyclic diols 107 (equation 82)151. A similar reaction with cyclobutenediol derivative 108 followed by oxidative cleavage of thus formed diol 109 yields a seven-membered ring product (equation 83). 

The bicyclic diol, VIII/J94, prepared according to Scheme VIII/35, was oxidized with lead tetraacetate to the ten-membered lactone, VIII/195. The latter was then transformed into phoracantholide I (see Chapter VII) [114]. 

The asymmetric transesterification of cyclic me o-diols, usually with vinyl acetate as an irreversible acyl transfer agent, includes monocyclic cycloalkene diol derivatives, bicyclic diols, such as the ej o-acetonide in eq 12, bicyclic diols of the norbomyl type, andorganometallic l,2-bis(hydroxymethyl)ferrocenepossessing planar chirality. 

It was later found that the bicyclic diol 54, accompanies the above bromoketones". Similar reaction sequence takes place with the saturated analogs". ... 

A chiral bicyclic diol 47 and its analogues such as 50 and 52 form spiral hydrogen-bonded spines -O-H -0-H- -0-H- -0-H- (48) around a threefold screw axis (Fig. 13) [61]. The molecules are assembled in a helical manner to give well-defined intrahelix canals 49,51, and 53 of different cross-sections) supported by six such spines. The cross-sectional area is 20 in the case of 49 and a variety... 

Fig. 13. Helical canals formed by chiral bicyclic diols 47,50, and 52...

A chiral bicyclic diol and its derivatives crystallize in a series of hydrogen-bonded species surrounding parallel channels in which guest molecules can be trapped by a cross section as large as 35 An example for a... 

Chiraldex G -PH Cyclic and bicyclic diols, steroids and earbohydrates. 

Monocyclic ethylenealcohols from bicyclic diol monosulfonates Fragmentation-type reductive ring opening... 

Reduction-triggered pericyclic reaction has been used for the biomimetic total synthesis of endiandric acids A-G [72]. Endiandric acids are polycychc natural products isolated from the Australian plant Endiandra introrsa and exist naturally as a racemic mixture which is found to have very high antibacterial effect [73]. In 1980, Black and coworkers [74] proposed a hypothesis that these polycyclic systems are formed in nature by a series of electrocycUzation reactions. On the basis of this hypothesis, Nicolaou et al. [72c] in 1982 reported an excellent domino reduction/electrocyclization process for the synthesis of endiandric acid A 127 (Scheme 9.25). Selective hydrogenation using a Lindlar catalyst of diacetylenic diol 123 afforded the bicyclic diol 126. The reaction presumably proceeds via polyene 124, which then undergoes a spontaneous 8 [i-electrocyclization to give 125. It follows a second 6n-electrocyclization to afford bicyclic 126, which is further converted to endiandric acid A 127. 

The bicyclic diol ea (9-2,eX(9-G-dihydroxy-2,6-dimethylbicyclo [3.3.1]-nonane (2) forms stable crystalline inclusion complexes when crystallised from a variety of common solvents. For example from ethyl acetate long trigonal needles of approximate composition (diol)ethyl acetate (2E) are produced and forcing conditions (60 C under reduced pressure) are required to remove the guest solvent molecules from these crystals. 

Monocyclic ethyleneketones from bicyclic diol monotosylates s. 19, 937... 

Cyclic and bicyclic diols and other larger compounds, including steroids and carbohydrates... 

The same authors have also investigated the DKR of bicyclic diols into their diacetates indueed by a combination of Candida antarctica lipase B (CALB) and the same ruthenium catalyst as above. As shown in Scheme 8.50, these ehiral diaeetates were produced in excellent yields and almost complete diastereo- and enantioselectivities. The utility of this methodology was demonstrated by its application to the total synthesis of sertraline. In addition, these eonditions were also applied to the DKR of a p-hydrojynitrile to provide the corresponding chiral acetate in 87% yield and enantioselectivity of 98% ee, as shown in Scheme 8.50. Again, this protocol was applied to the total synthesis of another biologically active product, such as (R)-duloxetine. 

Hydrosilation Agent. Another application of this difunctional hydrosilane is in the nickel-catalyzed hydrosilation of 1,7-octadiyne, which affords a 1,2-dialkylidenecyclohexane with a (Z)-vinylsilane moiety. This exocyclic silyl diene is treated with an allyl alcohol to give a silicon-tethered triene that undergoes intramolecular Diels-Alder reaction and subsequent oxidative cleavage of the silicon-carbon bond to afford a bicyclic diol (eq 2) ... 

This last operation did also work very nicely with the tricyclic starting material 357 and provided the bicyclic diol 358. 

In a recent application, the Shvo catalyst 1 was used to oxidize enantiomerically pure bicyclic diols (R,R)-3 to the hydroxyketones (/ )-4 in acetone [46]. The acetone acts as the hydrogen acceptor and, interestingly, under these conditions, it was possible to stop the reaction after oxidation of one of the hydroxyl groups to give the hydroxyketones 4 in 82-85% yield and 97-98% ee (5). The hydroxyketones obtained are useful starting materials for the synthesis of natural products and biologically active compounds, and (f )-4b was used for the synthesis of Sertraline [46]. 

Krumlinde, P., Bogar, K., and Backvall, J. E. (2010). Asymmetric synthesis of bicyclic diol derivatives through metal and enzyme catalysis Application to the formal synthesis of sertraline. Chem. Eur.., 16,4031-4036. 

Backvall et al. have recently reported on an interesting application of the DYKAT methodology for producing optically active ra 5-bicyclic diol derivatives. These starting... 

SCHEME 57.18. DYKAT of bicyclic diols and synthesis of sertraline. 

Krespan ° has prepared a number of macrocycles, having both aza- and oxa-linkages in them, based on the 3,3-dimethyleneoxetane unit (see also Sect. 8.4 and Eq. 8.12). Typically, 3,3-bis(chloromethyl)oxetane is treated with a diol as shown in Eq. (3.40), in the presence of base. Once the bicyclic system is formed, further treatment with other nucleophiles (e.g., ammonia) can lead to opening of the 4-membered ring. 

Following Uskokovic s seminal quinine synthesis [40], Jacobsen has very recently reported the first catalytic asymmetric synthesis of quinine and quinidine. The stereospecific construction of the bicyclic framework, introducing the relative and absolute stereochemistry at the Cg- and expositions, was achieved by way of the enantiomerically enriched trans epoxide 87, prepared from olefin 86 by SAD (AD-mix (3) and subsequent one-pot cyclization of the corresponding diol [2b], The key intramolecular SN2 reaction between the Ni- and the Cg-positions was accomplished by removal of the benzyl carbamate with Et2AlCl/thioanisole and subsequent thermal cyclization to give the desired quinudidine skeleton (Scheme 8.22) [41],... 

In a recent total synthesis of the novel neurotrophic agent merrilactone A (22, Scheme 4) by Inoue and Hirama [24], key intermediate 21 with the cis-bicyclo[3.3.0] octane framework embedded within the caged pentacycle 22 was elaborated from cyclobutane 18 by a sequence of RCM and immediate cleavage of the resulting bicyclic vicinal diol 19 to raeso-diketone 20. Cyclooctenedione 20 then underwent regioselective transannular aldol reaction at low temperature (LHMDS, THF, -100 °C) to produce a 3 1 mixture of isomers in 85% combined yield. The major isomer 21 with the required stereochemistry was then converted into the racemic natural compound ( )-22 in 19 steps. 

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