Enantioselective halocyclization reaction using a chiral titanium complex

Kitagawa, Osamu; Hanano, Tokushi; Toko, Kiyoshi; Shiro, Motoo; Taguchi, Takeo

doi:10.1039/c39920001005

Cited by 77 publications

(41 citation statements)

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“…[9] Prior to further biocatalytic reaction, we thought to correlate the reactivity of the benzylic position with one of the pro-chiral hydroxymethyl groups of compound 1. A stereoselective halocyclization reaction [12] was explored for that purpose. Thus when compound 1 was treated with NIS (1.5 equiv.…”

Section: Resultsmentioning

confidence: 99%

“…Working model for predicting the enantiopreferences of primary alcohols (2,(11)(12)(13)(14)(15) in PPL-catalyzed kinetic resolution.…”

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confidence: 99%

“…[a] Compound 4 was taken as a racemic mixture, Compounds 9 and 10 were synthesized in our laboratory by EKR (enzymatic kinetic resolution). [9] [b] All the tricyclic compounds obtained are racemic (2,(11)(12)(13)(14)(15) except for 16 and 17. ).…”

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confidence: 99%

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Stereoselective Desymmetrization of 2,2‐Bishydroxymethyl‐1‐tetralones by Iodocyclization, Synthesis of Novel Enantiopure [6.6.5] Tricyclic Framework and Chemoenzymatic Diversity Generation

2011

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Stereoselective halocyclization of prochiral 2,2-bishydroxymethyl-1-tetralone derivatives with N-halosuccinamides afforded an interesting tricyclic scaffold found in many naturally occurring hasubanan alkaloids. Enantiopure tricyclic scaffolds are synthesized by using enzymatic kinetic resolution (EKR) of the parent racemic compound. Microbial ketoreductase (Geotrichum candidum, Aspergillus niger and Candida parapsilosis) mediated stereoselective reduction reactions have been successfully employed to these enantiopure tricyclic scaffolds which, followed by functional group manipulation, provides novel cyclic frameworks.

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Section: Resultsmentioning

confidence: 99%

“…Working model for predicting the enantiopreferences of primary alcohols (2,(11)(12)(13)(14)(15) in PPL-catalyzed kinetic resolution.…”

mentioning

confidence: 99%

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Stereoselective Desymmetrization of 2,2‐Bishydroxymethyl‐1‐tetralones by Iodocyclization, Synthesis of Novel Enantiopure [6.6.5] Tricyclic Framework and Chemoenzymatic Diversity Generation

2011

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“…(For examples of discrimination of prochiral two olefinic groups by halocyclization using chiral auxiliary, see refs 12-18.) [12][13][14][15][16][17][18] (2)Based on this idea, we studied the intramolecular haloetherification reaction of cyclohexa-1,4-dienes 1 having the C 2 -symmetric acetal on the side chain and found that the reaction discriminated the two prochiral olefins in a highly diastereoselective manner to give 2 as the major product (Chart 1).19) The alkoxy group of the mixed acetals was then converted to an alkyl group. The obtained alkylated compounds 3 were subjected to several transformation reactions forming optically active cyclohexane derivatives with multichiral centers.…”

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confidence: 99%

“…(For examples of discrimination of prochiral two olefinic groups by halocyclization using chiral auxiliary, see refs 12-18.) [12][13][14][15][16][17][18] (2)…”

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Asymmetric Synthesis by the Intramolecular Haloetherification Reaction of Ene Acetal: Discrimination of Prochiral Dienes in Cyclohexane Systems

Fujioka

Kotoku

Sawama

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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Asymmetric synthesis based on the desymmetrization of symmetric compounds is one of the most powerful ways to get optically pure compounds, especially for the substrates having prochiral carbon atom(s), and many methodologies by chemical reactions, for examples refs. 1-4, [1][2][3][4] and enzymatic ones, for examples refs. 5-9, 5-9) have already been developed. Recently, we have developed a new asymmetric synthesis of 1,4-and 1,5-diols from the ene aldehydes involving the intramolecular haloetherification reaction of their C 2 -symmetric acetals as a key step (Eq. 1). 10,11) (1)We then planned to extend this methodology to the symmetric compounds with two prochiral olefins. If the reaction can successfully discriminate the diastereotopic groups and their faces, it will be quite useful for constructing optically active compounds because it can produce chiral non-racemic compounds bearing multichiral centers and the remaining olefin can be used for further transformations (Eq. 2). (For examples of discrimination of prochiral two olefinic groups by halocyclization using chiral auxiliary, see refs 12-18.) [12][13][14][15][16][17][18] (2)Based on this idea, we studied the intramolecular haloetherification reaction of cyclohexa-1,4-dienes 1 having the C 2 -symmetric acetal on the side chain and found that the reaction discriminated the two prochiral olefins in a highly diastereoselective manner to give 2 as the major product (Chart 1).19) The alkoxy group of the mixed acetals was then converted to an alkyl group. The obtained alkylated compounds 3 were subjected to several transformation reactions forming optically active cyclohexane derivatives with multichiral centers. We now present the full details of our study. Results and DiscussionThe optically active monosubstituted cyclohexadiene acetals (1a, b) were synthesized as follows (Chart 2). The cyclohexadiene acetals (4, 5) were prepared from benzoic acid according to a literature procedure. 20) Their transacetalization with (ϩ)-hydrobenzoin 21) gave 1a and 1b in good yields. The disubstituted cyclohexadiene acetals (1c, d) were synthesized from compound 6, which was obtained by reductive alkylation 22) of methyl benzoate followed by reduction with DIBAL-H (Chart 3). Protection of the hydroxy group of 6 by the tert-butyldiphenylsilyl (TBDPS) group and selective deprotection of the resulting disilyl ether afforded 7 in good yield. The Swern oxidation 23) of 7 followed by acetalization with (ϩ)-hydrobenzoin produced the optically active 3,3-disubstituted cyclohexadiene acetal silyl ether 1c. The desilyla- A novel asymmetric synthesis of the cyclohexane derivative functionalized by some substituents has been developed from the diene acetals (1), prepared from the corresponding diene aldehyde and (؉)-hydrobenzoin. The treatment of 1 with NBS in the presence of MeOCH 2 CH 2 OH predominantly afforded 2 in a stereoselective manner. Subsequent alkylation of the methoxyethoxy group produced the optically active cyclohexene compounds (3) in good yields. The stereoselective ch...

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(4R,5R)-2,2-Dimethyl-4,5-bis(hydroxydiphenylmethyl)-1,3-dioxolane-Titanium(IV) Chloride

Narasaka

Iwasawa

2001

Encyclopedia of Reagents for Organic Synthesis

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Enantioselective halocyclization reaction using a chiral titanium complex

Abstract: Enantioselective halocyclizations of diallyl-2-hydroxyacetic acid 1 and 2-hydroxymethylpent-4-en-I -01 6 have been developed using a chiral titanium complex.

Cited by 77 publications

References 7 publications

Stereoselective Desymmetrization of 2,2‐Bishydroxymethyl‐1‐tetralones by Iodocyclization, Synthesis of Novel Enantiopure [6.6.5] Tricyclic Framework and Chemoenzymatic Diversity Generation

Stereoselective Desymmetrization of 2,2‐Bishydroxymethyl‐1‐tetralones by Iodocyclization, Synthesis of Novel Enantiopure [6.6.5] Tricyclic Framework and Chemoenzymatic Diversity Generation

Asymmetric Synthesis by the Intramolecular Haloetherification Reaction of Ene Acetal: Discrimination of Prochiral Dienes in Cyclohexane Systems

(4R,5R)-2,2-Dimethyl-4,5-bis(hydroxydiphenylmethyl)-1,3-dioxolane-Titanium(IV) Chloride

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