2.3.3 Intramolecular Cyclization of Hydroxyl Allene
The intramolecular nucleophilic addition of a hydroxyl group to an allene
substituted by an electron-withdrawing phenylsulfonyl group was employed in
the synthesis of the eight-membered oxacycle of (Æ)-lauthisan [155] (Scheme 44).
Exposure of the allene 208 to t-BuOK in t-BuOH at room temperature for 40 min
furnished (E)-8-ethyl-2-hexylidene-3-(phenylsulfonyl) oxocane 209 in 81 % yield.
Dephenylsulfonylation with Mg in MeOH followed by the reduction of the enol
ether moiety with Et 3 SiH afforded (Æ)-lauthisan in 73 % yield.
These basic conditions also allowed the rapid endo-mode ring closure of the
allene derivatives 210 to furnish 2,3,6,7-tetrahydro-9-methyloxonines 211 in good
yield as single isomers [156]. In the case of sulfonyl derivative 210 (R ¼ SO 2 Ph),
the endo-mode reaction proceeded as expected to give the cyclic products in 66 %
yield as a mixture of 211 and its isomer 212 with an exo-methylene moiety in a ratio
of ca. 2:1.
2.3.4 Metal-Mediated Heterocyclization
Hanaoka et al. developed a method for the preparation of oxocane as well as the
oxonane skeletons by taking advantage of the inherent property of the
alkyne–Co 2 (CO) 6 complexes, easily prepared by the addition of Co 2 (CO) 8 to
propynyl alcohols or ethers. These complexes led, upon treatment with a Lewis
acid, to the corresponding propynyl cation species, which were subsequently
captured by various nucleophiles (Nicholas reaction). This method is a powerful
tool for the preparation of medium-sized oxygen atom-containing heterocycles
[157] (Scheme 45). For instance, the oxonane 217 was synthesized following this
approach from propargylic alcohol 216.
Martin et al. also reported the synthesis of cyclic ethers based on intramolecular
Nicholas reaction. Thus, they focused on the intramolecular attack of a hydroxy
Scheme 44 Formation of eight- and nine-membered cyclic ethers by intramolecular nucleophilic
addition of a hydroxy group to an allene
Synthesis of Eight- to Ten-Membered Ring Ethers
353
The intramolecular nucleophilic addition of a hydroxyl group to an allene
substituted by an electron-withdrawing phenylsulfonyl group was employed in
the synthesis of the eight-membered oxacycle of (Æ)-lauthisan [155] (Scheme 44).
Exposure of the allene 208 to t-BuOK in t-BuOH at room temperature for 40 min
furnished (E)-8-ethyl-2-hexylidene-3-(phenylsulfonyl) oxocane 209 in 81 % yield.
Dephenylsulfonylation with Mg in MeOH followed by the reduction of the enol
ether moiety with Et 3 SiH afforded (Æ)-lauthisan in 73 % yield.
These basic conditions also allowed the rapid endo-mode ring closure of the
allene derivatives 210 to furnish 2,3,6,7-tetrahydro-9-methyloxonines 211 in good
yield as single isomers [156]. In the case of sulfonyl derivative 210 (R ¼ SO 2 Ph),
the endo-mode reaction proceeded as expected to give the cyclic products in 66 %
yield as a mixture of 211 and its isomer 212 with an exo-methylene moiety in a ratio
of ca. 2:1.
2.3.4 Metal-Mediated Heterocyclization
Hanaoka et al. developed a method for the preparation of oxocane as well as the
oxonane skeletons by taking advantage of the inherent property of the
alkyne–Co 2 (CO) 6 complexes, easily prepared by the addition of Co 2 (CO) 8 to
propynyl alcohols or ethers. These complexes led, upon treatment with a Lewis
acid, to the corresponding propynyl cation species, which were subsequently
captured by various nucleophiles (Nicholas reaction). This method is a powerful
tool for the preparation of medium-sized oxygen atom-containing heterocycles
[157] (Scheme 45). For instance, the oxonane 217 was synthesized following this
approach from propargylic alcohol 216.
Martin et al. also reported the synthesis of cyclic ethers based on intramolecular
Nicholas reaction. Thus, they focused on the intramolecular attack of a hydroxy
Scheme 44 Formation of eight- and nine-membered cyclic ethers by intramolecular nucleophilic
addition of a hydroxy group to an allene
Synthesis of Eight- to Ten-Membered Ring Ethers
353