TY - CHAP

T1 - Utilization Boundaries of the Nicholas-Type Cyclization in the Synthesis of Heteroenediyne Systems

AU - Khmelevskaya, Ekaterina A.

AU - Danilkina, Natalia A.

AU - Lyapunova, Anna G.

AU - Balova, Irina A.

PY - 2022/4/22

Y1 - 2022/4/22

N2 - The Nicholas reaction is a general-purpose synthetic tool for the incorporation of a propargylic moiety to different types of nucleophilic organic substrates through stabilized Co2(CO)6 complexes of propargylic carbocations.[1] Recently the Nicholas-type cyclization was shown to be the key step in the synthesis of 10-membered heteroenediynes.[2]The aim of the work was to explore the scope and limitations of the intramolecular Nicholas reaction in the synthesis of 10-membered heteroenediynes, including enediynes with additional functional groups. We tested various nucleophilic groups responsible for the Nicholas reaction (X-LG = OH, S-Ac, NH-SO2Ar, NH-Bz, NH-Bn) attached to the acyclic enediyne core and additional functional groups, which should stay untouched during the Nicholas-type cyclization(Y = Ar NH2 and COOMe) (Fig. 1). The Nicholas-type cyclization through OH proceeded smoothly giving 2a,b. It was insensitive towards the additional ester group. S-Cyclization through S-Ac group gave thiaenediyne 2c in moderate yield. However, the cyclization efficiency through the N-atom was dependent on a substituent (see 2c−g). The cyclization gave the desired enediyne cycles in good to moderate yield only in the case of sulfonamide derivatives 2d,e. It is important, that in the case of sulfanilamide function free NH2-group should be protected by acylation (2e). In summary, both OH and arenesulfonamide groups are good nucleophilic functions for the 10 membered ring closure by the Nicholas-type cyclization. The synthesis of active derivatives of enediynes through the additional functional groups (terminal alkyne, ester) is ongoing.

AB - The Nicholas reaction is a general-purpose synthetic tool for the incorporation of a propargylic moiety to different types of nucleophilic organic substrates through stabilized Co2(CO)6 complexes of propargylic carbocations.[1] Recently the Nicholas-type cyclization was shown to be the key step in the synthesis of 10-membered heteroenediynes.[2]The aim of the work was to explore the scope and limitations of the intramolecular Nicholas reaction in the synthesis of 10-membered heteroenediynes, including enediynes with additional functional groups. We tested various nucleophilic groups responsible for the Nicholas reaction (X-LG = OH, S-Ac, NH-SO2Ar, NH-Bz, NH-Bn) attached to the acyclic enediyne core and additional functional groups, which should stay untouched during the Nicholas-type cyclization(Y = Ar NH2 and COOMe) (Fig. 1). The Nicholas-type cyclization through OH proceeded smoothly giving 2a,b. It was insensitive towards the additional ester group. S-Cyclization through S-Ac group gave thiaenediyne 2c in moderate yield. However, the cyclization efficiency through the N-atom was dependent on a substituent (see 2c−g). The cyclization gave the desired enediyne cycles in good to moderate yield only in the case of sulfonamide derivatives 2d,e. It is important, that in the case of sulfanilamide function free NH2-group should be protected by acylation (2e). In summary, both OH and arenesulfonamide groups are good nucleophilic functions for the 10 membered ring closure by the Nicholas-type cyclization. The synthesis of active derivatives of enediynes through the additional functional groups (terminal alkyne, ester) is ongoing.

M3 - Conference abstracts

SP - 173

BT - VI North Caucasus Organic Chemistry Symposium

Y2 - 18 April 2022 through 22 April 2022

ER -