Conjugate systems in the construction of heterocycles and quaternary stereocenters

Abstract

The synthetic application of 4,5-bis-alkylidene-1,3-oxazolidin-2-ones led to the efficient and regioselective synthesis of 2-(3H)-benzoxazolones and diarylamines with a short methodology. They were also valuable synthons in a total synthesis of naturally occurring carbazoles. New enantiopure 4-oxazoline-2-one and 4-methylene-2-oxazolidinone were prepared via a one-pot microwave (MW)-promoted condensation of α-ketols and an enantiopure isocyanate. These enamides were efficient nucleophiles when added to Michael acceptors to give a series of compounds with quaternary stereocenters in fairly good stereoisomeric ratios. The novel approach for the synthesis of benzofurans and indoles by intramolecular cyclization of enaminones has been applied in the preparation of furobenzofurans starting from benzo-bis-enaminones.

Enantiopure 4‐oxazolin‐2‐ones and 4‐methylene‐2‐oxazolidinones as chiral building blocks in a divergent asymmetric synthesis of heterocycles

“… Following method A for the preparation of 1a / 2a , the mixture of 3a (0.144 g, 1.64 mmol), 4b (0.200 g, 1.36 mmol), and Et 3 N (0.275 g, 2.72 mmol) provided 1b (0.221 g, 75%) as an amber oil. According to method B for the preparation of 1a / 2a , the mixture of 3a (0.072 g, 0.818 mmol), 4b (0.100 g, 0.68 mmol), and Et 3 N (0.069 g, 0.68 mmol) was irradiated with MW (200 W) at 140°C for 8 minutes to furnished a mixture of 1b (0.023 g, 16%) as an amber oil and 2b (54:46) (0.058 g, 39%) as a pale yellow powder. Data for 1b : R f 0.35 (hexane/EtOAc, 8:2). [α] D 26 = −33.8 ( c 0.500, CHCl 3 ).…”

“…46 Although this methodology was also efficient for the preparation of the corresponding 3-substituted 4-oxazolin-2-thiones 6 and 4methylene-1,3-oxazolidin-2-thiones 7, 47 these heterocycles were not able to undergo further reactions when utilizing the thioenamide functionality as a nucleophile. [44][45][46] In contrast, compounds 1 behave as an enolate equivalent in the presence of a Michael acceptor, in which the regioselectivity was totally controlled by the enamide moiety, leading to the addition product at C-5 of compound 9 (R 2 = Me). The use of acrolein (8a) as the electrophile did not afford the expected conjugated addition product 9 (R 2 = H), but instead, the bicyclic pyranyl compound 10 or to the cyclohexadiene product 11, depending on the reaction conditions.…”

“…On the basis of the previously developed regioselective synthesis of N ‐substituted 4‐oxazolin‐2‐ones 1 and 4‐methylene‐2‐oxazolidinones 2 , resulting from the condensation of α‐ketol 3a and isocyanates 4 (Scheme ), in a preliminary report, we presented the one‐pot synthesis of the optically pure version of heterocycles 1‐2 by introducing the N ‐( S )‐methylbenzyl moiety as the chiral auxiliary . Although this methodology was also efficient for the preparation of the corresponding 3‐substituted 4‐oxazolin‐2‐thiones 6 and 4‐methylene‐1,3‐oxazolidin‐2‐thiones 7 , these heterocycles were not able to undergo further reactions when utilizing the thioenamide functionality as a nucleophile . In contrast, compounds 1 behave as an enolate equivalent in the presence of a Michael acceptor, in which the regioselectivity was totally controlled by the enamide moiety, leading to the addition product at C‐5 of compound 9 ( R 2 = Me).…”

“…In contrast, compounds 1 behave as an enolate equivalent in the presence of a Michael acceptor, in which the regioselectivity was totally controlled by the enamide moiety, leading to the addition product at C‐5 of compound 9 ( R 2 = Me). The use of acrolein ( 8a ) as the electrophile did not afford the expected conjugated addition product 9 ( R 2 = H), but instead, the bicyclic pyranyl compound 10 or to the cyclohexadiene product 11 , depending on the reaction conditions . More severe thermal conditions for the reaction between substrates 1 and 8b , or thermal treatment of the 1,4‐addition product 9 yielded the fused bicyclic compounds 10 or 11 ( R 2 = Me), respectively.…”

“…The use of acrolein (8a) as the electrophile did not afford the expected conjugated addition product 9 (R 2 = H), but instead, the bicyclic pyranyl compound 10 or to the cyclohexadiene product 11, depending on the reaction conditions. 45,46 More severe thermal conditions for the reaction between substrates 1 and 8b, or thermal treatment of the 1,4-addition product 9 yielded the fused bicyclic compounds 10 or 11 (R 2 = Me), respectively.…”