Silyldienolates in Organocatalytic Enantioselective Vinylogous Mukaiyama-Type Reactions: A Review

Abstract

Mukaiyama aldol, Mannich, and Michael reactions are arguably amongst the most important C–C bond formation processes and enable access to highly relevant building blocks of various natural products. Their vinylogous extensions display equally high potential in the formation of important key intermediates featuring even higher functionalization possibilities through an additional conjugated C–C double bond. Hence, it is much desired to develop highly selective vinylogous methods in order to enable unconventional, more efficient asymmetric syntheses of biologically active compounds. In this regard, silyl-dienolates were discovered to display high regioselectivities due to their tendency toward γ-additions. The control of the enantio- and diastereoinduction of these processes have been for a long time dominated by transition metal catalysis, but it received serious competition by the application of organocatalytic approaches since the beginning of this century. In this review, the organocatalytic applications of silyl-dienolates in asymmetric vinylogous C–C bond formations are summarized, focusing on their scope, characteristics, and limitations.

Enantioselective Distal Functionalization of 3-Cyano-4-methylcoumarins through Direct Vinylogous Conjugate Addition to Maleimides

“…1- (3,4,. Yellow solid; mp = 134−137 °C; 100 mg, 46% yield; 1 H NMR (500 MHz, CDCl 3 ) δ 6.9 (s, 2H), 6.8 (s, 2H), 2.3 (s, 6H), 2.2 (s, 3H); 13 C NMR 13 C NMR (125 MHz, CDCl 3 ) δ 170.0, 137.7, 135.8, 134.3, 128.0, 125.6, 77.4, 77.2, 76.9, 20.8, 15.4 3.90 (q, J = 9.5 Hz, 1H), 3.30−3.41 (m, 2H), 3.08 (dd, J = 18.4, 8.0 Hz, 1H), 2.91 (dd, J = 18.2, 4.9 Hz, 1H), 2.35 (s, 6H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 176.…”

“…6, 172.9, 161.7, 156.0, 154.0, 135.8, 134.5, 131.1, 130.8, 126.5, 126.4, 126.4, 126.4, 126.0, 125.5, 118.5, 116.7, 113.7, 103.6, 40.1, 34.6, 33. ; 1 H NMR (500 MHz, CDCl 3 ) δ 7.89 (d, J = 7.9 Hz, 1H), 7.75 (t, J = 7.8 Hz, 1H), 7.46 (t, J = 8.1 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 8.2 Hz, 2H), 3.89 (q, J = 9.7 Hz, 1H), 2H),3.08 (dd,J = 18.2,7.8 Hz,1H),2.91 (dd,J = 18.2,4.7 Hz, 1H), 2.39 (s, 3H); 13 C{ 1 H} NMR (125 MHz, CDCl 3 ) δ 176. 2, 173.6, 162.1, 156.1, 153.9, 139.1, 135.7, 130.0, 128.7, 126.7, 126.3, 125.9, 125.7, 118.3, 116.7, 113.6, 103.4, 40.1, 34.6, 33.2, 21. ; 1 H NMR (500 MHz,) δ 7.89 (d, J = 7.9 Hz, 1H), 7.75 (t, J = 7.7 Hz, 1H), 7.47 (t, J = 7.6 Hz, 2H), 7.22 (d, J = 8.7 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H), 3.90 (q, J = 9.7 Hz, 1H), 3.84 (s,3H),2H),3.09 (dd,J = 18.1,8.2 Hz,1H),2.92 (dd,J = 18.1,4.7 Hz, 1H); 13 C{ 1 H} NMR (125 MHz, CDCl 3 ) δ 176. 3, 173.7, 162.0, 162.0, 159.8, 156.1, 154.0, 135.7, 127.5, 125.9, 125.7, 124.0, 118.4, 116.8, 114.6, 113.6, 103.5, 55.5, 40.1, 34.6, 33.2; HRMS (ESI-TOF) m/z [M + Na] + calcd for C 22 H 16 N 2 NaO 5 411.0951, found 411.0967.…”

“…Among these reactions, amine and Brønsted base catalyzed generation of a conjugated π-system leading to remote (vinylogous) induction of a stereocenter has taken a center stage, and catalysts enabling such transformations are much in demand . Though asymmetric vinylogous reactions with modified Mukaiyama-type dienolates have been well explored, the corresponding direct nucleophile would be more attractive, convenient, and atom economical. Hence, the exploration of advanced molecular scaffolds as nucleophiles for vinylogous addition reaction has turned out to be a powerful approach toward distinctly functionalized molecules .…”

Site-Selective, Photocatalytic Vinylogous Amidation of Enones

“…The concept of vinylogy, established by Fuson in 1935, postulates that the influence of a functional group can be propagated through a conjugated system of unsaturated bonds. This phenomenon is particularly important for the functionalization of α,β-unsaturated carbonyl compounds, which are versatile starting materials in organic synthesis. − Typically, in vinylogous reactions, π-extended carbonyl derivatives of type I are transformed into dienolates II that contain two nucleophilic sites (Scheme ). Consequently, the addition of electrophiles can occur at either α-position ( III ) or more remote γ-position ( IV ). , The regio- and stereoselectivity of these transformations are affected by multiple factors, such as the presence of bulky substituents, a catalyst (if any), or the electron density at the nucleophilic carbon sites, and remain one of the most challenging issues that have to be addressed. − ,− …”

Enantioselective Synthesis of Fused Butyrolactones via Organocatalytic Formal [2 + 2 + 2] Annulation of γ-Butenolides, Methylene Indolinones, and Nitroolefins

“…As a widely used textbook reaction, the vinylogous addition reaction has played an important role in the total synthesis of natural products . In recent years, it has attracted a lot of interest in the field of asymmetric catalysis . In this area, direct asymmetric reactions in which γ-butenolides were involved as vinylogous precursors of 2-hydroxyfurans have drawn great attention because of their high atom- and step-economy compared to that with Mukaiyama-type additions of preformed 2-silyloxyfurans .…”