Kinetic Resolution of Racemic Aldehydes through Asymmetric Allenoate γ-Addition: Synthesis of (+)-Xylogiblactone A

Abstract

A synthesis of (+)-xylogiblactone A has been achieved from t-butyl 2-methylbuta-2,3-dienoate in a linear three-step sequence. The key elements of the synthesis include a kinetic resolution of racemic 2-silyoxyaldehyde through the allenoate γ-addition to yield the γ-adduct as a single isomer and the subsequent gold catalysis to form the butenolide core. For a general method, the kinetic resolution of several racemic 2-silyloxyaldehydes is also performed to provide products in high levels of stereoselectivity with unusual anti-Felkin–Anh addition fashion.

Deciphering the Chameleonic Chemistry of Allenols: Breaking the Taboo of a Onetime Esoteric Functionality

“…(+)-Xilogyblactone ( 685 ) was obtained after acidic hydrolysis of the TBSO group through a short three-step sequence and a 41% overall yield ( Scheme 112 ). 388 A related gold-catalyzed cycloisomerization of allenyl carboxylates has also provided the γ-butyrolactone unit in the total synthesis of Xestospongienes E, F, G, and H. 389 …”

Gold-Catalyzed Reactions of Specially Activated Alkynes, Allenes, and Alkenes

“…This reaction has been employed by Yu, Kim and coworkers as a means to substantiate a new access to allenes 441 and was also exploited in the total synthesis of (+)-Xylogiblactone A (Scheme 251, part B). 442 The group of Hammond has studied this transformation in greater detail with respect to its mechanism and the reactivity of its intermediates. It was shown that a series of aurated butenolides 1079 could be obtained by reacting allenoates 1078 at room temperature with a stoichiometric amount of a phosphine gold(I) complex in combination with AgOTf (Scheme 252, part A).…”

“…This transformation involves the formation of key intermediate 1077 , which evolves into 1076 by a sequence of fragmentation of the tert -butyl group and protodeauration. This reaction has been employed by Yu, Kim and coworkers as a means to substantiate a new access to allenes and was also exploited in the total synthesis of (+)-Xylogiblactone A (Scheme , part B) …”

Synthesis of (+)-Hypoxylactone through Allenoate γ-Addition: Revision of Stereochemistry

“…The organic layer was dried over MgSO 4 and evaporated to give a crude oil, which was purified by column chromatography on SiO 2 (hexane/EtOAc = 40:1 to 20:1) to afford the ester ent-11a (1.05 g, 3.93 mmol, 99%) as a colorless oil. The NMR data were identical with those of the reported racemic ester: 20 Preparation of (2S,3S)-2-((tert-Butyldimethylsilyl)oxy)-3chlorobutanal (8a). To a solution of ent-11a (1.05 g, 3.93 mmol) in CH 2 Cl 2 (0.16 M, 25 mL) was added dropwise a solution of Dibal-H (1.1 M in cyclohexane, 7.4 mL, 8.17 mmol) at −78 °C.…”

“…8 Concise synthesis of (+)-xylogiblactone A (4) through the allenoate γ-addition of unprecedented kinetic resolution of racemic aldehydes clearly demonstrates the efficacy and applicability of this methodology. 9 The characteristic features of this approach, in terms of the chemical efficiency of the unusual stereoselective assembly and the structural features of the products, have prompted us to carry out further investigations as depicted in Scheme 1. It was envisaged that syntheses of 3 and 4, potential precursors for hypoxylactone, could be realized in a predictable fashion by the allenoate γ-additions with chiral aldehydes 7 and 8.…”