Facile access to diverse all-carbon quaternary center containing spirobicycles by exploring a tandem Castro–Stephens coupling/acyloxy shift/cyclization/semipinacol rearrangement sequence

Abstract

An efficient construction of spirocyclo[4.5]decane derivatives is developed via a Castro–Stephens coupling/1,3-acyloxy shift/cyclization/semipinacol rearrangement sequence.

A Concise Total Synthesis of (+)‐Waihoensene Guided by Quaternary Center Analysis

“…In this way, the original ester, alkyne, and ketone functional groups of 12 would serve as the only functional group lynchpins needed to achieve all bond formations, chain homologations, and other elements of tailoring required to reach the final target. As validation for the power of this approach, as well as interest in waihoensene as a target in general, a synthesis of (+)‐waihoensene by Yang, Huang, and co‐workers was published while this paper was under review using similar key bond constructions, albeit in unique ways, as was an additional model study from Tu and Wang …”

“…Scheme 1); [6b] a slightly higher yield was obtained by performing the reduction and oxidation steps separately. However, despite the facility of this operation, subsequent conversion of the aldehyde within 26 to the chain homologated alkyne needed for the Pauson-Khand step (i.e., 10) proved quite challenging. Many efforts proved fruitless, either due to an inability to forge the alkyne of 10 or to afford the natural product using a differentially functionalized version of 10.…”

“…As validation for the power of this approach, as well as interest in waihoensene as a target in general, a synthesis of (+)-waihoensene by Yang, Huang, and co-workers was published while this paper was under review using similar key bond constructions, albeit in unique ways, [9] as was an additional model study from Tu and Wang. [10] Our efforts began with the preparation of a chiral and protected version of 12 in the form of 19 as shown in Scheme 2. Following the reaction of Grignard reagent 14 [11] with 13 to afford functionalized a,b-unsaturated ketone 15, use of Hoveydas asymmetric conjugate addition chemistry, [12] as guided by N-heterocyclic carbene complex 16, generated the all-carbon quaternary center of 17 in excellent yield (81-92 %) and high enantioselectivity (82-92 % ee), variable based on the scale of the reaction.…”

Recent Progress in the Synthesis of Sesquiterpenoid Involving Spirocyclic Carbon Framework

“…(-)-Erythrodiene (97) and (+)-spirojatamol (98) were isolated from the roots of the Caribbean soft coral Erythropodium caribaeorum and the Indian plant Nardostachys jatamansi, 24) by Derksen et al 12 respectively, and have opposite absolute configurations for their quaternary carbon centers. 24,25 Wang et al completed the total syntheses of racemic erythrodiene (97) and spirojatamol (98) by constructing the spiroyclic ring through a tandem Castro-Stephens coupling/1,3-acyloxy shift/cyclization/semipinacol rearrangement sequence 26 (Figure 10). 27 Addition of 2-lithioprop-1-ene to cyclobutanone 81 followed by protection of the tertiary alcohol and subsequent allylic bromination provided allylbromide 83.…”

Recent development and applications of semipinacol rearrangement reactions

“…On the basis of this work, Wang and Tu further developed a two-step Castro–Stephens coupling/tandem acyloxy shift/cyclization/semipinacol rearrangement sequence for the synthesis of such cyclohexenes in a more modular fashion ( Scheme 13b ). 60 The coupling of terminal alkynes 52 with allylic bromides 53 was followed by a Au( i )-catalyzed cascade mechanistically similar to the allene-cyclization/rearrangement process. Specifically, activation of the alkyne group of 54 by Au( i ) would trigger an acyloxy shift to generate an allylic carbenium 56 that could induce the cyclization/semipinacol rearrangement, as in the reaction of allene 50 , to finally give rise to the spirocyclic ketones 57 .…”