Diversity-Oriented Approach to Novel Spirocyclics via Enyne Metathesis, Diels-Alder Reaction, and a [2+2+2] Cycloaddition as Key Steps

Abstract

A simple protocol for the synthesis of indane-based spirocyclics has been developed via enyne metathesis, Diels-Alder reaction, and a [2+2+2] cycloaddition as key steps starting from indane-1,3-dione. The key diene building block was assembled by enyne metathesis. In this sequence, rongalite is used as a green reagent to prepare the sultine intermediate, which is a useful precursor to generate the transient diene.Indane derivatives 1 are useful building blocks for the synthesis of several natural and non-natural products. 2 Hudlicky has remarked that generation of a spiro center is a highly difficult task because it involves the creation of a quaternary center. 3 Many intricate compounds, such as fredericamycin, 4 fenestrindane 5 (Figure 1), alicyclic [5.5.5.5]fenestrane, 6 and spiranes, 7 contain the spiro linkage as a core structural element. There are several approaches to synthesize spirocycles. 8 These methods include alkylation, 9 transition-metalbased strategies, 10 rearrangement-based approaches, 11 radical-mediated procedures, 12 and ring-closing metathesis. 13 However, some of these methods have severe limitations due to functional-group incompatibility and may also be restricted to a limited substitution pattern. Therefore, there remains a need to design new and simple synthetic strategies to spirocyclics where the newly generated functionality at the end of the sequence can be used for additional synthetic transformations. Several intricate natural and non-natural products have been synthesized using an atom-economic ring-closing enyne metathesis as a key step. 14 In connection with our interest to generate new synthetic methods to spirocyclics, 8f we had shown that the diene building block 3 can provide linearly annulated spiro indane derivatives with various dienophiles such as dimethyl acetylenedicarboxylate 4 when the aromatized product 5 was obtained directly under toluene reflux conditions. 16d Alternatively, a [2+2+2]-cycloaddition sequence was also applied to synthesize linearly annulated indane-based spiro derivatives containing silicon substituents (Scheme 1).To expand the building-block approach 8c to various spirocyclics, we have identified that the diene building blocks 9 and 10 are suitable to generate a library of spiro indane Scheme 1 Indane-based spirocyclic compounds by [4+2] and [2+2+2] approach O O

New Dimensions in Rongalite Chemistry: The Land of Opportunities in Organic Synthesis and Material Sciences

“…Therefore, synthetic routes for the generation of sulfones without the use of thiols and simple procedure are always of rich desire and to my awareness using rongalite chemistry is one of the most alternative methods reported till date. A list of sulfone derivatives assembled through rongalite chemistry are displayed in Figure . As can be inspected from the Scheme , two different mechanistic pathways for the generation of sulfones have been demonstrated which began with the nucleophilic attack to the alkyl bromide followed by the extrusion of formaldehyde and further nucleophilic attack of sulfur atom to provide directly sulfone (path a) or sultine derivative (path b).…”

Design and Synthesis of Spirocycles

“…Subsequently, treatment with DDQ furnished the desired aromatized products 230 (Scheme , Path A) . Production of a series of spirobarbituric acids 230ia – d and spiroindan‐1,3‐diones 230ja – d in good yields by use of a similar strategy was also reported (Figure ).…”

“…A highly efficient and general approach to the synthesis of indan‐based spirocycles 201 has been achieved . Monopropargylation of indan‐1,3‐dione ( 35 ) in the presence of 10 % KOH and catalytic amounts of copper powder followed by monoallylation under PTC conditions was found to be a more efficient route than monoallylation and monopropargylation for the synthesis of enyne building block 199 .…”

An Elusive Nonaromatic Goal behind the Centropolyindanes: Aufbau of Veratrolo‐Annelated Centropolyquinanes and Ozonolytic Abbau

“…The synthesis of the corresponding spirodiketone 32 turned out to be less straightforward. In contrast with the very extensive literature on 1,3‐indanediones, we required improved access to larger amounts of the literature‐known 5,6‐dimethoxy‐1,3‐indanedione ( 39 ) . From extended experiments, we found that diketone 39 can be obtained readily by oxidation of the corresponding monoketone 38 with chromium trioxide in yields up to 54 %, a method that is known to be suitable for electron‐rich para ‐alkylanisoles .…”