Benzannulation of Enynes with Alkynes

SCHEME 14.1 Danheiser [4 -I- 2] benzannulation reaction of conjugated en5me with alkyne. 

With the aid of transition metals, intermolecular catalytic analogs for this transformation became available, opening easy access to densely substituted aromatic 

Transition-Metal-Mediated Aromatic Ring Construction, First Edition. Edited by Ken Tanaka. 2013 John Wiley Sons, Inc. Published 2013 by John Wiley Sons, Inc. 

SCHEME 14.2 Transition-metal-catalyzed benzannulation reactions of conjugated enynes with alkynes. 

2 BENZANNULATION OF ENYNE WITH ALKYNE GOLD-CATALYZED BENZANNULATION REACTION 

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Transition-metal-catalyzed [4 -I- 2] benzannulation reaction of enyne with alkyne enynophile was reported by Toste group [6]. The reaction between enynes 4 and propargyl ethers 5 in the presence of a gold catalyst led to the formation of multisubstituted arenes 6 via a formal [4-1-2] cross-benzannulation reaction (Scheme 14.3). 

Two possible approaches were shown for the Sonogashira cross-coupling/ benzannulation of enyne with diyne cascade transformation (Scheme 14.19) [11a]. Accordingly, three-component coupling between dihalide 41 and two molecules of terminal diyne produced phenanthren-9(10//)-one derivatives 43 with modest yields under Sonogashira cross-coupling conditions (path A). Incorporation of two different substituents to the final product 46 was achieved via a stepwise addition of terminal alkynes (path B). 

The scope of the reaction discussed in Sect. B is somewhat limited since the only practical synthetic procedure consists of the cyclodimerization of the two identical enynes, and therefore the same substituents are attached at the phenyl group and the vinyl group of the reaction product. The attempted cross-annulation of conjugated enynes with alkynes or dienes turned out to be unsuccessful. However, the scope of the benzannulation reaction could be extended significantly by introducing conjugated... 

Synthesis of aromatic compounds with variations in the metal-catalyzed Bergman cycloaromatization is an alternative to the catalysis by transition metals of [2-f2-f2] cyclotrimerization of alkynes and [4-1-2] benzannulation of enynes [261-263]. On the other hand, much less attention has been paid to the use of transition metal catalysis in enyne-allene cycloaromatization [264]. 

A completely new benzannulation reaction of conjugated enynes and alkynes catalysed by Pd complexes to give substituted benzenes has been developed recently. When the 1,3-enyne 150 is treated with a Pd(0) catalyst, homocyclodimerization of the enyne takes place to give the 2,6-disubstituted styrenes 151 as a single product in good yield [64], An interesting application of this reaction is the preparation of paracyclophane 153 by the intramolecular reaction of the bis-enyne 152 [65],... 

Mechanistically, this unusual multicomponent trimerization can be rationalized as a sequence of a Pd-catalyzed alkyne dimerization [154,155] giving rise to the regioselective formation of the enyne 218, which undergoes subsequent Pd-catalyzed [4 + 2]-benzannulation [158,159] with a butadiyne as an enynophile to furnish the benzene 216 via an allenyl-Pd species 219 (Scheme 90). Upon submitting an electron-deficient alkyne together with a terminal alkyne in equimolar amounts to the sequence, the unsymmetri-cal alkyne dimerization gives a trisubstituted enyne to set the stage for the formation of pentasubstituted benzene derivatives 217. 

The gold-catalyzed benzannulation of o-alkynylbenzaldehydes 11 proceeded not only with alkynes or alkenes, but also with carbonyl compounds 47 (Scheme 15.19) [32], The reaction proceeded even with conjugated enyne aldehydes 20. Paraldehyde 49 can be used as a masked acetaldehyde in this reaction. 

The fact that pentacarbonyl carbene complexes react with enynes in a chemo-selective and regiospecific way at the alkyne functionality was successfully applied in the total synthesis of vitamins of the Kj and K2 series [58]. Oxidation of the intermediate tricarbonyl(dihydrovitamin K) chromium complexes with silver oxide afforded the desired naphthoquinone-based vitamin K compounds 65. Compared to customary strategies, the benzannulation reaction proved to be superior as it avoids conditions favouring (E)/(Z)-isomerisation within the allylic side chain. The basic representative vitamin K3 (menadione) 66 was synthesised in a straightforward manner from pentacarbonyl carbene complex 1 and propyne (Scheme 38). 

Cyclopropanation of the alkene unit by the alkyne moiety in the enynes 28 yields the cycloprop[c]pyrans 29 which on treatment with acid afford chromans. This new benzannulation presumably proceeds by a retro DA opening of the pyran ring followed by cyclisation and dehydration <04OL3191>. 

A highly atom-economical cascade transformation employs Trost s Pd-catalyzed dimerization of alkynes [15] and consequent Pd-catalyzed benzannulation reaction [16] (Scheme 14.20). A formal [2 - - 2 - - 2] cycloaddition reaction proceeded through the formation of 2,4-enyne followed by a formal [4 - - 2] benzannulation reaction with diyne, representing a highly chemo- and regioselective trimerization reaction of alkynes. Homo-dimerization of terminal acetylenes followed by a benzannulation... 

Phosphine oxides are among various functionalities that can be introduced into aromatic alkynes via a Pd-catalyzed benzannulation reaction. Thus, the reaction between readily available enynes 70 with 5,7-dodecadiyne resulted in the formation of the corresponding benzylphosphine oxide 71 in good yields [20] (Scheme 14.28). 

Benzoannelated enyne-allenes with aryl substituents in the alkyne branch are precursors of 5-aryl-llH-benzofluorenes. There are several synthetic routes to benzannulated enyne-allene systems, including in situ generation of the corresponding enediynes, that are the 5-substituted derivatives of llH-benzo[ ]fluorene. Typically, treatment of benzannulated enediyne 3.614 with potassium er -butoxide in refluxing toluene for 6 hours promotes 1,3-prototropic rearrangement to form benzoannu-lated enyne-allene, which in turn converts to 5-(2,3-dibromphenyl)-llH-benzo[f ]fluorene 3.615 in a sequential cascade of Schmittel cyclizations (Scheme 3.51) [300]. It is interesting to note that the benzo[fe]fluorene... 

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