Electron-deficient enyne

A platinum- and Lewis acid catalyzed enyne metathesis was used as the key step in the formal total synthesis of antibiotics streptorubin B and metacycloprodigiosin by A. Furstner. The electron-deficient enyne was cyclized with either a platinum halide or a hard Lewis acid (e.g., BF3-OEt2) to the desired mefa-pyrrolophane core of the target molecules. A few more steps completed the formal synthesis. 

Chen, Z., Zhang, J. (2009). Highly functionalized 4-alkylidenebicyclo[3.1.0]hex-2-enes by tandem Michael addition and annulation of electron-deficient enynes. Chemistry - An Asian Journal, 4, 1527-1529. 

The difference in enyne reactivity allowed for control of selective cross-benzannulation reaction between two enynes [9] (Scheme 14.10). Thus, reaction between highly active electron-deficient enynes A and less reactive enynes B occurred in a regio- and chemoselective manner, which was achieved via a slow addition of more reactive enyne. Notably, only one isomer of two potential cross-benzannulation products was generally obtained. 

In the coupling of the allenyl ester 7 with a terminal alkyne, an electron-deficient phosphine (Ph3P) gave the enyne-conjugated ester 8 as the major product, while an electron-rich phosphine (TDMPP or TTMPP) yielded the non-conjugated enyne esters ( )- and (Z)-9[4],... 

The cross metathesis of acrylic amides [71] and the self metathesis of two-electron-deficient alkenes [72] is possible using the precatalyst 56d. The performance of the three second-generation catalysts 56c,d (Table 3) and 71a (Scheme 16) in a domino RCM/CM of enynes and acrylates was recently compared by Grimaud et al. [73]. Enyne metathesis of 81 in the presence of methyl acrylate gives the desired product 82 only with phosphine-free 71a as a pre-... 

Since the PK reaction with electron-defident alkynes was also problematic, even when stoichiometric Co2(CO)g was employed, promoters such as trialkylamine N-oxide were required for the reaction to proceed [14]. Alternatively, W(CO)5-THF may be employed semi-catalytically for this class of substrates [9cj. The rhodium catalyst [RhCl(CO)2]2, has shown great versatility for electron-deficient alkynes (Scheme 11.4) the reaction times are much shorter (1-3 h) than those of the usual examples (Tab. 11.3). This rhodium-catalyzed PK reaction may be extended to the synthesis of 6,5-fused ring analogs, as exemplified in the synthesis of bicyclo[4.3.0]nonenone 2o from the 1,7-enyne lo (Eq.4) [13 bj. 

Species (A) and (B) constitute the main class of unsaturated carbenes and play important roles as reactive intermediates due to the very electron-deficient carbon Cl [1]. Once they are coordinated with an electron-rich transition metal, metal vinylidene (C) and allenylidene (D) complexes are formed (Scheme 4.1). Since the first example of mononuclear vinylidene complexes was reported by King and Saran in 1972 [2] and isolated and structurally characterized by Ibers and Kirchner in 1974 [3], transition metal vinylidene and allenylidene complexes have attracted considerable interest because of their role in carbon-heteroatom and carbon-carbon bond-forming reactions as well as alkene and enyne metathesis [4]. Over the last three decades, many reviews [4—18] have been contributed on various aspects of the chemistry of metal vinylidene and allenylidene complexes. A number of theoretical studies have also been carried out [19-43]. However, a review of the theoretical aspects of the metal vinylidene and allenylidene complexes is very limited [44]. This chapter will cover theoretical aspects of metal vinylidene and allenylidene complexes. The following aspects vdll be reviewed ... 

Radhakrishnan, U. Stang, P. J. Palladium-catalyzed arylation of enynes and electron-deficient alkynes using diaryliodonium salts. Org. Lett. 2001, 3, 859-860. 

Synthetic methods for the preparation of dienes and enynes abound, yet the use of alkenyl iodonium salts offers distinct advantages. Their coupling reactions with electron-deficient alkenes and alkenyl- or alkynylstannanes constitute a valuable extension to the previously existing methodology, because of mild conditions, ease of operation, high stereoselectivity and good yields. The simplest reaction of this category is with unsaturated carbonyl compounds and requires palladium catalysis. 

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. 

Enynes without the cycloalkene moiety can also react with electron-deficient alkenes by a cascade ring-closing metathesis-cross metathesis (RCM-CM) process [23] (Scheme 10). The use of Hoveyda s catalyst is necessary, not to stop the reaction at the RCM step, but to perform the subsequent CM step. Indeed, the organic product arising from the RCM is first formed and then reacts with the alkene in the presence of the ruthenium complex to give the CM reaction. 

Scheme 3.6 Intramolecular phosphane-catalyzed [3 + 2] cycloaddition of electron-deficient 1,7-enynes...

Enyne RCM reactions have been successfully coupled with a CM event [16]. Thus, a domino enyne RCM/CM process with enyne 65 and methyl vinyl ketone was used as the final step in a concise total synthesis of the bioactive sesquiterpene lactone (+)-8-epi-xanthatin (66) (Scheme 2.25) [16a,b. Using the phosphine-free ruthenium catalyst 4, an efHcient transformation was achieved with the required electron-deficient co-olefin. 

Genet and Michelet have reported the gold(I)-catalyzed cydization/amination of 1,6-enynes with carboxamides and electron-deficient aromatic amines [27]. Reaction of 1,6-enyne 32 with o-cyanoaniline and a catalytic 1 1 mixture of (PPh3)AuCl and AgSbFg in dioxane at room temperature for 20 h led to isolation of methylene cyclopentane 33 in 93% yield as a single diastereomer (Eq. (11.19)). Gold(I)-catalyzed... 

Allylic alkynoates are a group of special enynes with an electron-deficient triple bond and an ester linkage between the double bond and triple bond. Based on the reaction described in Sect. B.iv.a, an intramolecular version could be developed, for example, au a-alkylidene-y-butyrolactone structure could easily be assembled through halopallada-tion, carbon-carbon double bond insertion, and dehalopalladation " (Scheme 13). The mechanism may be sununatized as shown in Scheme... 

SCHEME 21.39 Pd-catalyzed homo-[4+2] cycloaddition of electron-deficient disubstituted enynes. 

Compared to the hydroamination of alkynes, the protocols for more readily available olefins were rather limited. Ackermann presented a TiCU-catalyzed hydroamination reaction of norbornene using a variety of functionalized amines. Regioselective hydroarylation occurs as a competing reaction and the chemose-lectivity for hydroamination products ranges from poor to excellent [312]. This protocol can also be utilized in the hydroamination of vinylarenes with some electron-deficient amines [313] and the hydroamination of enyne compound. In the latter reaction, a subsequent rearrangement gives rise to a tetrahydroisoquinoline derivative (Scheme 14.134). 

Sonogashira-type Palladium-catalyzed Phenylation of Enynes and Electron-deficient Alkynes. DiphenyUodonium... 

In the 1970s and 1980s, it was discovered that electron-deficient alkenes, such as tetracyanoethylene (TCNE, 55) reacted with metallated alkynes 54 to furnish a metallated hexasubstituted 1,3-diene unit 56, an overall transformation akin to enyne metathesis (Scheme 1.8) [37, 39]. In a recent (2012) addition to this work, the Bruce group reported the synthesis of a ruthenated [3]dendralene 58 via insertion of phenylacetylene (57) into 56 (Scheme 1.8) [38]. The metallated dendralene synthesis is low yielding and, as yet, an isolated example, but presents an interesting avenue for future investigations. 

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