Enynes preparation

The radical cyclization of enynes by the use of tris(phenylseleno)borane has been utilized for the synthesis of a-kainoids, a class of compounds with neuroexcitant properties. An example is shown in equation 38 where the enyne, prepared by alkylation of 4,4-diethoxycarbonyl-4-trifluoroacetamidobut-2-enoates withprop-2-ynyl bromide, was treated with (PhSe)3B and AIBN to give in 55% the desired product. 

Vote 2. A large excess of R MgCl is required, as the subsequent metallation of the enyne is rapid. In the case of C2H5 the Grignard reagent was prepared from ethyl bromide. 

Another interesting transformation is the intramolecular metathesis reaction of 1,6-enynes. Depending on the substrates and catalytic species, very different products are formed by the intramolecular enyne metathesis reaction of l,6-enynes[41]. The cyclic 1,3-diene 71 is formed from a linear 1,6-enyne. The bridged tricyclic compound 73 with a bridgehead alkene can be prepared by the enyne metathesis of the cyclic enyne 72. The first step of... 

The organoborate intermediates can also be generated from alkenylboronic esters and alkyllithium or Grignard reagents, or from ttialkylboranes and alkenyllithium compounds. Conjugated symmetrical and unsymmetrical diynes (289—291), stereochemically pure 1,3-dienes (292,293), and 1,3-enynes (294) including functionali2ed systems can be prepared (289,295). 

Fluonnated ylides have also been prepared in such a way that fluonne is incorporated at the carhon P to the carbamonic carbon Vanous fluoroalkyl iodides were heated with tnphenylphosphine in the absence of solvent to form the necessary phosphonium salts Direct deprotonation with butyUithium or hthium dusopropy-lamide did not lead to yhde formation, rather, deprotonation was accomparued by loss of fluonde ion Flowever deprotonation with hydrated potassium carbonate in thoxane was successful and resulted in fluoroolefin yields of45-S0% [59] (equation 54) P-Fluorinated ylides may also be prepared by the reaction of an isopropyli-denetnphenylphosphine yhde with a perfluoroalkanoyl anhydnde The intermediate acyl phosphonium salt can undergo further reaction with methylene tnphenylphosphorane and phenyUithium to form a new yhde, which can then be used in a Wittig olefination procedure [60] (equation 55) or can react with a nucleophile [6/j such as an acetyhde to form a fluonnated enyne [62] (equation 56)... 

An example of the reaction of hydrazones with enynes is reported in a German patent (91GEP4001600). The alkynylpyrazoles were prepared by treating of RNHN=CR C02R2 with CH2=CR 0R" (R =C1, Br R = alkyl) followed by aromatization with acid (Scheme 26). 

TABLE IV. 4-Alkynylpyrazoles Prepared from Enynes and Diazomethane [97JCS(P1)695]. 

Several preparative applications of tlie 1,6-cuprale addition lo acceplor-substiluled enynes have been described in recent years. In addition lo its use in tlie fDtnialion of... 

TIPSCH2C=CTIPS (preparation given, but not detailed) was metallated (21) by treatment with n-BuLi in hexane (1 eq.) in THF at -20 °C for 15 min. Addition of cyclohexane carboxaldehyde (1 eq.) to the anion in THF at -78 °C was followed by gradual warming to ambient temperature over 6 h. Normal extraction procedures followed by chromatography on silica gel afforded the (Z)-enyne, 71%, >20 1 (Z) ( ). 

Clark s group also reported on ring-closing enyne metathesis for the preparation of six- and seven-membered cyclic enol ethers 428 n= 1,2) as potential building blocks for the synthesis of marine polyether natural compounds such as brevetoxins and ciguatoxins. Metathesis products 428 were obtained from ene-ynes 427 in 72-98% yield when the NHC-bearing catalyst C was used (Scheme 84) [179]. 

Enynes 79 can also undergo cycloisomerisation reactions in presence of NHC/ transition metal complexes (Scheme 5.32). The cycloadduct 124 can be prepared either in presence of complex 110 [36] or in presence of a NHC-Ni complex (prepared in situ from a mixture of [ (COD) ] and IDTB 123 [37]). In the latter case, the active catalytic species is believed to be a Ni-H species that is generated via C-H activation of the carbene ligand. 

Gold catalysts containing NHC ligands can also promote cycloisomerisation reactions. Bicyclo[3.1.0]hexanes 137-139 can be prepared from the cycloisomerisation of 1,5-enynes bearing a propargyUc acetate (135) in the presence of catalytic amounts of [AuCl(lPr)]/AgBF (Scheme 5.36) [41]. The cycloisomerisation reaction of 135 occurs by a 1,3-OAc shift/aUene-ene cyclisation/l,2-OAc shift sequence. Experimental results with allenyl acetate 136 support this hypothesis as 139 is obtained in higher ratios than 137 and 138 [41b],... 

AUylzirconium complexes are conveniently obtained by the regio- and stereoselective hydrozirconation of allene [127-133] and can be, for example, used subsequently for the MAO-catalyzed allylzirconation of alkynes to prepare enyne derivatives [132]. Alternatively, the preparation of (E)-l,3-dienes from aldehydes and the appropriate allylstannane zirconocene derivative (R = SnBu,) is accomplished (Scheme 8-17) [131], Note that addition of [Cp2Zr(H)Cl[n (1) on the aUenyl reagent with the... 

Grubbs and coworkers [238] used the ROM/RCM to prepare novel oxa- and aza-heterocyclic compounds, using their catalyst 6/3-15 (Scheme 6/3.9 see also Table 6/3.1). As an example, 6/3-35 gave 6/3-36, by which the more reactive terminal alkene moiety reacts first and the resulting alkylidene opens the five-membered ring. In a similar reaction, namely a domino enyne process, fused bicyclic ring systems were formed. In this case the catalyst also reacts preferentially with the terminal alkene moiety. 

Kaliappan and coworkers [249] prepared dioxa-triquinanes 6/3-68 together with the spiro compound 6/3-67 by a domino enyne RCM of the ene-yne 6/3-66 (Scheme 6/3.19). 

A wide variety of organoalkynyl derivatives of cotarnine hydrochloride, a cyclic iminium salt with rich biological activity, were prepared from the direct alkynylation of cotarnine hydrochloride using silver(l) alkynyls.180 Substituted enynes were prepared from the coupling reactions of silver alkynyls with the palladium allyl intermediates, which was... 

The reductive cyclization of enynes has been used to prepare exo-methylene-cycloalkanes. Two systems have proven successful in this transformation, namely PMHS/Pd2(dba)3 CHCl3245 (Eq. 102) and Et3SiH/Pd(dppe)Cl2/HC02H (Eq. 103).246... 

Diels-AIder reactions were utilized to prepare isoquinoline derivatives. Various tetrahydroisoquinoline-3-carboxylic acid derivatives were prepared by an enyne metathesis followed by a Diels-AIder reaction. For example the enyne 71 was treated with Grubb s catalyst to afford diene 72 in 65% yield. Subsequent Diels-AIder reaction and oxidation gave tetrahydroisoquinoline 73 in 93% yield <0OCC5O3>. Dihydrosoquinoline 75 was prepared... 

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