1- Chloro-1,3-enyne

Scheme 5.60. Formation and reactivity of lithiated 1-chloro enynes[331].

The 1,5-substitution of l-chloro-2-en-4-ynes with Grignard reagents has been described by Dulcere and co-workers [41] but lacks generality with regard to the nucleophile (see Section 2.3). In contrast, the regioselective reaction of enyne acetates 47 with various lithium cuprates proceeds smoothly in diethyl ether, furnishing exclusively vinylallenes 48 with variable substituent patterns (Scheme 2.17) [42],... 

So-called domino or cascade reactions have become more and more important for the efficient synthesis of complex organic molecules [1211. In this respect methyl 2-chloro-2-cyclopropylideneacetate (1-Me) has been used as a dieno-phile to trap cyclic dienes which were produced by intramolecular Heck reactions in Diels-Alder cycloadditions. Thus, the spirocyclopropanated functionalized bicyclo[4.3.0lnonenes 248,250 (Fig. 11) were obtained from the bromo-diene 247 or enynes 249 in 56-83% yield (Scheme 71) [122,1231. 

This type of disconnection is mainly used for the preparation of dipeptides of type Xaai >[ , CH=CH]Gly. It allows control of the stereochemistry of the Xaa residue by starting from chiral a-amino aldehydes. For the construction of the /ram -p,y-unsaturated carboxylic acid moiety, the use of the triphenylphosphonium salt 31 (Scheme 9) derived from 3-chloro-propanoic acid was not suitable.14 Instead, the trimethylsilylprop-2-ynyl phosphonium salt 33 serves as a three-carbon unit, which can be converted into the P,y-unsaturated acid by hydroboration and oxidation. The required Boc-protected a-amino aldehyde 32 can be prepared using virtually racemization-free procedures. 37 However, at the end of the reaction sequence, racemization has been detected, especially for Boc-Phet )[ , CH=CH]Gly-OH, but not for the Ala and Pro analogues. 63 A mixture of E- and Z-enynes 34 and 35 is formed (8 2 to 9 1), which can be separated by column chromatography. 4,48 50 53 64 65 ... 

The compound of formula (4) is coupled with isoprene chloroacetate (1-acetoxy-4-chloro-3-methylbut-2-ene) (4a) to form the basic C2o skeleton of dehydrophytol. The chloroacetate is known and prepared by the chlorhydrination of isoprene in glacial acetic acid as described in an article by W. Oroshnik and R. A. Mallory, J. Amer. Chem. Soc. 72, 4608 (1950). The coupling reaction results in the preparation of 3,7,11,15-tetramethyl-l-acetoxyhexadec-2-en-5-yne (5), a C2o enyne. The coupling reaction may be carried out employing several methods. The following methods are preferred. 

Diynes.4 A general method for preparation of 1,3-diynes, particularly terminal ones, involves palladium-catalyzed coupling of alkynylzinc derivatives with (E)-l-iodo-2-chloroethylene. This alkene is obtained in 83% yield by reaction of acetylene with iodine monochloride in 6N HC1. Coupling results in a 1-chloro-l, 3-enyne (1), which is converted into a l-sodio-l,3-diyne (2), which in turn can be reduced or alkylated to give a 1,3-diyne. 

Tetrahedrane (11) is the ruthenium analog of the much-studied tricobaltnonacarbonyl clusters Co3(CO)9CR see Cobalt Organometallic Chemistty). The substitution chemistry of (11) has been studied. A starting material is prepared from (11) by reaction with BX3 (equation 2), which gives the chloro and bromo compounds (12). In addition, (11) can also be treated directly with compounds such as diynes to yield interesting substitution products. For example, when (11) is refluxed in THF with diphenylbutadiyne, cis- and trans-alkene isomers of two alkyne insertion regioisomers are formed (equation 3). The product seems to arise from dehydrogenation of one end of the diyne to yield cis and trans enynes and an imsaturated monohydride cluster intermediate, which then reacts with the enynes to yield the allylic derivative products... 

A THF solution of 4-chlorobutylzinc iodide (7 mmol, 1.4 equiv) prepared in over 90% yield from 4-chloro-l-iodobutane [40 °C, 2h, then 23 °C, lOh] was added at —10 °C to a solution of CuCN-2LiCl (7 mmol) in THF (7 mL). After 5 min at 0 C, the yellow-green solution was cooled to —78 °C and the 1-bromoalkyne 22 (925 mg, 5 mmol) in THF was slowly added. The reaction mixture was stirred for 18 h at —65 °C. After the usual workup and purification by flash chromatography (Si02, hexane), the pure enyne 23 was obtained (800 mg, 81% yield). 

A mixture of cis- or rr zn5-3-chloro-2-methyltetrahydrofuran and Sml2 in THE refluxed for 5-165 h (E)-3-pentenol. Y 75-90% (>95% E). With Na (cf. Synth. Meth. 6, 6), a mixture of geoisomers are normally obtained from tetrahydrofuran derivs. There was no over-reduction by this method, which was also applied to pyran ring opening. F.e. inch 1,3-enyne and styrene derivs., and effect of additives, s. L. Crombie, L.J. Rainbow, Tetrahedron Letters 29, 6517-20 (1988). 

Although not specified in the table, electrophilic addition to conjugated enynes (as in Scheme 6.70) appears to provide both 1,2- and 1,4-addition simultaneously. Thus, as shown in Scheme 6.71, the addition of hydrogen chloride across the conjugated enyne, but-3-en-l-yne (vinylacetylene, HC C-CH=CH2) produces both 2-chloro-l,3-butadiene (chloroprene [H2C=C(C1)CH=CH2]) and 4-chloro-l,2-butadiene (H20C=CHCH2C1). 

The coupling of allylic chlorides with trimethylsilylalkynes in the presence of [PdCl2(PhCN)a] also exhibits good regio- and stereo-selective control to give 4-trimethylsilyl-5-chloro-l,4( )-dienes. Furthermore, upon treatment with fluoride, these produce the corresponding 1,4-enynes. Dicyclopentadienylzirconium diene complexes are readily carbonylated, and the adducts, after hydrolysis with acid, afford cyclopent-3-enones, sometimes in synthetically useful yields. ... 

---