Stereoselective synthesis alkynes

Figure 6 Stereoselective synthesis alkyne-bridged dinuclear species. ...

The coupling of alkenylboranes with alkenyl halides is particularly useful for the stereoselective synthesis of conjugated dienes of the four possible double bond isomers[499]. The E and Z forms of vinylboron compounds can be prepared by hydroboration of alkynes and haloalkynes, and their reaction with ( ) or (Z)-vinyl iodides or bromides proceeds without isomerization, and the conjugated dienes of four possible isomeric forms can be prepared in high purity. 

It was shown (654) that the sequence terminal alkyne hydrozirconation, Zr to Zn exchange and addition to nitrones, is a good method to the stereoselective synthesis of (E)-N-allylhydroxylamines, under mild conditions and in good yield. 

The use of chiral azomethine imines in asymmetric 1,3-dipolar cycloadditions with alkenes is limited. In the first example of this reaction, chiral azomethine imines were applied for the stereoselective synthesis of C-nucleosides (100-102). Recent work by Hus son and co-workers (103) showed the application of the chiral template 66 for the formation of a new enantiopure azomethine imine (Scheme 12.23). This template is very similar to the azomethine ylide precursor 52 described in Scheme 12.19. In the presence of benzaldehyde at elevated temperature, the azomethine imine 67 is formed. 1,3-Dipole 67 was subjected to reactions with a series of electron-deficient alkenes and alkynes and the reactions proceeded in several cases with very high selectivities. Most interestingly, it was also demonstrated that the azomethine imine underwent reaction with the electronically neutral 1-octene as shown in Scheme 12.23. Although a long reaction time was required, compound 68 was obtained as the only detectable regio- and diastereomer in 50% yield. This pioneering work demonstrates that there are several opportunities for the development of new highly selective reactions of azomethine imines (103). 

Another approach in the study of the mechanism and synthetic applications of bromination of alkenes and alkynes involves the use of crystalline bromine-amine complexes such as pyridine hydrobromide perbromide (PyHBts), pyridine dibromide (PyBn), and tetrabutylammonium tribromide (BiMNBn) which show stereochemical differences and improved selectivities for addition to alkenes and alkynes compared to Bn itself.81 The improved selectivity of bromination by PyHBn forms the basis for a synthetically useful procedure for selective monoprotection of the higher alkylated double bond in dienes by bromination (Scheme 42).80 The less-alkylated double bonds in dienes can be selectively monoprotected by tetrabromination followed by monodeprotection at the higher alkylated double bond by controlled-potential electrolysis (the reduction potential of vicinal dibromides is shifted to more anodic values with increasing alkylation Scheme 42).80 The question of which diastereotopic face in chiral allylic alcohols reacts with bromine has been probed by Midland and Halterman as part of a stereoselective synthesis of bromo epoxides (Scheme 43).82... 

I - Alkyny lphenyl selenides. Benzeneselenenyl bromide and silver nitrite (1 equiv.) rcncl to form a reagent (presumably C6H5SeN02) that converts 1-alkynes into 1-nlkynyl phenyl selenides (equation I).1 The same reaction has been effected in generally lower yields with phenyl selenocyanate catalyzed by Cu(I).2 The products tire useful intermediates for regio- and stereoselective synthesis of vinyl selenides. 

The stereoselective synthesis of 1,4-disubstituted-l,3-dienes proceeds by head-to-head oxidative coupling of two alkynes with formation of an isolable metallacyclic biscarbene ruthenium complex [23], as shown in Scheme 6. Several key experiments involving labeled reagents and stoichiometric reactions and theoretical studies support the formation of a mixed Fischer-Schrock-type biscarbene complex which undergoes protonation at one carbene carbon atom whereas the other becomes accessible to nucleophilic addition of the carboxylate anion (Scheme 6) [23]. 

Acetylenic zinc reagents are readily accessible from 1-alkynes by a deprotonation-transmetallation sequence, and consequently have been successfully used to couple with vinyl halides in many cases (see equation 81), including butadiynyl ones161. Among these, coupling reactions with vinyl bromides have been used in the stereoselective synthesis of enediynes and applied to the synthesis of trienic natural products162. 

Tandem intramolecular silylformylation-allylation reaction of diallylhydrosilyl ethers derived from homoallyl alcohols is convenient for rapid, stereoselective synthesis of 1,3,5-triols convertible to more oxygen-functionalized compounds (Scheme 12).142,142a,142b 143 [ he second uncatalyzed allylation step would be facilitated by the formation of a strained silacycle intermediate, which has enough Lewis acidity to activate the formyl group. A similar tandem reaction via alkyne silylformylation has been reported.144... 

Various functionalized alkynes can be submitted to carbocupration reactions, such as alkoxyalkynes,150 alkynyl carbamates,151 acetylenic orthoesters,152 and thioalkynes.153 The carbocupration of orthoesters, for example, 204, has been used to prepare a-substituted esters of the type 206 by acidic hydrolysis of the adduct 205 (Scheme 51).152 This allows the formation of regioisomers that are not accessible by copper-mediated addition to acetylenic esters. A stereoselective synthesis of trisubstituted alkenes has been described by Normant et al.lSd> starting from phenylthio-acetylene 207. Carbocupration with lithium di- -butylcuprate affords the intermediate 208 which, upon addition of /z-butyllithium, undergoes a 1,2-metalate rearrangement to the vinylcuprate 209. The latter can be trapped with various electrophiles, for example, ethyl propiolate, providing product 210 with complete regio- and stereocontrol. 

The stereoselective synthesis of the title compounds has been achieved. Thexylborane on reaction with 2 molar equivalents of 1-iodo-l-alkyne at 0 °C proceeds to near completion (88% for 1-iodo-l-hexyne) to form fully substituted organoborane (33), which upon treatment with 2 molar equivalents of sodium methoxide at 0 °C readily produces trans-1,2,3-butatrienes (Eq. 102) 157). The same reaction, however, with either 1-chloro or 1-bromo-l-alkynes is sluggish to form the thexyl-l-halo-l-alkenyl-borane31). 

An excellent, general procedure for the stereoselective synthesis of conjugated 13,13 dienes utilizes 1-halo-l-alkynes and thexylborane (36). We prepared the compound XXXX (which is the 13,13 isomer of the Lobesia botrana pheromone XXIX) in >98% stereochemical purity by this procedure (Figure 19). 

Alkenylboron compounds couple with the representative organic halides or triflates (Scheme 28). Hexaalkylbenzene was synthesized by sixfold alkenylation (55) of hexabromobenzene followed by catalytic hydrogenation of the double bonds 11521. The reaction of 1-alkenylborane with 1-bromo-l-alkyne stereose-lectively provided ( )-enyne (56) which was then converted into ( ,Z)-hexa-deca-10,12-dienal, a sex pheromone of the melonworm 11531. Due to the difficulty of purification of a geometrical mixture, the stereoselective synthesis is critical for such dienes or trienes. The PGEi derivatives (57) were synthesized... 

Alkyne Carbometallation as a Versatile Method for the Stereoselective Synthesis of Alkenes... 

The stereoselective synthesis of unsaturated oxetanes has recently been achieved by Feigenbaum and coworkers.Previous studies have indicated that photochemical cis-trans isomerization of enals is rapid and results in the formation of equivalent amounts of stereoisomeric alkene adducts. " For example, irradiation of rran.r-crotonaldehyde and 2,6-dimethylfuran produced a 1 1 mixture of alkenic isomers (174) and (175) in 64% yield. Irradiation of 4-trimethylsilylbutyn-2-one and furan provided with S 1 stereoselectivity the bicyclic oxetane (176) in which the methyl group occupies the exo position, presumably because of the small steric requirement of the triple bond. Desilyation of the protected al-kyne produced an alkynic oxetane which was hydrogenated under Lindlar conditions to bicyclic vinyl-oxetane (177) attempts to use the unprotected butyn-2-one gave low isolated yields of oxetane because of extensive polymerization. The stereochemical outcome thus broadens previous alkynyloxetane syn-theses and makes possible the preparation of new oxetane structures that may be synthetically useful. 

Both intermolecular and intramolecular additions of carbon radicals to alkenes and alkynes continue to be a widely investigated method for carbon-carbon bond formation and has been the subject of a number of review articles. In particular, the inter- and intra-molecular additions of vinyl, heteroatomic and metal-centred radicals to alkynes have been reported and also the factors which influence the addition reactions of carbon radicals to unsaturated carbon-carbon bonds. The stereochemical outcome of such additions continues to attract interest. The generation and use of alkoxy radicals in both asymmetric cyclizations and skeletal rearrangements has been reviewed and the use of fi ee radical reactions in the stereoselective synthesis of a-amino acid derivatives has appeared in two reports." The stereochemical features and synthetic potential of the [1,2]-Wittig rearrangement has also been reviewed. In addition, a review of some recent applications of free radical chain reactions in organic and polymer synthesis has appeared. The effect of solvent upon the reactions of neutral fi ee radicals has also recently been reviewed. ... 

Cross-coupling reactions between 1-alkynyl halides and 1-alkenylboranes, which are readily available via hydroboration of alkynes, can also be catalyzed by Pd-phosphine complexes. Stereoselective synthesis of conjugated ( )-enynes 143 was achieved by the coupling of the alkynyl bromide with an alkenylborane [Eq. (48)] [69]. 

An alternate strategy for the stereoselective synthesis of alkenes is to start with an alkyne and then transform the carbon-carbon triple bond to the double bond of the target molecule. This approach plays an important role in syntheses of alkenes because... 

R.S. Coleman and co-workers have developed a stereoselective synthesis of the 12-membered diene and triene lactones characteristic of the antitumor agent oximidines I and II, based on an intramolecular Castm-Stephens coupling. The effectiveness of this protocol rivals the efficiency of standard macrolactonization. The stereoselective reduction of the internai alkyne afforded the 12-membered ( ,Z)-diene lactone in good yield. 

The stereoselective synthesis of the C5-C20 subunit of the aplyronine family of polyketide marine macrolides was accomplished by J.A. Marshall and co-workers. The C15-C20 moiety was prepared using the original Seyferth-Gilbert homologation conditions. The diazophosphonate was deprotonated with potassium fert-butoxide at low temperature, and then the solution of the aldehyde was added slowly also at low temperature. Interestingly, the alternative Corey-Fuchs alkyne synthesis was unsuccessful on this substrate, since extensive decomposition was observed. 

Furstner, A., Guth, O., Rumbo, A., Seidel, G. Ring Closing Alkyne Metathesis. Comparative Investigation of Two Different Catalyst Systems and Application to the Stereoselective Synthesis of Olfactory Lactones, Azamacrolides, and the Macrocyclic Perimeter of the Marine Alkaloid Nakadomarin A. J. Am. Chem. Soc. 1999,121,11108-11113. 

Pirguliyev, N. S., Brel, V. K., Zefirov, N. S., Stang, P. J. Stereoselective synthesis of conjugated alkenynes via palladium-catalyzed coupling of alkenyl iodonium salts with terminal alkynes. Tetrahedron 1999, 55, 12377-12386. 

Synthesis of trans-disuhstituted olefins. Brown et al,3 have reported a new stereoselective synthesis of nvws-disubstituted olefins (4) utilizing thexylmonoalkylboranes (1) as intermediates. These are prepared by treating an olefin with thexylborane under N2 at -25° for 1 hr. A 1-bromo-l-alkyne is then added, and after 1 hr. the resulting... 

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