Propargyl synthons

Acetylenes can be hydrated to give ketones (frame 145) so propargyl bromide must provide a MeCOCH2 synthon ... 

The stereochemistry of the first step was ascertained by an X-ray analysis [8] of an isolated oxazaphospholidine 3 (R = Ph). The overall sequence from oxi-rane to aziridine takes place with an excellent retention of chiral integrity. As the stereochemistry of the oxirane esters is determined by the chiral inductor during the Sharpless epoxidation, both enantiomers of aziridine esters can be readily obtained by choosing the desired antipodal tartrate inductor during the epoxidation reaction. It is relevant to note that the required starting allylic alcohols are conveniently prepared by chain elongation of propargyl alcohol as a C3 synthon followed by an appropriate reduction of the triple bond, e. g., with lithium aluminum hydride [6b]. 

Enone disconnection reveals 1.4-diketone (20) and ring-chain disconnection requires synthon (21). Allyl or propargyl halides (p T 221 ) could fill this role. 

A CH-group, which bears vinyl and sulfide substituents, is acidic enough to be metallated by strong bases. Other d3-synthons may contain two activating functional groups in Imposition ( homoenolate -equivalents). Only one of the a-carbons is deprotonated under appropiate conditions (e.g. succinic diesters). Ano ther possibility is an acidic carbon and a non-acidic functional group in 1,3-positions (e.g. propargyl derivatives). Silyl ethers of a, -unsaturated alcohols can also be converted to anions, which react as d3-synthons (W. Oppolzer, 1976). 

The initial retrosynthetic analysis for a route to travoprost, using the Newton-Roberts route, provided three key synthons a) the a-chain was derived from the commercially available Wittig salt, (4-carboxybutyl)triphenylphosphonium bromide b) the co-chain required a route to the single enantiomer mixed cuprate reagent, most conveniently derived from the propargylic alcohol via the trans-vinyl iodide, to be developed and c) the cyclopentane core could be derived from the single enantiomer protected bromohydrin (Figure 30.3).llc 25... 

Propargyl phenyl selenide is a versatile multifunctional acrylate synthon, as shown in Scheme 12. The (Uanion is prepared and reacted successively with an alkylating agent (R— X) and an electrophile (E ). The oxidative rearrangement of the propargylic selenoxide (35) to an allenic selenenate (36), and thence to the a-phenylselenoenone (37), forms the keystone of this synthetic method, and ovendl yields firom propargyl phenyl selenide are in the range of 38-68%. Further elaboration of (37) is possible... 

Aldehydes are one of the most impotent synthons in organic chemistry. Many methods of preparation of formyl carboranes have been discussed previously (E. I. Rosemund method,14 Sonn-Miller reaction,14 reaction of dodecaborane with diacylal of propargyl aldehyde,14 Swem Oxidation15). Since oxazolines are rather good reagents for the preparation of aldehydes and nitriles, we developed a method of preparation of carboranyl oxazolines (Scheme 9). 

Pyrazole itself can be formed by the reaction of hydrazine with propargyl aldehyde. Using p-chloro-," P-alkoxy-" p-amino-" -enones as 1,3-dicarbonyl synthons are other ways to influence the regiochemistry of reaction." 2-(Dimethoxymethyl)-ketones react with arylhydrazines at the ketonic carbonyl, thus reversing the intrinsic reactivity of a p-keto-aldehyde." ... 

M. (1997) Propargyl alcohols as synthons for allenols in conjugate addition. Journal of the American Chemical Society, 119, 11319-11320. 

Allyl (7) and propargyl (22) haiides can act as latent unnatural synthons (24) and (2S) respectively by electrophilic addition to the double bond in (21) or hydration of the triple bond in (23). If the nucleophile is an enolate ion, a... 

Cyclopentenone (3) has been used in photochemical syntheses of four-membered rings. Disconnection gives keto aldehyde (4) and the branch point disconnection (a) gives aldehyde (5) and synthon (6) for which we might consider a-bromacetone (Chapter 25), allylic bromide (7) (Chapter 26), or propargyl bromide (8) (Chapter 26), using in each case the enamine of aldehyde (5) to ensure control. One successful synthesis is given. 

Alkylations. -Lithiocarbonyl synthons and propargyl anions are generated from the bromides by reacting with BuTeLi and then BuLi. (Z)-l,3-Butadien-l-yllithium is available from P-(organotelluro)acroleins. 

Rao and co-workers effected cycloaddition of 8 with the propargylic aldehyde 156 to afford the 2,3,4-trisubstituted furan 157 in 90% yield in their regioselective synthesis of the antitumor agent camptothecin (Fig. 3.47). Several steps were required to convert 157 to the butenolide 158, a key synthon for the D- and E-rings of... 

Preparation of an useful synthon, the cyclic carbamate of L-daunosaminal (104), was achieved by sequential catalytic transformations of a key intermediate. Suitably protected propargyl diol 101, which was obtained by diastereoselective addition of allenyl stannate 99 to 0-benzyl (S)-lactyl aldehyde 100, was transformed as depicted in Scheme 18. Cycloisomerization to 3-deoxyglycal 103 was achieved by irradiation in the presence of tungsten hexacarbonyl, and subsequent nitrene insertion was catalyzed by rhodium acetate. Overall yield of the bicyclic daunosaminal (104) derivative from lactic acid derivative amounted to 44% [78]. 

ENANTIOSELECTIVE SYNTHESIS OF PROPARGYL ALCOHOLS AS MULTIFUNCTIONAL SYNTHONS... 

Propynols are useful synthons in the synthesis of carotenoids and may be prepared by the zinc-mediated condensation of aldehydes and ketones with propargylic bromides. However, this condensation also produces isomeric allenic byproducts, as is illustrated by the condensation of 3-ionone (3) with propargyl bromide (63) x the presence of zinc to give 64 and 65 [35] (Scheme 14). Suppression of such allenic byproducts is possible by replacing zinc with magnesium or aluminium in the presence of mercuric salts [35,36],... 

The mixed vinyl acetylene cuprate (435) has been developed as an ethyl acrylate synthon. Whereas (435) does not react with alkyl bromides and iodides, it is reactive towards allylic (and propargylic) bromides, as exemplified by its reaction with 3-bromo-... 

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