Propargyl phosphates

Pd(Ph3P)2Cl2(Bu3SnH, benzene) or cobalt carbonyl. The palladium method cleaves allyl esters, propargyl phosphates, and propargyl carbamates as well. 

Mikami and Yoshida extended the scope of this method considerably by using propargyl phosphates and chiral proton sources [94], The propargylic phosphates thereby have been found to be advantageous owing to their high reactivity towards palladium and the extremely low nudeophilicity of the phosphate group [95]. In some cases, it was even possible to obtain allenes from primary substrates, e.g. ester 194 (Scheme 2.60) [96]. A notable application of this transformation is the synthesis of the allenic isocarbacydin derivative 197 from its precursor 196 [97]. 

Scheme 2.60 Palladium-catalyzed reduction of propargylic phosphates with Sml2. TBS = Si(tBu)Me2.

By employing chiral proton sources for the protonation of the intermediate samarium species 184/185, highly enantioenriched allenes were accessible in some cases [98]. Thus, in the reaction of propargylic phosphate 198, (R,Rj- 1,2-diphenyl-1,2-ethandiol (200) and (R)-pantolactone (201) were found to give the highest selec-tivities, affording allene 199 with up to 95% ee (Scheme 2.61). 

Palladium-catalyzed reduction of propargyl acetates is possible with Sml2 in the presence of a proton source (Scheme 3.17) [51]. The allene/alkyne selectivity is greatly influenced by the choice of the proton source. Propargyl phosphates were also converted into hydridoallenes by Pd-catalyzed reduction with Sml2 [52],... 

The enantioselective synthesis of an allenic ester using chiral proton sources was performed by dynamic kinetic protonation of racemic allenylsamarium(III) species 237 and 238, which were derived from propargylic phosphate 236 by the metalation (Scheme 4.61) [97]. Protonation with (R,R)-(+)-hydrobcnzoin and R-(-)-pantolactone provided an allenic ester 239 with high enantiomeric purity. The selective protonation with (R,R)-(+)-hydrobenzoin giving R-(-)-allcnic ester 239 is in agreement with the... 

In another reduction, the propargylic phosphate 64 is reduced with samarium(II) iodide in the presence of tetrakis(triphenylphosphine)palladium and tert-butanol as a proton source the allene 65 is produced almost exclusively, <1% of the isomeric alkyne 66 being present in the product mixture [19]. 

The steric course of this two-step process was examined with several chiral secondary propargylic phosphates (Eq. 9.35) [40], The derived propargylic stannanes were found to be formed with net inversion of configuration. Based on previous evidence that the initial formation of the allenyltitanium intermediate occurs with inversion, it can be deduced that stannylation proceeds by a syn pathway. This surprising result was attributed to coordination between the chlorine substituent of the Bu3SnCl and the electropositive titanium center (Scheme 9.11). 

Chiral allenyltitanium reagents, prepared from propargylic phosphates as outlined, react with alkylidene malonates to afford 1,4-adducts with excellent anti dia-stereoselectivity (Table 9.26) [42]. The addition is presumed to take place through an open antiperiplanar transition state (Scheme 9.12). 

An enantioenriched propargylic phosphate was converted to a racemic allene under the foregoing reaction conditions (Eq. 9.152) [124]. It is proposed that the racemization pathway involves equilibration of the allenyl enantiomers via a propargylic intermediate (Scheme 9.37). Both the allenylpalladium precursor and the allenylsamarium reagent could racemize by this pathway. When a chiral alcohol was used as the proton source, the reaction gave rise to enantiomerically enriched allenes (Table 9.61) A samarium alcohol complex is thought to direct the protonolysis (Scheme 9.38). 

When the propargyl phosphate 225 was heated in the presence of Pd2(DBA)3-CHCl3 and sodium acetate in THF, the central sp carbon atom of the (j-allenylpalladium complex, formed from the propargyl alcohol ester and Pd(0), was attacked by the lactam nitrogen atom to yield the carbapenam 226 with an exocyclic methylene group <2001TL4869>. 

Interestingly, DKR of a propargylic phosphate, such as rac-SS, to give the enan-tiomericaUy enriched allene (R)-87, has been achieved by a samarinm(II) iodide-mediated... 

It has been found that allenyltitaniums (134), prepared in situ by the reaction of optically active secondary propargyl phosphates (135) with a divalent titanium reagent, react readily with alkenylidenemalonates with excellent regio- and dia-stereoselectivity to afford the Michael addition products (136) with high optical purity (Scheme 33). ... 

Optically active allylstannanes, R3SnC HR (CH=CHR"), are formed from active secondary propargyl phosphates from the sequence of reactions shown in equation 9-4,8 using the Ti(OPr1)4/Pr1MgBr reagent.9 Presumably the titanium/tin transmetallation involves an Sn2 process. 

A changeover of regioselectivity was observed by Mikami et al. in the reduction of secondary propargylic phosphates by the SmI2/Pd(0)/proton source system [169]. ferf-Butanol and dimethyl (R,R)-tartrate gave allene and acetylene, respectively (Scheme 61). This process was modified in an asymmetric synthesis of chiral allenes [170]. 

Propargylamines. The 5 2 displacement of propargyl phosphates or acetates with amines is general for the preparation. (60-95% yield). Another pathway involves oxidative coupling of iV,A-dimethylanilines with 1-alkynes under oxygen. Other products of this reaction are the A-methylanilines and A-methylformanilides. 

The stereochemical course for the racemisation could be explained as follows. First, the oxidative addition to the propargylic phosphate gave an allenylpalla-dium(ii) through the back side attack of palladium(0). Thus, this enantio-enriched allenylpalladium(ii) was stereospecifically formed starting from the... 

The chirality of the propargyl phosphate is completely lost a j sphate is converted phate-aUene transformation (Scheme 40). Racemic proparg -fotooation with chiral to an optically active allene with high ee via dynamic kinnO F alcohols. 

More recently, Lalic and coworkers developed an asymmetric synthesis of allenes using propargylic phosphates (Scheme 8.6) [21,22], The tuning of the... 

IH-tetrazole as the basic promoter for the formation of an anhydride P-O-P bond (Scheme 15.6). To this end, guanosine monophosphate (GMP) was activated as the morpholidate 14 and coupled with propargyl phosphate 13. 

Effect of proton source on regioselectivity in the Sml2 mediated reduction of propargylic phosphates... 

Proton donors are known to exert considerable influence on the regiochemical and stereochemical outcome of several Sml2-mediated reactions. Yoshida and Mikami (1997) have reported the effect of proton source in the reduction of propargylic phosphates by Palladium(0)/Sml2/proton source system (eq. (42), table 1). The use of 2-methyl-2-propanol as the proton source results in the exclusive formation of allenes, while the diol, dimethyl tartarate ((+)-DMT) gave the alkyne as the major product. 

Yoshida et al. (1998) have also reported the effect of proton donors on the regioselectivity in the reduction of cinnamyl esters utilizing Pd(0)/Sml2/proton source system. Similar to the propargylic phosphates discussed above, fine tuning the proton source resulted in the selective synthesis of different products (eq. (43), table 2). 

Finally, alkylboranes have also been used in the NHC-copper-mediated synthesis of allenes by 8, 2 addition on a propargylic phosphates. It was shown that an efficient transfer of the chiral information was operating when enantioenriched substrates were used, thus leading to the formation of allenes with good ee s. 

The copper-catalysed y-selective coupling between propargylic phosphate (83) and alkylboron compound (84) afforded chiral multisubstituted allenes (85) with various functional groups (Scheme 20). ... 

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