Homopropargyl alcohols, formation

In the case of terminal alkynes having oxygenated functions in the linear chain (Scheme 10, route D), Martin, Padron, and coworkers found that homopropargylic alcohols reacted properly, yielding 2-substituted dihydropyrans as sole products, probably via a Prins-type cyclization. This cyclization provides a new approach toward 2-alkyM-halo-5,6-dihydro-2//-pyrans through a concomitant C-C and C-O bond formation (Scheme 21) [35]. 

The final cyclization manifold has been realized with a different ruthenium catalyst (Scheme 22). The cationic [Cp Ru(MeCN)3]PF6 induces exclusive endo-dig cyclization of both homopropargylic and bis-homopropargylic alcohols.29 73 The clean reaction to form a seven-membered ring is noteworthy for several reasons intramolecular exo-dig cyclization with bis-homopropargylic alcohols is not well established, the platinum-catalyzed case has been reported to be problematic,80 and the selectivity for seven-membered ring formation over the exo-dig cyclization to form a six-membered ring is likely not thermodynamic. The endo-dig cyclization manifold was thus significant evidence that a re-examination of alkyne hydrosilylation mechanisms is necessary (see Section 10.17.2). 

A single example of allene formation was briefly described for a reaction of 2-methylbut-l-en-3-yne (148) with catecholborane (149) [116]. The allenylborane 150 was not isolated but converted into the homopropargyl alcohol 151 in 57% yield by quenching with benzaldehyde (Scheme 3.76). 

The preference for a syn elimination pathway is higher for tertiary versus secondary carbonates, as illustrated in Eq. 9.31. The two-step sequence of allenyltitanium formation followed by addition to benzaldehyde affords the homopropargylic alcohol adduct with essentially complete retention of configuration. In contrast, the phosphate derivative yields a benzaldehyde adduct in which the propargylic center is... 

Reaction of the transient zinc intermediates with various electrophiles yielded the acetylenic substitution products and only minor amounts of allenes (Table 9.49). Reactions with aldehydes were non-selective, affording mixtures of stereo- and regioisomeric adducts. However, prior addition of ZnCl2 resulted in the formation of the homopropargylic alcohol adducts with high preference for the anti adduct, as would be expected for an allenylzinc chloride intermediate (Table 9.50). 

The excellent ability of late transition metal complexes to activate alkynes to nucleophilic attack has made them effective catalysts in hydroamination reactions. The gold(l)-catalyzed cyclizations of trichloroacetimidates 438, derived from homopropargyl alcohols, furnished 2-(trichloromethyl)-5,6-dihydro-4f/-l,3-oxazines 439 under exceptionally mild conditions (Equation 48). This method was successfully applied to compounds possessing aliphatic and aromatic groups R. With R = Ph, cyclization resulted in formation of 439 with complete (Z)-stereoselectivity <2006OL3537>. 

Homopropargylic alcohols as well as propargylic epoxides and pentynols readily form cyclic ruthenium alkoxycarbenes upon intramolecular nucleophilic addition of the OH group to the electrophilic a-carbon of ruthenium-vinylidene species. Their oxidation in the presence of N-hydroxysuccinimide leads to the formation of penta-lactones. The best catalytic system reported until now for this transformation of but-3-ynols is based on RuCl(C5H5)(cod), tris(2-furyl)phosphine, NaHCOs as a base, in the presence of nBu4NBr or nBu4NPp6, and N-hydroxysuccinimide as the oxidant in DMF-water at 95 °C (Scheme 8.11) [22]. 

Reactions of chiral allenes proceed with a preference for the formation of the syn diastereomer. The stereochemical outcome of these reactions can be rationalized by invoking an open transition state model for the addition reactions (Figure 12), which depicts an antiperiplanar orientation of the chiral allenylsi-lane to the aldehyde carbonyl. In this model, steric repulsion between the allenyl methyl and the aldehyde substituent is most likely responsible for the destabilization of transition state (B), which leads to the anti (minor) stereoisomer. This destabilizing interaction is minimized in transition state (A). Table 5 illustrates representative examples and summarizes the scope of the regiocontrolled synthesis of homopropargylic alcohols using allenylsilanes. 

The addition of a 160 to achiral aldehydes in the presence of SnCU produces only the anti homopropargylic alcohols (Scheme 10-67) [106]. The reaction is believed to proceed via transmetallation of the tributyistannyl moiety to the tri-chlorostannyl group. The formation of the anti product then occurs by a syn Skj2 pathway through a cyclic six-membered transition structure (product ee was identical to the ee of 160). 

In the reaction.s of allenylindium and allenylzinc reagents 392 and 391 derived from (R)-3S9, formation of the anti homopropargylic alcohol 393 is favored and highest levels of diastereoselectivity are obtained with branched aldehydes (e.g. cyclohexane carboxaldehyde. Table 11-22). The anti stereochemistry of adducts 393 indicates that these reactions occur through cyclic transitions state in a manner similar to the reactions of the trichloroallenylstannane reagent 226 (see above, Scheme 11-27). 

In additions to homopropargylic alcohols, addition products having both orientations are noted. Here the products of carbon—carbon bond formation at the nearer doublebond carbon are those expected from an anti addition, but the products from additions with the other orientation are mixtures of the compounds expected from syn and anti additions ... 

Saa, C. (2009) Cydoisomerization of aromatic homo- and bis-homopropargylic alcohols via catalytic Ru vinylidenes formation of benzofurans and isochromenes. Organic Letters, 11, 5350-5353. 

Allenic alcohols. Propargylic halides react with carbonyl compounds in the presence of CrCl2 Lil (2 cquiv.) in DMA to form allenic alcohols as the major products.1 (Use of other solvents increases the formation of homopropargylic alcohols as minor products.) Ester, cyano, or chloro groups have no effect on the regiosclcctivity, but an a-substituent can favor formation of propargylic alcohols. 

From a methodological point of view, it should be pointed out the formation of 51, which is a result of the addition of acetone to an allenylidene ligand. Heteroatom-containing cyclic metal-carbene complexes [24] have been conveniently prepared via metal co-haloacyl, carbamoyl, alkoxycarbonyl, or imido intermediates [25], opening of epoxides by deprotonated Fischer-type carbene complexes [26], and activation of homopropargylic alcohols with low-valent d complexes [27], including ruthenium(II) derivatives [28]. In general, the preparation of unsaturated cyclic carbene complexes requires the previous preparation of functional carbenes to react with P-dicarbonyl derivatives, acrylates, and enol ethers [29]. 

The intramolecular hydrosilation of homopropargyl alcohols also proceeds in a 5-exo manner to form five-membered cyclic vinylsilanes exclusively. Subsequent oxidation affords a p hydroxy ketone (eq 6). The vinylsilane also undergoes a Pd-catalyzed cross-coupling reaction with aryl or alkenyl halides stereoselectively (eq 6). The intramolecular hydrosilation thus provides an efficient methodology for the regio- and/or stereoselective functionalization and carbon-carbon bond formation of the alkyne moiety in homopropargyl alcohol. 

The formation of carbon-carbon bond leading to homopropargylic alcohols is possible from conjugated enynes and primary alcohols following the same type of... 

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