Propargylic epoxide

The reaction of propargylic epoxide 4 with excess amounts of dialkylcuprates gives a significant amount of reduction byproduct 6, but the use of RCu(CH2SOCHa)Li affords a-hy-droxyallene 5 in high yield94. 

The effectiveness of dimethyl sulfide as an additive for the selective formation of anti-product 22 from propargyl epoxide 20 may be due to the formation of stabilized copper species, which are less prone to undergo electron transfer processes. In this respect, other soft ligands which bind strongly to copper, in particular phosphines and phosphites [8h-j, 25, 28], have been used even more frequently. These additives also serve to suppress the formation of a common side product, i.e. an allene containing a hydrogen atom instead of the carbon substituent which should... 

With the proper choice of reaction conditions, diastereoselective synthesis of a-allenic alcohols 69 and 70 from propargylic epoxide 68 was achieved [80, 81], With RMgBr and 5 mol% of CuBr/2PnBu3, anti allenic alcohols 69 are obtained with up to 100% diastereoselectivity. On the other hand, syn allenic alcohols 70 can be prepared with 88-96% diastereoselectivity with RMgCl, Me3SiCl and 5mol% CuBr (Scheme 3.36). 

Ring-Opening Reactions of Propargyl Epoxides and Related Compounds... 

The iron-catalyzed addition of Grignard reagents to propargylic epoxides developed by Furstner and Mendez allows one to prepare a yw-allenol, which is an important intermediate for the synthesis of a precursor of the amphidinolide X (Scheme 67). 

Although the iron-catalyzed synthesis of allenes from propargylic halides was reported by Pasto and coworkers in 1978 [67], little progress was achieved in this field until recently [68]. In 2003, Fiirstner and coworkers discovered propargylic epoxides as valuable substrates for the reaction with Grignard reagents in presence of catalytic amounts of Fe(acac)3 to generate 2,3-allenol derivatives (Scheme 5.24) [69]. 

An interesting SN2 -syn addition of Grignard reagents to propargyl epoxides in the presence of Fe(acac)3 was reported by Fiirstner and Mendez (Scheme 7.19) [26], Based on earlier results from Pasto and coworkers [27], the method was developed into a powerful tool for the synthesis of optically active allenol derivatives. The... 

Scheme 7.19 Fe-catalyzed conjugate addition to propargylic epoxides.

Homopropargylic alcohols (but-3-ynols) as well as propargylic epoxides are suitable products to form cyclic ruthenium alcoxycarbenes upon intramolecular nucleophilic addition of the OH group to the electrophilic a-carbon of ruthenium vinylidene species. The recovery of the organic ligand as a lactone... 

Propargylic epoxides can be used as precursor for the carbocations. For example, complexation of (159) and reaction of the complex with borontrifluoride etherate give, stereoselectively, complex (160) (Scheme 231). This sequence was used in a synthesis of (—)-ichthyothereol. ... 

In 2003, Fiirstner s group reported applications of this methodology to total syntheses of some natural products, and to the stereospecific Sn2 reaction of alkyl and aryl Grignards with optically enriched propargyl epoxides to yield alkyl- and aryl-substituted 2,3-allenols with high stereochemical fidelity (equation 29). ... 

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]. 

The reaction is completely regioselective in favor of the 8 2 product, and the cross-coupling of propargyl epoxides with organocuprates give nearly an exclusive anti-product when dimethyl sulfur is present, but give mixtures of syn- and anti-products in its absence. 

More recently, Alexakis [32] reported the diastereoselective syn- or anti-opening of propargyl epoxides, with good to excellent 8 2 selectivity. Addition of two equivalents of phosphine as a ligand can influence the stereochemistry of the elimination step to afford either the syn- or anti-product, as shown in Eq. (73) and Table 19. 

Reaction of acyclic propargyl epoxides with Grignard reagents in the presence of Cu catalyst afforded the S 2 products exclusively, with high stereoselectivity toward the syn-product. For the trans-epoxide, the selectivities are higher, particularly for the syn-process [32 Eq. (75) and Table 21]. 

Metal-catalyzed cyclization/conjugate addition sequences involving substituted propargyl epoxides have also been employed in the synthesis of highly functionalized furans. These reactions are generally catalyzed by... 

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