Homopropargylic compounds

The observation that allenylboronic esters react with carbonyl compounds to afford homopropargylic compounds was first made by Favre and Gaudemar [132]. 

The addition of allenyl metal reagents to aldehydes affords homopropargylic alcohols with contiguous OH- and Me-substituted stereocenters, which serves as a complementary approach to the aldol condensation for polyketide synthesis. Marshall has developed this method extensively and this work is the subject of a more detailed review (cf. Chapter 9) [50]. The applications of this method to the synthesis of naturally occurring compounds have also been wide-ranging and a few are highlighted below. 

To form the stereocenter at C-3 a direct reduction-alkynylation sequence was applied, that provided the diastereomeric homopropargylic alcohols 83 in a ratio of syn anti=76l2A, The major isomer syn-S3 was isolated in 55% yield. The key step of the synthesis was an intramolecular imidotitanium-al-kyne [2+2] cycloaddition/acyl cyanide condensation. With this sequence the pyrrolidine ring was formed and all the carbon atoms of the alkyl side chain were established in acrylonitrile 84. The reduction of the imine double bond proceeded stereoselectively and the nitrile group was removed reductively en route to the target compound. 

Chiral allenylmetal compounds provide convenient access to enantioenriched homopropargylic alcohols through Se2 additions to aldehydes. The syn adducts can be obtained through addition of allenyl tributylstannanes in the presence of stoichiometric boron trifluoride etherate (BF3-OEt2). The use of allenylmetal halides derivatives of Sn, Zn, and In lead to the anti diastereomers. The former additions proceed through an acyclic transition slate whereas the latter are thought to involve a cyclic transition state, thus accounting for the difference in diastereoselectivity. 

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>. 

Excellent yields can be obtained when the mixture of RC=CLi and the epoxide in ammonia is allowed to stand for 12 to 24 hours [2]. With sodium acetylides, there is some risk of subsequent attack of the acetylenic alcoholate on the epoxide, especially when the latter compound is used in excess. The reaction of acetylenic magnesium halides, RCsCMgX, with epoxides also leads to homopropargylic alcohols, but this is generally not recommended as a satisfactory method, as impure products are often obtained [62], Coordination of the epoxide-oxygen atom with the Lewis acid may give rise to a Sjql-like attack of RCaC on... 

Enantio- and diastereomerically pure homopropargyl alcohols 38 constitute an interesting class of compounds, which have frequently served as building blocks in natural product synthesis (Scheme 1.3.17) [25]. 

Homopropargylic alcoholsIn the presence of TiCl4 this allene reacts with carbonyl compounds to form vinyl chlorides (2) and homopropargylic alcohols (3). 

Umpolung of propargyl compounds occurs in the presence of excess Et2Zn, and homopropargyl alcohols 187 are obtained by the reaction of propargyl benzoates (186) with benzaldehyde, although the exact mechanism is not known. Ethylallene, which is expected to be formed by transmetallation of the allenylpalladium with Et2Zn and reductive elimination, is not formed [41],... 

An iron(m)-catalyzed Prins-type cyclization between a homopropargylic alcohol and an aliphatic aldehyde provides 2-alkyl-3-halo-3,6-dihydropyrans in excellent yield (Equation 113). The solvent and the catalyst equally contribute to the halogen observed in the product therefore, a straightforward choice of catalyst and solvent provides a route to either monochlorinated 252 or monobrominated 3,6-dihydropyrans 253 (Equation 113). Indium compounds have also shown potential as catalysts for this process, with high yields also obtained <20030L1979>. 

Triple-bond participation has been mainly studied (by Hanack and his school) in reactions of homopropargyl derivatives 31 under solvolytic conditions. In all cases of Table 3, except 1 and 2, compounds 31 yield, besides (and very often instead of) the expected solvolysis products, cyclobutanone derivatives (32) and alkyl cyclopropyl ketones (33). 

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