Propargyl alcohol stereoselectivity

Hydromagnesiation (11, 163-164 12, 168-169). Cp2TiCl2-catalyzed syn-addition of isobutylmagnesium chloride to propargylic alcohols affords a stereoselective route to vinylmagnesium chlorides for further synthetic use. ... 

Most attention to date has been paid to the hydrostannation of propargyl alcohols and ethers where interaction of the Lewis-basic oxygen enhances the regio- and stereoselectivity and gives high yields of the Z-/3-adducts (e.g., Equations (20) and (21)), whereas hydrostannation with Bu3SnH gives only the Z-cr-adducts. 

A stereoselective synthesis of the enantiomerically enriched allenic hydrocarbons was described in 2001 (Scheme 18.11) [37]. For example, hydrostannylation of the chiral propargylic alcohol 28 (obtained with 82% ee by enantioselective reduction of... 

The boronic acid ester B was synthesized by transesterification of the corresponding pinacolester A with (lR,2R)-l,2-dicyclohexyl-l,2-dihydroxyethane. Stereoselective chlorination of B was carried out with (dichloromethyl) lithium and zinc chloride. Reaction of the obtained chloroboronic ester C with lithio 1-decyne followed by oxidation of the intermediate D with alkaline hydrogen peroxide afforded the propargylic alcohol E. Treatment with acid to saponify the tert-butyl ester moiety and to achieve ring closure, produced lactone F. Finally, Lindlar-hydrogenation provided japonilure 70 in an excellent yield and high enantiomeric purity. 

Whereas the Markovnikov addition of carboxylic acids to propargylic alcohols produces P-ketoesters, resulting from intramolecular transesterification [30, 31], the addition to propargylic alcohols in the presence of Ru(methallyl)2(dppe) 1 at 65 °C leads to hydroxylated alk-l-en-l-yl esters via formation of a hydroxy vinylidene intermediate [32, 33]. The stereoselectivities are lo ver than those obtained from non-hydroxylated substrates. These esters, which are protected forms of aldehydes, can easily be cleaved under thermal or acidic conditions to give conjugated enals, corresponding to the formal isomerization products of the starting alcohols (Scheme 10.6). 

SCHEME 25. Stereoselective synthesis of allylhydroperoxides starting from propargyl alcohols... 

The C-C triple bond in propargylic alcohols allows access to different functional groups also at C3 and/or C4. As an example the chlorohydrin (S)-28a was transformed highly stereoselectively into the corresponding enantiopure E- and Z-olefins (S)-31 in high yields (Scheme 2.2.7.17). 

The bromocyclization of A/,jV-dialkylaminomethyl ethers of allyl and propargyl alcohols to form oxa-zolidinium salts has been reported, but not used in synthesis.255 The heterocyclization of /V-acylamino-methyl ethers with mercury salts has been used for stereoselective synthesis of a variety of 1,2-amino alcohol systems. These cyclizations form rans-4,5-dialkyl oxazolidine products with good to excellent stereoselectivities (equation 120 and Table 33). As shown by entry 5, 6-endo cyclization predominates (6 3) with an internal double bond of ( )-configuration, but this mode of cyclization is reduced with substrates containing a (Z) double bond and/or allylic oxygen substitution (Table 33, entries 6-9). 

The enantiomerieally pure protected butynol 40 ahead) reflects the stereochemistry of the lactone Moreover, the chain can be ex tended by the missing CVunit in the reaction ol 40 with 11, and the alcohol at 0-4 arises simultaneously in a stereoselective way Finally, the propargylic alcohol is converted in only three steps into an a,(i-unsaturated lactone. 

The use of [Rh(COD)2]BF4 2PPh3 as the catalyst appears to be a better choice for this type of reaction. Thus, the reactions of sec- and /erf-propargylic alcohols 134 with HSiEt3 promoted by this rhodium catalyst system provide the desired ( )-y-silylallyllic alcohols 135 with 100% /-selectivity and virtually complete stereoselectivity (E/Z = > 99/1) in excellent yields (equation 54)136,137. 

Regio- and stereoselective reduction of the non-silylated triple bond, either by partial catalytic hydrogenation,13,14,15 or by lithium aluminum hydride reduction of the propargylic alcohols,11,16,17 afford (after desilylation), respectively, terminal (2)- and (E)-enynes. Furthermore, the remaining... 

The PdCb-catalysed cyclocarbonylation of propargylic amines (70) with CuCl2 and p-benzoquinone afforded ( )-o -chloroalkylidene-/3-lactams (71) in moderate to good yields. The formation of the corresponding Z-isomers or five-membered ring products was not observed. The stereoselectivity in this reaction is different from that observed with propargylic alcohols a mechanistic rationale has been proposed.83... 

In contrast with the catalytic system based on RuCl(rf-C9H7)(PPh3)2 in micellar solutions [32], the reaction of secondary propargylic alcohols in 2-propanol/ H20 at 100 °C in the presence of 5 mol % of RuCl(Cp)(PMe3)2 leads to conjugated enals with E stereoselectivity (Eq. 12) [88]. 

The cationic [Cp Ru(MeCN)3]+(PF6) complex, reported as a stereoselective catalyst for trans hydrosilylation of internal alkynes, has been successfully used in intermolecular endo-dig hydrosilylation of propargyloxyhydrosilanes synthesized in situ via silylation of propargylic alcohols by tetramethyldisilazane [116]. 

Chiral lithium bases have been used for enantioselective deprotonation to yield configurationally stable a-oxy carbanions. This holds potential for asymmetric [2,3]-Wittig rearrangement in stereoselective synthesis. Thus, treatment of propargylic ether 72 with (S,S)-3 in THF at — 70 °C to —15 °C afforded propargylic alcohol 73 in 82% yield and in 69% ee of the shown enantiomer96,97. This product was successfully employed as a precursor of (-l-)-Aristolactone (Scheme 55). 

In this synthesis (Scheme 6), the C2-symmetri-cal triacetonide of D-mannitol (32) is converted via the epoxide 33 and its nucleophilic addition product 34 to the propargylic alcohol derivative 35. From this intermediate, the Z-configured vinyl iodide 36 is stereoselectively obtained by hydroalumination/iodination. The Pd-catalyzed Heck cyclization then affords the isomerically pure product 37, which represents a potential building block for the synthesis of la,2y5,25-trihy-droxy-vitamin D, following the classical Wittig strategy of Lythgoe. 

A highly efficient synthesis of l-alkylidene-l,3-dihydrobenzo[f]furans from t>-hydroxymethyl iodoarenes and propargyl alcohols uses a bimetallic Pd/Cu-catalyzed Sonogashira coupling/cyclization reaction (Equation 132) <1999SL456>. Pd/l,4-bis(diphenylphosphino)butane (DPPB)-catalyzed reaction of t>-allylphenols under a CO atmosphere leads to carbonylative cyclization to form benzannulated lactones <2006ASC1855>. A similar carbonylative cyclization leads to the stereoselective formation of 3-alkenyl phthalides <2006T4563>. 

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