Propargylic alcohols reduction

Synthesis of trisubstituted olefins via LAH reduction of the propargylic alcohols and iodination as the key step (Ref. 1). 

Treatment of 4-arylamino-8-iodoquinoline 268 with propargyl alcohol in presence of iodo(phenyl)bis(triphenylphosphine) palladium and copper (I)iodide afforded 269 which upon catalytic reduction using Linder s catalyst gave 4//-pyrrolo[3,2,l-(/]quinoline 270 (97H2395) (Scheme 48). 

The stereochemistry of the first step was ascertained by an X-ray analysis [8] of an isolated oxazaphospholidine 3 (R = Ph). The overall sequence from oxi-rane to aziridine takes place with an excellent retention of chiral integrity. As the stereochemistry of the oxirane esters is determined by the chiral inductor during the Sharpless epoxidation, both enantiomers of aziridine esters can be readily obtained by choosing the desired antipodal tartrate inductor during the epoxidation reaction. It is relevant to note that the required starting allylic alcohols are conveniently prepared by chain elongation of propargyl alcohol as a C3 synthon followed by an appropriate reduction of the triple bond, e. g., with lithium aluminum hydride [6b]. 

The above two consecutive transformations provide straightforward access from propargyl alcohols to cyclopropene derivatives with an a- or /1-hydroxy group. This simple method is complementary to the access to 3-hydroxymethylcyclopropenes, via Rh2(OAc)4 catalyzed addition of diazoacetate to alkynes followed by reduction of the ester group, a route that is restricted to the access of primary cyclopropenyl alcohols [57], and is an alternative to the use of 2,2-dibromo-l-chlorocyclopropane via cyclopropenyl Uthium. 

LBADH also catalyzed the asymmetric reduction of a broad variety of differently substituted acetylenic ketones, including aromatic alkynones and a number of aliphatic derivatives [71]. For example, methyl alkynones bearing an aromatic unit attached to the triple bond were reduced to the corresponding (7 )-propargylic alcohols with >99% ee. Similarly, alkylsilyl-substituted... 

In 1963, an asymmetric synthesis of chloroallenes was reported by the SNi reaction of propargyl alcohols with thionyl chloride [34]. Since then, rearrangement of pro-pargylic precursors has been one of the most useful methodologies for the synthesis of allenes [35]. Treatment of 84, obtained by asymmetric reduction with LiAlH4-Dar-von alcohol complex, with thionyl bromide gave 86 as the major product via 85 (Scheme 4.21) [36],... 

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 reaction sequence outlined in Scheme 20.30 for the preparation of the chlorinated enyne-allenes was successfully adopted for the synthesis of the C44H26 hydrocarbon 251 having a carbon framework represented on the surface of C60 (Scheme 20.50) [83]. Condensation of the monoketal of acenaphthenequinone (243) with the lithium acetylide 101 afforded the propargylic alcohol 244. On exposure to thionyl chloride, 244 underwent a cascade sequence of reactions as described in Scheme 20.30 to furnish the chloride 248. Reduction followed by deprotection produced 250 to allow a repeat of condensation followed by the cascade transformation and reduction leading to 251. 

Pd OH)j(TPPMS)2] propargyl alcohol 1,3-pentad iene Selective reduction of alkynes and dienes to olefins [45]... 

Scheme 7.32 Reductive coupling reactions of propargylic alcohols.

The procedure described in this experiment exemplifies a general method [225] for the reduction of propargylic alcohols to -allylic alcohols. The first step in the reaction is the formation of the aluminium alkoxide -C=C-C-OAlH3. Subsequently one of the three hydrogen atoms attached to aluminum is transferred to the triple bond with formation of a 5-membered cyclic aluminum compound. Hydrolysis affords the -allylic alcohol. In the present case an -enyne alcohol is formed. 

Scheme 2.2.4.4 Reduction of alkynones to chiral propargylic alcohols using LB-ADH. NADPH regeneration was performed using 2-propanol as co-substrate.

However, as alcohol dehydrogenases can react stereo- as well as chemoselec-tively under very mild conditions, they should provide good access to enantiopure propargylic alcohols. This strategy would make it possible to start from a single substrate D which after enzymatic reduction affords either enantiomer of propargylic alcohol E and after further modifications a variety of different enantiopure products in only two to three steps (Scheme 2.2.7.12). 

The enzymatic reduction of T-configured alkenones represents a valuable alternative to the enzyme-catalyzed reduction of the corresponding alkynone with subsequent partial reduction of the C-C triple bond. Nevertheless, since in our results the Z-configured vinylic alcohols are not accessible in enantiopure form by enzyme-catalyzed reduction of the olefinic ketones, for this class of compounds the two-step process via the propargylic alcohols is a highly valuable new strategy. 

STEREOSPECIFIC REDUCTION OF PROPARGYL ALCOHOLS (E)-3-TRIMETHYLSILYL-2-PR0PEN-l-0L (2-Propen-l-ol, 3-(tr1i ethy1s11yl)-, (E)-)... 

STEREOSPECIFIC REDUCTION OF PROPARGYL ALCOHOLS (E)-3-TRIMETHYLSILYL-2-PROPEN-1-0L... 

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