Propargylic alcohols, chiral

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]. 

Tao B, Ruble JC, Hole DA, Fu GC (1999) Nonenzymatic kinetic resolution of propargylic alcohols by a planar-chiral DMAP Derivative crystallographic characterization of the acylated catalyst. J Am Chem Soc 121 5091-5092... 

In 2002, Braga el al. employed a chiral C2-symmetric oxazolidine disulfide as a ligand for the enantioselective synthesis of propargylic alcohols by direct addition of alkynes to aldehydes (Scheme 3.64). Good yields but moderate enantioselectivities (<58% ee) were obtained for the enantioselective alkyny-lation of aldehydes in the presence of ZnEt2. 

Equation (81)), while the other two C=C double bonds in the structure are intact. Under the same reaction conditions, the racemic carvone is also resolved kinetically with a KR/KS ratio of 33 1. Asymmetric hydrogenation of a,/Tacetylenic ketones to chiral propargylic alcohols is still unavailable. 

Rearrangement of dienynols to vinylallene sulfoxides. A few years ago, Oka-mura et al. (11, 39) reported the rearrangement of a dienynol to an allenyldiene with transfer of chirality of the propargylic alcohol. This rearrangement has now been used for an enantioselective synthesis of a sesquiterpene, (+ )-sterpurene (3).Thus reaction of the optically active propargylic alcohol 1 with C6H,SC1 at 25° results in a vinylallene (a) that cyclizes to the optically active sulfoxide 2. Nickel-... 

In this context, albeit not real isomerizations, the [2,3]-Wittig rearrangements induced by a tin-lithium exchange must also be mentioned. Starting from enantio-merically pure propargylic alcohols, high ee values for the axial chiral allenes could be observed as shown for 153 (Scheme 1.69) [505, 506],... 

Jin and Weinreb reported the enantioselective total synthesis of 5,11-methano-morphanthridine Amaryllidaceae alkaloids via ethynylation of a chiral aldehyde followed by allenylsilane cyclization (Scheme 4.6) [10]. Addition of ethynylmagnesium bromide to 27 produced a 2 1 mixture of (S)- and (R)-propargyl alcohols 28. Both of these isomers were separately converted into the desired same acetate 28 by acetylation or Mitsunobu inversion reaction. After the reaction of 28 with a silyl cuprate, the resulting allene 29 was then converted into (-)-coccinine 31 via an allenylsilane cyclization. 

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... 

Scheme 18.11 Synthesis of (R)-(—)-tricosa-9,l 0-diene (27a) from chiral propargylic alcohol 28 (AlBN = azobisisobutyronitrile) [37].

The virtue of performing the PKR in an enantioselective manner has been extensively elaborated during the last decade. As a result, different powerful procedures were developed, spanning both auxiliary-based approaches and catalytic asymmetric reactions. For instance, the use of chiral N-oxides was reported by Kerr et al., who examined the effect of the chiral brucine N-oxide in the intermolecular PKR of propargylic alcohols and norbornadiene [59]. Under optimized conditions, ee values up to 78% at - 60 °C have been obtained (Eq. 10). Chiral sparteine N-oxides are also able to induce chirality, but the observed enantioselectivity was comparatively lower [60]. 

Alkynyl ketones 63 are reduced to chiral propargylic alcohols with the same reagent in high optical and synthetic yields (82). The results are shown in Table 7. Reagent (S)-56 gave (S)-alkynylcarbinols, whereas (R)-56 gave the (R)-al-cohols. Several of the acetylenic alcohols are useful for transformation into insect pheromones. 

From unsymmetrical propargyl alcohol and propargyl amine derivatives as coupling partners of diynes, the corresponding axially chiral alcohols and amines were obtained in almost perfect diastereo- and enantioselectivities (Scheme 11.13). 

Table 3 Fu s planar chiral 4-DMAP catalyzed KR of iec-propargylic alcohols [83] 16 (1 mol %)...

Scheme 7.21 Enantioselective propargylic substitution reactions of various propargylic alcohols catalyzed by a chiral thiolate-bridged diruthenium complex.

The formation of chiral allenes from centrochiral propargylic alcohol derivatives and organocopper reagents, e.g., the conversion of (/ )-l-cthynylpentyl acetate to allene 928. 

Efficient kinetic resolution of chiral unsaturated secondary alcohols by irreversible enzyme-mediated acylation (with vinyl acetate as acylating agent, a crude preparation of Pseudomonas AK, and hexane as solvent) is possible, provided one relatively large and one small substituent are attached to the carbinol carbon. However, the method can be used to resolve substrates that are not amenable to asymmetric epoxidation (see examples 23, 25, 27, 29, where the double bond is either deactivated by an electron-withdrawing substituent, or is of the propargyl alcohol type). Acylation of the / -enantiomer consistently proceeds faster than that of the 5-enantiomer. An example of an allenic alcohol was also reported248. 

In 1993, Nicholas and his co-worker developed the stereospecific propargylic alkylation of chiral propargylic alcohols 30 with enol silanes 31 by using a stoichiometric amount of [Co2(CO)5L] (L = phosphite), but separation procedures of the produced diastereoisomers are necessary twice on the way to obtain the compounds specifically alkylated at the propargylic position 32 (Scheme 5). In 2001, Montana and his co-worker reported the diastereo-selective Nicholas alkylation of propargylic acetal complexes 33 bearing a chiral auxiliary with various enol silanes 34 (Equation (14)). A high diastereoselectivity is observed, but unfortunately, only low to moderate enantioselec-tivities are achieved in all cases. 

In fact, this approach constituted one of the earliest trials. One is introduction of a chiral ligand like glyphos on cobalt by replacing one of the carbon monoxides to obtain an enantiomerically enriched new metal-alkyne complex. The second approach is use of the propargyl alcohol bearing a chiral auxiliary. Replacement of only one carbon monoxide would lead to a mixture of diastereomers. In both cases, a I I mixture of products was obtained, and each diastereomer was separated before the... 

Jeong and co-workers utilized a cobalt-alkyne complex to enhance enantioselectivity of the addition of bis (homoallyl)zinc to propargyl aldehydes 68 by the exaggeration of steric environment. The reaction provided optically enriched propargyl alcohol 69 in the presence of a chiral ligand and titanium tetra(isopropoxide) in excess. Adduct 69 was subjected to PKR to yield optically enriched bicyclic compounds 70 (Equation (39)). ... 

The high synthetic utility of alcohols 38 stems from the fact that terminal alkynes are among the most versatile functional groups for the further elaboration of a carbon skeleton. Asymmetric synthesis of alcohols 38 from aldehydes with the concurrent formation of the two stereogenic C atoms has been accomplished mainly by two methods. The first features synthesis of chiral nonracemic allenylmetal compounds from the corresponding chiral nonracemic propargyl alcohols and addition of the former to aldehydes [26] and the second method in-... 

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