Synthesis chiral propargylic alcohol

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. 

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 synthesis of a new enantiopure, conformationally constrained 1,4-amino alcohol (25) has been reported, starting from commercially available reagents from the chiral pool.107 This 1,4-amino alcohol has been used as a chiral ligand in the addition of Et2Zn to aldehydes (best ee 98%) and in the synthesis of chiral propargylic alcohols (best ee 70%) by alkynylzinc species. 

Smith has employed a related process using the ligand 3 developed by Jiang to obtain a chiral propargyl alcohol. This served as a key building block in an elegant synthesis of (-)-indolizidine 223AB (Eq. 21) [26],... 

This reduction was applied to the synthesis of some natural products. Cate-cholborane reduction is also effective for the synthesis of chiral propargylic alcohols (Scheme 7). In this case the catalyst of choice is 59 (Fig. 3) [85]. 

A direct synthesis of chiral propargylic alcohols from 1-alkynes and aldehydes in the presence of Zn(OTf)2, EtjN, and (+)-A-methylephedrine has a broad scope. Several new ligands are found suitable for inducing asymmetric addition of R2Zn (mostly diethylzinc) to aldehydes. These include 42, 43, 44, 45, and Other (3-amino alcohols that show desirable features are S-ew-morpholinoisoborneol, which is more stable in air than the dimethylamino analogue, (S)-2-(pyrrolidin-l-yl)-l,2,2-triph-enylethanol, and a polymer-supported A-alkyl-a,a-diphenyl-L-prolinols. A,A-Dibutyl-norephedrine is useful in a solvent-free reaction. ... 

More highly functionalised chiral propargyl alcohols are available by the chiral pool approach. For example, both fragments (34) and (35) were prepared from D-xylose, as intemediates for the synthesis of LTB (Scheme 55). ... 

Torn et al. have utilized the asymmetric sulfoxide precursor for the synthesis of chiral propargylic alcohol (Scheme 21.15). The e.e. values of the products was greater than 99% in a few cases. The reaction of the a-carbanion derived from (irimethylsilyl)vinyl sulfoxides with aldehydes afforded a diastereomeric mixture of products R-4 and S-5. They were... 

DESYMMETRIZATION AND ENZYMATIC STRATEGIES FOR CHIRAL PROPARGYL ALCOHOL SYNTHESIS... 

In this chapter we have highlighted several practical approaches for the synthesis of chiral propargyl alcohols by various methods, the most practical ones being the asymmetric alkynation of carbonyl compounds in the presence of chiral auxiliaries and the p-eUmination of stereochemically well-defined a,p-dioxyhalides. These two approaches have been utilized efficiently in the synthesis of several bioactive natural products. 

Kinugasa Reaction The aUcynes-nitrones cycloaddition, commonly known as the Kinugasa reaction, has emerged as a powerful tool for the synthesis of diverse types of P-lactams. Treatment of the chiral propargyl alcohols 45 with diaryl nitrones 46 furnished mainly the cis-fi-lactams 47 (Scheme 3.18) [51]. The... 

In 2014, Sherbum and coworkers disclosed a short synthesis of (-)-psendopterosins (G-J) aglycone 75 (Scheme 8.10) [30]. To bnild the carbocyclic scaffold, they delineated an unconventional strategy, which relies upon the nse of a diene-transmissive triple Diels-Alder reaction. The enantio-enriched 1,1-divinylallene 78 was prepared in three steps from the chiral propargyl alcohol 77 (chiral pool). This unusual diene was then subjected to a Diels-Alder reaction to provide the cycloadduct 79 in 61% yield and in good diastereomeric ratio. A second [4h-2] cycloaddition of 79 with acrolein using high-pressure conditions took place to afford the expected cycloadduct 80 in 15% yield. Although a... 

In 2011, Corey s group found that Inij and InBr3 were effective catalysts for the it activation of C=C triple bonds to initiate the conversion of chiral propargylic alcohols or silyl ethers to polycyclic products in excellent yields with high stereoselectivity (Scheme 9.24) [35]. The method was applied to the synthesis of chiral fused hexacyclic ring systems with the creation of multiple new stereocenters. 

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-... 

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. 

As the integrity of chiral alcohols are retained in the phase-transfer catalysed O-alkylation, the procedure is valuable for the synthesis of chiral ethers under mild conditions as, for example, in the preparation of alkoxyallenes via the initial formation of chiral propargyl ethers [8]. It has been proposed that a combination of 18-crown-6 and tetra-n-butylammonium iodide provide the best conditions for the O-benzylation of diethyl tartrate with 99% retention of optical purity [9]. 

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-... 

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). 

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