Asymmetric alkynylation

Table 1.6 Asymmetric Diels-Alder reactions of alkynyl aldehydes catalyzed by 8 [lOc]...

Vinyl boranes add to conjugated ketones in the presence of a rhodium catalyst (with high asymmetric induction in the presence of BINAP) 7 Alkynyl-boranes also add to conjugated ketones, in the presence of... 

Zinc catalysts have shown a major increase in their possible applications. Some examples of catalysis using halide complexes, including immobilized catalytic systems, have been discussed in Section 6.8.8. Some areas such as asymmetric alkynylation of aldehydes have been recently reviewed.930... 

A hydrosilylation/cyclization process forming a vinylsilane product need not begin with a diyne, and other unsaturation has been examined in a similar reaction. Alkynyl olefins and dienes have been employed,97 and since unlike diynes, enyne substrates generally produce a chiral center, these substrates have recently proved amenable to asymmetric synthesis (Scheme 27). The BINAP-based catalyst employed in the diyne work did not function in enyne systems, but the close relative 6,6 -dimethylbiphenyl-2,2 -diyl-bis(diphenylphosphine) (BIPHEMP) afforded modest yields of enantio-enriched methylene cyclopentane products.104 Other reported catalysts for silylative cyclization include cationic palladium complexes.105 10511 A report has also appeared employing cobalt-rhodium nanoparticles for a similar reaction to produce racemic product.46... 

Another practically perfect asymmetric catalysis has been observed in reactions using (2-alkynyl-5-pyrimidyl)alkanols as the catalyst. The asymmetric autocatalysis shown in Scheme 8-59 gives the corresponding product in high yield with over 99% ee.116... 

Carreira and co-workers developed a highly efficient enantioselective addition of terminal alkynes to aldehydes giving propargyl alcohols by the mediation of zinc tri-flate and N-methylephedrine [17]. This reaction serves as a convenient and powerful synthetic route to a wide variety of enantioenriched allenes via propargyl alcohols. Dieter and Yu applied this alkynylation to the asymmetric synthesis of allenes (Scheme 4.12) [18]. Reaction of phenylacetylene with isobutyraldehyde afforded the propargyl alcohol in 80% yield with 99% ee, which was mesylated to 49 in quantitative yield. Reaction of 49 with the cyanocuprate 50 afforded the desired allene 51 with 83% ee. 

Scheme 4.12 Asymmetric synthesis of allene 51 via Carreira s alkynylation.

Recently, Hiroi and co-workers reported a palladium-catalyzed asymmetric transformation of chiral 2-alkynyl sulfmates 142 into allenyl sulfones 145 (Scheme 4.38) [58], Treatment of 142 with Pd(OAc)2 in the presence of a phosphine ligand afforded allenylsulfones 145 with high stereospecificities (73-89%) in good yields, probably through intermediates 143 and 144. 

A cuprate prepared in situ from tBuPh2SiLi and Cul has been found to react with alkynyl epoxides to afford allenylsilanes (Eq. 9.43) [50]. Enantioenriched alkynyl epoxides, which are readily prepared in high yield through Sharpless asymmetric epoxidation [51], afford chiral allenylsilanes with anti stereoselectivity. 

Extensive theoretical studies of the alkynyl coupling reactions have been reported. An early MO study of the relationship between L2M(/r-C2R)2ML2 and L2M(/z-RC4R)ML2 used EH and MNDO techniques and encompassed a range of Main Group elements as well as Ti and Zr ° and showed the transition between symmetrical, asymmetric, and linked C4 ligands. The structural evidence... 

The asymmetric alkynylation of isoquinoline iminium ion was reported in the presence of CuBr/QUINAP system (Scheme 5.7). ° Various alkynyl tetrahydroiso-quinolines were obtained in excellent yields and enantiomeric excesses. A natural product, homolaudanosine, was synthesized by the reduction of the obtained propargyl tetrahydroisoquinoline. 

Other Systems In contrast to the highly successful alkynylation of imines, copper catalysts failed in the asymmetric alkynylation of aldehydes. On the other hand, the combination of various Uewis acids and chiral amines were studied extensively to... 

Scheme 5.6. Asymmetric alkynylation of iminiums generated from aldehydes and amines.

Section 14.2 describes the highly stereoselective cyclopropanation chemistry of the donor/acceptor-carbenoids (Fig. 14.1a) [16]. This section introduces the range of vinyl, aryl, alkynyl, and heteroaryl functionalities that have been used as donor groups in this chemistry. Also, chiral auxiliaries and chiral catalysts that achieve high asymmetric induction in this chemistry are described [25]. The next two sections cover chemistry that is unique to the vinylcarbenoid system, namely [3-t4] cycloaddition with dienes (Fig. 14.1b see also Section 14.3) [13] and [3-1-2] cycloaddition with vinyl... 

Asymmetric synthesis of stavudine and cordycepin, anti-HIV agents, and several 3 -amino-3 -deoxy-P-nudeosides was achieved utilizing this cycloisomerization of 3-butynols to dihydrofuran derivatives [16]. For example, Mo(CO)6-TMNO-promoted cyclization of the optically active alkynyl alcohol 42, prepared utilizing Sharpless asymmetric epoxidation, afforded dihydrofuran 43 in good yield. Iodine-mediated introduction of a thymine moiety followed by dehydroiodination and hydrolysis of the pivaloate gave stavudine in only six steps starting from allyl alcohol (Scheme 5.13). 

One of the severest challenges of asymmetric synthesis is the direct enantioselective construction of quaternary stereogenic centers. Brian Pagenkopof of the University of Texas has reported (Chem. Communications 2003 2592) that alkynyl aluminum reagents will open a trisubstituted epoxide such as 10 at the more substituted center, with inversion of absolute configuration. As the epoxide 10 is available in high from 9 by the method of Yian Shi of Colorado State (J. Am. Chem. Soc. 119 11224, 1997), this opens a direct route to quaternary cyclic stereogenic centers. 

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