Mukaiyama reaction, synthesis

In the synthesis shown in Scheme 13.15, racemates of both erythro- and threo-juvabione were synthesized by parallel routes. The isomeric intermediates were obtained in greater than 10 1 selectivity by choice of the E- or Z-silanes used for conjugate addition to cyclohexenone (Michael-Mukaiyama reaction). Further optimization of the stereoselectivity was achieved by the choice of the silyl substituents. The observed stereoselectivity is consistent with synclinal TSs for the addition of the crotyl silane reagents. 

An enantiospecific synthesis of longifolene was done starting with camphor, a natural product available in enantiomerically pure form (Scheme 13.31) The tricyclic ring was formed in Step C by an intramolecular Mukaiyama reaction. The dimethyl Multistep Syntheses substituents were formed in Step E-l by hydrogenolysis of the cyclopropane ring. 

Another Japanese group developed the Baccatin III synthesis shown in Scheme 13.58. The eight-membered B-ring was closed early in the synthesis using a Lewis acid-induced Mukaiyama reaction (Step B-l), in which a trimethylsilyl dienol ether served as the nucleophile. 

Mukaiyama s Synthesis. Mukaiyama s synthesis starts with construction of the B-ring moiety, and aldol reactions are used extensively throughout the entire synthesis process.34 The retro synthesis is outlined in Scheme 7-66. 

The copper-catalyzed conjugate addition of methyhnagnesium iodide to cyclohexenone and trapping of the resulting enolate as its trimethylsilyl enolate, followed by TrSbCle-catalyzed Mukaiyama reaction, are the first steps of an elegant synthesis of enantiomeri-caUy pure clerodanes (equation 45). 

The copper-catalyzed conjugate addition of methyl magnesium iodide to cyclohexenone and trapping the enolate as its trimethylsilyl enol ether, followed by a trityl hexachloro-antinomate-catalyzed Mukaiyama reaction, is apphed to / -(—jcarvone. C-2, C-3 functionalized chiral cyclohexanones are converted into their a-cyano ketones, which are submitted to Robinson annulation with methyl vinyl ketone. Highly functionalized chiral decalones are obtained that can be used as starting compounds in the total synthesis of enantiomerically pure clerodanes (equation 70). 

Aliphatic nitro compounds are versatile building blocks and intermediates in organic synthesis,14 15 cf. the overview given in the Organic Syntheses preparation of nitroacetaldehyde diethyl acetal.16 For example, Henry and Michael additions, respectively, lead to 1,2- and 1,4-difunctionalized derivatives.14 18 1,3-Difunctional compounds, such as amino alcohols or aldols are accessible from primary nitroalkanes by dehydration/1,3-dipolar nitrile oxide cycloaddition with olefins (Mukaiyama reaction),19 followed by ring cleavage of intermediate isoxazolines by reduction or reduction/hydrolysis.20 21... 

A catalytic asymmetric vinylogous Mukaiyama reaction between silyl dienolate 896 and aliphatic ketone 897 provides the 5,6-dihydropyran-2-one 898, a key intermediate during a formal synthesis of enantiopure taurospongin A (Equation 361) <2005JA7288>. 

Asymmetric cyanation of aldehydes is important in organic synthesis. Mukaiyama and Minowa have developed a new chiral Lewis acid catalyst which is readily prepared from l,l -dimethylstannocene, triflic acid, and (+)-cinchonine [49]. In the presence of this Lewis acid reaction of TMSCN with aldehydes proceed smoothly at -78 °C in dichloromethane to give the corresponding cyanohydrin trimethylsilyl ether in high yield with good to excellent ee. In this reaction the products are isolated as trimethylsilyl ethers and the reaction proceeds smoothly in the presence of 30 mol % tin(II) Lewis acid (Eq. 31). The catalyst, Sn(II) monoalkoxymonotriflate, is assumed to be regenerated from the initially produced Sn(II) alkoxide and trimethylsilyl triflate. 

Lewis acid catalyzed intramolecular alkylations of silyl enol ethers containing 5n1-reactive functionality provide useful routes to a variety of carbocyclic systems. - Smith et al have employed an intramolecular Mukaiyama reaction of the enol derivative (76) to produce the tetracyclic system (77) (equation 7). This transformation was a key step in their elegant synthesis of jatrophone. The synthesis... 

A vinylogous Mukaiyama reaction, similar to that utilized in our synthesis, was employed to introduce the C-, stereocenter in Nicolaou s synthesis and also in the synthesis of preswinholide A reported by the Nakata group I53k One notable reaction in Nakata s synthesis of preswinholide A was the auxiliary-controlled aldol reaction shown in Scheme 9-31. Here the Evans auxiliary is used to couple two relatively complex fragments 91 and 92 to give 93. Unusually, this reaction was best performed using the lithium enolate of imide 91. 

The total synthesis of ( )-trichostatin A has been carried out by two routes [67] one uses the y-alkylation of a silyl dienol ether with an acetal which gives the ether in a Mukaiyama reaction. A Wittig olefination followed by DDQ oxidation gives a ketoester which reacts with hydroxylamine to give trichostatin A in 22% overall yield (Scheme 20). 

A more direct access to heptulosonic acid analogues have been described on [4+3] carbon atoms incorporation [156]. The Mukaiyama reaction of frans-a,P-epoxyaldehydes with ethyl 2-(trimethylsililoxy)-2-propenoate, in the presence of the Lewis acid - BF3 etherate - led to the direct synthesis of a mixture of 5- and 6-fluoroheptulosonic analogues in their pyranosidic or furanosidic form [156],... 

Mukaiyama reaction, a redox condensation approach to peptide synthesis. A disulfide (2,2 -dipyridyldisulfide) reduction combined with a phosphine (triphenylphos-phine) oxidation provides the driving force for the condensation of the carboxy component with the amino component [T. Mukaiyama et al., in The Peptides Analysis, Synthesis, Biolc, Volume 2, E. Gross,... 

The aldol reaction and related processes have been of considerable importance in organic synthesis. The control of syn/anti diastereoselectivity, enantioselectivity and chemoselectivity has now reached impressive levels. The use of catalysts is a relatively recent addition to the story of the aldol reaction. One of the most common approaches to the development of a catalytic asymmetric aldol reaction is based on the use of enantiomerically pure Lewis acids in the reaction of silyl enol ethers with aldehydes and ketones (the Mukaiyama reaction) and variants of this process have been developed for the synthesis of both syn and anti aldol adducts. A typical catalytic cycle is represented in Figure 7.1, where aldehyde (7.01) coordinates to the catalytic Lewis acid, which encourages addition of the silyl enol ether (7.02). Release of the Lewis acid affords the aldol product, often as the silyl ether (7.03). 

This reaction was first reported by Breckpot in 1923. It is the synthesis of )0-lactam via the cyclization of esters of /3-amino acids with Grignard reagent and is known as the Breckpot -lactam synthesis. This reaction has been modified to form )0-lactam by the treatment of )0-amino acid with Mukaiyama s reagent, or the /3-amino ester with /V-methyl pyridinium salt." ... 

Although no examples are presented in this chapter where amino acids are prepared via an Aldol condensation, "Aldol-like" reactions have been used. The Mukaiyama Aldol reaction (or just the Mukaiyama reaction) involves the condensation of a silyl enol ether with an aldehyde, catalyzed by metal salts such as TiCLt. This approach has been reported several times for the synthesis of amino acids. This section will show the basic approach, along with some variations that have proved to be useful. 

The aldol or aldol-type reaction is well recognized as one of the most important carbon-carbon bond forming reactions in organic synthesis. As shown in Scheme 8.1, two stereogenic centers could be generated in this aldol reaction. The classical aldol condensation between an aldehyde and a ketone is often catalyzed by a base or an acid. Another approach is the acid-catalyzed cross-aldol reaction of silyl enol ethers with carbonyl compounds, the so-called Mukaiyama reaction. 

Madelung synthesis (indole) 137 Marckwald cleavage, of furans 79 Marckwald synthesis (imidazole) 224 Meth-Cohn synthesis (quinoline) 402 Meyer s oxazoline method 183 Morin reaction 456 Mukaiyama reaction 380 Mukaiyama reagents 53, 380... 

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