Nozaki reaction

Nozaki reaction (12, 137 14, 96 15, 95). An intramolecular version of this reaction can effect cyclization even to a strained nine-membered ring. Thus 1 on treatment with CrCl2 at a low temperature cyclizes mainly to 2, a mixture of epimers in which a cyclononadiyne ring is fused to a cyclopentene ring. After acetylation of the secondary hydroxyl group, the mixture is dehydrated to 3, with a nine-membered enediyne ring. 

Intramolecular Nozaki reaction. The addition of a vinyl-chromium compound to an aldehyde (12, 137 14, 96) is useful for macrocyclization, particularly if the CrCl2 reagent is activated by a catalytic amount of Ni(acac)2. Under these conditions, the vinyl iodide with a w-formyl group (1) cyclizes to (+ )-brefeldin C 12) and the 4-epimer as a 1 4 mixture in 60% yield.1... 

What relative stereochemistry is to be expected from the Nozaki reaction of step 1 ... 

In this case, the silylation of the metal alkoxide initially formed represents the key step of the overall process which releases the chromium salt from the organic product. The other crucial parameter is the use of the stoichiometric reducing agent for the regeneration of the active Cr" species. Commercial Mn turned out to be particularly well suited, as it is very cheap, its salts are essentially non-toxic and rather weak Lewis acids, and the electrochemical data suggest that it will form an efficient redox couple with Cr . Moreover, the very low propensity of commercial Mn to insert on its own into organic halides guarantees that the system does not deviate from the desired chemo- and diastereoselective chromium path. Thus, a mixture of CrX ( = 2, 3) cat., TMSCl and Mn accounts for the first Nozaki reactions catalytic in chromium [13]. 

This method applies to aryl, alkenyl, allyl and alkynyl halides as well as to alkenyl Inflates and exhibits the same selectivity profile as its stoichiometric precedent (Scheme 4). Moreover, it does not matter if the catalytic cycle is started at the Cr or Cr " stage as implied by Scheme 3. Therefore it is possible to substitute cheap and stable CrClj for the expensive and air-sensitive CrCf previously used for Nozaki reactions. In some cases other chromium templates such as [Cp2Cr or [CpCrCl2] can be employed, improving the total turnover number of this transformation even further [13, 14]. 

Scheme 4. The scope of Nozaki reactions catalyzed by chromium resembles that of tbe stoichiometric version.

Although chlorosilanes are an obvious choice as mediators for catalysis on account of their high affinity for oxygen, low price and lack of toxicity, several other additives can also be envisaged. The recent publication on the electrochemical version of the Nozaki reaction mentioned above simply employs the Li cations of the supporting electrolyte for this very purpose [15], whereas another titanium-catalyzed pinacol... 

Lewis acid breaks up the closed transition state normally found in thermal reactions. Contrary to the Hiyama-Nozaki reaction the induced stereoselections for allylstannanes-i-Lewis acids are extremely high, due to chelate-Cram controlled mechanisms [reaction (91), Scheme 30] [76]. Reagent controlled diastereoselec-tivity may be exerted in terms of 1,3- [reaction (92)] [77] and 1,5-inductions [reaction (93)] [78]. 

The Kishi-Nozaki reaction [71] is the key step in the preparation of methyl C-isomaltoside (Scheme 40) [72]. Coupling of vinyl iodide 150 with the xylose derivative 151, readily available in six steps from L-xylose, afforded the corresponding allylic alcohol with a diastereomeric ratio of 15 1 in favor of 152. Finally, selective hydrogenation of the double bond and oxidation of the primary alcohol led to the C-disaccharide 153, which could be converted to its methyl glycoside 21. A useful dideuterated derivative of C-isomaltoside 154 for solution conformation studies was also accessible from this synthetic approach via the m-deuteration of the alkene intermediate 152 with Pt on AI2O3 and D2. 

From a historical perspective it is interesting to note that the Nozaki experiment was, in fact, a mechanistic probe to establish the intermediacy of a copper carbe-noid complex rather than an attempt to make enantiopure compounds for synthetic purposes. To achieve synthetically useful selectivities would require an extensive exploration of metals, ligands and reaction conditions along with a deeper understanding of the reaction mechanism. Modern methods for asymmetric cyclopropanation now encompass the use of countless metal complexes [2], but for the most part, the importance of diazoacetates as the carbenoid precursors still dominates the design of new catalytic systems. Highly effective catalysts developed in... 

The catalytic asymmetric cyclopropanation of an alkene, a reaction which was studied as early as 1966 by Nozaki and Noyori,63 is used in a commercial synthesis of ethyl (+)-(lS)-2,2-dimethylcyclo-propanecarboxylate (18) by the Sumitomo Chemical Company (see Scheme 5).64 In Aratani s Sumitomo Process, ethyl diazoacetate is decomposed in the presence of isobutene (16) and a catalytic amount of the dimeric chiral copper complex 17. Compound 18, produced in 92 % ee, is a key intermediate in Merck s commercial synthesis of cilastatin (19). The latter compound is a reversible... 

For examples of this coupling reaction involving enol triflates derived from ketones, see Takai, K. Taga-shira, M. Kuroda, T. Oshima, K. Utimoto, K. Nozaki, H. J. Am. Chem. Soc. 1986, 108, 6048. 

In a recent synthesis of (-i-)-discodermolide, Nozaki-Hiyama reaction of the aldehyde 1617 with the unsaturated Peterson reagent 1618 then treatment with KH in THE gave the diene 1619 in 74% yield [19] (Scheme 10.8). 

Catalytic turn-over [59,60] in McMurry couplings [61], Nozaki-Hiyama reactions [62,63], and pinacol couplings [64,65] has been reported by Fiirst-ner and by Hirao by in situ silylation of titanium, chromium and vanadium oxo species with McaSiCl. In the epoxide-opening reactions, protonation can be employed for mediating catalytic turn-over instead of silylation because the intermediate radicals are stable toward protic conditions. The amount of Cp2TiCl needed for achieving isolated yields similar to the stoichiometric process can be reduced to 1-10 mol% by using 2,4,6-collidine hydrochloride or 2,6-lutidine hydrochloride as the acid and Zn or Mn dust as the reduc-tant (Scheme 9) [66,67]. 

The multi-component procedure is also effective for the chromium-catalyzed addition of organic halides to aldehydes (the Nozaki-Hiyama-Kishi reaction) [73]. The active Cr(II) species is recycled by redox interaction with Mn powder as the stoichiometric co-reductant in the presence of MesSiCl (Scheme 34), which mainly liberates the chromium catalyst from the alkoxide adduct. The chemo- and diastereo-selective addition reaction is performed with a variety of organic halides and alkenyl triflates. In the case of crotyl bromide, the addition is highly stereoconvergent, i.e., the respective anti-... 

Many chiral diphosphine ligands have been evaluated with regard to inducing enantioselectivity in the course of the hydroformylation reaction [25,26]. However, a real breakthrough occurred in 1993 with the discovery of the BI-NAPHOS ligand by Takaya and Nozaki [65]. This was the first efficient and rather general catalyst for the enantioselective hydroformylation of several classes of alkenes, such as aryl alkenes, 1-heteroatom-functionalized alkenes, and substituted 1,3-dienes, and is still a benchmark in this area [66,67]. But still a major problem in this field is the simultaneous control of enantio-... 

Grigg and coworkers developed bimetallic domino reactions such as the electro-chemically driven Pd/Cr Nozaki-Hiyama-Kishi reaction [69], the Pd/In Barbier-type allylation [70], Heck/Tsuji-Trost reaction/1,3 dipolar cycloaddition [71], the Heck reaction/metathesis [72], and several other processes [73-75]. A first example for an anion capture approach, which was performed on solid phase, is the reaction of 6/1-134 and 6/1-135 in the presence of CO and piperidine to give 6/1-136. Liberation from solid phase was achieved with HF, leading to 6/1-137 (Scheme 6/1.30) [76]. 

In 1966, Nozaki et al. reported that the decomposition of o-diazo-esters by a copper chiral Schiff base complex in the presence of olefins gave optically active cyclopropanes (Scheme 58).220 221 Following this seminal discovery, Aratani et al. commenced an extensive study of the chiral salicylaldimine ligand and developed highly enantioselective and industrially useful cyclopropanation.222-224 Since then, various complexes have been prepared and applied to asymmetric cyclo-propanation. In this section, however, only selected examples of cyclopropanations using diazo compounds are discussed. For a more detailed discussion of asymmetric cyclopropanation and related reactions, see reviews and books.17-21,225... 

These substitution reactions were discovered by Nozaki and Bartlett [57,58] in their study of benzoyl peroxide decomposition in different solvents. When benzoyl peroxide is decomposed, the formed benzoyloxyl radical attacks the solvent (RH), and the formed alkyl radical (R ) induces the chain decomposition of the peroxide (see Chapter 3). 

Bartlett and Nozaki [65] discovered the chain reaction of benzoyl peroxide decomposition in the presence of alcohols where the chain propagating step is the reaction of the ketyl radical with peroxide. 

For a review encompassing the Nozaki-Hiyama-Kishi reaction, see Marshall, J. A. McNulty, L. M. Chemtracts 1997, 10, 50-52. 

Certain transition metal complexes catalyze the decomposition of diazo compounds. The metal-bonded carbene intermediates behave differently from the free species generated via photolysis or thermolysis of the corresponding carbene precursor. The first catalytic asymmetric cyclopropanation reaction was reported in 1966 when Nozaki et al.93 showed that the cyclopropane compound trans- 182 was obtained as the major product from the cyclopropanation of styrene with diazoacetate with an ee value of 6% (Scheme 5-56). This reaction was effected by a copper(II) complex 181 that bears a salicyladimine ligand. 

Solutions to similar problems of achieving catalytic turnover [22] in McMurry couplings [23], Nozaki—Hiyama reactions [24], and pinacol couplings [25] have been reported by Fiirstner and by Hirao. The key step in these reactions is the in situ silylation of titanium and vanadium oxo species with Me3SiCl and reduction of the metal halides by suitable metal powders, e. g. zinc and manganese dust, as shown in Scheme 12.13. 

Scheme 12.14. Cozzi s catalytic enantio-selective Nozaki—Hiyama reaction.

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