Carbonyl compounds natural products synthesis

Chemoselective reduction of a,(3-epoxy carbonyl compounds to aldols and their analogs by organoseleniums and its application to natural product synthesis 98YGK736. 

Officially, the history of MCRs dates back to the year 1850, with the introduction of the Strecker reaction (S-3CR) describing the formation of a-aminocyanides from ammonia, carbonyl compounds, and hydrogen cyanide [4]. In 1882, the reaction progressed to the Hantzsch synthesis (H-4CR) of 1,4-dihydropyridines by the reaction of amines, aldehydes, and 1,3-dicarbonyl compounds [5], Some 25 years later, in 1917, Robinson achieved the total synthesis of the alkaloid tropinone by using a three-component strategy based on Mannich-type reactions (M-3CR) [6]. In fact, this was the earliest application of MCRs in natural product synthesis [7]. 

The [2+2]-photocycloaddition of carbonyl groups with olefins (Paterno-Buchi reaction) is one of the oldest known photochemical reactions and has become increasingly important for the synthesis of complex molecules. Existing reviews have summarized the mechanistic considerations and defined the scope and limitations of this photocycloaddition73. Although this reaction likely proceeds via initial excitation of the carbonyl compound and not the excited state of the diene, the many examples of this reaction in natural product synthesis justify inclusion in this chapter. 

The asymmetric arylation of ketone enolates represents an attractive method for the preparation of optically active carbonyl compounds with a stereogenic quaternary center at the a-position to the carbonyl group. Such types of compounds are important intermediates for natural product synthesis. Replacement of BINAP by 109 provides... 

The facile conversion of carbonyl groups into lactones via cyclobutanones offers many opportunities for synthetic applications considering the importance of butanol-ides in natural products synthesis. The iridoids vividly illustrate this potential. Allamandin (163) 135 c) and its dehydrated relative plumericin (164) 135 d), compounds possessing antifungal, antibacterial, and antitumor activity, pack a great deal of... 

Since the pioneering work by Sarel and co-workers on the iron carbonyl promoted transformation of vinylcyclopropanes and related compounds [1], a variety of transition metal complexes have been examined to achieve effective activation of the vinylcyclopropane-cyclopentene rearrangement which usually requires pyrolytic conditions. These reactions have been applied to natural product synthesis in some cases and have already been reviewed in several excellent articles [2-4]. 

Ruthenium is not an effective catalyst in many catalytic reactions however, it is becoming one of the most novel and promising metals with respect to organic synthesis. The recent discovery of C-H bond activation reactions [38] and alkene metathesis reactions [54] catalyzed by ruthenium complexes has had a significant impact on organic chemistry as well as other chemically related fields, such as natural product synthesis, polymer science, and material sciences. Similarly, carbonylation reactions catalyzed by ruthenium complexes have also been extensively developed. Compared with other transition-metal-catalyzed carbonylation reactions, ruthenium complexes are known to catalyze a few carbonylation reactions, such as hydroformylation or the reductive carbonylation of nitro compounds. In the last 10 years, a number of new carbonylation reactions have been discovered, as described in this chapter. We ex-... 

The formation of /3-hydroxyselenides through the reaction of a selenium-stabilized carbanion with carbonyl compounds has been extensively used also in the context of natural product synthesis. The phenylselenoalkyllithium compound 115 was reacted with aldehyde 116 to afford /3-hydroxyselenide 117. In a radical cyclization cascade the tricyclic molecule 118 was generated in good yields and subsequent transformations led to the synthesis of pentalenene 119 (Scheme 28).1 9 Also other natural products like zizaene and khusimone have been synthesized via a similar route.200... 

Treatment of a, -unsaturated carbonyl compounds 18 with nucleophilic selenium species affords -seleno carbonyl compounds 19 in good yields via Michael addition (Scheme 27) [46]. This reaction has been applied to protect a, -unsa-turated lactones [47], in natural product synthesis [48], and in asymmetric Michael additions in the presence of an alkaloid [49]. Michael addition also proceeds with selenolates that are prepared from diphenyl diselenide by cathodic reduction [22], reduction with the Sm-Me3SiCl-H20 system [19], and reduction with tributyl phosphine [25]. 

In a second part, the reactivity of a-phenylselanyl enolates, derived from ketones, esters, lactones and a,/i-unsatm ated carbonyl compounds, is discussed. Alkylation, aldolisation and Michael reactions are considered as the use of selenium-stabilized carbanions in the natural product synthesis. Others a-fimctionalyzed species are also presented. 

Alkoxycyclopropanes are commonly prepared from alkyl enol ethers by one of the Simmons-Smith modifications (see Chapter 7). According to Wenkert and coworkers they are cleaved by strong acids to the a-methylated carbonyl compound, thus establishing an overall a-methylation of a ketone or an aldehyde (equation 64). This method has often been used for natural product synthesis (e.g. valerane " ). 

The reagents 128—130 are stable crystalline compounds which form anions easily with BuLi. Addition to aldehydes or ketones give protected (3,7-unsaturated carbonyl compounds, e. g. 131, after completion of the Homer-Wittig reaction, and hence the ketones 132 themselves. These methods have not yet been used in natural product synthesis. 

The application of Lewis acids, such as the europium salt Eu(fod)3, in [4+2] cycloadditions of carbonyl compounds (e.g. glyoxylates and aldehydes) with 1-methoxy-3-trimethylsilyloxy-l,3-butadiene (Danishefsky s diene) has been intensively examined by Danishefsky et al. and employed in natural product synthesis. ... 

Intermolecular " or intramolecular [2+2+2]-cycloadditions " of 1,6-enynes and carbonyl compounds take place in the presence of cationic gold catalysts. The latter have been used successfully in natural products synthesis. A skeletal rearrangement of a gold carbene intermediate is the key step in these transformations. 

This review is devoted to an overview of phenol dearomatization and its application in natural product synthesis through the use of a special class of phenolophile reagents that has attracted much attention in recent years, the hypervalent iodine reagents. These polyvalent iodine compounds, also called iodanes, are oxidizing electrophiles that can mediate a wide number of diverse chemical transformations not only of (hetero)aromatic compounds, but also of inter alia alkenes, alkynes, alcohols, sulfides, amines and amides, (enolizable) carbonyl... 

A (trimethylsilyl)cyclopentene annulation method has been developed that leads to a regiocontrolled approach to the synthesis of five-membered rings/ Thus, it was shown that (trimethylsilyl)allenes could be persuaded to react at -78 C with unsaturated carbonyl compounds in the presence of titanium tetrachloride (Scheme 16). The methodology is presently being applied to polyquin-ane natural product synthesis. 

When ketoaldehydes, compounds that are unsymmetrical per se, are submitted to intramolecular aldol condensation the ketone usually acts as the CH-acidic component whereas the aldehyde plays the role of the carbonyl active counterpart. This regiochemical outcome is also favored when the conditions of a thermodynamic control are used. Again, this type of aldol condensation has been used in a variety of natural products synthesis. A steroid synthesis, the aldolization step of which is given in Eq. (10), is an illustrative example [26]. 

Yus, M. Najera, C. Foubelo, F. The Role of 1,3-Dithianes in Natural Product Synthesis Tetrahedron 2003, 59, 6147-6212. Groebel, B. T. Seebach, D. Umpolung of the Reactivity of Carbonyl Compounds Through Sulfur-Containing Reagents Synthesis 1977, 357-402. Seebach, D. Corey, E. J. Generation and Synthetic Applications of 2-Lithio-l,3-dithianes /. Or f. Chem. 1975, 40, 231-237. 

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