Cyclopropanone preparation

In general, the cyclopropanones which have been prepared by the above routes are too unstable to be isolated, and are therefore usually trapped by alcohols, amines or as other carbonyl addition products. One particularly useful, stable cyclopropanone source is the acetic acid addition product reported by van Tilborg . This material can easily be purified, and readily yields the parent ketone in situ on reaction with nucleophiles. A summary of cyclopropanones prepared by this route has been reported. ... 

In contrast, 2,2-dimethylcyclopropanone yielded the ring-opened products, i.e. a-chloro ketones, when treated with hydrogen chloride, or acetic acid, rather than the cyclopropane derivatives. Upon the addition of glacial acetic acid to an ethereal solution of cyclopropanone, prepared in situ from diazomethane and an excess of ketene, 1,1-diacetoxycyclo-propane (5) could be isolated in 30% yield. ... 

The transition metal-catalyzed cyclopropanation of alkenes is one of the most efficient methods for the preparation of cyclopropanes. In 1959 Dull and Abend reported [617] their finding that treatment of ketene diethylacetal with diazomethane in the presence of catalytic amounts of copper(I) bromide leads to the formation of cyclopropanone diethylacetal. The same year Wittig described the cyclopropanation of cyclohexene with diazomethane and zinc(II) iodide [494]. Since then many variations and improvements of this reaction have been reported. Today a large number of transition metal complexes are known which react with diazoalkanes or other carbene precursors to yield intermediates capable of cyclopropanating olefins (Figure 3.32). However, from the commonly used catalysts of this type (rhodium(II) or palladium(II) carboxylates, copper salts) no carbene complexes have yet been identified spectroscopically. 

Due to their physiological importance, considerable efforts are currently devoted towards the total synthesis of 2,3-methanoamino acids (ACCs). The parent compound ACC 71 has been readily prepared from acrolein, through the base-induced (K2CO3) cyclization of 2-amino-4-chlorobutyronitrile [96] or from one-pot Strecker reaction of cyclopropanone hemiacetal [97]. 

Schemes. Preparation of alkyl 2-bromo-2-cyclopropylideneacetates 11 a-c by olefination of the cyclopropanone hemiacetal 9 [18 c, 19]...

While these rearrangements are used most often to prepare large rings, the expansion of cyclopropanone to azetidinones is also practical (Scheme 24 CHEC 5.09.3.3.3). 

To avoid destructive side reactions, cyclopropanones have to be prepared at low temperatures in the absence of nucleophiles. A good example is the synthesis of cyclopropanone itself from ketene and diazomethane (see Section 16-4 A) ... 

Sustituted l-azolin-5-ones have been described thus, 2-ethoxy-1-azolin-5-one (24) is a stable compound that has been prepared from succinimide [80OS(59) 132]. 2-Ethoxy-l-azolin-5-one undergoes a photochemical ring contraction giving cyclopropanone derivatives. The photochemical reaction of (24) in /< r/-butylalcohol as solvent yield tert-butyl A-(l-ethoxy-cyclopropyl)cabamate (25). 

Until quite recently, cyclopropanones were known only as transient intermediates, or in the form of derivatives such as the hydrate or hemi-acetal. x> During the past decade, however, through the work of the groups at Columbia 2> and Amsterdam 3> among others, methods have been developed for preparing a number of representatives of this class. Table 1 lists various cyclopropanones which have been isolated as well as several, more elusive examples which have been characterized in solution. 

In reviewing the methods available for preparing cyclopropanones (Section 2), it becomes clear that a reliable, general method for the preparation of three-membered ketones has still to be devised. For example, the key combination of X and Y substituents and conditions needed to effect a conversion such as shown in Scheme 1 has not yet been discovered. 

A versatile synthesis of cyclopropanones and closely related derivatives is provided by the diazoalkane-ketene reaction as shown in Scheme 2. Using this method, the parent ketone 2>3> and alkyl-substituted cyclopropanones 1()) have been prepared in yields of 60—90% based upon the concentration of diazoalkaneb) (Table 2). The reaction is rapid at Dry Ice-acetone temperatures and is accompanied by evolution of nitrogen. Although most cyclopropanones are not isolable, dilute solutions of 3 (0.5—0.8 M) may be stored at — 78 °C for several days or at room temperature in the presence of suitable stabilizing agents.15) The hydrate and hemiketal derivatives are readily prepared by the addition of water or alcohols to the solutions of. .2>8>5)... 

Similarly, cyclopropanones have not been found among the products from the reaction of ethyl diazoacetate with dimethylketene or diphenylketene although cyclopropanone intermediates may be involved (see Section 4.1.5).20) Attempts to prepare the cyclic thioketal 5C) by the addition of diazomethane to the trithiane 6 were also unsuccessful.21)... 

The reaction of carbenes with appropriately substituted olefins provides a useful method for the preparation of many cyclopropanone derivatives. The Simmons-Smith procedure 22> and reactions involving base-generated carbenes, e.g. CHC13/KO-7-Bu, are particularly useful. 

Cyclopropanone acetals may also be prepared by the addition of other one-carbon species to ketene acetals as shown in Table 3. Thus, McElvain and Weyna have synthesized several cyclopropanone deriv-... 

Schollkopf and co-workers have synthesized a number of cyclopropanone acetals by the addition of various sulfur- and oxygen-containing carbenes to ketene diethylacetals (Table 3).26>27> Similarly, cyclopropanone dithioacetals may be prepared by the addition of the Ws-thiomethyl and Ws-thiobenzylcarbenes 12a, b to olefins.29) However, cyclopropanone acetal formation by this method requires double bonds with considerable electron enrichment and the yields are generally low. With unsubstituted olefins such as cyclohexene, the carbenes 12 a, b tend to form dimeric and trimeric products such as 13 and 14, instead of the double bond addition products. 

The preparation of cyclopropanones by photochemical decarbonylation 8-i°) js illustrated by the formation of 1-ethoxycyclopropanol from the photolysis of tetramethylcyclobutane-l,3-dione (17) in ethanol.9 a> As shown in Scheme 4, the desired hemiacetal is accompanied by a number of side products including ethyl isobutyrate which results from the... 

In other special cases, cyclopropanones have been prepared by photochemical rearrangements. For example, 9,9 -dianthracyl ketone (27) 32> and carbinol (28) 33> undergo ring closure to their respective... 

A variety of cyclopropanone dithioketals have been prepared by the dehydrohalogenation of 3-halo dithioketals. 21,40,41) This method was... 

The classic labeling studies of Loftfield 49a> have demonstrated that cyclopropanones are intermediates in the Favorskii reaction 49b) — the base-induced rearrangement of a-haloketones (Scheme 8). The related reaction of a,a -dibromoketones has, in fact, become a convenient preparative route for cyclopropenones, e.g., 48 ->- 49 via 50.50>... 

The first cyclopropanone to be isolated under Favorskii conditions was obtained from the reaction of the sterically hindered a-bromodineo-pentyl ketone (57) with potassium >-chlorophenyl-dimethylcarbinolate.13> The product, 7f MS-2,3-di-f-butylcyclopropanone (52) (20—40%) was later prepared independently by the valence isomerism of l,3-di-7-butyl-allene oxide 51> (see Section 2.6). 

Another possible route to cyclopropanones is via the isomerism of allene oxides, i.e., 60 61. While valence isomerism has been established in related systems such as 62 63 54>, only two cyclopropanones have as yet been prepared by this method and its usefulness appears limited. 

Recently, the bicyclic cyclopropanones 78 and 79 were prepared in high yield by the Diels-Alder addition of cyclopropenone to the diphenyl-isobenzofuran 80 and the dimethylanthracene 57.62>... 

Optically active fr ws-2,3-di-/-butylcyclopropanone has been prepared by asymmetric destruction of the racemic compound with d-amphetamine.64> The (+)-cyclopropanone, [a]ls6+76° (c 0.5, CCI4) exhibits a positive Cotton effect with a peak at 370 nm. Racemization occurs upon heating. 

Other hemiacetals which have been prepared include the methyl 8<9a>, ethyl 9b), and isopropyl hemiacetals 81) of tetramethylcyclopropanone, the phenyl, a- and (3-naphthyl hemiacetals of cyclopropanone 82>, and the benzyl hemiacetal of 2,3-di-f-butylcyclopropanone. 13> In the last case, the benzylic methylene protons display an AB pattern in the PMR spectrum indicating that the two Ybutyl groups are trans to one another. Although derivatization of this di-f-butyl ketone was possible, carbonyl addition may be hindered by steric factors as suggested by the lack of reaction of 2,2-diY-butylcyclopropanone with methanol. 55a>... 

Presumably, 1-acetoxycyclopropanol (88) is the intermediate in this reaction as well as that between the hydrate and ketene. 80> Although 88 has not been isolated in the above cases, it may be prepared from acetic acid and cyclopropanone and reacts with ketene to give 87. 5>15>... 

Cyclopropanones react with ammonia and aliphatic amines to form carbinol amines which usually undergo further amine substitution. For example, attempts to prepare the carbinol amines f> from dimethylamine and cyclopropanone resulted only in the isolation of the 1,1-diamino derivative 94. 86> When methyl amine is added to cyclopropanone, the... 

Cyclobutanones may be prepared in a one-step procedure, i.e., without isolating the intermediate cyclopropanone, simply by adding the ketene to excess diazoalkane. 97>98) That cyclopropanones are intermediates has been established by carbon-14 labeling studies "> and... 

An extension of this reaction leading to a general synthesis of N-substituted (3-lactams involves the addition of a primary amine to a freshly prepared solution of cyclopropanone, conversion of the resulting carbinol amine to the N-chloro derivative, and then decomposition of this intermediate with silver ion in acetonitrile. 87a> The method permits one to prepare N-substituted (3-lactams of great variety (Table 14), including those constructed from amino acid esters. 87b The use of valine ethyl ester (123) as a nitrogen source leading to 124 is illustrated. 

Cyclopropanone diselenoacetals 122 prepared by lithium diisopropylamide induced ring closure of 3-chloro l,l-di(methylseleno)- or 3-chloro-l,l-di(phenylseleno)-propane, have been transformed into the corresponding 1-selenocyclopropyllithium derivatives 123 upon treatment with n-butyllithium in THF at —78 °C. These intermediates have been trapped at —78 °C with aldehydes and ketones to produce the corresponding P-hydroxyselenides 124 in good yields, Eq. (37)66). 

In analogy to the preparation of the cyclopropanone hemiacetal 3 (vide supra, Eq. (1)7), reductive cyclization of the piperidide of 3-chloropropionic acid 193 with sodium in ether in the presence of ClSiMe3, gave the 1-piperidino-l-trimethylsilyloxy-cyclopropane 194 a which was converted to the cyclopropanol 194 b upon treatment with methanolic tetrabutylammonium fluoride. Both 194 a and 194 b can be used for the ready generation of cyclopropane derivatives thus the silyl ether 194a could be reacted directly with the vinylic Grignard reagents 195 to provide the vinyl cyclopropane derivative 196, (Eq. (61)128). 

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