Diastereoselective Simmons-Smith

As (—)-pulegone is not readily available, subsequent work addressed the natural enantiomer by different methods [12], but all completed their synthesis via Snider s enone (17). Asaoka utilised a TMS group as temporary directing volume (Scheme 5) [12a]. Cossy applied a photore-ductive cyclopropane ring opening, which was obtained by a diastereoselective Simmons-Smith reaction [12b]. Schmalz finally used a planar-chiral arene complex to synthesise enone 17 with interesting CrfCO), chemistry [12c]. 

Recently reported uses of optically pure stilbene diol in asymmetric synthesis include. (1) the dimethyl ether as a ligand for effecting enantioselective conjugate addition (2) the preparation of a,p-unsaturated ketals for achieving diastereoselective Simmons-Smith cyclopropanation <3 (3) the preparation of enantlomercially pure p-halohydrins i and (4) the preparation of chirai crown... 

Besides transition metal-catalyzed methylenations with diazomethane, diastereoselective Simmons-Smith cyclopropanations have been extensively studied. ... 

Example 3, Diastereoselective Simmons-Smith cyclopropanations of allylic amines and carbamates ... 

A number of chiral acetal derivatives have also proved effective in asymmetric cyclopropanation reactions, with auxiliaries based on tartaric acid proving to be partieularly usefiil. In the case of cyclic a,P unsaturated compounds, di-O-benylthreitol derivatives (see 51) imdergo efficient and diastereoselective Simmons-Smith reactions to give the cyclopropanated products SS. ... 

Marsh has showcased the use of chiral acetals as auxiliaries in diastereoselective Simmons-Smith cyclopropanation reactions [41]. When acetal 66 was allowed to react with CH2I2 in the presence of Zn/Cu couple, cyclopropane 67 was formed in excellent yield and 20 1 dr (Equation 5). 

The reaction was first carried out with the substrate bearing the chiral auxiliary. Scheme 5-64 shows the asymmetric cyclopropanation reaction using 2,4-pentandiol as a chiral auxiliary.115 Scheme 5-65 illustrates the use of optically pure 1,2-frafts-cyclohexanediol as a chiral auxiliary in asymmetric Simmons-Smith cyclopropanation.116 Excellent yield and diastereoselectivity are obtained in most cases. 

Homochiral molecules readily available from inexpensive sources are useful synthetic building blocks and chiral auxiliaries. 1,4-01-0-benzyl-L-threitol has been used in construction of homochiral crown ethers that are useful as enzyme model systems. Topologically controlled diastereoselective delivery of the Simmons-Smith reagent for 2-cycloalken-l-one 1,4-d1-0-benzyl-L-threitol ketals was recently reported. ... 

In the case of the seven-membered ring, the diastereoselection dropped to 9 1 using the Simmons-Smith reagent. A reversal of relative stereocontrol was observed with eight-and nine-membered cychc aUylic alcohol derivatives. This reversal was explained using a simple conformational analysis of the ground state in which attack from the hydroxy side of the most stable conformation led to the anti isomer (Figure 4). 

Diastereoselective cyclopropanation of enones.1 The homochiral ketals of cyclic a,p-enones obtained by reaction with 1,4-di-O-benzyl-L- or D-threitol2 undergo diastereoselective cyclopropanation on reaction with the Simmons-Smith reagent (8-20 1). The diastereoselectivity is less in the case of ketals of cyclic p, 7-enones (2 1). 

Resolved P-hydroxy sulfoximines derived from cyclic enones undergo dias-tereoselective Simmons-Smith cyclopropanation reactions to give, after thermolysis, cyclopropylketones in high enantiomeric purity (94-98%). Cyclopropanation occurs syn to the hydroxyl group of the P-hydroxy sulfoximine. This method is less diastereoselective for acyclic enones.73... 

The examples mentioned above illustrate the progress in the field of stereocontrolled cyclopropanation. Nowadays, the asymmetric Simmons Smith cyclopropanation may well be mentioned in the line with other asymmetric reactions like epoxidation or dihydroxylation. Fligh enan-tioselectivity and diastereoselectivity can be... 

An auxiliary-directed asymmetric Simmons-Smith reaction was used by a Hoff-mann-La Roche group88 for the synthesis of an ethynyl cyclopropane that served as the A-ring precursor to Vitamin D derivatives [Scheme 2.41]. High diastereoselectivity was achieved with the aid of the dioxolane ring prepared from (/ft/f)-(-)-butane-2,3-diol. The acid conditions for hydrolysis of the dioxolane ring were mild enough to leave the cyclopropane ring unperturbed. Dia-stereoselective cyclopropanation of acetals derived from 1,2-di-O-benzyl-L-threi-tol have also been reported 90... 

An early stage in the synthesis of the antifungal metabolite FR-900848 exploited a double Simmons-Smith cyclopropanation directed by two di-isopropyl tartrate acetals [Scheme 2.42] 9192 The diastereoselectivity of the reaction can be attributed to intramolecular delivery of a zinc carbenoid co-ordinated to one of the ester carbonyls and an oxygen of the dioxolane ring.93 Note the use of the Noyori protocol (see above) for the bis-dioxolanation of the highly reactive mu-conaldehyde ... 

Tertiary amines form complexes with Simmons-Smith reagents. These complexes are activated by -BuLi to undergo [2,3]-rearrangements. Using oxazolidine 222 this process afforded compound 223 as the main product with very high diastereoselectivity <03OL1757>. 

The diastereoselective and enantioselective preparation of cyclopropanes has attracted attention since chiral cyclopropanes were found to occur in many natural products [11]. Moreover, cyclopropanes are useful intermediates in organic synthesis. There are many methods of cyclopropane ring opening that transfer stereochemical information from the substrate to acyclic products in a stereocontrolled manner [12]. Among the methods used for the preparation of cyclopropanes from olehns, the Simmons-Smith and related reactions as well as reactions of diazoalkanes catalyzed by rhodium, copper and cobalt salts have frequently been applied [13]. The preparatively simple Makosza reaction [14] has scarcely been used. 

This method was utilized for the synthesis of the four stereoisomers of coronamic acid [17]. The ( )-allylic (3-D-glucopyranoside 3 was cyclopropanated under Simmons-Smith conditions at — 30°C with high diastereoselectivity (>100 1). The reaction of the corresponding (Z)-allylic... 

The chiral version of the Simmons-Smith reaction requires the presence of proper ligands for the organozinc reagent. Representatives are 99, 100, 101 " for cyclopropanation of allylic alcohols. Enals undergo diastereoselective cyclopropanation (de >99%) via acetals with (+)-phenyl exo,ex o-2,3-dihydroxybomane-10-sulfonate. ... 

The formation of nonseparable mixtures of diastereomers in the asymmetric cyclopropanation of homochiral cycloalk-2-enone 1,4-0-benzyl-L-threitol acetals with the Simmons-Smith re-agent has been circumvented by acetalizing with ( —)-(5, S)-hydrobenzoin. Treatment of (5,5)-hydrobenzoin acetals with Simmons-Smith reagent in refluxing diethyl ether provided good yields of cyclopropane acetals with a diastereoselectivity of > 13 1 (Table 2). The products were recrystallized from anhydrous diethyl ether to give diastereochemically pure products. Hydrolysis of the acetals afforded enantiomerically pure cyclopropyl ketones. Since hydrobenzoin is available in both enantiomeric forms, either enantiomer of a particular cyclopropyl ketone can be prepared via this methodology. ... 

As in the case of the / -series, the a-anomer with a free hydroxy group at C2 also showed good diastereoselectivity (13 1) in the Simmons-Smith cyclopropanation with diethylzinc/ diiodomethane in fert-butyl methyl ether at 0 C. Several substituted allylic ethers, e g. 70, were subjected to this reaction with success. While the auxiliary can be easily removed by a ring-contraction method to give cyclopropylmethanol derivatives, this methodology provides an efficient method to prepare both enantiomers. 

The Simmons-Smith cyclopropanation of the same 3-(2-phenylcydopropyl)prop-2-enol (110) in its racemic form afforded an inseparable mixture of and a t/-bicyclopropanes 111 in a 1.3 1 ratio. Therefore, the Charette protocol (p 286) was used first to prepare the required allylic alcohol in its optically pure form and the cyclopropanation was carried out in the presence of the tartrate derived dioxaborolane 93. By using (+)- and (— )-tartrate derived dioxaborolane 93, both the syn- and antf-bicyclopropyls 111 were obtained. The diastereoselectivities observed in their formation were consistently greater than 12 1. ... 

The zinc metal in the Simmons-Smith reaction was replaced by samarium for the cyclopropanation of allylic alcohols with chloroiodomethane. High yields of cyclopropanes, often with high diastereoselectivities, were obtained using samarium amalgam/diiodomethane. Cyclo-hex-2-enol (115a) gave exclusively s y -bicyclo[4.1.0]heptan-2-ol (116a), no traces of the anti-... 

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