Allyl carbamates metallated

The substituted A,A-diisopropyl enol carbamates 563 were prepared by reaction of metallated allylic carbamates with aldehydes839-843. The stereoselective deprotonation of compound 563 can be performed with f-BuLi841 or n-BuLi-TMEDA839 in THF at —70 to —85 °C to give the lithio derivatives 564 (Scheme 153). These intermediates reacted with... 

The addition of heteroatom-substituted allylic anions to aldehydes has found particular interest as it represents a homoaldoi reaction. Metalated allyl carbamates seem to be the most valuable reagents developed for this purpose as they are prepared easily and exhibit high y-selectivity and dia-stereoselectivity, at best in their titanated form (Scheme 79). ... 

Heteroatom-assisted metallation reactions are very common and especially useful for the selective o-functionalisation of aromatic compounds. More recently, activation of non-aromatic substrates has attracted attention but only a few examples pertinent to protecting groups will be cited here. Kerrick and Beak [Scheme 1.53] showed that pyrrolidine protected with a /err-butoxycarbonyl (Boc) group 53.1 is enantioselectively deprotonated by 5cc-BuLi activated by the alkaloid (-)-Sparteine (533). Enantioselective deprotonations mediated by (-)-Sparteine were first exploited by Hoppe and co-workers for the metallation of saturated and allylic - carbamates. 

According to Eq. (99), stereochemically homogeneous 3-carbonyl-substituted tetrahydrofurans are constructed in a brick-box system by sequential ho-moaldol and aldol reaction. The metallated allyl carbamate serves as an equivalent for the chiral dianion A, which accepts two different aldehydes B and C in a highly controlled manner [226]. 

The anti-Markovnikov addition of carbamates to terminal alkynes was introduced as the first example of catalytically active metal vinylidene in 1986. The development of this concept to other O-nucleophiles followed immediately and carboxylic adds, water and allylic alcohols were used to produce the corresponding addition produds. The... 

Similarly, tetrahydropyrans 189, containing the all-cis substitution pattern could be easily synthesized by using the Z-enol carbamate 188, the geometric isomer of 181. Such a compound was readily prepared by applying the modified allyl-metallation protocol reported by Hoppe to the carbamate derivative 187 (Scheme 13.66) [83-85],... 

The cyclohexene 121, which was readily accessible from the Diels-Alder reaction of methyl hexa-3,5-dienoate and 3,4-methylenedioxy-(3-nitrostyrene (108), served as the starting point for another formal total synthesis of ( )-lycorine (1) (Scheme 11) (113). In the event dissolving metal reduction of 121 with zinc followed by reduction of the intermediate cyclic hydroxamic acid with lithium diethoxyaluminum hydride provided the secondary amine 122. Transformation of 122 to the tetracyclic lactam 123 was achieved by sequential treatment with ethyl chloroformate and Bischler-Napieralski cyclization of the resulting carbamate with phosphorus oxychloride. Since attempts to effect cleanly the direct allylic oxidation of 123 to provide an intermediate suitable for subsequent elaboration to ( )-lycorine (1) were unsuccessful, a stepwise protocol was devised. Namely, addition of phenylselenyl bromide to 123 in acetic acid followed by hydrolysis of the intermediate acetates gave a mixture of two hydroxy se-lenides. Oxidative elimination of phenylselenous acid from the minor product afforded the allylic alcohol 124, whereas the major hydroxy selenide was resistant to oxidation and elimination. When 124 was treated with a small amount of acetic anhydride and sulfuric acid in acetic acid, the main product was the rearranged acetate 67, which had been previously converted to ( )-lycorine (108). 

The alkylation of carbamates and ureas is similarly difficult as the alkylation of amides. Non-deprotonated carbamates or ureas are weak nucleophiles which will react only with carbocations or other, similarly reactive alkylating agents. Metalated carbamates and ureas, on the other hand, are strong bases but poor nucleophiles, and most of the reported examples of their alkylation are limited to methylations, allylations, or benzylations, or to cyclic carbamates and ureas. Two examples of the alkylation of N-aryl carbamates are given in Scheme 6.26. 

The increasing application of direct metallation methods and the importance of primary amines as synthetic intermediates have created a need for new aminating reagents. In particular, reagents that could directly transfer an N-protected group rather than a free amino group. In this context several N.O-diprotected hydroxyl-amines have been recently reported (Scheme 2) terr-butyl and allyl iV-[(arylsul-fonyl)oxy]carbamate 6 [5] and the Af,0-bis(trimethylsilyl)hydroxylamine 7 [6]. 

Allyl acetals,21 and carbamates,17 can be lithiated and quenched with metallic electrophiles at the a-position to provide allylmetals, for example, the allyl boronate 22.21 Allyl and benzyl esters have also been lithiated a to O.22... 

Alkenes with a variety of substituents such as acetal, amine, amide, carbamate, ester, ether, isocyanate, ketone, oxirane, and snlfide can be hydrosilated, usually without affecting the ftinctional group. However, this is not always fine for example, allyl chloride gives a considerable amount of the reduction product (see equation 26). Table 4 lists representative examples of hydrosilation. It is not so remarkable in the case of radical hydrosilation, but reactivity is high for hydrosUane, which has electronegative group in the case of transition metal catalyzed hydrosilation. 

Lewis acids such as silyl triflates7 or boron trifluoride8 initiate the rearrangement of allyl acetates, usually with low stereoselectivity. But soft electrophilic metal ions such as Hg2+ or Pd2 + catalyze the rearrangement of allylic esters and carbamates (Table l)9. 

Z = OAc, heating in THE with an excess of Sml2 followed by treatment with dilute aq. HCl gives an alkene. When Z = I and the other Z is an oxygen of an oxazo-lone (a carbamate unit), heating with indium metal in methanol leads to an allylic... 

Following the pioneering work of Breslow and Gellman, transition metal-catalyzed inter- and intramolecular C-H functionalizations (aminations or amidations) have advanced tremendously in recent decades/ """ Characteristic examples are Rh-catalyzed insertions into allylic or benzylic C-H bonds [Eq. (6.134)] and the transformation of carbamates to oxazolidi-nones [Eq. (6.135)] ... 

Methylations with methyl iodide were observed to proceed with high yields and stereoselectivities. Longer-chain alkyl iodides failed in most attempts. Allyl bromide reacts smoothly - however, products of low enantioenrichment (see 146g) result. We explain the fact by a single electron transfer (SET) during the alkylation. The intermediate formation of a mesomerically stabilized allyl radical supports the SET pathway [89]. A solution to this problem was most recently published by Taylor and Papillon who converted a lithio carbamate into the corresponding zinc cuprate prior to allylation [90]. Studies on the stereochemistry in a few metal-exchange reactions have been published by Nakai et al. [91]. 

The chemoselectivity of the reaction favors insertion in the most electron-rich C—H bond available to produce an oxazolidinone (Eqs. (5.6) and (5.7)) [33, 49, 50). When a bicyclic system is formed, the C—H amination reaction leans toward the formation of the cis-isomer. The scope of the reaction is large and many examples of carbamates derived from primary and tertiary alcohols are known. The use of carbamates derived from secondary alcohols is, however, more limited to substrates having conformational bias and/or very reactive C—H bonds (benzylic and allyl-ic) [51, 52]. Otherwise the formation of the corresponding ketone is observed, probably via a hydride shift process, similar to what is observed in C—H bond insertion with metal carbene [53, 54). 

Amides, carbamates, imides, and their metal salts also serve as reactive nucleophiles (Scheme 3). Sodium p-toluenesulfonamide attacks l-acetoxy -chloro-cyclohex-2-ene to give an allylic amide in a highly chemoselective manner with retention of conflgura-tion.t Sodium salt of methylcarbamate is also alkylated in DMSO or HMPAJ ° (A, 0)-Bis-fer-Boc hydroxylamine reacts with an aUylic carbonate chemo- and regioselectively to provide a protected A-allylhydroxylamine, in which an ethoxy anion, a counterion of Pd in a 7r-allylpalladium complex, serves to generate an anion of (A, 0)-bis-ter-Boc hydroxylamine.f Preparation of primary allylamines by a selective monoallylation of ammonia is not possible and they are prepared by indirect methods. The monoallylation... 

---